A Multicenter Cohort Study on the Association between Metformin Use and Hearing Loss in Patients with Type 2 Diabetes Mellitus Using a Common Data Model.

We attempted to explore the association between metformin use and hearing loss in in a large-scale study. This retrospective multicenter cohort study assessed the data of patients with type 2 diabetes mellitus (DM) aged over 40 years using the Observational Health Data Science and Informatics open-source software and the Common Data Model database from 1 January 2002 to 31 December 2019. Each participant was selected using the ICD-10-CM diagnosis code E11 for type 2 DM with sensorineural hearing loss. The participants were divided into metformin and non-metformin users. The outcome measure was the first occurrence of hearing loss after the diagnosis of DM as measured by the CDM cohort study. A total of 80,596 patients, including 46,152 metformin users and 34,444 non-metformin users from three hospitals were assessed. After calibration, we compared the risk of hearing loss using Kaplan-Meier curves, and found significant differences between the groups. The calibrated hazard ratio in the three hospitals (0.79 [95% confidence interval, 0.57-1.12]) was summarized. These findings suggest that the probability of hearing loss-free survival in the metformin user group is higher than that in the non-metformin user group.

Analysis of auditory brain stem response and otoacoustic emission in unilateral tinnitus patients with normal hearing.

OBJECTIVE: In patients with unilateral tinnitus with normal hearing, several studies have compared the ipsilateral and contralateral ears; however, few studies have investigated its relationship with the duration of tinnitus. We compared the auditory brainstem response and otoacoustic emission parameters between ipsilateral and contralateral ears in adults with unilateral tinnitus and normal hearing. METHODS: This retrospective review included 84 patients with unilateral tinnitus and normal hearing who underwent auditory brainstem response and otoacoustic emission; they were categorized according to the duration of tinnitus. The latencies and amplitudes of waves I, III, and V, and V/I ratio of both ears in auditory brainstem response, and the results of distortion-product otoacoustic emission and transient evoked otoacoustic emission were examined. The auditory brainstem response parameters, distortion-product otoacoustic emission parameters, and transient evoked otoacoustic emission parameters between the ipsilateral and contralateral ears along the duration of tinnitus were analyzed. Moreover, the failure rates of both distortion-product otoacoustic emission and transient evoked otoacoustic emission between the ears along with the duration and the effects of the variables on the amplitude and latency of each wave were examined. RESULTS: In this study, laterality seemed to have an effect on wave I latency in the multiple linear regression analysis. The distortion-product otoacoustic emission failure rate of the ipsilateral ear was higher than that of the contralateral ear in all patients. However, there was no remarkable difference between the ears in the distortion-product otoacoustic emission and transient evoked otoacoustic emission parameters throughout the duration. CONCLUSION: We found that outer hair cells and the distal portion of the cochlear nerve are possible pathologic lesions in tinnitus with normal hearing and cochlear synaptopathy could be suspected. Further studies, including those on inner hair cells and higher central cortex, are needed.

Functional Outcomes of Single-Stage Ossiculoplasty in Chronic Otitis Media With or Without Cholesteatoma.

BACKGROUND: Two-stage ossiculoplasty has been widely used for hearing improvement in chronic otitis media with or without cholesteatoma. However, the outcomes of single-stage ossiculoplasty have not been fully clarified.The aim of this study is to determine whether the outcomes of single-stage ossiculoplasty are comparable with those of 2-stage ossiculoplasty in chronic otitis media with or without cholesteatoma. METHODS: Medical records of 191 cases (187 patients) who underwent single-stage ossiculoplasty from January 2011 to May 2018 at our hospital were retrospectively reviewed. RESULTS: Polycel and titanium were used in 56 and 135 cases, respectively. In chronic otitis media without cholesteatoma, the success rate of polycel and titanium partial ossicular replacement prosthesis was 80.7% and 81.6%, respectively. In chronic otitis media with cholesteatoma, the success rate of polycel and titanium partial ossicular replacement prosthesis was 63.6% and 64.6%, respectively, while that of polycel and titanium total ossicular replacement prosthesis was 45.9% and 47.8%, respectively. CONCLUSION: These results suggest that single-stage ossiculoplasty is a suitable option for recovering postoperative hearing in chronic otitis media with or without cholesteatoma. Thus, if middle ear inflammation can be sufficiently treated in the first stage, single-stage ossiculoplasty is a suitable option for chronic otitis media with or without cholesteatoma.

A clinical trial of a patient-customized virtual reality intervention for tinnitus.

Virtual reality (VR) has recently been used as a clinical treatment because it can efficiently simulate situations that are difficult to control in real-world settings. In our study, we assessed the potential of VR in patients with chronic subjective tinnitus. An evaluation of its clinical benefits was performed based on analyses of patient electroencephalograms (EEGs) and by questionnaire responses after 6-8 weeks of patient involvement in our VR-based alleviation program. Clinical trials were performed at a tertiary academic hospital. Nineteen patients (aged 33-64 years) who visited our hospital with chronic subjective tinnitus over 3 months were enrolled in the study. The intervention consisted of trashing the tinnitus avatar in VR. We expected that the patients would have the subjective feeling of controlling tinnitus through our intervention. The VR environment comprised four different sessions in four different settings: a bedroom, a living room, a restaurant, and a city street. We analyzed changes in the source activities of the prefrontal regions related to tinnitus in these patients using standardized low-resolution brain electromagnetic tomography. The Tinnitus Handicap Inventory (THI), the total score (from 50.11 to 44.21, P = 0.046) and the grade (from 3.16 to 2.79, P = 0.035) were significantly improved after the VR-based tinnitus treatment program (P < 0.05). The Pittsburgh Sleep Quality Index also showed improved outcomes (P = 0.025). On the other hand, a Tinnitus Handicap Questionnaire, Quality of Life Assessment (WHO-QOL), Hospital Anxiety and Depression Scale, Profile of Mood States revealed no significant change after the intervention. The baseline EEG data showed that brain activity in the orbitofrontal cortex significantly increased in the alpha and theta frequency bands. Furthermore, patients who showed a THI score improvement after the intervention showed specific increases in brain activity for the theta and high beta bands in the orbitofrontal cortex. Our findings suggest that the virtual reality-based program, as in parts of cognitive behavioral treatment, may help to alleviate tinnitus-related distress in patients with chronic subjective tinnitus.

Growth inhibition of luteolin on HepG2 cells is induced via p53 and Fas/Fas-ligand besides the TGF-ß pathway.

Flavonoids, a class of natural polyphenolic compounds, inhibit cell cycle progression and induce apoptosis. This study was performed to investigate the antiproliferative effect of luteolin, the flavonoid isolated from Ixeris sonchifolia Hance, and to elucidate the detailed apoptotic mechanism in HCC cells. According to the result of MTT assay luteolin possessed antiproliferative effect, and HepG2 cells were the most sensitive to luteolin. Propidium iodide staining, fluorescence activated cell sorting analysis, western blot analysis and RT-PCR were applied to compare the difference of apoptotic event between the two HCC cell lines, with wild-type p53 (HepG2) or not (Hep3B) based on time and concentration. The treatment of luteolin upregulated the expression levels of transforming growth factor ß1 (TGF­ß1), p21WAF1/CIP1, p27KIP1, Smad4, and Fas in HCC cells. Thus, the expression of p21WAF1/CIP1 was controlled by another factor, such as TGF­ß1 in addition to p53, and notably the key factor might be p21WAF1/CIP1 in the remarkable switch to G1 cell cycle arrest in HepG2 cells rather than p27KIP1. Luteolin induced apoptotic cell death in Hep3B cells while caused G1 arrest in HepG2 cells. Taken together, we conclude that luteolin induces apoptosis from G1 arrest via three signaling pathways of TGF­ß1, p53, and Fas/Fas-ligand in HCC cells.