Increased risk of psychiatric disorder in patients with hearing loss: a nationwide population-based cohort study.

BACKGROUND: Hearing loss has been shown to be a risk factor for psychiatric disorders. In addition, long-term hearing loss is associated with increased hospitalization and mortality rates; however, the increased risk and duration of effect of hearing loss in combination with other chronic diseases on each psychiatric disorder are still not clearly defined. The purpose of this article is to clarify the risk of hearing loss for each disorder over time. METHODS: This was a retrospective cohort study, and a national health insurance research database in Taiwan was utilized. All (n = 1,949,101) Taiwanese residents who had a medical visit between 2000 and 2015 were included. Patients with hearing loss and a comparative retrospective cohort were analyzed. Every subject was tracked individually from their index date to identify the subjects who later received a diagnosis of a psychiatric disorder. The Kaplan‒Meier method was used to analyze the cumulative incidence of psychiatric disorders. Cox regression analysis was performed to identify the risk of psychiatric disorders. RESULTS: A total of 13,341 (15.42%) and 31,250 (9.03%) patients with and without hearing loss, respectively, were diagnosed with psychiatric disorders (P < 0.001). Multivariate analysis indicated that hearing loss significantly elevated the risk of psychiatric disorders (adjusted HR = 2.587, 95% CI 1.723-3.346, p < 0.001). CONCLUSION: Our findings indicate that patients with hearing loss are more likely to develop psychiatric disorders. Furthermore, the various psychiatric disorders are more likely to occur at different times. Our findings have important clinical implications, including a need for clinicians to implement early intervention for hearing loss and to pay close attention to patients' psychological status. Trial registration TSGHIRB No. E202216036.

Solitary Bone Plasmacytoma of the Skull Base With an Unusual Presentation.

Solitary bone plasmacytoma (SBP) is a rare hematological malignancy that usually occurs in the spine and rarely in the skull. It rarely presents in the skull base, but presenting symptoms are associated with cranial nerve involvement depending on the site of the disease. We present the case of a 61-year-old man with an unusual presentation of hoarseness secondary to vocal fold palsy. Imaging showed a large bony lesion in the temporo-occipital region with involvement of the jugular foramen. Further detailed diagnostic procedures confirmed SBP of the skull base. Radiotherapy was given with an uneventful recovery of vocal fold function. Skull base plasmacytoma can be considered as a differential diagnosis of causes of unilateral vocal fold palsy. Early therapeutic management may improve vocal fold function.

GRAIL gene knockout mice protect against aging-related and noise-induced hearing loss.

BACKGROUND: Hearing loss is a global health issue and its etiopathologies involve complex molecular pathways. The ubiquitin-proteasome system has been reported to be associated with cochlear development and hearing loss. The gene related to anergy in lymphocytes ( GRAIL ), as an E3 ubiquitin ligase, has not, as yet, been examined in aging-related and noise-induced hearing loss mice models. METHODS: This study used wild-type (WT) and GRAIL knockout (KO) mice to examine cochlear hair cells and synaptic ribbons using immunofluorescence staining. The hearing in WT and KO mice was detected using auditory brainstem response. Gene expression patterns were compared using RNA-sequencing to identify potential targets during the pathogenesis of noise-induced hearing loss in WT and KO mice. RESULTS: At the 12-month follow-up, GRAIL KO mice had significantly less elevation in threshold level and immunofluorescence staining showed less loss of outer hair cells and synaptic ribbons in the hook region compared with GRAIL WT mice. At days 1, 14, and 28 after noise exposure, GRAIL KO mice had significantly less elevation in threshold level than WT mice. After noise exposure, GRAIL KO mice showed less loss of outer hair cells in the cochlear hook and basal regions compared with WT mice. Moreover, immunofluorescence staining showed less loss of synaptic ribbons in the hook regions of GRAIL KO mice than of WT mice. RNA-seq analysis results showed significant differences in C-C motif chemokine ligand 19 ( CCL19 ), C-C motif chemokine ligand 21 ( CCL21 ), interleukin 25 ( IL25 ), glutathione peroxidase 6 ( GPX6 ), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 ( NOX1 ) genes after noise exposure. CONCLUSION: The present data demonstrated that GRAIL deficiency protects against aging-related and noise-induced hearing loss. The mechanism involved needs to be further clarified from the potential association with synaptic modulation, inflammation, and oxidative stress.

The association between hormone therapy and the risk of lung cancer in postmenopausal women: a 16-year nationwide population-based study.

OBJECTIVE: Although an association between hormone therapy (HT) and the risk of developing lung cancer has been reported, the results on the topic are inconsistent. Our study objective was to investigate whether postmenopausal women who undergo HT exhibit a risk of developing lung cancer. METHODS: In this matched cohort study, we obtained the data of 38,104 postmenopausal women older than 45 years who were treated using HT between 2000 and 2015 from Taiwan's National Health Insurance Research Database, and 152,416 matched participants who were not treated using HT were enrolled as controls at a 1:4 ratio. RESULTS: We used a Cox proportional hazards regression model to identify the risk of developing lung cancer during 16 years of follow-up, and the results indicate no significant difference in the proportion of postmenopausal women treated using HT ( P = 0.129) who developed lung cancer and that of those not treated using HT (0.866% [330 of 38,104] vs 0.950% [1,449 of 152,416]). After adjustment for age and other variables, the adjusted hazard ratio was 0.886 (95% CI, 0.666-1.305, P = 0.433), indicating no association between HT and lung cancer development in postmenopausal women. In a subgroup analysis, the risk of lung cancer was significantly lower in the women who were treated using HT when the HT cumulative dosage was ≥401 mg or when the therapy duration was ≥5 years compared with in those not treated using HT; the adjusted hazard ratios were 0.633 (95% CI, 0.475-0.930; P < 0.001) and 0.532 (95% CI, 0.330-0.934; P < 0.001), respectively, after adjustment. CONCLUSIONS: Our results indicate that HT is not associated with the risk of lung cancer development in postmenopausal women; furthermore, a higher cumulative dosage and the long-term effects of HT reduce the risk of developing lung cancer.

Inflammatory Pseudotumour of Temporal Bone in a Multiple-Comorbidity Patient.

Inflammatory pseudotumour (IPT) of the temporal bone is relatively rare in the head and neck, but it is important for clinicians to be aware of this emerging entity. A 39-year man presented with a protruding reddish mass over the left external ear. High-resolution Computed Tomography and Magnetic Resonance Imaging of temporal bone showed soft tissue collection in the left external ear, middle ear, and mastoid cavity with bony erosion. The patient first received modified radical mastoidectomy. Several surgeries were required for recurrences with eventual intracranial invasion within 2 years. The pathology showed chronic inflammation without malignancy, autoimmune or infectious pathologies. Based on the clinical manifestations, IPT was diagnosed. Finally, radiation therapy (RT) with 30 Gy was given. There was no recurrence following the RT course. Early recognition of IPT presenting as a recurrent and locally aggressive inflammatory lesion in the temporal bone is necessary to achieve favorable outcomes. Key Words: Inflammatory pseudotumour, Temporal bone, Radiation therapy.

The Association Between Dextromethorphan Use and the Risk of Dementia.

Dementia is one of neurodegenerative disease without preventive medicine currently. Dextromethorphan (DXM) has been reported to reduce neuronal damage and neurodegeneration in animal and human models. The effect of DXM on the dementia has not been fully examined. We examined the medical records over 40 years old in Taiwan's National Health Insurance Research Database between 2000 and 2015 to establish matched cohorts. We used a Cox regression hazard model to identify risk factors of dementia during 16 years of follow-up, and the results indicate that a significantly lower percentage of subjects with DXM use (P < .001) developed dementia compared with those without DXM use (11.38%, 4541/39 895 vs 18.66%, 29 785/159 580). After adjustment for age and other variables [adjusted hazard ratio: .567 (95% confidence interval: .413-.678, P < .001)], this study also demonstrated that DXM use appeared to reduce the risk of developing dementia. DXM use may potentially provide a protective effect against dementia.

Gastrointestinal Endoscopy Performed by Gastroenterologists: Opportunistic Screening Strategy for Newly Diagnosed Head and Neck Cancers.

Aim: Approximately 66% of head and neck cancers are diagnosed at an advanced stage. This prospective study aimed to detect newly diagnosed head and neck cancers using regular upper gastrointestinal (UGI) endoscopy with oral-pharynx-larynx examination. Methods: A total of 2,849 patients underwent UGI endoscopy with an additional oral-pharynx-larynx examination. Patients aged < 20 years, those who were pregnant, had a history of head and neck cancers, were undergoing emergency endoscopy, and had a poor laryngopharyngeal view were excluded. The symptoms, incidence, location, pathology, and stage of malignant neoplasms were investigated. Results: A total of 2,720 patients were enrolled. Endoscopically observable 23 abnormal findings (0.85%) included 18 (0.66%) benign lesions and 5 (0.18%) newly diagnosed malignant neoplasms. Notably, 4 (80%) of 5 patients with malignant neoplasms were diagnosed at an early stage (Stage 0, I, and II). Conclusions: UGI endoscopy with oral-pharynx-larynx examination can achieve opportunistic head neck cancer screening and is recommended for every patient in endoscopy units.

Solitary neurofibroma in the external auditory canal.

Significance Statement: Neurofibromas, derived from perineural cells, are usually benign in the nervous system. Although neurofibromas are common in the head and neck, they rarely affect the external auditory canal (EAC), and few cases have been reported. We describe a case of a solitary EAC neurofibroma with otoscopy, radiological imaging, a surgical approach, and an uneventful outcome.

Bilateral sudden sensorineural hearing loss in patient with Behçet disease.

Bacckground: Approximately 80% to 85% of sudden sensorineural hearing loss (SSNHL) is idiopathic, but immune-mediated mechanisms are thought to be involved. Behçet disease is an autoinflammatory vasculitis that may involve vessels of the inner ear. It can cause sensorineural hearing loss (SNHL) and an increased risk of SSNHL. Study Sample: We report a 21-year-old man who was diagnosed with Behçet disease in childhood and presented to our clinic with a 10-day history of abrupt hearing deterioration in both ears. Pure-tone audiometry showed severe to profound bilateral SNHL. Results: Oral prednisolone was prescribed for 3 weeks. Concurrent intratympanic steroid injections (ITSIs) were administered in each ear every 2 days for 5 days. A total of 15 daily sessions of hyperbaric oxygen therapy (HBOT) were completed. Acupuncture was performed every 2 days for 1 month. After these combined therapies, the patient's hearing threshold by 20 dB and his speech recognition threshold were improved. Conclusions: Some patients with SSNHL recover no hearing improvement after routine treatment, and alternative treatments including ITSI, HBOT, and acupuncture can be considered as optional. We used an aggressive multimodal approach to treat severe bilateral SSNHL in patient with Behçet disease.

Ultrasound Microbubble-Facilitated Inner Ear Delivery of Gold Nanoparticles Involves Transient Disruption of the Tight Junction Barrier in the Round Window Membrane.

The application of ultrasound microbubbles (USMBs) enhances the permeability of the round window membrane (RWM) and improves drug delivery to the inner ear. In this study, we investigated the efficiency of USMB-aided delivery of chitosan-coated gold nanoparticles (CS-AuNPs) and the mechanism of USMB-mediated enhancement of RMW permeability. We exposed mouse inner ears to USMBs at an intensity of 2 W/cm2 and then filled the tympanic bulla with CS-AuNPs or fluorescein isothiocyanate-decorated CS-AuNPs (FITC-CS-AuNPs). The membrane uptake of FITC-CS-AuNPs and their depth of permeation into the three-layer structure of the RWM, with or without prior USMB treatment, were visualized by z-stack confocal laser scanning microscopy. Ultrastructural changes in the RWM due to USMB-mediated cavitation appeared as sunburn-like peeling and various degrees of depression in the RWM surface, with pore-like openings forming in the outer epithelium. This disruption of the outer epithelium was paralleled by a transient reduction in tight junction (TJ)-associated protein levels in the RWM and an enhanced delivery of FITC-CS-AuNPs into the RWM. Without prior USMB exposure, the treatment with CS-AuNPs also caused a noticeable reduction in TJ proteins of the RWM. Our findings indicated that the combined treatment with USMBs and CS-AuNPs represents a promising and efficient drug and gene delivery vehicle for a trans-RWM approach for inner ear therapy. The outer epithelial layer of the RWM plays a decisive role in controlling the transmembrane transport of substances such as CS-AuNPs following the administration of USMBs. Most importantly, the enhanced permeation of AuNPs involved the transient disruption of the TJ-created paracellular barrier in the outer epithelium of the RWM.

Ultrasound Microbubbles Enhance the Efficacy of Insulin-Like Growth Factor-1 Therapy for the Treatment of Noise-Induced Hearing Loss.

The application of insulin-like growth factor 1 (IGF-1) to the round window membrane (RWM) is an emerging treatment for inner ear diseases. RWM permeability is the key factor for efficient IGF-1 delivery. Ultrasound microbubbles (USMBs) can increase drug permeation through the RWM. In the present study, the enhancing effect of USMBs on the efficacy of IGF-1 application and the treatment effect of USMB-mediated IGF-1 delivery for noise-induced hearing loss (NIHL) were investigated. Forty-seven guinea pigs were assigned to three groups: the USM group, which received local application of recombinant human IGF-1 (rhIGF-1, 10 µg/µL) following application of USMBs to the RWM; the RWS group, which received IGF-1 application alone; and the saline-treated group. The perilymphatic concentration of rhIGF-1 in the USM group was 1.95- and 1.67- fold of that in the RWS group, 2 and 24 h after treatment, respectively. After 5 h of 118 dB SPL noise exposure, the USM group had the lowest threshold shift in auditory brainstem response, least loss of cochlear outer hair cells, and least reduction in the number of synaptic ribbons on postexposure day 28 among the three groups. The combination of USMB and IGF-1 led to a better therapeutic response to NIHL. Two hours after treatment, the USM group had significantly higher levels of Akt1 and Mapk3 gene expression than the other two groups. The most intense immunostaining for phosphor-AKT and phospho-ERK1/2 was detected in the cochlea in the USM group. These results suggested that USMB can be applied to enhance the efficacy of IGF-1 therapy in the treatment of inner ear diseases.

Quantitative spectroscopic comparison of the optical properties of mouse cochlea microstructures using optical coherence tomography at 1.06†µm and 1.3†µm wavelengths.

Currently, the cochlear implantation procedure mainly relies on using a hand lens or surgical microscope, where the success rate and surgery time strongly depend on the surgeon's experience. Therefore, a real-time image guidance tool may facilitate the implantation procedure. In this study, we performed a systematic and quantitative analysis on the optical characterization of ex vivo mouse cochlear samples using two swept-source optical coherence tomography (OCT) systems operating at the 1.06-µm and 1.3-µm wavelengths. The analysis results demonstrated that the 1.06-µm OCT imaging system performed better than the 1.3-µm OCT imaging system in terms of the image contrast between the cochlear conduits and the neighboring cochlear bony wall structure. However, the 1.3-µm OCT imaging system allowed for greater imaging depth of the cochlear samples because of decreased tissue scattering. In addition, we have investigated the feasibility of identifying the electrode of the cochlear implant within the ex vivo cochlear sample with the 1.06-µm OCT imaging. The study results demonstrated the potential of developing an image guidance tool for the cochlea implantation procedure as well as other otorhinolaryngology applications.

Combined Acupuncture-Hyperbaric Oxygen-Steroids Therapy for Idiopathic Sudden Sensorineural Hearing Loss: A Retrospective Observational Study.

Objectives: Acupuncture, widely used in Chinese society, has been studied as an adjunct treatment of idiopathic sudden sensorineural hearing loss (ISSNHL). The purpose of this study is to investigate the effectiveness of combined acupuncture and hyperbaric oxygen therapy (HBOT) with conventional steroid therapy for ISSNHL. Methods: This retrospective chart review enrolled 154 patients who met the ISSNHL criteria and were categorized into three groups according to the different treatment regimens. Among these patients, 43 underwent steroid therapy only (S) group, 74 received steroid and HBOT (S-H) group, and the remaining 37 were treated with combined acupuncture-HBOT in addition to steroid therapy (S-H-A) group. The outcome was determined by comparing the differences in pure-tone thresholds and absolute hearing gains after treatment calculated at each audiometric octave frequency or grouped frequencies of audiograms. Hearing recoveries classified into three grades: complete, partial, and poor were also analyzed and compared among different treatment groups. Results: All subjects presented with initial severe hearing loss with averaged hearing thresholds >70 dB. The S-H-A group exhibited good hearing improvement outcomes at each audiometric octave frequency and grouped frequencies of audiograms, with greater hearing gain and had more favorable outcomes in hearing recovery grades compared with the S group and the S-H group. Conclusions: The results obtained in this study revealed a preliminary finding of ISSNHL patients benefiting from combined acupuncture, HBOT, and conventional steroid therapy. Acupuncture is a safe and nonpharmacologic treatment option and can be considered as an initial treatment strategy in such a clinical scenario.