Cholesteatoma, which potentially results from tympanic membrane retraction, is characterized by intractable local bone erosion and subsequent hearing loss and brain abscess formation. However, the ...pathophysiological mechanisms underlying bone destruction remain elusive. Here, we performed a single-cell RNA sequencing analysis on human cholesteatoma samples and identify a pathogenic fibroblast subset characterized by abundant expression of inhibin βA. We demonstrate that activin A, a homodimer of inhibin βA, promotes osteoclast differentiation. Furthermore, the deletion of inhibin βA /activin A in these fibroblasts results in decreased osteoclast differentiation in a murine model of cholesteatoma. Moreover, follistatin, an antagonist of activin A, reduces osteoclastogenesis and resultant bone erosion in cholesteatoma. Collectively, these findings indicate that unique activin A-producing fibroblasts present in human cholesteatoma tissues are accountable for bone destruction via the induction of local osteoclastogenesis, suggesting a potential therapeutic target.
This study was performed to determine whether endolymphatic sac surgery improves vestibular and cochlear endolymphatic hydrops 2 years after sac surgery and to elucidate the relationship between the ...degree of improvement of endolymphatic hydrops and the changes in vertigo symptoms, the hearing level, and the summating potential/action potential ratio (−SP/AP ratio) by electrocochleography (ECochG) in patients with Ménière’s disease (MD).
Twenty-one patients with unilateral MD who underwent sac surgery were included in this study. All patients underwent gadolinium-enhanced magnetic resonance imaging (Gd-MRI) before and 2 years after sac surgery. We evaluated the difference in vestibular and cochlear endolymphatic hydrops between before and after surgery in both ears and compared these findings with the frequency of vertigo attacks, hearing level, and ECochG findings.
In affected ears, the presence of vestibular endolymphatic hydrops and the frequency of vertigo attacks significantly decreased after surgery. However, affected ears showed no significant improvement in the presence of cochlear endolymphatic hydrops or the −SP/AP ratio by ECochG; there was also no significant improvement or deterioration in the hearing level.
The present findings suggest that sac surgery reduces vestibular endolymphatic hydrops and prevents aggravation of cochlear endolymphatic hydrops, and these changes lead to a reduction of vertigo attacks and suppress the progression of hearing impairment associated with vertigo attacks.
Bone homeostasis is maintained by a balance in activity between bone-resorbing osteoclasts and bone-forming osteoblasts. Shifting the balance toward bone resorption causes osteolytic bone diseases ...such as rheumatoid arthritis and periodontitis. Osteoclast differentiation is regulated by receptor activator of nuclear factor κB ligand (RANKL), which, under some pathological conditions, is produced by T and B lymphocytes and synoviocytes. However, the mechanism underlying bone destruction in other diseases is little understood. Bone destruction caused by cholesteatoma, an epidermal cyst in the middle ear resulting from hyperproliferation of keratinizing squamous epithelium, can lead to lethal complications. In this study, we succeeded in generating a model for cholesteatoma, epidermal cyst-like tissue, which has the potential for inducing osteoclastogenesis in mice. Furthermore, an in vitro coculture system composed of keratinocytes, fibroblasts, and osteoclast precursors was used to demonstrate that keratinocytes stimulate osteoclast differentiation through the induction of RANKL in fibroblasts. Thus, this study demonstrates that intercellular communication between keratinocytes and fibroblasts is involved in the differentiation and function of osteoclasts, which may provide the molecular basis of a new therapeutic strategy for cholesteatoma-induced bone destruction.
Abstract
Conclusions: To establish a system of differential diagnosis for vertigo/dizziness at the Emergency Department (ED), careful history-taking of complications and examinations of nystagmus ...should be helpful and therefore prepared by ED staff. Objectives: Vertigo/dizziness could come from various kinds of organs for equilibrium, sometimes resulting in an emergency due to the central origin. In the present study, we checked patients' background data at the ED in advance of a definitive diagnosis at the Department of Otolaryngology and examined the significance of the correlation between the data and the diagnosis. Methods: We studied a series of 120 patients with vertigo/dizziness, who visited the Departments of Emergency and Otolaryngology between April 2011 and March 2012. At the ED, we first checked patients' backgrounds and carried out neurologic and neuro-otologic examinations. At the Department of Otolaryngology, we finally diagnosed all the patients according to the criteria and classified the origins of vertigo/dizziness into central and non-central diseases. Results: The ratio of patients with disease of central origin was 12.5% and that for non-central origin was 87.5%. The risk factors for cerebrovascular disease such as hypertension, heart disease, and diabetes were also the risk factors for central vertigo/dizziness by the chi-squared test. To predict a central origin for vertigo/dizziness, only gaze nystagmus was the significant factor by multivariate regression analysis.
Abstract Objectives Some patients with sudden sensorineural hearing loss (SSNHL) are frustrated by residual tinnitus even after accomplishment of the treatment for SSNHL. In the present prospective ...study, we examined patients’ backgrounds of sex, laterality and age together with changes in hearing level and the tinnitus score after the onset of SSHNL to determine the prognostic factors of residual tinnitus after the final day of medical treatment for SSNHL. Methods Forty-four patients with SSNHL were all treated with systemic administration of steroids for 2 weeks and oral intake of vasoactive drugs and vitamin B12 for 6 months before accomplishment of the treatment for SSNHL. The hearing improvement rate (HIR) was determined by comparing the hearing level before and 6 months after the start of treatment. Tinnitus was subjectively evaluated by the tinnitus scoring questionnaire before, 6 and 24 months after the start of treatment. The score of a five-step evaluation of subjective tinnitus feelings, “loudness”, “duration” and “annoyance”, was recorded. Results HIR was significantly correlated with tinnitus score improvement (TSI) in “duration” at 6 months after the start of treatment compared with before treatment. The tinnitus score of all 3 items was significantly improved 6 months after the start of treatment compared with that before treatment but it was not significantly changed between 6 and 24 months after the start of treatment. TSI in “duration” between 6 and 24 months was significantly correlated with the patients’ age and HIR using multiple regression analysis. Conclusion According to the tinnitus scoring questionnaire, “duration” is the most reliable item for subjective evaluation of tinnitus accompanied by SSNHL. Generally, subjective feelings for residual tinnitus 6 months after the start of treatment for SSNHL are supposed to be almost the same, even at the 24th post-treatment month. Especially, younger patients with better hearing improvement are predicted to achieve further improvement of tinnitus between 6 and 24 months after the start of treatment.
The purpose of this study was to evaluate the functional duration and survival rate of tympanostomy ventilation tubes and the complications associated with their use in pediatric patients who ...underwent tube insertion for otitis media with effusion (OME). Complications were analyzed including recurrence and tympanic membrane perforation after the tube removal or extrusion.
Altogether, 447 ears from 234 pediatric patients younger than 15 years of age were studied retrospectively. All patients had undergone long-term tympanostomy ventilation tube: the Goode T-tube insertion for OME at the Osaka Women's and Children's Hospital, which is the pediatrics specialty hospital between April 2014 and March 2016. They were typically followed up every 3–4 months or more frequently if necessary due to otorrhea or tube infection. Subsequently, the tube duration, survival rates of the tube especially at 22 months after insertion defined as “full-term placement”, and the rates of recurrence and perforation were calculated and statistically evaluated.
Of 447 ears, 335 ears from 184 patients underwent their first tube insertion, and 112 ears from 64 patients underwent their second or subsequent tube insertion within the targeted period. Two hundred ears from 106 patients were associated with a cleft palate. The survival rate at full-term placement was 51.7%. The recurrence rate was 56.3%, and the rate of the tympanic perforation was 8.5%.
Approximately half of the tubes survived for 22 months. The perforation rate was relatively low; however, recurrence of OME was seen in more than half the ears.
Cholesteatoma starts as a retraction of the tympanic membrane and expands into the middle ear, eroding the surrounding bone and causing hearing loss and other serious complications such as brain ...abscess and meningitis. Currently, the only effective treatment is complete surgical removal, but the recurrence rate is relatively high. In rheumatoid arthritis (RA), osteoclasts are known to be responsible for bone erosion and undergo differentiation and activation by receptor activator of NF-κB ligand (RANKL), which is secreted by synovial fibroblasts, T cells, and B cells. On the other hand, the mechanism of bone erosion in cholesteatoma is still controversial. In this study, we found that a significantly larger number of osteoclasts were observed on the eroded bone adjacent to cholesteatomas than in unaffected areas, and that fibroblasts in the cholesteatoma perimatrix expressed RANKL. We also investigated upstream transcription factors of RANKL using RNA sequencing results obtained via Ingenuity Pathways Analysis, a tool that identifies relevant targets in molecular biology systems. The concentrations of four candidate factors, namely interleukin-1β, interleukin-6, tumor necrosis factor α, and prostaglandin E2, were increased in cholesteatomas compared with normal skin. Furthermore,
interleukin-1β
was expressed in infiltrating inflammatory cells in the cholesteatoma perimatrix. This is the first report demonstrating that a larger-than-normal number of osteoclasts are present in cholesteatoma, and that the disease involves upregulation of factors related to osteoclast activation. Our study elucidates the molecular basis underlying bone erosion in cholesteatoma.
Networked control systems (NCSs) using the Internet will soon become widespread. In NCSs, time delays and information losses cause system performance degradation and destabilization. It is known that ...a communication disturbance observer (CDOB)-based compensator can estimate and suppress the effect of time delays on the system as a network disturbance. We applied a CDOB-based compensator to NCSs with not only time delays but also information losses and theoretically analyzed the information-loss compensation scheme. However, the performance of the CDOB-based compensator for only information losses in real NCSs has not been experimentally evaluated. This letter demonstrates an information-loss compensation scheme using a CDOB for NCSs. Experiments using a networked motion control system show that the CDOB-based compensator can estimate and suppress the effect of information losses on an NCS.
AbstractConclusions: Serum squamous cell carcinoma antigen (SCC-Ag) level was an independent prognostic factor for survival in patients with head and neck squamous cell carcinoma (HNSCC), and the ...prognostic value depended on the carcinoma site. Objectives: To assess the value of SCC-Ag as a prognostic indicator in patients with HNSCC and to determine the effect of primary tumor site on prognosis. Methods: We reviewed 493 patients with HNSCC between 2004 and 2012. The chi-squared test was used to assess associations between SCC-Ag levels and TNM classification. A Cox proportional hazard model was used to assess the hazard ratio of SCC-Ag at different sites for death, and it was analyzed as a continuous variable. Results: The median serum level of SCC-Ag was 1.1 ng/ml (range 0-20). SCC-Ag was significantly higher in patients with advanced T and N classification tumors. Primary sites in the oral cavity, in the hypopharynx, advanced T and N classification, distant metastasis, and SCC-Ag were negatively associated with survival in univariate analysis. Multivariate analysis revealed that SCC-Ag was a significant risk factor for overall survival in cancers of the oral cavity, hypopharynx, and larynx, but not in oropharyngeal cancer.
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