Expression Profiling of MicroRNAs in the Inner Ear of Elderly People by Real-Time PCR Quantification.

The molecular mechanisms underlying age-related hearing loss are unknown, and currently, there is no treatment for this condition. Recent studies have shown that microRNAs (miRNAs) and age-related diseases are intimately linked, suggesting that some miRNAs may present attractive therapeutic targets. In this study, we obtained 8 human temporal bones from 8 elderly subjects at brain autopsy in order to investigate the expression profile of miRNAs in the inner ear with miRNA arrays. A mean of 478 different miRNAs were expressed in the samples, of which 348 were commonly expressed in all 8 samples. Of these, levels of 16 miRNAs significantly differed between young elderly and old elderly subjects. miRNAs, which play important roles in inner ear development, were detected in all samples, i.e., in both young and old elderly subjects, whether with or without hearing loss. Our results suggest that these miRNAs play important roles not only in development, but also in the maintenance of inner ear homeostasis.

[Clinical Analysis of Evaluation of the Swallowing Function before Gastrostomy in an Acute-care Hospital for Elderly People].

The Ministry of Health, Labour and Welfare, while defining a significant reduction of the medical fee points for gastrostomy in the medical fee revision of fiscal year 2014, assigned additional fee points for evaluation of the swallowing function by videofluoroscopy (VF) or videoendoscopy (VE) prior to gastrostomy. In addition, for facilities that carried out more than 50 gastrostomy operations, evaluation of the swallowing function was made mandatory in all cases and 35% of oral ingestion recovery rate to require the full amount calculation. Therefore, we evaluated the data on swallowing function evaluation in patients and gastrostomy at our hospital. During a 3-year period from February 2012, 114 patients who underwent gastrostomy at our hospital were enrolled. We evaluated the background disease, indications for gastrostomy, conduct/non-conduct of swallowing function tests prior to gastrostomy, videoendoscopic score (VE score), and the functional oral intake score before and after gastrostomy in the patients. The predominant background diseases were cerebrovascular disease (33%), Parkinson's syndrome (26%), and Alzheimer's disease (11%). The indications for gastrostomy were dysphagia (38%), request for gastrostomy from other hospitals or nursing care home (24%), and malnutrition due to anorexia (18%). The severity of the dysfunction was classified based on the VE score as mild (28%), moderate (47%), or severe (25%). Dysphagia did not reach the majority of reasons for gastrostomy and not few of background diseases were progressive neurological diseases such as Parkinson's disease. Therefore, it remains under debate whether it is necessary to perform swallowing functional evaluation by VE or VF in all cases prior to gastrostomy. In some cases in which gastrostomy was indicated, the VE scores were not so high. Therefore, a comprehensive evaluation based on the pathophysiology and social background is needed to judge the indication for gastrostomy. Leading support and participation in the calculation of additional fee points for the evaluation of swallowing function is an urgent issue for otolaryngologists.

[What is the role of otolaryngologists in deglutition practice?--A survey for medical practitioners in different fields].

The advent of a super aging society is causing a rapid increase in the number of patients with dysphagia, and, in response, the use of percutaneous endoscopic gastrostomy (PEG) has become markedly widespread over the past decade. As the result of its rapid spread, PEG is controversial both ethically and economically, and, in the revision of medical treatment fees for 2014, the preoperative deglutition usability test of all cases is fixed for the full amount request requirements of gastrostomy. Thus, the demands on dysphagia practice are rising. Therefore, we conducted a survey of the dysphagia practice of otolaryngologists, doctors, and speech therapists in charge of dysphagia practice in hospitals, home medical care clinics, and dental offices in Itabashi-ku, Tokyo, and we considered the role of otolaryngologists in dysphagia practice. According to the survey, the roles that are expected of otolaryngologists in dysphagia practice are the evaluation of swallowing function using videoendoscopic examination of swallowing in over 50% of home medical care clinics and dental offices. On the other hand, surgical treatment is expected of otolaryngologists in over half in the hospital group. A total of 64% of the home care clinic group and 47% of the dental group did not coordinate with otolaryngologists in dysphagia practice because there are no otolaryngologists to consult. The home care clinic group indicated a demand of the swallowing function test in short-term admission or home practice. In the survey of departments of otolaryngology in hospitals or otolaryngology clinics, 40% of these institutions evaluate deglutition, while the other institutions did not perform evaluations because of the lack of human resources or deficient facilities. The otolaryngologist specializes in the laryngopharynx where aspiration occurs, and not only diagnoses local organic disease, but also directs the patient to a doctor in an appropriate department on the basis of understanding the patient's background diseases. We conclude that organized participation and leadership in this region are urgent tasks of otolaryngologist.

[Paratracheal lymph node metastasis from papillary thyroid carcinoma presented as a middle mediastinal cyst;report of a case].

The majority of middle mediastinal cysts are benign diseases. However, some cases of middle mediastinal cysts are revealed to be malignant tumor. We herein report a case of a middle mediastinal cyst, which proved to be a right paratracheal lymph node metastasis from the thyroid papillary carcinoma. The patient was a 67-year-old lady who had underwent thyroidectomy and regional lymph node dissection for papillary thyroid carcinoma 6 years before. Follow-up computed tomography revealed a growing cyst at the right-side of the intrathoracic trachea. Metastasis from thyroid cancer was suspected from her history. The right upper mediastinal lymphadenectomy through thoracoscopy was performed. Pathologically, the cyst was diagnosed as a metastasis from thyroid cancer, showing cystic change.

COVID-19 Omicron variant-induced laryngitis.

OBJECTIVES: The COVID-19 omicron variant has a low affinity for the lower respiratory tract. However, upper respiratory tract symptoms, such as nasal discharge and sore throat, characterize the infection with this variant. Therefore, in laryngeal stenosis, disease severity assessment through blood oxygen saturation has not been useful. METHODS: We report the case of "omicron laryngitis" in a 59-year-old male who visited the ear, nose, and throat (ENT) clinic with complaints of a sore throat and difficulty in swallowing saliva that persisted for a day. RESULTS: Laryngoscopy revealed severe swelling of the transglottic region and exudates on the larynx. He was then diagnosed with COVID-19 and subjected to emergency tracheostomy for airway management. Until the emergence of the omicron variant, COVID-19 showed mainly lower airway and mild upper airway inflammatory features. However, upper airway stenosis should be suspected in cases presenting with "muffled speech," "dysphagia," "severe pain on swallowing," and "inspiratory dyspnea or stridor." CONCLUSION: Therefore, laryngeal and pharyngeal evaluation using a flexible laryngoscope under appropriate infection control measures is necessary, considering the possibility of progression to fatal laryngeal stenosis, as noted in this case.

[Physician Burnout in COVID-19 Pandemic].

The coronavirus disease 2019 (COVID-19) outbreak has placed a heavy burden on healthcare workers. We conducted a burnout survey in three hospitals designated as COVID-19 priority hospitals in Tokyo during the third wave of the COVID-19 pandemic. The Japanese Burnout Scale showed higher values than the existing survey of physicians. In particular, burnout is caused by a "lack of motivation" due to the inability to provide general medical services. Based on this survey, we discuss the burnout experienced by physicians during the pandemic.

COVID-19 findings revealed via otolaryngological examination: Findings of a Japan Otorhinolaryngologist Association questionnaire.

OBJECTIVE: In Japan, many otolaryngologists provide primary care for patients with coronavirus disease 2019 (COVID-19). The purpose of this study was to analyze the characteristics of otorhinolaryngological findings in order to improve COVID-19 diagnostic systems in a primary care setting. METHODS: A total of 351 patients (mean age, 36.0 ± 15.4 years) diagnosed with COVID-19 by otolaryngologists who belong to the Japan Otorhinolaryngologists Association were included in the study. A web-based questionnaire was used to collect information regarding the timing of positive identification of COVID-19, the route of infection, symptoms, and findings in the tonsils, nasal cavity, pharynx, ear, and neck. A modified Centor score was calculated for cases in which age, symptoms, and tonsil and neck findings were described. RESULTS: Symptoms included fever (56%), olfactory disturbance (46%), and a sore throat (56%). Of the individuals considered, 63% had ordinary rhinoscopic findings, 21% experienced watery rhinorrhea, and 12% had observable mucosal redness. Further, 87% had ordinary tonsillar findings, 13% displayed tonsillar redness, with enlargement and white mucus observe in 2% and 1% of participants, respectively. A total of 193 patients had a calculated Centor score of 3 points in 2%, and scores of the remaining participants were ≤2 points. CONCLUSION: Of all patients considered, 40% had nasal findings and 4% had purulent nasal discharge. In contrast, only 13% of the patients had tonsillar findings, and no patients had Centor scores ≥4 points. Symptom differentiation from that of bacterial infections is difficult. In areas where COVID-19 is prevalent, the disease should be considered in patients presenting with fever, olfactory disturbances, and sore throat with minimal or no clinical findings in the nasal cavity and pharynx.

Management of tracheostomy in COVID-19 patients: The Japanese experience.

OBJECTIVE: Involvement in the tracheostomy procedure for COVID-19 patients can lead to a feeling of fear in medical staff. To address concerns over infection, we gathered and analyzed experiences with tracheostomy in the COVID-19 patient population from all over Japan. METHODS: The data for health-care workers involved in tracheostomies for COVID-19-infected patients were gathered from academic medical centers or their affiliated hospitals from all over Japan. RESULTS: Tracheostomies have been performed in 35 COVID-19 patients with a total of 91 surgeons, 49 anesthesiologists, and 49 surgical staff members involved. Twenty-eight (80%) patients underwent surgery more than 22 days after the development of COVID-19-related symptoms (11: 22-28 days and 17: ≥29 days). Thirty (85.7%) patients underwent surgery ≥ 15 days after intubation (14: 15-21 days, 6: 22-28 days, and 10: ≥29 days). Among the total of 189 health-care workers involved in the tracheostomy procedures, 25 used a powered air-purifying respirator (PAPR) and 164 used a N95 mask and eye protection. As a result, no transmission to staff occurred during the 2 weeks of follow-up after surgery. CONCLUSION: No one involved in tracheostomy procedures were found to have been infected with COVID-19 in this Japanese study. The reason is thought to be that the timing of the surgery was quite late after the infections, and the surgery was performed using appropriate PPE and surgical procedure. The indications for and timing of tracheostomy for severe COVID-19 patients should be decided through multidisciplinary discussion.

Questionnaire survey on nurses and speech therapists regarding dysphagia rehabilitation in Japan.

OBJECTIVE: Current interventions of dysphagia are not generalizable, and treatments are commonly used in combination. We conducted a questionnaire survey on nurses and speech therapists regarding dysphagia rehabilitation to understand the current situation in Japan. METHODS: The questionnaire was sent to 616 certified nurses in dysphasia nursing and 254 certified speech-language-hearing therapists for dysphagia. Based on "Summaries of training methods in 2014" by JSDR, 24 local indirect exercises, 11 general indirect exercises, and 13 direct exercises were selected. The Likert scale "How do you feel about each method" was used as follows: A; Frequency, B; Ease, C; Adherence, D; Effectiveness (1-5))?". RESULTS: Two hundred fifty (40%) nurses and 145 (57%) speech-language-hearing therapists (ST) responded to the questionnaire. The direct exercise was associated with a significantly high score in every question. In indirect exercises, "Cervical range of motion exercise," "Orofacial myofunctional exercise," "Lip closure exercise." "Ice massage of pharynx" and "Huffing" were used relatively frequently. "Balloon dilatation therapy" and "Tube exercise" was associated with a relatively high discrepancy for two questions. Frequency" and the sum of "Ease," "Adherence," and "Effectiveness." was significantly correlated for local indirect exercises (r2 = 0.928, P < 0.01), general indirect exercises (r2 = 0.987, P < 0.01), and direct exercises (r2 = 0.996, P < 0.01) (Fig. 5). CONCLUSION: This study examined the current situation of dysphagia rehabilitation in Japan. Our results aid to increase understanding and selection of rehabilitative treatments for dysphagia patients in Japan.

Extensive and rapid screening for major mitochondrial DNA point mutations in patients with hereditary hearing loss.

Sensorineural hearing loss (HL) is one of the most frequent clinical features in patients with mitochondrial diseases caused by mitochondrial DNA (mtDNA) mutations, and hearing is impaired in over half of all cases with mitochondrial disorders. This study analyzed 373 patients with suspected hereditary HL using an extensive and rapid suspension-array screening system for 29 major mtDNA mutations, including the m.1555A>G homoplasmic mutation in the MT-RNR1 gene, which causes non-syndromic sensorineural HL and aminoglycoside-induced HL, and the m.3243A>G heteroplasmic mutation in the MT-TL1 gene. This method is rapid and suitable for large-scale screening because universal 96-well plates are available for use, and because an analysis of each plate can be completed within 1 h. This system detected five different mtDNA mutations in 24 of the 373 (6.4%) patients. The m.1555A>G and m.3243A>G mutations were detected in 11 (2.9%) and 9 (2.7%) patients, respectively. In addition, three mutations, that is, m.8348A>G in the MT-TK gene, m.11778G>A in the MT-ND4 gene and 15498G>A in the MT-CYB gene were detected in one patient for each. This screening system is useful for the genetic diagnosis and epidemiological study of both syndromic and non-syndromic HL.

Value of barium swallow studies in predicting the response to rabeprazole in elderly patients with laryngopharyngeal reflux disease and nonerosive reflux disease in particular.

OBJECTIVES: Laryngopharyngeal reflux disease (LPRD) is an important cause of throat discomfort in the elderly. Our objective was to investigate the usefulness of barium swallow studies for the diagnosis of LPRD. METHODS: The subjects were 59 patients at least 60 years of age with LPRD suspected on laryngoscopic findings. We evaluated esophageal clearance using a barium swallow study and the upper gastrointestinal tract endoscopic findings of gastroesophageal reflux disease according to the revised Los Angeles classification, and correlated these findings with the effect of rabeprazole, a proton pump inhibitor. RESULTS: Among subjects with positive reflux findings in the esophageal phase of the barium swallow, rabeprazole was significantly effective (p = 0.0025). To identify nonerosive reflux disease, we analyzed the 50 cases with a negative Los Angeles classification of upper gastrointestinal tract endoscopic findings. Rabeprazole was again significantly effective in patients with positive findings for esophageal reflux (p = 0.0025). CONCLUSIONS: Among elderly patients with suspected LPRD, there was a positive correlation between impaired esophageal clearance on the barium swallow study and the effectiveness of rabeprazole. The barium swallow study could be a screening test for LPRD in elderly patients with throat discomfort.

Society of swallowing and dysphagia of Japan: Position statement on dysphagia management during the COVID-19 outbreak.

On April 14, the Society of Swallowing and Dysphagia of Japan (SSDJ) proposed its position statement on dysphagia treatment considering the ongoing spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The main routes of transmission of SARS-CoV-2 are physical contact with infected persons and exposure to respiratory droplets. In cases of infection, the nasal cavity and nasopharynx have the highest viral load in the body. Swallowing occurs in the oral cavity and pharynx, which correspond to the sites of viral proliferation. In addition, the possibility of infection by aerosol transmission is also concerning. Dysphagia treatment includes a broad range of clinical assessments and examinations, dysphagia rehabilitation, oral care, nursing care, and surgical treatments. Any of these can lead to the production of droplets and aerosols, as well as contact with viral particles. In terms of proper infection control measures, all healthcare professionals involved in dysphagia treatment must be fully briefed and must appropriately implement all measures. In addition, most patients with dysphagia should be considered to be at a higher risk for severe illness from COVID-19 because they are elderly and have complications including heart diseases, diabetes, respiratory diseases, and cerebrovascular diseases. This statement establishes three regional categories according to the status of SARS-CoV-2 infection. Accordingly, the SSDJ proposes specific infection countermeasures that should be implemented considering 1) the current status of SARS-CoV-2 infection in the region, 2) the patient status of SARS-CoV-2 infection, and 3) whether the examinations or procedures conducted correspond to aerosol-generating procedures, depending on the status of dysphagia treatment. This statement is arranged into separate sections providing information and advice in consideration of the COVID-19 outbreak, including "terminology", "clinical swallowing assessment and examination", "swallowing therapy", "oral care", "surgical procedure for dysphagia", "tracheotomy care", and "nursing care". In areas where SARS-CoV-2 infection is widespread, sufficient personal protective equipment should be used when performing aerosol generation procedures. The current set of statements on dysphagia management in the COVID-19 outbreak is not an evidence-based clinical practice guideline, but a guide for all healthcare workers involved in the treatment of dysphagia during the COVID-19 epidemic to prevent SARS-CoV-2 infection.

Improving the Quality of Life of Patients With Severe Dysphagia by Surgically Closing the Larynx.

OBJECTIVES:: The aim of this study was to elucidate the utility of the Kano method with surgical closure of the larynx by cricoid cartilage removal in improving quality of life in patients with severe dysphagia and their caregivers. METHODS:: Nine patients with severe dysphagia who underwent the Kano method were evaluated for oral intake and activities of daily living using the functional oral intake scale and the Barthel index, respectively, as indices of quality of life. Additionally, nutritional status, inflammation, and postoperative complications were assessed. Furthermore, 7 family caregivers were queried regarding frequency of sputum suction, mood of family caregivers, and postoperative satisfaction. RESULTS:: Functional oral intake scale and Barthel index scores as well as inflammation improved significantly after surgery ( P < .05). There were no severe complications or other complications requiring surgical intervention. The frequency of sputum suction was reduced postoperatively ( P < .05). The mood of family caregivers was significantly improved and satisfaction level was high postoperatively. CONCLUSIONS:: Surgical closure of the larynx is an appropriate choice for patients with irreversible severe dysphagia and impaired articulation or vocal function because quality of life is improved for both patients and family caregivers and the satisfaction of family caregivers is sufficient.

A 3-Dimensional Model of the Human Round Window Membrane.

OBJECTIVES: The round window membrane (RWM) is small in size, making it difficult to clarify its shape and structure. The authors examined a 40x magnified 3-dimensional model of the human RWM to clarify its morphologic aspects and characteristics. METHODS: An RWM specimen was obtained from an archival, formalin-fixed, decalcified, left temporal bone of an 84-year-old female cadaver. The data obtained by laser scanning microscopy were input into a 3-dimensional printer. After a model of the RWM was created, the following features were examined: striae on the surfaces, curvatures, thickness, and areas. Cross sections of the original specimen were made for histological observations. RESULTS: The contour of this RWM model was approximately elliptic, with a saddle shape. When illuminated from the scala tympani side, the surface facing the fossula exhibited dark anterior and clear posterior portions. A borderline appeared where the 2 portions were bound along the short axis of the ellipse. This borderline was identified as the line of inflection. Collagen fibers were shown to run parallel to the borderline in the posterior portion but were fanned out in the anterior portion. CONCLUSIONS: The magnified 3-dimensional model clarified gross anatomy and characteristics of the RWM. It is good teaching material for small tissues, such as the RWM.

Successful treatment of eosinophilic otitis media associated with severe bronchial asthma with an anti-IL-5 monoclonal antibody, mepolizumab.

Eosinophilic otitis media (EOM), which is characterized by the accumulation of eosinophils in middle ear effusion and the middle ear mucosa, is a refractory type of otitis media that is often associated with asthma. Although an early diagnosis and appropriate treatment are necessary to prevent the progression of hearing loss in patients with EOM, there are currently no well-established treatments for this condition. We treated a 60-year-old male patient with asthma and EOM. The patient's asthma was poorly controlled, despite the use of high-dose inhaled corticosteroids, long-acting beta-agonist treatment, and the regular use of systemic corticosteroids. Mepolizumab, an anti-IL-5 monoclonal antibody, was started to treat the patient's refractory asthma. At 4 months after the initiation of mepolizumab treatment, the patient's asthma, hearing, and middle ear effusion improved. The present case suggests that mepolizumab therapy can control EOM and asthma.

Quantitative analysis of mRNA in human temporal bones.

CONCLUSION: Well-preserved mRNA could be extracted from frozen human inner ears. Therefore, this study demonstrates that analysis of mRNA could be performed to study the molecular mechanisms of inner ear disorders using human specimens. OBJECTIVES: Analysis of RNA as well DNA is requisite to study the molecular mechanisms of inner ear disorders. Methods of isolating RNA from experimental animals have been established, while isolation of RNA from human inner ears is much more challenging. In the present study, we demonstrate a method by which messenger RNA (mRNA) was extracted from human inner ears and quantitatively analyzed. MATERIALS AND METHODS: COCH mRNA as well as GAPDH mRNA was extracted from membranous labyrinths dissected from three formalin-fixed and three frozen human temporal bones, removed at autopsy. The length of COCH mRNA and quantity of GAPDH mRNA was compared between the two groups by quantitative RT-PCR. RESULTS: COCH mRNA could be amplified as much as 976 bp in all three frozen specimens. By contrast, it was amplified to 249 bp in two of the three formalin-fixed specimens, with no amplification observed in the remaining. The quantity of amplifiable GAPDH mRNA in the formalin specimens was only 1% of that of the frozen specimens.

[When should tracheotomy be performed in bilateral vocal cord paralysis involving multiple system atrophy?].

OBJECTIVES: Bilateral vocal cord paralysis caused by central nervous system dysfunction results from such diverse causes as cerebrovascular disorder and neurodegenerative disease. Otolaryngologists are often consulted about indications of tracheostomy for such cases, but if their recognition of causative disease is insufficient, it is difficult to judge indications of tracheostomy. We reviewed tracheostomy cases due to bilateral vocal cord paralysis caused by multiple system atrophy (MSA) and considered points to keep in mind in such cases. MATERIALS AND METHODS: We diagnosed 9 cases of vocal cord midline fixation due to central bilateral vocal cord paralysis caused by MSA and treated by tracheostomy. We reviewed clinical conditions and suitable time for tracheostomy because it presents a specific clinical course. RESULTS: 7 cases were MSA-P and 2 cases were MSA-C. Inspiratory stridor in awaking and dysphasia was aggravated at the almost same time in 7 cases. DISCUSSION: Vocal cord abductor paralysis in MSA may cause sudden death, but when an otolaryngologist not familiar with this disease is asked for air way evaluation, it is possible to be diagnosed as no vocal cord paralysis because there is no an adductor disorder, so clinical course of MSA should be clarified more. In vocal cord midline fixation, it was expected that intervention by hypermyotony in the progress of Parkinsonism was a main factor, as was vocal cord abductor disorder due to a neurogenic change in the posterior cricoarytenoid muscle in MSA. The aggravation of dysphasia is an important index in judging the indication of tracheostomy.