EBF1 Limits the Numbers of Cochlear Hair and Supporting Cells and Forms the Scala Tympani and Spiral Limbus during Inner Ear Development.

Early B-cell factor 1 (EBF1) is a basic helix-loop-helix transcription factor essential for the differentiation of various tissues. Our single-cell RNA sequencing data suggest that Ebf1 is expressed in the sensory epithelium of the mouse inner ear. Here, we found that the murine Ebf1 gene and its protein are expressed in the prosensory domain of the inner ear, medial region of the cochlear duct floor, otic mesenchyme, and cochleovestibular ganglion. Ebf1 deletion in mice results in incomplete formation of the spiral limbus and scala tympani, increased number of cells in the organ of Corti and Kölliker's organ, and aberrant course of the spiral ganglion axons. Ebf1 deletion in the mouse cochlear epithelia caused the proliferation of SOX2-positive cochlear cells at E13.5, indicating that EBF1 suppresses the proliferation of the prosensory domain and cells of Kölliker's organ to facilitate the development of appropriate numbers of hair and supporting cells. Furthermore, mice with deletion of cochlear epithelium-specific Ebf1 showed poor postnatal hearing function. Our results suggest that Ebf1 is essential for normal auditory function in mammals.

Validation of indications for enucleation for benign parotid gland tumors.

BACKGROUND: Enucleation has been reported as a minimally invasive surgery for Warthin's tumor (WT). However, the definite indications for enucleation have not been clarified. METHODS: Enucleation was indicated by the following findings: findings of WT, cystic fluid, or benign leukocytes by fine-needle aspiration cytology; a well-margined and homogeneous pattern on imaging; and a tumor location in the tail or preauricular area of the parotid gland. We reviewed 552 cases treated with parotid gland surgery in our hospital. RESULTS: A total of 108 tumors were treated with enucleation and included no malignant solid tumors or pleomorphic adenoma. Enucleation demonstrated low invasiveness and complication rates. Revision surgery for WT reappearance after enucleation was rare and showed minimal scarring, with a lower risk of facial weakness. CONCLUSIONS: The indication criteria for enucleation were validated. Such enucleation is useful, as it is associated with minimal invasiveness, low complication rates, and safety in revision surgery.

A New Device for Fine-Needle Aspiration Cytology Consisting of a Vibrating Linear Resonant Actuator.

OBJECTIVE: To evaluate the efficacy of a new device for fine-needle aspiration cytology (FNAC) consisting of a vibrating linear resonant actuator (LRA). STUDY DESIGN: Prospective clinical study. METHODS: The LRA frequency was optimized by visualization of the needle motion using a high-speed camera. The FNAC device consists of a vibrating motor fixed to the stopper of a 5-ml syringe and piston. Upon insertion of the syringe needle into a thyroid nodule (with the stopper attached to the syringe piston), sufficient negative pressure with 1-ml suction was maintained. Subsequently, samples were obtained using vibration generated by an LRA or an eccentric rotating mass (ERM). Surgically resected thyroid specimens from 10 patients were evaluated. The number of follicular groups required for adequate diagnosis and the number of larger follicular groups were counted. Next, 254 thyroid nodules from 187 patients were also evaluated by FNAC. The inadequacy rate was determined, and final cytology was classified according to thyroid Bethesda categories. RESULTS: The optimized LRA frequency was 155 Hz. Both the LRA and ERM devices resulted in sufficient amounts of diagnostic material and achieved low inadequacy rates. The number of large follicular groups obtained was significantly greater with the LRA device compared with the ERM device. CONCLUSIONS: The vibrating device using an LRA for thyroid FNAC resulted in sufficient amounts of thyroid follicular groups and achieved low inadequacy rates. In addition, the LRA device allowed for collection of larger follicular groups sufficient to diagnose appropriate thyroid Bethesda categories. LEVEL OF EVIDENCE: 2 Laryngoscope, 131:E1393-E1399, 2021.

Successful treatment of eosinophilic chronic rhinosinusitis and eosinophilic otitis media using the anti-IL-5 receptor monoclonal antibody benralizumab: A case report.

Eosinophilic chronic rhinosinusitis (ECRS) is characterized by the presence of nasal polyps, dominant ethmoid shadows in computed tomography (CT) scans, and elevated levels of eosinophil infiltration into the nasal polyps and peripheral blood. ECRS is often accompanied by severe asthma. The recent development of monoclonal antibody-based biologics, including benralizumab, has offered new therapeutic approaches for the treatment of asthma and allergic diseases. Asthma and ECRS are closely related; hence, benralizumab could provide clinical benefit in ECRS patients with severe asthma. Herein, we report a case of a 47-year-old female patient with severe asthma that presented with nasal obstruction and hearing impairment. Nasal endoscopic and otoscopic examinations indicated the presence of bilateral nasal polyps in the middle nasal meatus, as well as a bilateral effusion in the tympanic cavity. Sinus and temporal CT images showed dominant ethmoid sinus and tympanic cavity shadows. Biopsy of nasal polyps revealed high numbers of eosinophils, which led to the diagnosis of ECRS; eosinophilic otitis media (EOM) with hypereosinophilia was also suspected. Treatment with benralizumab reduced the number of peripheral blood eosinophils and improved asthma symptoms. Prolonged benralizumab administration also resulted in a remarkable size reduction in bilateral middle nasal polyps and aeration of the tympanic cavity. In conclusion, benralizumab treatment improved the symptoms of severe asthma, ECRS, and EOM. Eosinophil depletion could be an important mechanism by which benralizumab improves ECRS and EOM. The use of benralizumab for the treatment of ECRS and EOM patients with severe asthma merits further investigation in large-cohort studies.

Real-Time Acoustic Voice Analysis Using a Handheld Device Running Android Operating System.

OBJECTIVES: We developed a highly accessible acoustic voice analysis system (VArt) using a handheld device running Android operating system. To provide stable and reliable analysis using readily obtainable equipment under unfavorable conditions, we modified the fundamental frequency (F0) extraction algorithm and designed an intuitive user interface representing a new hoarseness index (real-time Ra: Rart), which is a derivative of harmonics-to-noise ratio developed by Kojima and Shoji (Ra2). Since Rart continues to display analysis results in real time, unlike conventional acoustic analysis, it can be used for evaluation such as during phonosurgery and speech therapy. We evaluated the agreement between the earlier version of acoustic voice analysis software (VA) running on a Windows personal computer and VArt running on a handheld device. METHODS: F0, Ra2, and Rart were measured in voice samples of sustained vowel phonation /a/ from 10 healthy volunteers and 22 patients with voice disorders using VA running on a Windows personal computer and VArt running on two types of handheld devices in a sound-treated room or in a medical examination room. Intraclass correlation coefficients were calculated for both systems under both conditions. RESULTS: All of the comparisons were highly correlated. CONCLUSIONS: Measurements obtained using our newly developed VArt were highly consistent with those using VA, indicating high reliability. Moreover, the new system increases the clinical feasibility of acoustic voice analysis.

Adrenal insufficiency following nivolumab therapy in patients with recurrent or metastatic head and neck cancer.

Nivolumab, an anti-programmed cell death-1 monoclonal antibody, is currently used to treat many types of advanced cancers including recurrent and metastatic head and neck cancer. However, there are increasing reports concerning immune-related adverse events related to nivolumab therapy. Here, we report three patients who presented with adrenal insufficiency following nivolumab therapy. Two were diagnosed as having isolated adrenocorticotropic hormone (ACTH) deficiency and one was diagnosed as having primary adrenal insufficiency. All three patients complained of progressive fatigue and appetite loss, so we measured their blood cortisol and ACTH levels and diagnosed them as having adrenal deficiency. Treatment with nivolumab was discontinued for all three patients, and replacement therapy using hydrocortisone was successful after a few days in all cases. Two patients subsequently resumed nivolumab therapy because their general condition had improved. Complaints of fatigue and appetite loss during cancer treatment are common and tend to be regarded as unimportant. Although adrenal insufficiency due to nivolumab is relatively rare, complaints of these symptoms could lead to the detection of adrenal insufficiency at an early stage. The present report highlights the importance of the early recognition of adrenal insufficiency.

Real-World Outcomes and Prognostic Factors in Patients Receiving Nivolumab Therapy for Recurrent or Metastatic Head and Neck Carcinoma.

Recently, a global phase III study demonstrated that nivolumab markedly improved patient outcomes in recurrent or metastatic head and neck carcinoma (RMHNC). However, the efficacy of nivolumab in patients who are ineligible for clinical trials is unknown. We investigated nivolumab efficacy in real-world patients and prognostic factors associated with the response to nivolumab. This study was conducted at 11 institutes associated with Kyoto University and its Affiliated Hospitals-Head and Neck Oncology Group. In total, 93 patients with RMHNC who received nivolumab between May 2017 and May 2018 were retrospectively reviewed. Objective response rate (ORR), overall survival, and progression-free survival (PFS) were evaluated. Univariate and multivariate analyses were performed to identify prognostic factors. The ORRs in patients with squamous cell carcinoma (SCC) and non-SCC were 21.8% and 0%, respectively. In patients with SCC and non-SCC, the 1-year PFS rates were 28.7% and 8.9%, respectively. The hazard ratio (HR) for risk of PFS events (SCC versus non-SCC) was 2.28 (95% confidence interval: 1.21-4.1; log-rank p = 0.007). Univariate and multivariate analyses revealed radiotherapy history, platinum-refractory carcinoma, and treatment-related adverse events (TRAEs) as important prognostic factors associated with PFS in patients with SCC. In a real-world setting, non-SCC and platinum-refractory carcinoma were associated with a poorer prognosis, and a history of radiotherapy to the primary tumor, and the occurrence of TRAEs were associated with a better prognosis. These findings could be useful for clinicians and patients when selecting a treatment strategy.

Individualized kV selection and tube current reduction in excretory phase computed tomography urography: potential for radiation dose reduction and the contribution of iterative reconstruction to image quality.

OBJECTIVE: The objective of this study was to analyze radiation dose reduction and image quality by combining automated kV selection, tube current reduction, and iterative reconstruction. METHODS: This was a retrospective analysis of the excretory phase of 55 patients with 2 computed tomography urography examinations: automated kV selection with tube current reduction ("low-dose protocol": with filtered back projection vs iterative reconstruction) and routine dose examinations. Image quality was analyzed blindly and in side-by-side analyses, in addition to quantitative measurements. RESULTS: Low-dose protocol median dose change was -40% (-10.7 to +12.9 mGy); 100 kV was autoselected in 44 (80%) of 55 patients (body mass index range, 19-36 kg/m) with mean dose reduction of 42.5%. Whereas up to 19% of low-dose images with filtered back projection were inferior by blinded review (P < 0.001), low-dose iterative reconstruction images were not rated inferior (P = 1.0). CONCLUSIONS: The combination of iterative reconstruction, automated kV selection, and tube current reduction results in radiation dose reduction with preserved image quality and diagnostic confidence.