Intranasal administration of ceramide liposome suppresses allergic rhinitis by targeting CD300f in murine models.

Allergic rhinitis (AR) is caused by type I hypersensitivity reaction in the nasal tissues. The interaction between CD300f and its ligand ceramide suppresses immunoglobulin E (IgE)-mediated mast cell activation. However, whether CD300f inhibits the development of allergic rhinitis (AR) remains elusive. We aimed to investigate the roles of CD300f in the development of AR and the effectiveness of intranasal administration of ceramide liposomes on AR in murine models. We used ragweed pollen-induced AR models in mice. Notably, CD300f deficiency did not significantly influence the ragweed-specific IgE production, but increased the frequency of mast cell-dependent sneezing as well as the numbers of degranulated mast cells and eosinophils in the nasal tissues in our models. Similar results were also obtained for MCPT5-exprssing mast cell-specific loss of CD300f. Importantly, intranasal administration of ceramide liposomes reduced the frequency of sneezing as well as the numbers of degranulated mast cells and eosinophils in the nasal tissues in AR models. Thus, CD300f-ceramide interaction, predominantly in mast cells, alleviates the symptoms and progression of AR. Therefore, intranasal administration of ceramide liposomes may be a promising therapeutic approach against AR by targeting CD300f.

A Case of Woakes' Syndrome With A Bilateral, Large Nasal Polyp.

Woakes' syndrome, first reported by Edward Woakes in 1885, is an extremely rare, recurrent sinonasal polyposis leading to bone erosion of the sinus walls with consequent nasal pyramid deformity and facial disfigurement. We report a 66-year-old man who presented with severe nasal obstruction. His external nose was deformed and distended with complete obstruction of the bilateral nasal cavities by nasal polyps. The normal structure of the nose was disrupted. Thus, super-selective embolization was performed before surgery to minimize bleeding. The day after the embolization, polypectomy was performed with the navigation system. The progression was uneventful, and the patient was discharged on postoperative day 7. Pathological examination revealed inflammatory polyps with no eosinophil infiltration. Thus, we diagnosed it as Woakes' syndrome. Although there have been few reports of Woakes' syndrome in the past, these are the largest polyps reported to the best of our knowledge.

Generation and characterization of a human iPSC line (JUFMDOi007-A) from a patient with Usher syndrome due to mutation in USH2A.

Usher syndrome type 2A (USH2A) gene mutations have been identified as the most frequent genetic causes of hereditary deafness in Usher syndrome, and an effective treatment has yet to be established. The encoded protein, Usherin, is essential for the ankle link associated with extracellular connections between the stereocilia of inner ear hair cells. We report the generation of a patient-derived USH2A iPSC line with compound mutations c.1907_1912ATGTTT > TCACAG (p.D636V + V637T + C638G) and c.8328_8329delAA (p.L2276fs*12). The iPSC showed the expression of pluripotency markers, the ability to differentiate into three germ layers in vitro, and USH2A mutations with normal karyotype.

Efficacy of tokishakuyakusan and mecobalamin on post-infectious olfactory dysfunction: A prospective multicenter study.

OBJECTIVE: To determine if tokishakuyakusan (TSS) is effective for treating post-infectious olfactory dysfunction (PIOD) compared with vitamin B12 (mecobalamin). METHODS: We conducted a randomized, nonblinded clinical trial. Patients with PIOD enrolled in 17 hospitals and clinics from 2016 to 2020 were randomly divided into two groups, and we administered TSS or mecobalamin for 24 weeks. Their olfactory function was examined using interviews and T&T olfactometry. The improvement of olfactory dysfunction was assessed following the criteria of the Japanese Rhinologic Society. RESULTS: Overall, 82 patients with PIOD were enrolled in this study. In the TSS and mecobalamin groups, 39 patients completed the medication regimen. In the TSS and mecobalamin groups, olfactory dysfunction was significantly improved based on self-reports and olfactory test results. The improvement rate of olfactory dysfunction was 56% in the TSS group and 59% in the mecobalamin group. Early intervention within 3 months produced a better prognosis than the treatment initiated after 4 months. Furthermore, age and sex differences were not observed. Both medications produced no severe adverse events. CONCLUSION: The present study showed that TSS and mecobalamin might be useful for treating PIOD.

Creutzfeldt-Jakob disease with dizziness initially presenting to the otolaryngology department.

Creutzfeldt-Jakob disease is a fatal transmissible prion disease of the central nervous system. Dizziness as an initial manifestation of Creutzfeldt-Jakob disease is rare. However, patients with Creutzfeldt-Jakob disease and dizziness may initially visit the otolaryngology department, but this is uncommon. We report the case of a 56-year-old woman with Creutzfeldt-Jakob disease who initially presented with dizziness as an emergency patient to the otolaryngology department. Primary position upbeat nystagmus was identified using a charge-coupled device camera with infrared illumination. Electronystagmography revealed impaired smooth pursuit and diminished optokinetic nystagmus. Based on these findings, we immediately suspected an intracranial cause of dizziness and reached a presumptive diagnosis of sporadic Creutzfeldt-Jakob disease, thus preventing severe transmission. This case emphasizes that Creutzfeldt-Jakob disease should be included as a differential diagnosis for patients with dizziness and abnormal eye movements, such as primary position upbeat nystagmus, which might be caused by intracranial disease.

Cholesteatoma Surgery With a Dehiscent High Jugular Bulb Treated With Surgery Assisted With Underwater Endoscopy: A Case Report.

A dehiscent high jugular bulb would be a pitfall in middle ear surgery especially for cholesteatoma. We report a case of cholesteatoma attached to a dehiscent high jugular bulb successfully treated with surgery assisted with underwater endoscopy. To the best of our knowledge, no previous study has reported a case of cholesteatoma with dehiscent high jugular bulb treated with surgery assisted with underwater endoscopy. Owing to the risk of jugular bulb injury, underwater endoscopy is a good indication for middle ear cases with a dehiscent high jugular bulb to obtain a clear operative field and avoid an unexpected air embolism.

Inflammatory Myofibroblastic Tumor (IMT) of the Trachea Excised by Transtracheal Surgery: Case Report.

This report describes an extremely rare case of a primary inflammatory myofibroblastic tumor of the trachea. The patient underwent surgical resection by a transtracheal approach and reconstruction with esophageal tracheoplasty. This case report highlights the rarity of such tumors and a minimally invasive and safe surgical technique for tumors around the central neck structures.

Presence of anaerobic bacteria and symptoms supports diagnosis of odontogenic sinusitis.

PURPOSE: The present study aimed to investigate the diagnostic indicators of odontogenic sinusitis other than computed tomography (CT) findings and the history of dental treatment such as detected bacteria and symptoms. MATERIALS AND METHODS: We performed a retrospective analysis of 87 patients who underwent surgery for unilateral sinusitis between 2016 and 2020 (n = 87). Patients with cysts and fungal sinusitis were excluded from the study. We analyzed the relationship between the presence/absence of CT findings such as periapical lesions and oroantral fistulas; anaerobic bacteria; and symptoms in patients with unilateral sinusitis. RESULTS: There was a significant correlation between the detection of anaerobes and CT findings. Peptostreptococcus sp., Prevotella sp., Streptococcus anginosus group, and Fusobacterium sp. were the most commonly isolated species. Detection of these anaerobic bacteria supports the diagnosis of odontogenic sinusitis. Moreover, ODS often present with symptoms, such as a foul smell and facial pain. CONCLUSIONS: Our results suggest that not only the presence of CT findings such as PAL and OAF, but the detection of anaerobic bacteria, and the presence of any symptoms may aid in the diagnosis of ODS.

Impact of radiotherapy for head and neck cancer on obstructive sleep apnea: a prospective study.

BACKGROUND: In recent years, a relatively high prevalence of obstructive sleep apnea (OSA) in patients following radiotherapy (RT) for head and neck cancer (HNC) has been reported; however, little is known regarding the impact of RT on sleep disorders and the underlying mechanisms. This aim of this study was to elucidate the pathogenesis of OSA by comparing the clinical and sleep test parameters and magnetic resonance imaging (MRI) findings before and after HNC treatment with radiation. METHODS: This prospective study included patients scheduled for RT with or without chemotherapy or bioradiotherapy for HNC. Patients diagnosed with HNC between May 2017 and August 2020 were consecutively recruited. The results of the sleep tests were analyzed both before and after treatment. The clinical characteristics of the patients and cephalometric and MRI parameters were also measured. RESULTS: First, a total of 32 patients (64.8±11.8 years old; BMI, 22.7±3.6 kg/m2) underwent pre-treatment sleep tests. The prevalence of OSA [apnea hypopnea index (AHI) ≥5] in these patients was 81.3% (26 patients) before treatment, and the mean AHI was 20.8±19.0 events/hr. Next, 21 patients performed a sleep test both before and after treatment. Regarding subjective symptoms, there were no significant differences in the Epworth Sleepiness Scale (ESS) (P=0.142) or Pittsburgh Sleep Quality Index (PSQI) (P=0.935) after treatment; however, the BMI and neck circumference significantly decreased after treatment (P<0.0001 and P=0.0001, respectively). The incidence of OSA in these patients was 81.0% (17 patients) before treatment and 85.7% (19 patients) after treatment (P=1.0). Overall, the AHI was not significantly different, changing only from 14.5 to 14.9 after treatment (P=0.147). The MRI parameters showed that the retroglossal pharyngeal area increased significantly after treatment (P=0.007). CONCLUSIONS: This study found that the prevalence of OSA before and after RT for HNC was higher than that in the normal population, despite a significant decrease in BMI and increase in the retroglossal pharyngeal area after treatment. We suggest that physicians who manage patients with HNC should consider the occurrence of OSA before and after treatment.

Effects of an Active Noise Control Technology Applied to Earphones on Preferred Listening Levels in Noisy Environments.

BACKGROUND AND OBJECTIVES: The harmful effects of frequent exposure to loud sounds through portable music players (PMPs) in combination with earphones have been suggested to result in a high prevalence of recreational noise-induced hearing loss among children, adolescents, and young adults. The present study aimed to evaluate the effects of an active noise control technology applied to earphones on the preferred listening levels (PLLs) while listening to music in the presence of background noise. SUBJECTS AND METHODS: Twenty-three adults between 20 and 40 years with normal hearing were recruited for this study. PLLs for listening to pop-rock and classical music were measured in the participants' ear canal with a commercially available PMP for four earphone/headphone configurations in quiet and noisy conditions. Ear canal insertion loss was measured in open ear conditions as well as earphone/headphone conditions. RESULTS: The average PLL while using earphones and headphones exceeded 85 dBA corresponding to the sound level to induce hearing damage, but in the case of canal earphones with noise cancelling (NC), it was below 75 dBA, corresponding to potentially harmful levels. The background subway noise significantly increased the PLL measured in quiet conditions using any four earphone/headphone types except canal earphones with NC. Canal earphones with NC showed the lowest PLLs compared with participants' average PLLs using the other three earphone/headphone types. CONCLUSIONS: To minimize recreational noise exposure at the risk of PMP use, the use of earphones with NC is recommended in noisy environments.

Effects of salicylate derivatives on localization of p.H723R allele product of SLC26A4.

OBJECTIVE: Pendrin is a transmembrane protein encoded by the SLC26A4 gene that functions in maintaining ion concentrations in the endolymph of the inner ear, most likely by acting as a chloride/bicarbonate transporter. Variants in the SLC26A4 gene are responsible for sensorineural hearing loss. Although pendrin localizes to the plasma membrane, we previously identified that 8 missense allele products of SLC26A4 were retained in the intracellular region and lost their anion exchange function. We also found that 10 mM salicylate induced the translocation of 4 out of 8 allele products from the intracellular region to the plasma membrane and restored their anion exchanger activity. However, since 10 mM salicylate exhibits cytotoxicity, the use of chemical compounds with less cell toxicity is needed. In the present study, therefore, salicylate derivatives were used as the chemical compounds and their effects on the p.H723R allele products of SLC26A4 were investigated. METHODS: HEK293 cells were transfected with the cDNA of p.H723R. Cell proliferation, viability and toxicity assays were performed to investigate the response and health of cells in culture after treatment with four types of salicylate derivatives, i.e., 2-hydroxybenzyl alcohol, 2,3-dihydroxybenzoic acid, 2'-hydroxyacetophenone and methyl salicylate. The effects of these salicylate derivatives on the localization of the p.H723R were investigated by immunofluorescence microscopy. RESULTS: The application of 10 mM salicylate showed an increase in cell toxicity and decrease in cell viability, leading to a significant decrease in cell proliferation. In contrast, the application of 1 mM salicylate derivatives did not show any significant increase in cell toxicity and decrease in cell viability, corresponding to a logarithmic increase in cell concentration with an increase in culture time. Immunofluorescence experiments showed that the p.H723R retained in the endoplasmic reticulum (ER). Among the salicylate derivatives applied, 2-hydroxybenzyl alcohol induced the translocation of p.H723R from the ER to the plasma membrane 3 h after its application. CONCLUSION: The results obtained showed that 2-hydroxybenzyl alcohol restored the localization of the p.H723R allele products of SLC26A4 from the ER to the plasma membrane at a concentration of 1 mM by 3 h after its administration with less cytotoxicity than 10 mM salicylate.

A case of bisphosphonate-related osteonecrosis of the maxilla with orbital cellulitis.

Bisphosphonates are used for the treatment of bone metastases of cancer and prevention of osteoporosis. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) has unclear mechanisms, but its elucidation, prevention, and treatment are essential to improve patient outcomes.An 88-year-old woman who was taking oral bisphosphonates for 4 years presented with a 5-day history of gradual orbital pain. Computed tomography (CT) revealed bilateral maxillary sinusitis and bony destruction at the base of the right maxillary sinus and inferior orbital wall. We diagnosed her with bisphosphonate-related osteonecrosis of the maxilla. In addition to intravenous antibiotic treatment, an endoscopic sinus surgery was performed. The patient's postoperative course was uneventful.To the best of our knowledge, this is the first case report of BRONJ with orbital cellulitis. This condition should be considered among patients taking bisphosphonates, who manifest with symptoms of orbital cellulitis and bone destruction on imaging.

Subtotal Petrosectomy With Preservation of Chorda Tympani for Petrous Bone Cholesteatoma: Case Report.

A petrous bone cholesteatoma (PBC) is a rare epidermoid cyst of the petrous portion of the temporal bone. The main treatment is subtotal petrosectomy (SP), which generally involves sacrificing the chorda tympani. We report a case of extensive supralabyrinthine PBC in an elderly patient undergoing hemodialysis that was treated by SP with anatomical preservation of the chorda tympani. To the best of our knowledge, preservation of the chorda tympani during SP has not been previously reported. For maintenance of postoperative taste and appetite, preservation of the chorda tympani is a meaningful maneuver whenever possible.

Intraductal Papilloma Arising From the Minor Salivary Glands of the Larynx: A Case Report.

It is rare for intraductal papilloma, a benign papillary tumor, to occur in the salivary glands. To our knowledge, intraductal papilloma occurring in the minor salivary glands of the larynx has not been reported. In this report, we describe a case of intraductal papilloma that occurred in the minor salivary glands of the larynx. A woman in her 30s presented with hoarseness and dyspnea since a year. Fiber-optic laryngoscopy revealed a submucosal tumor involving the left aryepiglottic fold and the left false vocal fold. Computed tomography and magnetic resonance imaging revealed a 17 × 15 × 10 mm3 mass with homogenous isodensity, with regular, well-defined margins located on the left aryepiglottic fold and the left false vocal fold. Surgical resection was performed, and subsequently a diagnosis of intraductal papilloma was made by pathologic evaluation. During the follow-up period of over 3 years, the lesion has not recurred. In conclusion, intraductal papilloma of the minor salivary glands should be considered in the differential diagnosis of laryngeal submucosal tumors.

Association Between Earwax-Determinant Genotypes and Acquired Middle Ear Cholesteatoma in a Japanese Population.

OBJECTIVE: A single-nucleotide polymorphism 538G>A in the human ABCC11 gene is a determinant of the earwax morphotype. ABCC11 538GG and GA correspond to wet earwax and 538AA to dry earwax. Despite a putative positive correlation between the frequency of the 538G allele and the prevalence of cholesteatoma, minimal clinical information is currently available. We aimed to evaluate this association between the ABCC11 genotypes and acquired middle ear cholesteatoma. STUDY DESIGN: Case-control study. SETTING: Single-center academic hospital. METHODS: We recruited 67 Japanese patients with acquired middle ear cholesteatoma (cholesteatoma group) and 100 Japanese controls with no history of middle ear cholesteatoma. We assessed the ABCC11 genotypes for all participants. Clinical information was collected from the cholesteatoma group. The genotype data of 104 Japanese people from the 1000 Genomes Project who represent the general population were used. RESULTS: The proportion of participants with ABCC11 538GG or GA was significantly higher in the cholesteatoma group than in the control group or general Japanese population (P < .001). The ABCC11 538G allele frequency was also significantly higher in the cholesteatoma group than in the control group or general Japanese population (P < .001). Multivariate logistic regression analyses revealed a significant association between the ABCC11 genotype and acquired middle ear cholesteatoma (odds ratio, 5.49; 95% CI, 2.61-11.5; P < .001). CONCLUSION: Our results suggest that the ABCC11 genotypes could be associated with the development of acquired middle ear cholesteatoma among Japanese people.

Severe obstructive sleep apnea after concurrent chemoradiotherapy for laryngeal and hypopharyngeal cancer managed by CPAP.

Concurrent chemoradiotherapy (CCRT) is one of the most promising treatments for advanced head and neck cancer (HNC). On the other hand, CCRT may induce severe edema in laryngo-pharyngeal structures in association with radiation. This is a report of a 66-year-old man with severe obstructive sleep apnea (OSA) associated with edema in laryngo-hypopharynx after CCRT for advanced laryngeal and hypopharyngeal cancer. Tracheostomy was avoided and OSA was controlled by continuous positive airway pressure (CPAP). Subjective symptoms of sleepiness were improved. Though laryngeal edema appeared during the course of CCRT in this case, OSA was not evaluated until snoring had been pointed out and he complained of sleepiness. CCRT for laryngeal and hypopharyngeal cancer have a risk of occurrence of OSA due to irreversible mucous edema in the upper airway. Patients for whom CCRT is planned should be informed about the occurrence of OSA before the treatment because symptoms associated with OSA can negatively impact not only the daytime quality of life but also increase the risk of cardiovascular events. The OSA treatment for post CCRT would be expected to have a positive impact on not only cardiovascular and metabolic systems but also on the cancer treatment survival rate.

Combined underwater endoscopic and microscopic surgery for external auditory canal cholesteatoma: A case report.

Transcanal endoscopic ear surgery is a minimally invasive procedure that allows a clear visualization of the middle ear. Recently, indications for endoscopic surgery have been expanding. We performed combined underwater endoscopic and microscopic surgery for external auditory canal cholesteatoma, the computer tomography of which indicates the possibility of cholesteatoma not only in the canal wall but also in the mastoid. The 30° endoscope and underwater technique makes the surgical view clear, and we could remove the cholesteatoma without canalplasty. To the best of our knowledge, no case of external auditory canal cholesteatoma treated with underwater endoscopic and microscopic surgery has been previously reported. This case indicates that the procedure could be a good indication for external auditory canal cholesteatoma.

S100A7 Co-localization and Up-regulation of Filaggrin in Human Sinonasal Epithelial Cells.

OBJECTIVE: Filaggrin (FLG) is a protein expressed in the epidermis and involved in the maintenance of the epidermal barrier. However, the expression and localization of FLG in the upper airway remain controversial. The present study aimed to determine the significance of FLG and the effect of S100A7 on FLG expression in the upper respiratory mucosa. METHODS: Human nasal epithelial cells (HNECs) were cultured and examined for FLG expression and S100A7 effects by real-time polymerase chain reaction and Western blotting. The localization and distribution of FLG were assessed using sinonasal mucosa. RESULTS: A significant expression of FLG was detected at the mRNA and protein levels in HNECs. A moderate FLG immunoreactivity was observed in the epithelial cells, but no staining was seen in epithelial goblet cells. S100A7 increased the FLG mRNA level in HNECs in a dose-dependent manner and also up-regulated the FLG protein in a dose-dependent manner. CONCLUSION: This study significantly contributes to a better understanding of the role of FLG in the pathogenesis of airway inflammation from the viewpoint of the epithelial barrier function. FLG-related events in response to S100A7 protein may represent novel therapeutic targets for the treatment of upper airway inflammation.

Basal cell adenocarcinoma of the maxillary sinus: A case report.

Basal cell adenocarcinoma is a low-grade malignancy of the salivary glands. Basal cell adenocarcinoma of the minor salivary gland is an extremely rare disease that originates from the maxillary sinus. The histopathological characteristics of basal cell adenocarcinomas are similar to those of basal cell adenomas. However, basal cell adenocarcinomas can be differentiated from basal cell adenomas based on their tendency to invade surrounding tissues. Surgical resection is the first-line treatment for basal cell adenocarcinomas. An 86-year-old man underwent operations for a maxillary sinus tumor twice in our department. The pathological results of the tumor at both times revealed basal cell adenoma. After 4 and 5 years since the last operation, the tumor recurred, and the patient was treated with partial maxillectomy using Weber-Ferguson incision. We observed invasions to the surrounding tissue, and based on immunohistochemical findings, the patient was diagnosed with basal cell adenocarcinoma. Herein, we present an extremely rare case of basal cell adenocarcinoma arising from the maxillary sinus, in detail.

Effects of endoscopic sinus surgery on nasal spray deposition using dye-based methods for humans and a human silicone sinonasal cavity model.

OBJECTIVE: We have evaluated that the deposition patterns of corticosteroid nasal spray in the sinonasal cavity of both post-operated human cases, which were further compared with a computed tomography-based sinonasal airway model. METHODS: Fifty-one patients with chronic rhinosinusitis following an endoscopic sinus surgery were enrolled in this study. Nasal spray mometasone furoate hydrate (Nasonex®) containing 0.1% indigocarmine was applied to the patients' nasal cavities and the sinonasal cavity was observed by endoscopy and video documentation. A single plaster sinonasal model was used to quantify the sinonasal deposition of nasal sprays containing 10% red ink solution using 12 round paper strips. RESULTS: The predominant areas of the spray deposition of the operated sinonasal cavities were recognized in the ethmoid sinus and the olfactory cleft in the human study. The droplets were mainly deposited in the inferior turbinate followed by the posterior part of the ethmoid sinus, the olfactory cleft, and anterior part of the ethmoid sinus in a sinonasal model. CONCLUSION: The corticosteroid nasal spray efficiently reached the olfactory cleft and the ethmoid sinus in post-operative conditions, which was demonstrated by post-operated human cases and a computed tomography-based sinonasal airway model.