A Mutation in Tmem135 Causes Progressive Sensorineural Hearing Loss.

Transmembrane protein 135 (TMEM135) is a 52 kDa protein with five predicted transmembrane domains that is highly conserved across species. Previous studies have shown that TMEM135 is involved in mitochondrial dynamics, thermogenesis, and lipid metabolism in multiple tissues; however, its role in the inner ear or the auditory system is unknown. We investigated the function of TMEM135 in hearing using wild-type (WT) and Tmem135 FUN025/FUN025 ( FUN025 ) mutant mice on a CBA/CaJ background, a normal-hearing mouse strain. Although FUN025 mice displayed normal auditory brainstem response (ABR) at 1 month, we observed significantly elevated ABR thresholds at 8, 16, and 64 kHz by 3 months, which progressed to profound hearing loss by 12 months. Consistent with our auditory testing, 13-month-old FUN025 mice exhibited a severe loss of outer hair cells and spiral ganglion neurons in the cochlea. Our results using BaseScope in situ hybridization indicate that TMEM135 is expressed in the inner hair cells, outer hair cells, and supporting cells. Together, these results demonstrate that the FUN025 mutation in Tmem135 causes progressive sensorineural hearing loss, and suggest that TMEM135 is crucial for maintaining key cochlear cell types and normal sensory function in the aging cochlea.

Treatment of elderly patients with head and neck cancer in an aging society: Focus on geriatric assessment and surgical treatment.

Previous studies of the treatment of elderly head and neck cancer (HNC) patients were very limited and sometimes controversial. Although conclusions differ across various reports, it is often concluded that advanced chronological age does not directly affect prognosis, but that comorbidities and declines in physical and cognitive functions promote the occurrence of adverse events, especially with surgical treatment. Geriatric assessment (GA) and its screening tools are keys to help us understand overall health status and problems, predict life expectancy and treatment tolerance, and to influence treatment choices and interventions to improve treatment compliance. In addition, personal beliefs and values play a large role in determining policies for HNC treatment for elderly patients, and a multidisciplinary approach is important to support this. In this review, past research on HNC in older adults is presented, and the current evidence is explained, focusing on the management of elderly HNC patients, with an emphasis on the existing reports on each treatment stage and modality, especially the surgical procedures.

Effect of wearing masks on odor detection and recognition.

BACKGROUND: The effect of wearing masks on olfaction remains unclear. OBJECTIVES: This study aimed to clarify the differences between the effects of no masks, surgical masks, and N95 respirator masks by conducting both identification and threshold olfaction tests. METHODS: Young, healthy volunteers aged ≥ 18 years and < 30 years without awareness of apparent olfactory disorder were included. All participants filled out a questionnaire on olfaction and completed an acuity smell identification test (Open Essence test) and an olfactory threshold test (T&T olfactometry) while wearing no masks, surgical masks, or N95 respirator masks. RESULTS: In the Open Essence tests, the no-mask group score was significantly higher than those of the surgical- and N95-mask groups. Using T&T olfactometry, the median-detection threshold of the no-mask group was significantly lower than that of the surgical-mask group, and the surgical-mask group threshold was significantly lower than that of the N95-mask group. Similar patterns were observed for the median-recognition threshold. CONCLUSIONS: Wearing masks, especially an N95 mask, reduces the ability to detect and identify odors. This disadvantage should be considered by professionals such as healthcare workers, who require proper olfaction to perform appropriate tasks.

Cochlear aqueduct revisited: A histological study using human fetuses.

BACKGROUND AND AIM: The cochlear aqueduct (CA) connects between the perilymphatic space of the cochlea and the subarachnoid space in the posterior cranial fossa. The study aimed to examine 1) whether cavitation of the CA occurs on the subarachnoid side or the cochlear side and 2) the growth and/or degeneration of the CA and its concomitant vein. METHODS: We examined paraffin-embedded histological sections from human fetuses: 15 midterm fetuses (crown-rump length or CRL, 39-115 mm) and 12 near-term fetuses (CRL, 225-328 mm). RESULTS: A linear mesenchymal condensation, i.e., a likely candidate of the CA anlage, was observed without the accompanying vein at 9-10 weeks. The vein appeared until 15 weeks, but it was sometimes distant from the CA. At 10-12 weeks, the subarachnoid space (or the epidural space) near the glossopharyngeal nerve rapidly protruded into the CA anlage and reached the scala tympani, in which cavitation was gradually on-going but without epithelial lining. However, CA cavitation did not to occur in the anlage. At the opening to the scala, the epithelial-like lining of the CA lost its meningeal structure. At near-term, the CA was often narrowed and obliterated. CONCLUSION: The CA develops from meningeal tissues when the cavitation of the scala begins. The latter cavitation seemed to reduce tissue stiffness leading, to meningeal protrusion. The so-called anlage of CA might be a phylogenetic remnant of the glossopharyngeal nerve branch. A course of cochlear veins appears to be determined by a rule different from the CA development.

Epidemiology of postoperative bleeding after endoscopic nasal and sinus surgery and factors associated with bleeding.

PURPOSE: Endoscopic nasal and sinus surgery is a surgical procedure frequently performed by otolaryngologists. Postoperative bleeding is detrimental to both healthcare providers and patients. We investigated the epidemiology of postoperative bleeding during endoscopic nasal and sinus surgery and explored possible bleeding triggers. METHODS: We evaluated the patients who underwent endoscopic nasal and sinus surgery. Data regarding the age, sex, presence of hypertension, and abnormal coagulability, including oral anticoagulants, diagnoses, operative procedures, intraoperative use of drills and blood loss, and postoperative antimicrobial administration of eligible patients, were extracted from medical records and retrospectively reviewed. RESULTS: One hundred and eighty-six patients underwent endoscopic nasal or sinus surgery during the study period, and postoperative bleeding occurred in 9 patients (4.8%). Posterior nasal neurotomy (PNN) was the procedure most likely to cause postoperative bleeding (4 surgeries, 13.3%). Postoperative antimicrobial administration significantly reduced the incidence of postoperative bleeding (p = 0.04). CONCLUSIONS: Postoperative bleeding requiring intervention occurs in 4.8% of cases, and PNN is associated with a high risk of postoperative bleeding. Wound infection is a potential cause of postoperative bleeding, and antimicrobial administration should be considered in addition to local treatment.

Characteristic findings in the human fetus vestibule: A human temporal bone study.

OBJECTIVE: The "collapse," a highly flexed, dented, or caved membrane between the endo- and peri-lymph of the saccule and utricle in adults, is considered as a morphological aspect of Ménière's syndrome. Likewise, when mesh-like tissues in the perilymphatic space are damaged or lost, the endothelium loses mechanical support and causes nerve irritation. However, these morphologies were not examined in fetuses. METHODS: By using histological sections from 25 human fetuses (crown-rump length[CRL] 82-372 mm; approximately 12-40 weeks), morphologies of the perilymphatic-endolymphatic border membrane and the mesh-like tissue around the endothelium were examined. RESULTS: The highly flexed or caved membrane between the endo- and peri-lymphatic spaces was usually seen in the growing saccule and utricle of fetuses, especially at junctions between the utricle and ampulla at midterm. Likewise, the perilymphatic space around the saccule, utricle and semicircular ducts often lost the mesh-like tissues. The residual mesh-like tissue supported the veins, especially in the semicircular canal. CONCLUSION: Within a cartilaginous or bony room showing a limited growth in size but containing increased perilymph, the growing endothelium appeared to become wavy. Owing to a difference in growth rates between the utricle and semicircular duct, the dentation tended to be more frequently seen at junctions than at free margins of the utricle. The difference in site and gestational age suggested that the deformity was not "pathological" but occurred due to unbalanced growth of the border membrane. Nevertheless, the possibility that the deformed membrane in fetuses was an artifact caused by delayed fixation is not deniable.

HDR syndrome, detected in the neonatal period by newborn hearing screening.

Hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome is an autosomal dominant disorder. Because HDR syndrome is caused by haploinsufficiency in GATA3, it exhibits variation in the onset and progression of hearing loss. In previous reports, the automated auditory brainstem response (AABR) was considered insufficient to detect sensorineural hearing loss caused by HDR syndrome. We report a case of HDR syndrome whose congenital hearing loss was detected by newborn hearing screening (NHS) using AABR. In this case, HDR syndrome was suspected due to hearing loss, hypocalcemia, and her family history. Genetic testing confirmed the diagnosis of HDR syndrome at 5 months of age. Because the phenotype of hearing loss due to HDR syndrome is variable and includes progressive hearing loss, these cases may not be detected by the HNS. However, most of the previous reports were published before the NHS became common and given the frequency of hearing loss complications in HDR syndrome. We consider that there is a reasonable number of HDR syndrome cases with abnormalities on the NHS. We believe that the NHS may also be useful for early detection of hearing loss due to HDR syndrome.

Fatty acid binding protein type 7 deficiency preserves auditory function in noise-exposed mice.

Fatty acid-binding protein 7 (FABP7) is vital for uptake and trafficking of fatty acids in the nervous system. To investigate the involvement of FABP7 in noise-induced hearing loss (NIHL) pathogenesis, we used Fabp7 knockout (KO) mice generated via CRISPR/Cas9 in the C57BL/6 background. Initial auditory brainstem response (ABR) measurements were conducted at 9 weeks, followed by noise exposure at 10 weeks. Subsequent ABRs were performed 24 h later, with final measurements at 12 weeks. Inner ears were harvested 24 h after noise exposure for RNA sequencing and metabolic analyses. We found no significant differences in initial ABR measurements, but Fabp7 KO mice showed significantly lower thresholds in the final ABR measurements. Hair cell survival was also enhanced in Fabp7 KO mice. RNA sequencing revealed that genes associated with the electron transport chain were upregulated or less impaired in Fabp7 KO mice. Metabolomic analysis revealed various alterations, including decreased glutamate and aspartate in Fabp7 KO mice. In conclusion, FABP7 deficiency mitigates cochlear damage following noise exposure. This protective effect was supported by the changes in gene expression of the electron transport chain, and in several metabolites, including excitotoxic neurotransmitters. Our study highlights the potential therapeutic significance of targeting FABP7 in NIHL.

Postoperative Swallowing Function in Patients with Deep Neck Infection.

Introduction: Early detection of dysphagia risk, initiating rehabilitation, and resumption of appropriate diet based on swallowing function is important during deep neck infection (DNI) control. This study aimed to evaluate the extent of cervical abscess development, particularly in the deep neck space, and its relationship to postoperative swallowing function. Methods: A retrospective chart review was performed for all DNI cases treated between April 2015 and April 2021. Deep neck spaces were divided into categories based on computed tomography findings. Functional Oral Intake Scale (FOIS) scores of 4 or higher was defined as normal or slight swallowing disorder and 3 or lower as dysphagia. Results: Seventeen cases were included in the analysis. Based on FOIS, 14 cases were classified into the dysphagia group at 2 weeks after surgery, 11 cases at 4 weeks, and 8 cases at 8 weeks. There was no significant difference between the location of the abscess and dysphagia at 2 weeks after surgery. Patients with anterior cervical space abscess significantly increased dysphagia 4 weeks (p = 0.018) and 8 weeks (p = 0.036) after surgery. Conclusion: Abscess formation in the anterior cervical space may be associated with prolonged dysphagia after treatment due to inflammation and scarring of the muscles associated with swallowing.

Sensorineural Hearing Loss due to Acute Carbon Monoxide Poisoning.

Carbon monoxide (CO) can cause "irreversible" severe-to-profound sensorineural hearing loss. However, there are few reports of detailed hearing test results. Here, we report a case of acute sensorineural hearing loss caused by acute CO poisoning with partial hearing recovery, evaluated by a detailed hearing examination. A 25-year-old woman was brought to the emergency department for attempted suicide. On admission, her consciousness was impaired, and she was treated for severe CO poisoning, including using hyperbaric-oxygen therapy. After regaining consciousness, symptoms of hearing loss and tinnitus were discovered, and a detailed audiological examination revealed bilateral hearing loss, suggesting cochlear damage. Steroids were systemically administered, and her hearing impairment was partially resolved. Sensorineural hearing loss caused by acute CO poisoning includes cochlear pathology and may be partially treatable. The early evaluation of hearing in patients with severe CO poisoning is advisable for early treatment.

Immunohistochemical localization of CD31, CD34, and periostin in vocal fold polyps.

BACKGROUND: Long-term voice-abuse or sudden vocal fold microvascular disruption can lead to injury and subsequent repair/remodeling of the vocal fold mucosa. Periostin is known to be involved in airway remodeling and in various otolaryngological diseases. In ischemic heart disease, increased CD31 expression has been observed around cardiomyocytes during remodeling, and endothelial proliferation has been reported to occur at these sites. OBJECTIVES: We investigated the expression and the roles of CD31, CD34, and periostin in the formation of vocal fold polyps. MATERIALS AND METHODS: Fifty-seven samples of vocal fold polyps were investigate histopathologically and immunohistochemically. RESULT: Expression of CD31 and CD34 was detected in 41 (71.9%) and 53 (93.0%) samples, respectively, obtained from patients with vocal fold polyp. Expression of periostin was detected in 41 (71.9%) samples obtained from patients with vocal polyps. The vocal polyp samples could be classified into three histological subtypes. Three patterns of CD31 and CD34 expression were observed in the vocal polyp. Four patterns of periostin expression were observed in vocal polyps. An association was observed between the CD31 expression pattern and the histological subtype of vocal fold polyps. CONCLUSION AND SIGNIFICANCE: In vocal fold polyps, evaluation of vascular endothelial markers may be useful for staging.

Impact of palatoplasty techniques on tympanic membrane findings and hearing prognosis in children with cleft palate.

OBJECTIVE: Children with cleft palate (CP) are at high risk of developing otitis media with effusion (OME) due to Eustachian tube (ET) dysfunction. Palatoplasty has been reported to decrease the frequency of middle ear disease and improve ET function, and although various techniques have been developed, there is no consensus on the differences in the impact of different techniques on the middle ear. The purpose of this study was to determine the differential effects of palatoplasty on middle ear function and hearing. METHODS: We performed a retrospective observational survey of pediatric patients who underwent palatoplasty for CP between June 2010 and October 2018 at Tohoku University Hospital. Cases were divided into three groups depending on the palatoplasty procedures performed: the push-back palatoplasty group, the two-flap palatoplasty group, and the Furlow double-opposing Z-plasty group. We examined the differences in clinical characteristics between patients who underwent each procedure. The primary outcome variable was tympanic membrane (TM) findings, and the secondary outcome was hearing test results. RESULTS: Children who underwent the two-flap palatoplasty had a higher tympanostomy tube (TT) insertion rate and a higher total number of TT insertions than those who underwent the Furlow double-opposing Z-plasty or the push-back palatoplasty. The TM retraction rate tended to be lower in the Furlow double-opposing Z-plasty group than in the push-back palatoplasty group or the two-flap palatoplasty group. The hearing test results at the last visit were not significantly different among the three groups. CONCLUSIONS: Children who underwent the two-flap palatoplasty had a higher rate of TT insertions, potentially increasing the risk of TM perforation. In contrast, the Furlow double-opposing Z-plasty group had a lower tendency for TM regression, possibly due to improved ET function and reduced incidence of OME. It is important to understand the advantages and disadvantages of each technique before selecting one suitable for the child's cleft and arch width. Additionally, it is important to conduct regular follow-up of TM findings and hearing test results even after palatoplasty.

Effects of zinc deficiency on the regeneration of olfactory epithelium in mice.

The olfactory epithelium can regenerate after damage; however, the regeneration process is affected by various factors, such as viral infections, head trauma, and medications. Zinc is an essential trace element that has important roles in organ development, growth, and maturation. Zinc also helps regulate neurotransmission in the brain; nevertheless, its relationship with olfactory epithelium regeneration remains unclear. Therefore, we used a severe zinc deficiency mouse model to investigate the effects of zinc deficiency on olfactory epithelium regeneration. Male wild-type C57BL/6 mice were divided into zinc-deficient and control diet groups at the age of 4 weeks, and methimazole was administered at the age of 8 weeks to induce severe olfactory epithelium damage. We evaluated the olfactory epithelium before and 7, 14, and 28 days after methimazole administration by histologically analyzing paraffin sections. RNA sequencing was also performed at the age of 8 weeks before methimazole administration to examine changes in gene expression caused by zinc deficiency. In the zinc-deficient group, the regenerated olfactory epithelium thickness was decreased at all time points, and the numbers of Ki-67-positive, GAP43-positive, and olfactory marker protein-positive cells (i.e. proliferating cells, immature olfactory neurons, and mature olfactory neurons, respectively) failed to increase at some time points. Additionally, RNA sequencing revealed several changes in gene expression, such as a decrease in the expression of extracellular matrix-related genes and an increase in that of inflammatory response-related genes, in the zinc-deficient group. Therefore, zinc deficiency delays olfactory epithelium regeneration after damage in mice.

The Transition of Pediatric Tracheobronchial Foreign Body Cases in the Past 36 Years: A Retrospective Single-Center Study in Japan.

Tracheobronchial foreign bodies (TFBs) are pediatric airway emergencies frequently seen. We aimed to examine the changes in the clinical characteristics of pediatric TFB patients in a single institution within the past 36 years. We retrospectively reviewed the data of 85 patients aged 0-10 years with TFBs lodged in the trachea or bronchus admitted at the Department of Otolaryngology-Head and Neck Surgery at Tohoku University Hospital between 1986 and 2021. We also compared the characteristics, diagnostic methods, and treatments of the previous 64 cases (1986-2005) with those of the recent 21 cases (2006-2021). The number of TFB patients decreased later in this study (3.2 vs. 1.3 patients per year). The proportion of TFB patients aged > 3 years was significantly higher in the later period (6.3% vs. 23.8%, p = 0.038). Peanut was the most common cause of TFBs in both periods, and the overall incidence of peanut aspiration significantly decreased in the later period (68.8% vs. 38.1%, p = 0.019). No patient had an undetected TFB for more than 1 month after the onset of symptoms in the later period. Foreign body extraction using rigid bronchoscopy was performed in all patients earlier, whereas flexible bronchoscopy was used in 14.3% later. Our study revealed a recent trend in the clinical characteristics of pediatric TFB patients in a single institution in Northeast Japan. The prevention and treatment of pediatric TFBs should be considered following the recent trends.

Long-term voice evaluation after arytenoid adduction surgery in patients with unilateral vocal fold paralysis.

PURPOSE: Laryngeal framework surgery, including medialization laryngoplasty and arytenoid adduction (AA), is expected to have a lasting or permanent effect in patients with unilateral vocal fold paralysis (UVFP); however, there are few reports about the long-term outcomes of AA. This study aimed to evaluate the long-term postoperative effects of AA surgery and examine its stability and reliability. METHODS: This study collected the voice handicap index (VHI) questionnaire from patients with UVFP who underwent AA more than 2 years previously. The VHI values preoperatively and 3 months postoperatively (early postoperative evaluation) were retrospectively calculated, and VHI values more than 2 years after surgery (late postoperative evaluation) were collected by mailing a sheet to the patients and asking to fill and return it. Possible influenced subscales such as age, sex, causes of UVFP, affected side, and surgeons were also analyzed. RESULTS: A total of 77 patients with UVFP who underwent AA had significantly lower early and late postoperative evaluations than preoperative evaluations. In 38 patients with no missing values, there were no significant differences between early and late postoperative evaluations, measured at a median of approximately 5 years. There were also no significant differences between early and late postoperative evaluations in any of the subscale groups. CONCLUSION: Patients with UVFP who underwent AA surgery achieved stable voice improvement in the long term after surgery.

Transient connection between the vestibular aqueduct and utricle: A study using sagittal sections of human embryonic heads.

BACKGROUND: The aqeductus vestibuli (aqueduct) is believed to connect to the saccule in embryos and adults. However, in embryos, the saccule and utricle are known to communicate widely to provide a common endolymph space "atrium". METHODS: Using sagittal histological sections from five embryos (crown-rump length or CRL, 14-21 mm), nine early fetuses (CRL 24-35 mm) and 12 midterm and near-term fetuses (CRL 82-272 mm), we revisited the development and growth of the human ear aqueduct. RESULTS: The atrium took on a thick tube-like appearance as an antero-inferior continuation of the aqueduct, but soon divided into multiple gulfs. Most of the gulfs corresponded to the ampullae of semicircular ducts, while one gulf at the antero-medio-inferior corner corresponded to the future saccule. Notably, in eight of the 14 embryos and early fetuses, the aqueduct ended at the utricle near the primitive ampulla of the anterior (superior) or posterior semicircular duct. Conversely, an embryo of CRL 21 mm was the smallest specimen in which the aqueduct joined the gulf-like saccule. At midterm and near-term, the growing perilymph space separated the aqueduct from the utricle and appeared to push the aqueduct toward the saccule. A topographical change occurred between the embryonic superiorly located utricle and the inferiorly-located saccule to create the antero-posterior arrangement in adults. CONCLUSIONS: Consequently, the vestibular end of the aqueduct was most likely to migrate anteriorly from the utricle to the saccule at 6-8 weeks possibly due to differential growth of the endothelium. Previous reconstructions of the embryonic aqueduct might be biased by the adult morphology.

A Preoperative Imaging Evaluation to Avoid Orbital Complications in Functional Endoscopic Sinus Surgery.

Functional endoscopic sinus surgery has become popular worldwide. However, serious complications have been reported with it. A preoperative imaging evaluation is thus essential to avoid complications. The authors compared 0.5 mm slice computed tomography (CT) images reconstructed from sinus CT data with conventional 2 mm slice CT images. The authors evaluated patients who underwent endoscopic surgery. Data regarding age, sex, history of craniofacial trauma, diagnosis, operative procedure, and CT findings of eligible patients were extracted from medical records and retrospectively reviewed. One hundred twelve patients underwent endoscopic surgery during the study period. Six patients (5.4%) had orbital blowout fractures, and half of them could only be identified by 0.5 mm slice CT images. The authors presented the usefulness of 0.5 mm slice CT images in the preoperative imaging evaluation of functional endoscopic sinus surgery. Surgeons should also recognize that a small number of patients have "stealth" (asymptomatic and unrecognized) blowout fractures.

Salivary gland cancer organoids are valid for preclinical genotype-oriented medical precision trials.

Salivary gland cancers (SGCs) are heterogeneous tumors, and precision oncology represents a promising therapeutic approach; however, its impact on SGCs remains obscure. This study aimed to establish a translational model for testing molecular-targeted therapies by combining patient-derived organoids and genomic analyses of SGCs. We enrolled 29 patients, including 24 with SGCs and 5 with benign tumors. Resected tumors were subjected to organoid and monolayer cultures, as well as whole-exome sequencing. Organoid and monolayer cultures of SGCs were successfully established in 70.8% and 62.5% of cases, respectively. Organoids retained most histopathological and genetic profiles of their original tumors. In contrast, 40% of the monolayer-cultured cells did not harbor somatic mutations of their original tumors. The efficacy of molecular-targeted drugs tested on organoids depended on their oncogenic features. Organoids recapitulated the primary tumors and were useful for testing genotype-oriented molecular targeted therapy, which is valuable for precision medicine in patients with SGCs.