The use of basic fibroblast growth factor to treat intractable Bell's palsy administered via transcanal endoscopic ear surgery.

PURPOSE: Facial nerve decompression surgery is an invasive procedure which has hitherto been the main option for patients with severe intractable Bell's palsy which is resistant to drug treatment. We have developed a new salvage treatment for such patients by using minimally invasive transcanal endoscopic ear surgery (TEES) to deliver the biological regenerative agent, basic fibroblast growth factor (bFGF), to the damaged facial nerve. MATERIALS AND METHODS: An endoscopic salvage treatment group was studied prospectively and was made up of severe intractable Bell's palsy patients who did not respond to high dose steroid treatment and had an ENoG value of 5 % or less. This surgery group was retrospectively compared to a similar control group who had received high dose steroid only. RESULTS: Complete recovery to House-Brackmann (HB) Grade I was achieved by 44.8 % of the endoscopic salvage treatment group which was significantly higher than the 21.2 % of the control group at one-year follow up. Patients with an ENoG value of 1 % to 5 % exhibited a significantly higher complete recovery rate of 71.4 % in the endoscopic salvage treatment group than the 28.6 % of the control group. In addition, no complications were observed including hearing loss. CONCLUSIONS: bFGF delivered via TEES shows considerable promise as a new salvage treatment of severe intractable Bell's palsy that is resistant to high dose steroid treatment without the risks presented by facial nerve decompression surgery.

The iArmS Robotic Armrest Prolongs Endoscope Lens-Wiping Intervals in Endoscopic Sinus Surgery.

Objective. Fouling of the endoscope lens is a major problem in endoscopic sinus surgery (ESS). We examined whether the use of the intelligent arm support system (iArmS), a robotic armrest, could prolong endoscope lens-wiping intervals in ESS and thus allow for continuously clear endoscopic images. Study Design. This study is a prospective, nonrandomized crossover study. Methods. Three surgeons who performed ESS at 2 centers each conducted 3 operations with the iArmS and 3 operations without the iArmS; thus, 18 operations were assessed. To blind the assessments, we performed them prospectively without informing subjects of the endpoints. We recorded the operations and observed the recordings at a later date; endoscope lens-wiping times were noted in seconds to determine the endoscope lens-wiping intervals. Our examination was based on the null hypothesis that endoscope lens-wiping intervals would not differ according to the use or nonuse of the iArmS. Results. The median endoscope lens-wiping intervals with and without using the iArmS were 361 seconds and 135 seconds, respectively. Based on the Wilcoxon rank-sum test, this difference was significant (P = 0.001); thus, the null hypothesis was rejected. This result indicated that endoscope lens-wiping intervals are greatly prolonged by the use of the iArmS. Conclusion. The iArmS robotic armrest is suitable for ESS, prolongs endoscope lens-wiping intervals, and facilitates obtaining continuous clear endoscopic images.

Expression and localization of diacylglycerol kinase ζ in guinea pig cochlea and its functional implication under noise-exposure stress conditions.

Cochlear hair cells are essential for the mechanotransduction of hearing. Sensorineural hearing loss can be irreversible because hair cells have a minimal ability to repair or regenerate themselves once damaged. In order to develop therapeutic interventions to prevent hair cell loss, it is necessary to understand the signaling pathway operating in cochlear hair cells and its alteration upon damage. Diacylglycerol kinase (DGK) regulates intracellular signal transduction through phosphorylation of lipidic second messenger diacylglycerol. We have previously reported characteristic expression and localization patterns of DGKs in various organs under pathophysiological conditions. Nevertheless, little is known about morphological and functional aspects of this enzyme family in the cochlea. First RT-PCR analysis reveals predominant mRNA expression of DGKα, DGKε and DGKζ. Immunohistochemical analysis shows that DGKζ localizes to the nuclei of inner hair cells (IHCs), outer hair cells (OHCs), supporting cells and spiral ganglion neurons in guinea pig cochlea under normal conditions. It is well known that loud noise exposure induces cochlear damage, thereby resulting in hair cell loss. In particular, OHCs are highly vulnerable to noise exposure than IHCs. We found that after 1 week of noise exposure DGKζ translocates from the nucleus to the cytoplasm in damage-sensitive OHCs and gradually disappears thereafter. In sharp contrast, DGKζ remains to the nucleus in damage-resistant IHCs. These results suggest that DGKζ cytoplasmic translocation is well correlated with cellular damage under noise-exposure stress conditions and is involved in delayed cell death in cochlear outer hair cells.

Malignancies in Patients with IgG4-Related Diseases in Head and Neck Regions.

Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized disease, characterized by high serum IgG4 concentrations and IgG4-producing plasma cell expansion with fibrotic or sclerotic changes in affected organs. Recent work has focused on the relationship between IgG4-RD and malignancies, but there is no report of malignancies associated with IgG4-RD in head and neck regions. The aim of this study was to analyze the clinicopathological characteristics of malignancies in patients with IgG4-RD in head and neck regions. We retrospectively analyzed 26 patients with IgG4-RD (12 men and 14 women aged 60.6 ± 11.6 years). The mean follow-up period was 26.6 months (from 12 to 96 months). These patients were divided into single-lesion group (n = 12) with IgG4-RD only in head and neck regions and multiple-lesion group (n = 14) with IgG4-RD in other regions. There was no significant difference in serum IgG4 concentrations between the single-lesion group (459.4 ± 336.4 mg/dL) and the multiple-lesion group (908.0 ± 739.2 mg/dL) (P = 0.07), whereas the IgG4/IgG ratio was significantly lower in the single-lesion group (22.8 ± 11.0%; n = 11) compared with the multiple-lesion group (31.7 ± 15.0%; n = 11, P = 0.02). Among the 26 patients, two patients (7.7%), both in the multiple-lesion group, developed life-threatening malignancies (salivary duct carcinoma in the submandibular gland and lymphoma in the orbital tissue). All physicians need to keep in mind the possible coexistence of malignancies in patients with IgG4-RD with high IgG4/IgG ratio and multiple lesions at the time of diagnosis.

Clinical utility of dynamic-enhanced MRI in salivary gland tumors: retrospective study and literature review.

PURPOSE: To improve the diagnoses of the salivary gland tumors, a dynamic-enhanced MRI (dMRI) was investigated. METHODS: We conducted a retrospective chart review of 93 cases of salivary gland tumors. The histological diagnoses were obtained from all patients using a surgical specimen and/or an open biopsy specimen. The dMRI as well as fine-needle aspiration cytology (FNAC) and intraoperative frozen section (IFS) were analyzed. This study focused on the time-intensity curve (TIC) after injection, peak time (Tpeak), washout ratio (WR) as well as the gradient of enhancement and washout profile. RESULTS: The histological diagnoses included pleomorphic adenoma (PMA) in 53 cases, the Warthin tumors (WT) in 14 cases and malignant tumors (MT) in 26 cases. Incorrect diagnosis rate of FNAC and IFS were 5.2 and 8.3%, respectively. The TIC revealed differences among the three types of tumors. Tpeak as well as WR also revealed significant differences (p < 0.001). Tpeak were lower in order of WT, MT, PMA, respectively. WR of TICs at 30, 45 and 105 s after Tpeak were higher in order of WT, MT, PMA, respectively (p < 0.001). The gradient of increment and washout in the TIC curve was also an important parameter to distinguish the three types of tumors. In MT, the rapid enhancement pattern was found in high or intermediate histological grade tumors, whereas the slow enhancement pattern was exhibited in low grade tumors. CONCLUSIONS: Our findings indicate that using Tpeak and WR, it is possible to distinguish between WT, PMA and MT. Additionally, a rapid enhancement pattern may be a potential marker for these tumors.

Role of the N-terminal hydrophobic residues of DGKε in targeting the endoplasmic reticulum.

The endoplasmic reticulum (ER), comprised of an interconnected membrane network, is a site of phospholipid and protein synthesis. The diacylglycerol kinase (DGK) enzyme family catalyzes phosphorylation of diacylglycerol to phosphatidic acid. Both of these lipids are known not only to serve as second messengers but also to represent intermediate precursors of lipids of various kinds. The DGK family is targeted to distinct subcellular sites in cDNA-transfected and native cells. Of DGKs, DGKε localizes primarily to the ER, suggesting that this isozyme plays a role in this organelle. Using experiments with various deletion and substitution mutants, this study examined the molecular mechanism of how DGKε is targeted to the ER. Results demonstrate that the N-terminal hydrophobic sequence 20-40 plays a necessary role in targeting of DGKε to the ER. This hydrophobic amino acid segment is predicted to adopt an α-helix structure, in which Leu22, L25, and L29 are present in mutual proximity, forming a hydrophobic patch. When these hydrophobic Leu residues were replaced with hydrophilic amino acid Gln, the mutant fragment designated DGKε (20-40/L22Q,L25Q,L29Q) exhibits diffuse distribution in the cytoplasm. Moreover, full-length DGKε containing these substitutions, DGKε (L22Q,L25Q,L29Q), is shown to distribute diffusely in the cytoplasm. These results indicate that the N-terminal hydrophobic residues play a key role in DGKε targeting to the ER membrane. Functionally, knockdown or deletion of DGKε affects the unfolding protein response pathways, thereby rendering the cells susceptible to apoptosis, to some degree, under ER stress conditions.

Expressions and roles of periostin in otolaryngological diseases.

Periostin is a 90-kDa member of the fasciclin-containing family; it functions as part of matricellular proteins, and its production by airway epithelial cells is induced by IL-4 and IL-13. Periostin is secreted by fibroblasts and upregulated in the airway epithelia of patients with bronchial asthma; it is considered to contribute to remodeling under this pathological condition. However, despite many studies in diverse research areas, our overall understanding of this intriguing molecule is still inadequate. Here, we integrate the available evidence on periostin expression and its roles in otolaryngological diseases, including allergic rhinitis, chronic rhinosinusitis with nasal polyps, aspirin-induced asthma, organized hematoma, eosinophilic otitis media, and IgG4-related disease. Periostin might be involved as an important structural mediator in pathological processes such as insult and injury, Th2-driven inflammation, extracellular matrix restructuring, fibrosclerosis, tumor angiogenesis, and tissue remodeling.

Clinical course of five patients definitively diagnosed with idiopathic perilymphatic fistula treated with transcanal endoscopic ear surgery.

Objectives: An idiopathic perilymphatic fistula (PLF) can be difficult to diagnose because patients present with sudden sensorineural hearing loss (SSHL) and/or vestibular symptoms without any preceding events. In such cases, we currently test for cochlin-tomoprotein (CTP) to confirm the diagnosis of idiopathic PLF because CTP is only detected in the perilymph. In this study, we report the clinical course of five patients definitively diagnosed with idiopathic PLF who underwent PLF repair surgery using transcanal endoscopic ear surgery (TEES). Patients and methods: Five patients were initially treated with intratympanic dexamethasone for SSHL, at which time a CTP test was also performed (preoperative CTP test). Due to refractory hearing loss and/or fluctuating disequilibrium, PLF repair surgery using TEES was performed to seal the oval and round windows using connective tissue and fibrin glue. These patients were diagnosed with definite idiopathic PLF based on pre- or intra-operative CTP test results (negative, < 0.4 ng/mL; intermediate, 0.4-< 0.8 ng/mL; and positive, > 0.8 ng/mL). We evaluated pre- and intra-operative CTP values, intraoperative surgical findings via a magnified endoscopic view, and pre- and post-operative changes in averaged hearing level and vestibular symptoms. Results: Pre- and intra-operative CTP values were positive and intermediate in three patients, positive and negative in one patient, and negative and positive in one patient. None of the patients had intraoperative findings consistent with a fistula between the inner and middle ears or leakage of perilymph. Only two patients showed a slight postoperative recovery in hearing. Four patients complained of disequilibrium preoperatively, of whom two had resolution of disequilibrium postoperatively. Conclusion: A positive CTP test confirms PLF in patients without obvious intraoperative findings. The CTP test is considered more sensitive than endoscopic fistula confirmation. We consider that CTP test results are important indicators to decide the surgical indication for idiopathic PLF repair surgery. In our experience with the five cases, two of them showed improvements in both hearing and vestibular symptoms.

Effects of cholesterol alterations are mediated via G-protein-related pathways in outer hair cells.

Cholesterol is an essential component of cell membranes, and determines their rigidity and fluidity. Alterations in membrane cholesterol by MßCD or water-soluble cholesterol affect the stiffness, capacitance, motility, and cell length of outer hair cells (OHCs). This suggests that reconstruction of the cytoskeleton may be induced by cholesterol alterations. In this study, we investigated intracellular signaling pathways involving G proteins to determine whether they modulate the changes in voltage-dependent capacitance caused by cholesterol alterations. Membrane capacitance of isolated guinea pig OHCs were assessed using a two-sine voltage stimulus protocol superimposed onto a voltage ramp (200 ms duration) from -150 to +140 mV. One group of OHCs was treated with 100 µM guanosine 5'-O-(3-thiotriphosphate) tetralithium salt (GTPγS), the GTP analog, administrated into individual cells via patch pipettes. Another group of OHCs was internally perfused with 600 µM guanosine 5'-(ß-thio) diphosphate trilithium salt (GDPßS), the GDP analog. A third group was perfused with internal solution only as a control. Application of 1 mM MßCD shifted non-linear capacitance curves to the depolarized direction of the control group with reduction of the peak capacitance (C mpeak). After the 10-min application of MßCD, shifts of voltage at C mpeak (V cmpeak) and reduction of C mpeak were 73.32 ± 11.09 mV and 9.09 ± 2.10 pF, respectively (n = 4). On the other hand, in the GTPγS-treated group, the shift of V cmpeak and reduction of C mpeak were attenuated remarkably. The shift of V cmpeak and reduction of C mpeak in the 10-min application of MßCD were 9.73 ± 10.92 mV and 3.08 ± 1.91 pF, respectively (n = 7). MßCD decreased the cell length by 16.53 ± 4.27 % in the control group and by 6.45 ± 6.22 % in the GTPγS group. In addition, we investigated the effects of GDPßS on cholesterol-treated OHCs. One millimolar cholesterol was externally applied after the 4-min application of 1 mM MßCD because the shift of V-C m function caused by cholesterol alone was small. Application of cholesterol shifted V-C m curves of the control group to the hyperpolarized direction with increase of the C mpeak. After the 10-min application of cholesterol, changes of V cmpeak and C mpeak were -9.19 ± 6.68 mV and 2.14 ± 0.44 pF, respectively (n = 4). On the other hand, in the GDPßS-treated OHCs, the shift of V cmpeak and increase of C mpeak were attenuated markedly. The shift of V cmpeak and increase of C mpeak after 10 min were 5.13 ± 10.46 mV and -0.55 ± 1.39 pF, respectively (n = 6). This study demonstrated that internally perfused GTPγS inhibited the MßCD effects and GDPßS inhibited the cholesterol effects, raising the possibility that G proteins may be involved in outer hair cell homeostasis as well as the possibility that cholesterol response may be G protein mediated. More study is required to clarify the detailed role of G proteins in the relation between cholesterol and the OHC cytoskeleton.

Expression of pendrin and periostin in allergic rhinitis and chronic rhinosinusitis.

BACKGROUND: Pendrin and periostin are newly identified mediators of the inflammatory process. The expression of these proteins in human sinonasal tissue and their roles in allergic rhinitis and chronic rhinosinusitis remain to be elucidated. This study investigated the expression of pendrin and periostin in sinonasal tissue of patients with allergic rhinitis, chronic rhinosinusitis, and aspirin-induced asthma. Prospective control study conducted at Yamagata University, Japan. METHODS: Surgical samples were investigated by means of real-time reverse transcription-polymerase chain reaction to evaluate the expression of pendrin and periostin mRNA. The presence and location of pendrin and periostin were determined by immunohistochemistry and Western blotting. RESULTS: Pendrin and periostin production was significantly higher in patients with nasal disorders than in controls. Further significant increases in periostin expression were noted in patients with chronic rhinosinusitis with nasal polyps and in those with aspirin-induced asthma. Immunohistochemistry revealed positive staining for pendrin in epithelial cells and submucosal glands and for periostin in the basement membrane in all three disorders, and additionally for periostin in nasal polyp tissue in chronic rhinosinusitis and aspirin-induced asthma. CONCLUSIONS: Production of pendrin and periostin is upregulated in allergic rhinitis, chronic rhinosinusitis with nasal polyps, and aspirin-induced asthma. These findings suggest that pendrin can induce mucus production and that periostin can induce tissue fibrosis and remodeling in the nasal mucosa. Therefore, these mediators may be therapeutic target candidates for allergic rhinitis, chronic rhinosinusitis with nasal polyps, and aspirin-induced asthma.

The Feasibility and Treatment Results of Transcanal Endoscopic Myringoplasty.

OBJECTIVE: We reported on transcanal endoscopic myringoplasty in 25 cases preliminarily in 2014. Now our number of transcanal endoscopic myringoplasty reached to 209 ears and allowed us to adequately investigate the visibility, necessity of canalplasty, treatment results, and multivariate analysis. STUDY DESIGN: A prospective case series. SETTING: Tertiary referral center. PATIENTS: Transcanal endoscopic myringoplasty was performed on 209 ears in 201 patients between 2011 and 2019 and followed up over 1 year. METHODS: Preoperative endoscopic and microscopic views for the same patient were compared. We examined success rates at 1 year after surgery according to operation type, perforation size, operation side, gender, cause of perforation, and age, and also examined hearing results. Logistic regression analysis was performed to investigate the basic demographic and clinical characteristics of the patients associated with perforation closure. RESULTS: The anterior edge of the preoperative perforation was not visible under microscopy in 14.4% of patients. In contrast, endoscopic views revealed the entire tympanic membrane in one field. However, canalplasty was required in 2.4% of tympanic procedures due to difficulty of manipulation. The overall closure rate for perforations was 90.4%. Logistic regression analysis revealed that age > 11 was the only significant factor associated with perforation closure. The average reduction in air-bone gap was 12.1 dB. CONCLUSION: The endoscopic myringoplasty produced better visualization, the same or better closure rates, and the same or lower complication rates as compared with traditional microscopic techniques.

Adverse reactions to BNT162b2 mRNA COVID-19 vaccine in medical staff with a history of allergy.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) vaccination is progressing globally. Several adverse reactions have been reported with vaccination against COVID-19. It is unknown whether adverse reactions to COVID-19 vaccination are severe in individuals with allergies. METHODS: We administered the COVID-19 vaccine to the medical staff at Yamagata University Hospital from March to August 2021. Subsequently, we conducted an online questionnaire-based survey to investigate the presence of allergy and adverse reactions after vaccination and examine the association between allergy and adverse reactions after immunization. RESULTS: Responses were collected from 1586 to 1306 participants after the first and second administration of the BNT162b2 mRNA COVID-19 vaccine, respectively. Adverse reactions included injection site pain, injection site swelling, fever, fatigue or malaise, headache, chills, nausea, muscle pain outside the injection site, and arthralgia. The frequency of some adverse reactions and their severity were higher, and the duration of symptoms was longer in participants with allergies than in those without allergies. Although several participants visited the emergency room for treatment after the first and second vaccinations, no participant was diagnosed with anaphylaxis. CONCLUSIONS: This study suggests that the frequency and severity of adverse reactions after injection of BNT162b2 mRNA COVID-19 vaccine were higher in individuals with allergy; however, no severe adverse reactions such as anaphylaxis or death were observed. These results indicate that individuals with allergic histories may tolerate the BNT162b2 mRNA COVID-19 vaccine.

Benefits of High-Dose Corticosteroid and Antiviral Agent Combination Therapy in the Treatment of House-Brackman Grade VI Ramsay Hunt Syndrome.

OBJECTIVE: Few large-scale investigations have been conducted on treatment of House-Brackmann grade VI (HB grade VI) Ramsay Hunt syndrome (RHS) patients. We compared recovery rates among patients receiving a normal-dose corticosteroid (prednisolone [PSL] 60 mg/d) or high-dose corticosteroid (PSL 200 mg/d), both with or without an antiviral agents. Recovery rates were also examined based on the order of presentation of herpetic vesicles versus facial palsy. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: A total of 128 patients with HB grade VI RHS were treated in our department between 1995 and 2017. These patients were divided into four treatment groups based on corticosteroid dosage and use of an antiviral agent. METHODS: We assessed treatment outcomes for HB grade VI patients together with logistic regression analysis to investigate factors that can impact treatment outcomes, that is, sex, age, days to start of treatment, PSL dosage, and antiviral agent administration. RESULTS: Recovery rates were best in the high-dose corticosteroid group with an antiviral agent (71.1%) in comparison with the normal-dose corticosteroid group with an antiviral agent (60.0%) or high-dose corticosteroid alone (57.1%). Significant factors for treatment outcomes were high-dose corticosteroid administration and early initiation of treatment. A better recovery rate was also found when the herpetic vesicles appeared before facial palsy. CONCLUSION: We showed that a combination of a high-dose corticosteroid and antiviral agent produced the best outcomes for patients with HB grade VI RHS. However, our results were not statistically significant because of small sample size.

Daily short-term intratympanic dexamethasone treatment alone as an initial or salvage treatment for idiopathic sudden sensorineural hearing loss.

OBJECTIVE: Intratympanic (IT) steroid therapy has been proposed as an alternative treatment option for patients with idiopathic sudden sensorineural hearing loss (ISSNHL). However, the number and frequency of IT treatments and drug delivery methods remain to be determined. The purpose of this study was to evaluate the efficacy of daily short-term IT dexamethasone (DEX) treatment alone in ISSNHL patients using laser-assisted myringotomy (LAM) for the drug delivery route as an initial and/or salvage treatment. STUDY DESIGN: Retrospective study. SETTING: University hospital. PATIENTS: Seventy-six ISSNHL patients receiving IT DEX. Patients with low-tone hearing loss, unilateral or bilateral fluctuating hearing loss or contralateral hearing loss were excluded. INTERVENTION: DEX (4 mg/ml) was injected through a perforation made by LAM. IT DEX administration was performed on 8 sequential days. MAIN OUTCOME MEASURES: Pre- and postprocedure hearing levels. The average hearing level was determined by 5 frequencies (250, 500, 1000, 2000 and 4000 Hz). RESULTS: Nineteen out of 76 patients fit the criteria for initial treatment in the study (group I), while 24 patients, who had failed systemic therapy, received salvage treatment (group S). The mean age of the patients in groups I and S was 56.2 years with a range from 31 to 73 years of age and 46.0 years with a range from 11 to 76 years of age, respectively. The mean number of days from onset of symptoms to IT therapy in groups I and S was 4.8 days with a range of 1-23 days and 15.3 days with a range of 6-28 days, respectively. In group I, 18 of the 19 patients (95%) showed improvement of more than 10 dB in the pure-tone audiogram, with a mean improvement of 40 dB. Twelve patients (63%) recovered completely and 16 patients (84%) demonstrated successful results with an improvement of more than 30 dB. In group S, 14 of the 24 patients (58%) showed improvement of more than 10 dB with a mean improvement of 16 dB. Two (8%) of the 7 patients (29%) with successful results recovered completely. CONCLUSIONS: Daily short-term IT DEX administration using LAM for ISSNHL patients without concurrent therapy showed a high response rate and high cure rate and proved to be an alternative therapeutic option to high-dose systemic steroids as a first- and/or second-line treatment.

Hearing impairment and cognitive function among a community-dwelling population in Japan.

BACKGROUND: Hearing impairment is a prevalent and chronic condition in older people. This study investigated the relationship between cognitive function and hearing impairment in a Japanese population. METHODS: A pure-tone average (0.5-2.0 kHz) was used to evaluate hearing impairment in 846 participants of the Iwaki Health Promotion Project who were aged at least 50 years old (310 men and 536 women). We also administered the Mini-Mental State Examination (MMSE), the Center for Epidemiologic Studies for Depression (CES-D) scale, Starkstein's apathy scale (AS) and the Short Form Health Survey Version 2 (SF-36v2). A multiple linear regression analysis assessed the association between hearing impairment and mental correlates. RESULTS: The overall prevalence of hearing impairment in this study population was 37.7%. The participants with hearing impairment were older and less educated compared to those with no hearing problems. We observed significant differences in the MMSE and AS scores between the mild/moderate to severe groups versus the non-impaired group. After adjusting for age, gender and amount of education, hearing impairment was significantly associated with MMSE and AS scores, but not with CES-D scores. Hearing impairment was significantly related to the social functioning (SF) and role emotional (RE) scores of the SF-36v2. CONCLUSIONS: Hearing impairment is common among older people and is associated with cognitive impairment, apathy and a poor health-related quality of life. Screening for and correcting hearing impairments might improve the quality of life and functional status of older patients.

Consistent removal of hair cells in vestibular end organs by time-dependent transtympanic administration of gentamicin in guinea pigs.

BACKGROUND: Vestibular hair cell loss and its role in balance disorders are not yet completely understood due largely to the lack of precise hair cell damage protocols. NEW METHOD: Our damage protocol aims to selectively remove type I hair cells in a way that produces consistent and predictable lesions that can be used for reliable inter-animal and inter-group comparison in balance research. This objective is achieved by transtympanic injection of gentamicin on both the round window membrane and oval window over a fixed time period followed by thorough washing. RESULTS: We achieved nearly total and consistent loss of type I hair cells at 94 % for the crista ampullaris of the lateral semicircular canal (LSC) and 86 % for the utricular macula with negligible loss of type II hair cells at 4% for the crista ampullaris of the LSC and 6% for the utricular macula. While the vestibular function was compromised in the relevant study group, this group had a zero mortality rate with no significant suppression of body weight gain. COMPARISON WITH EXISTING METHODS: Gentamicin is typically administered via intraperitoneal systemic injection or, more recently, transtympanic injection. The intraperitoneal method is simple, but mortality rate is high. The transtympanic injection method produces ototoxic damage but with inconsistent lesion size. This inconsistency prevents reliable comparisons among animals. CONCLUSIONS: This protocol employs a transtympanic injection method which selectively targets type I hair cells for removal in the vestibular epithelia in a time-dependent manner, uniformly damages vestibular function, and causes uniform hair cell loss.

Y-27632, a ROCK inhibitor, improved laser-induced shock wave (LISW)-induced cochlear synaptopathy in mice.

Recently, a pathological condition called cochlear synaptopathy has been clarified, and as a disorder of the auditory nerve synapses that occurs prior to failure of hair cells, it has been recognized as a major cause of sensorineural hearing loss. However, cochlear synaptopathy is untreatable. Inhibition of rho-associated coiled-coil containing protein kinase (ROCK), a serine-threonine protein kinase, has been reported to have neuroprotective and regenerative effects on synaptic pathways in the nervous system, including those in the inner ear. We previously demonstrated the regenerative effect of the ROCK inhibitor, Y-27632, on an excitotoxic cochlear nerve damage model in vitro. In this study, we aimed to validate the effect of ROCK inhibition on mice with cochlear synaptopathy induced by laser-induced shock wave (LISW) in vivo. After the elevation of ROCK1/2 expression in the damaged cochlea was confirmed, we administered Y-27632 locally via the middle ear. The amplitude of wave I in the auditory brainstem response and the number of synapses in the Y-27632-treated cochlea increased significantly. These results clearly demonstrate that ROCK inhibition has a promising clinical application in the treatment of cochlear synaptopathy, which is the major pathology of sensorineural hearing loss.

Multicenter phase III trial of regenerative treatment for chronic tympanic membrane perforation.

OBJECTIVE: To evaluate the efficacy and safety of regenerative treatment for tympanic membrane perforation (TMP) using gelatin sponge, basic fibroblast growth factor (bFGF), and fibrin glue. METHODS: This was a multicenter, non-randomized, single-arm study conducted at tertiary referral centers. Twenty patients with chronic TMP (age 23-78 years, 6 males, 14 females) were registered from three institutions. All treated patients were included in the safety analysis population. The edges of the TMP were disrupted mechanically by myringotomy and several pieces of gelatin sponge immersed in bFGF were placed and fixed with fibrin glue to cover the perforation. The TMP was examined 4 ± 1 weeks later. The protocol was repeated up to four times until closure was complete. The main outcome measures were closure or a decrease in size of the TMP, hearing improvement, and air-bone gap evaluated 16 weeks after the final regenerative procedure (FRP). Adverse events (AEs) were monitored throughout the study. RESULTS: Total closure of the TMP at 16 weeks was achieved in 15 out of 20 patients (75.0%, 95% confidence interval [CI]: 50.9%-91.3%) and the mean decrease in size was 92.2% (95%CI: 82.9%-100.0%). The ratio of hearing improvement and the air-bone gap at 16 weeks after FRP were 100% (20/20; 95%CI: 83.2%-100%) and 5.3 ± 4.2 dB (p <0.0001), respectively. Thirteen out of 20 patients (65.0%) experienced at least one AE, but no serious AEs occurred. CONCLUSION: The results indicate that the current regenerative treatment for TMP using gelatin sponge, bFGF, and fibrin glue is safe and effective.

International Survey of Operative Practices for Otologists and Neurotologists During the COVID-19 Crisis.

OBJECTIVE: To investigate the influence of the COVID-19 pandemic on operative practices of otology and neurotology providers internationally. STUDY DESIGN: Cross-sectional survey. METHODS: A 78-question survey was distributed to otologists and neurotologists between May 12, 2020 and June 8, 2020 to assess the impact of the pandemic on surgical practices. Sections within the survey delineated time periods: prior to the crisis, onset of the crisis, during the crisis, postcrisis transition. RESULTS: Of 396 survey respondents, 284 participants from 38 countries met inclusion criteria.Respondents were 16.9% female and 82.4% male, with a most common age range of 40 to 49 years (36.3%). 69.8% of participants had been in practice for over 10 years and most respondents worked in an academic medical center (79.2%). The average operative weekly caseload was 5.3 (SD 3.9) per surgeon prior to the crisis, 0.7 (SD 1.2) during the COVID-19 crisis, and 3.5 (SD 3.3) for those who had begun a postcrisis transition at the time of survey administration (p < 0.001). 71.5% of providers did not perform an elective otologic or neurotologic operative procedure during the initial crisis period. 49.8% reported modifying their surgical technique due to the COVID-19 pandemic. Use of powered air-purifying respirators and filtering facepiece 2 or 3 (FFP2/FFP3) respirators were in minimal supply for 66.9% and 62.3% of respondents, respectively. CONCLUSION: The COVID-19 pandemic impacted the otology and neurotology community globally, resulting in significant changes in operative volume and case selection. Modification of surgical technique and shortages of personal protective equipment were frequently reported.