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OBJECTIVES/HYPOTHESIS To translate and cross-culturally adapt vestibular disorders activities of daily living (VADL) scale to Chinese population, and verify its psychometric characteristics. STUDY DESIGN A methodology study to translate, validate, and verify the reliability of the VADL scale. METHODS The translation of the VADL from English to Chinese was carried out in accordance with the recommendations proposed by the Process of Cross-Cultural Adaptation guideline. All 185 Subjects with chief complaints of dizziness or vertigo were continuously invited to the study from January 2021 to June 2021. Investigation using the Chinese version of VADL (VADL-C) was completed by all the participants. Complete data from all 124 participants were used for reliability and internal consistency analysis by using SPSS 22.0. RESULTS Through careful and complete translation and adaptation, the VADL-C was successfully created. The content validity of the VADL-C was 0.887, the internal consistency was 0.951, and the test-retest reliability was 0.989. CONCLUSIONS The VADL-C has an excellent internal consistency, test-retest reliability, and content validity. It will be a new tool to be used in China and for overseas Chinese speakers to explore the functional capacity of individuals with vestibular diseases and guide therapy planning, particularly in vestibular rehabilitation training program. Laryngoscope, 2021.

Triaging patients into correct severity categories in an emergency department is an advanced skill that depends on a quick assessment after obtaining very little information. The purpose of this study was to assess specific risk factors associated with hospital admissions in the emergency department environment of the specialized Eye, Ear, Nose, and Throat hospital located in Shanghai, China.This study was a retrospective cohort study. Patients visiting the emergency department in a tertiary hospital in eastern China from February 2008 to August 2015 were included. Univariate and multivariate analyses were used to identify the risk factors related to hospital admissions. Combining variables calculated from the regression equation of multivariate analysis (binary logistic regression analysis) enabled the risk factors quantification. The receiver operating characteristic analysis was used to identify the most informative cutoff point of the combining predictors.A total of 188715 patients were enrolled in the study. Of them, 8395 patients (4.4%) required hospital admission. Hour of visit, season, age, sex, chief complaint, anatomical location, and locale of patients were independent risk factors of hospital admission by univariate and multivariate analysis. Combining predictors were calculated from the equation of the multivariate logistic model. The area under the curve of the combining predictors was 0.949, and the 95% confidence interval was 0.947 to 0.951 (P.001), with a sensitivity of 95.2% and a specificity of 85.6%. A cutoff score of less than -35.1975 was associated with hospital admission.This study provided a method to build a feasible predictive model of hospital admission during triage. Understanding risk factors is an important part of the triage process in order to correctly assign priorities to the patients served. The outcomes of this study would add additional information for the triage nurse to consider in assessing the patient and assigning acuity ratings. The model developed here requires validation in future research.

Studies of saccular and utricular function in patients with obstructive sleep apnea (OSA) are rare. We noticed that some OSA patients also had positive results in vestibular function tests, and this inspired our interest in exploring the vestibular function patterns of OSA patients.To investigate otolithic organ function in severe OSA patients who lack vestibular symptoms and systemic disease.32 patients (64 ears) with severe OSA and 22 healthy controls (44 ears) were enrolled. The ocular and cervical vestibular-evoked myogenic potentials (oVEMP and cVEMP) and the caloric test were recorded and analyzed.The response rates of oVEMP (73.4%) and cVEMP (82.8%) in patients with severe OSA were significantly lower than those in controls. In oVEMP, elevated thresholds (Disappearance or impairment of VEMPs could be observed in patients with severe OSA, and reflects different degrees of impairment in the utricle and saccule.

As part of the inner ear, the vestibular system is responsible for sense of balance, which consists of three semicircular canals, the utricle, and the saccule. Increasing evidence has indicated that the noncanonical Wnt/PCP signaling pathway plays a significant role in the development of the polarity of the inner ear. However, the role of canonical Wnt signaling in the polarity of the vestibule is still not completely clear. In this study, we found that canonical Wnt pathway-related genes are expressed in the early stage of development of the utricle and change dynamically. We conditionally knocked out β-catenin, a canonical Wnt signaling core protein, and found that the cilia orientation of hair cells was disordered with reduced number of hair cells in the utricle. Moreover, regulating the canonical Wnt pathway (Licl and IWP2) in vitro also affected hair cell polarity and indicated that Axin2 may be important in this process. In conclusion, our results not only confirm that the regulation of canonical Wnt signaling affects the number of hair cells in the utricle but also provide evidence for its role in polarity development.

To assess any differences in spatial listening ability of cochlear implant recipients when using both or only one of two bilateral cochlear implants (BCIs) for stimuli originating from behind the subject.Twelve loudspeakers were placed in the rear horizontal plane of the subjects to test the sound localisation performance of BCI users and normal-hearing listeners (NHLs) with or without interfering noise. Stimuli were presented via two rear loudspeakers simultaneously during the speech recognition test. In the tone recognition test, another anechoic chamber was used with stimuli presenting from a loudspeaker behind the participants.Twenty-seven NHLs and eleven BCI users.Average root-mean-square (RMS) error for the bilateral condition was significantly lower than that for the right and left cochlear implant (CI) conditions with or without interfering noises (Sound localisation with BCIs was significantly more accurate than with either implant alone. Speech and tone recognition scores were not better with two compared to those of one activated implant. Given the small number of subjects, the results should be considered as preliminary.

Intratympanic injection of gentamicin has proven to be an effective therapy for intractable vestibular dysfunction. However, most studies to date have focused on the cochlea, so little is known about the distribution and uptake of gentamicin by the counterpart of the auditory system, specifically vestibular hair cells (HCs). Here, with a combination of in vivo and in vitro approaches, we used a gentamicin-Texas Red (GTTR) conjugate to investigate the mechanisms of gentamicin vestibulotoxicity in the developing mammalian utricular HCs. In vivo, GTTR fluorescence was concentrated in the apical cytoplasm and the cellular membrane of neonatal utricular HCs, but scarce in the nucleus of HCs and supporting cells. Quantitative analysis showed the GTTR uptake by striolar HCs was significantly higher than that in the extrastriola. In addition, the GTTR fluorescence intensity in the striola was increased gradually from 1 to 8 days, peaking at 8-9 days postnatally. In vitro, utricle explants were incubated with GTTR and candidate uptake conduits, including mechanotransduction (MET) channels and endocytosis in the HC, were inhibited separately. GTTR uptake by HCs could be inhibited by quinine, a blocker of MET channels, under both normal and stressed conditions. Meanwhile, endocytic inhibition only reduced GTTR uptake in the CoCl2 hypoxia model. In sum, the maturation of MET channels mediated uptake of GTTR into vestibular HCs. Under stressed conditions, MET channels play a pronounced role, manifested by channel-dependent stress enhanced GTTR permeation, while endocytosis participates in GTTR entry in a more selective manner.

Hair cells (HCs) in the mammalian cochleae cannot spontaneously regenerate once damaged, resulting in permanent hearing loss. It has been shown that Atoh1 overexpression induces hair cell-like cells (HCLCs) in the cochlea of newborn rodents, but this is hard to achieve in adult mammals. In this study, we used a three-dimensional cochlear culture system and an adenoviral-mediated delivery vector to overexpress Atoh1 in adult mouse cochleae. HCLCs were successfully induced from 3 days after virus infection (3 DVI) in vitro, and the number increased with time. HCLCs were myosin7a positive and distinguishable from remnant HCs in a culture environment. Meanwhile, patch-clamp results showed that noninactive outward potassium currents (sustained outward potassium currents) could be recorded in HCLCs and that their magnitude increased with time, similar to normal HCs. Furthermore, transient HCN currents were recorded in some HCLCs, indicating that the HCLCs experienced a developmental stage similar to normal HCs. We also compared the electrophysiological features of HCLCs from adult mice with native HCs and found the HCLCs gradually matured, similar to the normal HCs. Meanwhile, HCLCs from adult mice possessed the same bundles as developmental HCs. However, these HCLCs did not express prestin, which is a special marker for outer hair cells (OHCs), even at 13 DVI. These results demonstrate that Atoh1 overexpression induces HCLC formation in the adult mammalian cochlea and that these HCLCs were functional and experienced a developmental process similar to that of normal HCs.

Objective To elucidate the pathophysiological process by analyzing the correlation between morphological and functional changes in patients with delayed endolymphatic hydrops (DEH). Methods Twenty-nine patients diagnosed with DEH were enrolled in this retrospective study. All patients were assessed using the caloric test, cervical and ocular vestibular evoked myogenic potentials, and gadolinium-enhanced magnetic resonance imaging (MRI) of the inner ear. Results According to the MRI, the hydrops localization was categorized as hydrops in the vestibule (saccule and utricle) (14%), hydrops in the vestibule and cochlea (72%), and hydrops in the vestibule, cochlea, and lateral semicircular canal (LSCC) (14%). Vestibular hydrops could definitely be observed as function declined; however, a dysfunction of both the saccule and utricle was not always present when vestibular hydrops was detected with MRI. In the LSCC, a decline in functional tests was not necessarily accompanied by morphological abnormalities. However, dysfunction could definitely be detected when LSCC hydrops was observed with MRI. Conclusions Hydrops can be found mainly in the vestibule as shown by MRI. In the vestibule, abnormalities are commonly morphologic rather than functional, whereas in the LSCC a functional deterioration can be detected more frequently than morphological changes. Significance Our findings can provide a new perspective on the functional and morphological characteristics of patients with DEH.

OBJECTIVES The purpose of this study was to develop a deep-learning framework for the diagnosis of chronic otitis media (COM) based on temporal bone computed tomography (CT) scans. DESIGN A total of 562 COM patients with 672 temporal bone CT scans of both ears were included. The final dataset consisted of 1147 ears, and each of them was assigned with a ground truth label from one of the 3 conditions: normal, chronic suppurative otitis media, and cholesteatoma. A random selection of 85% dataset (n = 975) was used for training and validation. The framework contained two deep-learning networks with distinct functions: a region proposal network for extracting regions of interest from 2-dimensional CT slices; and a classification network for diagnosis of COM based on the extracted regions. The performance of this framework was evaluated on the remaining 15% dataset (n = 172) and compared with that of 6 clinical experts who read the same CT images only. The panel included 2 otologists, 3 otolaryngologists, and 1 radiologist. RESULTS The area under the receiver operating characteristic curve of the artificial intelligence model in classifying COM versus normal was 0.92, with sensitivity (83.3%) and specificity (91.4%) exceeding the averages of clinical experts (81.1% and 88.8%, respectively). In a 3-class classification task, this network had higher overall accuracy (76.7% versus 73.8%), higher recall rates in identifying chronic suppurative otitis media (75% versus 70%) and cholesteatoma (76% versus 53%) cases, and superior consistency in duplicated cases (100% versus 81%) compared with clinical experts. CONCLUSIONS This article presented a deep-learning framework that automatically extracted the region of interest from two-dimensional temporal bone CT slices and made diagnosis of COM. The performance of this model was comparable and, in some cases, superior to that of clinical experts. These results implied a promising prospect for clinical application of artificial intelligence in the diagnosis of COM based on CT images.

Background: Petrous bone cholesteatoma (PBC) is a rare but local aggressive lesion which can lead to severe complications. Surgery is the mainstay for its treatment. Objectives: To analyse the clinical characteristics and surgical outcomes in a series of patients with PBC, paying special attention to cochlea preservation and use of endoscope. Materials and methods: Retrospective study of 51 patients with PBC who underwent surgery at our centre. Results: Hearing loss (72.5%) and facial paralysis (58.8%) were the two most common symptoms. According to Sanna's classification, supralabyrinthine subtype (51.0%) was the most common subtype, followed by the massive subtype (33.3%). In most patients, PBC was radically removed using subtotal petrosectomy (80.4%). Endoscope was used for assistance in six cases. Various managements of facial nerve were used in different cases. Hearing rehabilitation was not emphasized (44 postoperative dead ear); however, cochlea was preserved as far as possible (45.3%). Recurrence was identified in five patients by MRI with diffusion weighted imaging (DWI) sequence. No recurrence was detected in patients underwent surgery with endoscope assistance. Conclusions and significance: radical excision and functional reconstruction constitute the framework of PBC surgery. Cochlea preservation is critical for possible cochlear implantation in the future. Use of endoscope has the potential to enhance surgical precision and reduce recurrence.

A new floating piezoelectric microphone (NFPM), driven by the acoustic vibration of the ossicles, has been manufactured in the lab.This study aimed at exploring the stability and bio-compatibility of this NFPM.The NFPM was implanted into the cat tympanic cavity by clamping it to the handle of the malleus, and then a temporal bone computed tomography (CT) plain scan and three dimensional reconstruction were performed to observe its coupling with the handle of the malleus. After six months of implantation, cats' blood samples were taken for pro-inflammatory factor analysis. Then, the operative cavity was opened to check the NFPM, the auditory ossicular chain and some granulation tissue surrounding the NFPM.The NFPM was firmly clamped to the handle of the malleus of the cats during the six months of implantation. Besides, there was no obvious systemic inflammatory response in the experimental animals. In addition, local proliferation of granulation tissue occurred in the tympanic cavity without hampering the movement of the auditory ossicle,or causing ischemia of the auditory ossicle.The NFPM could be implanted in our experimental cats for a long period of time and had good bio-compatibility.

Objectives To identify genes that are related to delayed endolymphatic hydrops (DEH) in patients by RNA-Seq analysis. Design Observational study. Setting Eye & ENT Hospital, Fudan University (Shanghai, China). Participants We collected the entire vestibular system from four patients with DEH who underwent labyrinthectomy. Three control samples were collected from patients with acoustic neuroma or facial neuroma treated via the translabyrinthine approach. High-throughput RNA-Seq analysis was performed to investigate gene expression in the pathological vestibular system. Main outcome measures Our bioinformatics analysis identified 17 genes that were upregulated and eight genes that were downregulated in patients with DEH compared to the controls. Results The altered gene expression profile suggested that DEH is closely related to neuropathy and autoimmune disease. In addition, many of the differentially regulated genes were involved in cell adhesion, suggesting a role of cell adhesion in DEH. Immunofluorescence analysis confirmed the expression of PMP2 and CLDN19 in the cytoplasm of hair cells and scattered expression of MPZ at cell junctions. The protein expression levels were higher in specimens from patients with Meniere's disease and DEH compared to controls. Conclusions The protein expression profile of vestibular organs in patients with endolymphatic hydrops exhibited a degree of similarity to that of Meniere's disease. Endolymphatic hydrops is characterized by autoimmune abnormalities. DEH and Meniere's disease are likely to be different manifestations of the same disease, with disparate clinical symptoms. RNA-Seq is a useful analytical tool to characterise the vestibular pathology based on its transcriptome.

Objective The purpose of this study was to investigate the effect of a dilated vestibular aqueduct on conductive hearing loss (CHL). A biomechanical method was proposed for modeling the patterns of CHL in patients with large vestibular aqueduct syndrome (LVAS). Study design High resolution computed tomography (CT) scans and pure tone audiometry (PTA) were retrospectively collected from 16 patients who were diagnosed with LVAS. Seventeen ears with measurable air-bone gaps (ABGs) on PTA were applied for model development. The sizes of midpoint, operculum and distal segment were measured from CT to calculate the biomechanical parameters of each vestibular aqueduct. The mechanical effect of the dilated vestibular aqueduct on sound conduction was simulated using a lumped-parameter model. The CHL levels predicted by the model were compared with the observed ABGs at 250, 500 and 1000 Hz respectively. Results The model was able to predict the trend that greater ABGs occurred at lower frequencies, which were consistent with clinical observations. However, deviations between the predicted and the observed ABGs became larger as the frequency increased. None of the correlation coefficients between the radiologic measures and the observed ABG levels were significant. Conclusion These findings lend support to the feasibility of this approach in modeling CHL in LVAS. The presence of a dilated vestibular aqueduct leads to altered impedance and sound pressure, suggesting the impact of a pathological third window. High individual variability of the observed ABGs implies additional factors may also be involved, especially at 500 Hz and 1000 Hz.

OBJECTIVES To determine the clinical characteristics of papilloma involving the external auditory canal (PEAC) in a region of China. STUDY DESIGN A retrospective study. METHODS Demographics, manifestations, imaging results, histopathology, and treatment of 67 patients diagnosed with PEAC in a period of 6 years were analyzed at Shanghai Eye, Ear, Nose and Throat Hospital in China. RESULTS PEAC were encountered in patients between the ages of 12 and 82 years (mean 53.8 years). It was more prevalent in men (82%) than in women (18%) (P

To evaluate surgical outcomes for chronic otitis media with mucosa defect underwent titanium ossicular chain reconstruction (OCR) in single stage canal wall down tympanoplasty (CWD).A clinical retrospective study was performed on 83 cases of the chronic otitis media with mucosa defect and 123 ears with mucosa integrity according to intraoperative findings that underwent synchronous titanium OCR in single stage CWD form January 2012 to January 2018. Pre- and postoperative air conduction threshold (AC), air-bone gap (ABG) and ABG closure at 0.5, 1, 2, and 4 kHz were investigated.The overall mean AC threshold of 53.4 ± 16.5 dB was lowered to 41.2 ± 15.9 dB postoperatively (p 0.01). The mean pre- and postoperative ABG of all patients were 27.9 ± 9.9 dB and 17.2 ± 9.3 dB (p 0.01), respectively, with a mean ABG closure of 10.7 ± 8.4 dB. The total rate of success, postoperative ABG ≤ 20 dB was achieved in 71.4%. In the mucosa defect group underwent TORP, the mean pre- and postoperative ABG were 28.1 ± 9.8 dB and 20.1 ± 9.0 dB (p 0.01), respectively, with the ABG closure was 8.0 ± 7.9 dB. In the mucosa defect group underwent PORP, the mean pre- and postoperative ABG were 27.9 ± 10.1 dB and 16.5 ± 9.1 dB (p 0.01), respectively, with the ABG closure was 11.4 ± 8.6 dB. Furthermore, in the mucosa defect group, there was significant difference in success rate of achieved postoperative ABG ≤ 20 dB between the TORP (48.9%) and PORP (77.5%) (p 0.05).It is revealed PORP in single stage CWD tympanoplasty for the patients suffered from chronic otitis media with mucosa defect is favored.

Objective Microsurgery is the reference standard treatment of petrous bone cholesteatoma (PBC). In most cases, radical removal of an extensive PBC can only be achieved at the cost of sacrificing the cochlea. Such treatment will result in the impossibility of future cochlear implantation for hearing rehabilitation purposes. To address this issue, a modification of the traditional translabyrinthine (TL) approach with endoscopic assistance has been developed for radical removal of extensive PBC with preservation of the cochlea. Methods From June 2017 to December 2017, 3 patients with a massive PBC underwent surgical removal using the modified TL approach by the senior author in our department. We reviewed the patient characteristics and retrospectively studied the surgical outcomes and postoperative complications. In the present report, we have described our modified TL approach in detail. Results Complete resection of the PBC and successful cochlea preservation were achieved in all 3 patients. No recurrence had developed during the follow-up period. However, various degrees of cochlear ossification were observed in 2 patients postoperatively. Conclusions This modified TL approach provides the possibility of fully exposing the whole petrous apex without removing the cochlea in selected cases. However, the development of long-term cochlear ossification requires further investigation to allow for successful cochlear implantation.

Loss of hair cells from vestibular epithelium results in balance dysfunction. The current therapeutic regimen for vestibular diseases is limited. Upon injury or Atoh1 overexpression, hair cell replacement occurs rapidly in the mammalian utricle, suggesting a promising approach to induce vestibular hair cell regeneration. In this study, we applied simultaneous gentamicin-mediated hair cell ablation and Atoh1 overexpression to induce neonatal utricular hair cell formation in vitro. We confirmed that type I hair cells were the primary targets of gentamicin. Furthermore, injury and Atoh1 overexpression promoted hair cell regeneration in a timely and efficient manner through robust viral transfection. Hair cells regenerated with type II characteristics in the striola and type I/II characteristics in non-sensory regions. Rare EdU+/myosin7a+ cells in sensory regions and robust EdU+/myosin7a+ signals in ectopic regions indicate that transdifferentiation of supporting cells in situ, and mitosis and differentiation of non-sensory epithelial cells in ectopic regions, are sources of regenerative hair cells. Distinct regeneration patterns in in situ and ectopic regions suggested robust plasticity of vestibular non-sensory epithelium, generating more developed hair cell subtypes and thus providing a promising stem cell-like source of hair cells. These findings suggest that simultaneously causing injury and overexpressing Atoh1 promotes hair cell regeneration efficacy and maturity, thus expanding the understanding of ectopic plasticity in neonatal vestibular organs.

BACKGROUND Kanamycin and subsequent furosemide administration was applied to the healthy guinea pigs to induce deafness. MATERIAL AND METHODS Of the deafened guinea pigs, 10 were further infused with anti-infection procedures (Group B) and the other 10 animals did not undergo anti-infection procedures (Group C). In Group B, the deafened animals were able to restore cochlear and middle ear functions following the anti-infection procedure. In Group C, all animals developed cochlear and middle ear infections. RESULTS Compared to the healthy guinea pigs, hair cells and spiral ganglion neurons (SGN) of deafened animals (in Group B and Group C) were severely damaged. SGN density of deafened animals was significantly lower than that of healthy control animals in all ear turns except the basal turn. There was no significant difference between Group B and Group C in SGN density. The average optical density value of neurofilaments of deafened animals was also significantly decreased after the ototoxic drug administration. Notably, the density of the neurons in the cochlear nucleus region (CNR) of the brainstem were not significantly different between the healthy control guinea pigs and deafened animals. CONCLUSIONS Mimic cochlear implant surgery-induced cochlear infection caused no significant damage to the auditory pathway in ototoxic drug-induced deafened guinea pigs.

To analyze and summarize the effect of bilateral large vestibular aqueducts in peripheral vestibular organ function.Eighteen patients with bilateral large vestibular aqueduct syndrome (LVAS; Study Group) and 18 healthy volunteers (Control Group) were investigated using audiometry, caloric test, sensory organization test (SOT), and vestibular-evoked myogenic potential (VEMP) tests.All 18 patients (36 ears) exhibited sensorineural hearing loss. For cervical VEMP (cVEMP), the Study Group showed lower thresholds (Study Group vs.71.4vs. 75.3dBnHL; p=0.006), N1 latencies (24.1vs. 25.2ms; p=0.026) and shorter P1 (15.3vs. 16.6ms; p=0.003), and higher amplitudes (400.7vs. 247.2µV; p0.001) than the Control Group. For ocular VEMP (oVEMP), the Study Group had lower thresholds (79.3vs. 81.8dBnHL; p=0.046) and higher amplitudes (40.6vs. 14.4µV; p0.001) than the Control Group. Fourteen of 16 patients (87.5%) who completed caloric tests had abnormal results, and 10 of 18 patients (55.6%) exhibited abnormal results in SOTs.The hyperfunction of vestibular test in otolithic organs and the hypofunction of vestibular test in semicircular canals, as well as the dysfunction in the balance test were demonstrated in patients with LVAS.Our findings can help clinicians gain a better understanding of the characteristics of vestibular organ function in patients with LVAS, which can facilitate optimal targeted treatment.

Planar cell polarity (PCP) signalling specifies the orientation of epithelial cells and regulates directional beating of motile cilia of multiciliated epithelial cells. Clinically, defects in cilia function are associated with nasopharyngeal symptoms. The polarity of the nasopharyngeal epithelium is poorly understood. Here, we demonstrated PCP in the nasopharyngeal epithelium. Multiciliated cells (MCCs) were uniformly aligned with their long axis parallel to the tissue axis of the nasopharynx (NP). In addition, PCP proteins exhibited an asymmetrical localisation between adjacent cells. Motile cilia were uniformly aligned in the same direction within both individual cells and neighbouring cells, which manifested as cilial polarity in MCCs. Mutation of Vangl2, a mammalian homologue of the Drosophila PCP gene, resulted in significant disruption of the orientation of epithelial cells. Finally, keratin-5-positive basal cells constantly replenished the luminal ciliated cells; the new dynamic ciliated cells were also oriented parallel to the tissue axis. These results indicate a role for the PCP pathway in the uniform orientation of dynamically replenished epithelial cells in the NP.

Objective: The objective of this study is to describe the clinical features, managements and outcomes of a rare coexistence of congenital ossicular anomaly and localized cholesteatoma. A literature review on these cases and each congenital disorder is also presented. Methods: A retrospective chart review was performed on patients diagnosed with congenital ossicular anomaly with concurrent localized cholesteatoma from 2008 to 2017. Clinical data of these patients were collected. Results: A total of 10 patients were identified. All patients presented with unilateral hearing loss. Pure-tone audiometry showed conductive hearing loss in all affected ears with an average air conduction (AC) threshold of 59 dB. High-resolution computed tomography scans of the temporal bone diagnosed ossicular anomaly for 90% (9/10); however, only 50% (5/10) had a diagnosis of localized cholesteatoma. A transcanal exploratory tympanotomy under the microscope was performed to discover whether the localized tiny-sized cholesteatoma around the ossicular chain did not have direct contact with the ossicular chain, which could be diagnosed as congenital cholesteatoma. We removed the localized cholesteatoma and reconstructed the ossicular chain in each patient. All localized cholesteatomas were found in the posterior-superior quadrant of the middle ear. Ossicular chain anomalies were associated with the incus and/or the stapes in all cases. Hearing improvement was achieved in each of the 6 patients who were followed up postoperatively, with an average AC threshold of 35 dB. The clinical features of congenital ossicular anomaly with concurrent congenital cholesteatoma were compared with those of each congenital disorder. The pathogenesis of each condition was also discussed. Conclusions: Congenital ossicular anomaly with concurrent congenital cholesteatoma is rare. It shares similar clinical features with congenital ossicular anomaly occurring alone, therefore awareness should be raised for a possible concurrent congenital cholesteatoma which was easy to miss in the diagnosis (50%) by the radiologist. A patient’s hearing level can be improved by removal of the cholesteatoma and reconstruction of the ossicular chain. Localized cholesteatoma does not usually show residuals or recurrence.

The new floating piezoelectric microphone is feasible for use as an implantable middle ear microphone in a totally implantable cochlear implant.A piezoelectric sensor that is driven by the acoustic vibration of the ossicles is one possible design for a microphone for a totally implantable cochlear implant. Such a new floating piezoelectric microphone has been manufactured in the lab. The purpose of this article was to study the frequency response of the new floating piezoelectric microphone in the intact ossicular chain and to identify whether it is usable and implantable.The frequency response of the new floating piezoelectric microphone was analyzed using in vitro testing of fresh cadaveric heads. The microphone, which was designed with an integrated unibody structure to ensure good biocompatibility and capsulation, was attached to the long process of the incus by a titanium clip, or placed in the tympanic cavity and stimulated with pure tones of different frequencies.The new floating piezoelectric microphone can pick up the vibration of the long process of the incus and convert it into electrical signals sensitively and flatly.

Loss of inner ear hair cell (HC) is an irreversible process in mammals and is the most common cause of human hearing and balance disorders especially in the elderly. Cell therapy based on highly scalable generation of HC linage and inner ear transplantation is one of the most promising therapeutic approaches for HC impairment. For fibroblast is quite abundant and readily available in human body, it is an ideal endogenous cell source to generate HC lineage for transplantation purpose. In the present study, by using a cell activation and signaling directed method, we demonstrate that adult fibroblast can be direct reprogrammed into a kind of cell which expresses lots of HC markers. At the same time, an intermediate progenitor stage exists during such a lineage conversion and activation of FGF pathway is critical for its formation. Although these reprogrammed cells still lack some of the key features of HC such as mechanosensitive ion channel hence have not acquired the functional properties of HC, the findings reported here raise the possibility of reprogramming endogenous fibroblasts into functional HC for regenerative purpose.

Objective: This study aims to assess the effectiveness of endoscopic tympanoplasty without mastoidectomy in the management of active mucosal chronic otitis media (COM) patients with mastoid and tympanic antrum lesions. Methods: It is a prospective controlled study where 42 patients with active mucosal COM with mastoid and tympanic antrum lesions or normal aeration were recruited from the outpatient clinic of the otology department, Eye Ear Nose and Throat Hospital of Fudan University. All patients underwent endoscopic tympanoplasty without mastoidectomy by using the underlay technique with tragal cartilage graft with one side-perichondrium. The follow-up period was at least 3 months and results were evaluated in terms of graft uptake, ear dryness and hearing improvement. Results: Statistics showed no significant difference in graft uptake between the mastoid and tympanic antrum lesions group (90.5%) and the normal aeration group (95.2%). There was no significant difference in ear dryness between the mastoid and tympanic antrum lesions group (95.2%) and the normal aeration group (100%). Hearing improvement was comparable in the 2 groups. Conclusion: Regardless of the occurrence of soft density shadows in temporal bone showed by high-resolution computerized tomography in the mastoid and tympanic antrum, mastoidectomy is an unnecessary procedure for dealing with active mucosal COM without cholesteatoma. Therefore, this study shows that endoscopic tympanoplasty without mastoidectomy may be applied to active mucosal COM without cholesteatoma.

Emerging evidence and clinical case reports have observed a risk of cytotoxic effects of triptolide in patients. We aimed to investigate the triptolide-induced toxicity in mouse inner ear stem cells. The utricular sensory epithelium from adult BALB/C6 mice was used for the isolation of inner ear stem cells. Sphere formation assay was applied to examine the stemness of the cells. Cell count kit-8 and Bromodeoxyuridine assays were employed to detect the cell proliferation ability. Cell apoptosis was measured with Annexin V-FITC & propidium iodide Apoptosis kit. The relative expression levels of gamma H2A histone family member X (γH2AX), tumor suppressor p53-binding protein 1 (53BP1) and optic atrophy 1 (OPA-1) were measured by Western Blot. Mitochondrial function was analyzed by the MitoGreen green-fluorescent mitochondrial dye kit. Triptolide significantly inhibited the cell viability and proliferation and suppressed the capability of sphere formation. Furthermore, triptolide induced apoptosis as indicated by increased expression of DNA damage repair markers γH2AX and 53BP1. Moreover, triptolide influenced the function of mitochondria by inducing the cleavage of OPA-1. Our work clarifies the toxicity of triptolide in mouse inner ear stem cells, which provides clues of the toxicology mechanism for future studies and basis for clinical use.

Objective Neurorrhaphy with interpositional graft is a practical technique to achieve facial reanimation when the continuity of the facial nerve is interrupted and a large gap between the proximal and distal stump exists. The aim of this study was to report long-term outcomes of neurorrhaphy for facial reanimation with interpositional graft. The roles of some variable factors in the outcome of neurorrhaphy with interpositional graft were also evaluated and compared. Methods A retrospective case series from a single tertiary referral center comprised 23 patients with facial nerve interruptions who underwent neurorrhaphy with interpositional graft using either end-to-end anastomosis or end-to-side hypoglossal-facial technique. Preoperative data (age, sex, primary lesion, interval from paralysis to surgery, facial nerve function), intraoperative data (surgical approach, graft and type of neurorrhaphy), and postoperative data (facial nerve function) were collected and analyzed. Results Mean follow-up time was 26.6 ± 11.9 months. Patients who underwent neurorrhaphy for facial reanimation within 1 year after onset of facial paralysis were more likely to achieve House-Brackmann grade ≤3 compared with patients who underwent neurorrhaphy >1 year after onset of facial paralysis (odds ratio = 23.85, P = 0.04). No other factors were associated with improved outcomes. Conclusions Early neurorrhaphy with interpositional graft (≤1 year) for facial reanimation resulted in better final facial nerve function outcomes compared with a delayed procedure.

We aimed to investigate the beneficial effect of Celastrol on inner ear stem cells and potential therapeutic value for hearing loss. The inner ear stem cells were isolated and characterized from utricular sensory epithelium of adult mice. The stemness was evaluated by sphere formation assay. The relative expressions of Atoh1, MAP-2 and Myosin VI were measured by RT-PCR and immunoblotting. The up-regulation of MAP-2 was also analysed with immunofluorescence. The in vitro neuronal excitability was interrogated by calcium oscillation. The electrophysiological property was determined by inward current recorded on patch clamp. Our results demonstrated that Celastrol treatment significantly improved the viability and proliferation of mouse inner ear stem cells, and facilitated sphere formation. Moreover, Celastrol stimulated differentiation of mouse inner ear stem cells to neuronal-like cells and enhanced neural excitability. Celastrol also enhanced neuronal-like cell identity in the inner ear stem cell derived neurons, as well as their electrophysiological function. Most notably, these effects were apparently associated with the upregulation of Atoh1 in response to Celastrol treatment. Celastrol showed beneficial effect on inner ear stem cells and held therapeutic promise against hearing loss.

Mucous cell metaplasia/hyperplasia in the middle ear epithelium is associated with the occurrence of otitis media with effusion during infections. However, the mechanism by which Notch signaling regulates cell fate in the middle ear epithelium is unclear. The aim of the present study was to elucidate this mechanism by investigating the localization of Notch receptors, such as Notch1 and Notch2, and Notch ligands, such as Jagged1, in the normal mouse middle ear epithelium (NMMEE) using immunofluorescence. Furthermore, the mRNA expression levels of Notch receptors and ligands were evaluated using reverse transcription polymerase chain reaction (PCR). The effects of the γ-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine tert-butyl ester (DAPT) on epithelial cell proliferation were determined using 5-ethynyl-2′-deoxyuridine (EdU) staining and immunofluorescence staining of the apoptosis marker caspase-3 and the epithelial proliferation marker pan-cytokeratine. In addition, the differentiation of the NMMEE cells was characterized by evaluating the mRNA expression levels of the mucous cell-associated genes Arg2, Muc2, Spdef, Spink4 and Tff1 using quantitative PCR. Notch1, Notch2 and Jagged1 were observed to be co-localized throughout the mouse middle ear epithelium. Furthermore, Notch1-4, Jagged1, Jagged2, Dll1 and Dll4 mRNAs were expressed in the NMMEE cells. The inhibition of Notch by DAPT resulted in fewer EdU-positive cells and the upregulation of the expression levels of various mucous cell-associated genes. The results indicate that DAPT suppresses the proliferation of NMMEE cells while promoting their differentiation into mucous cells. Therefore, DAPT may provide a specific therapeutic strategy for the reversal of multiple pathological processes that are associated with epithelium thickening in the middle ear.

Aims: This study aims to investigate the roles of the number of accelerations and rotation angle in the treatment of posterior semicircular canal benign paroxysmal positional vertigo (PC-BPPV). Methods: We enrolled 344 patients with unilateral PC-BPPV. Of these, 167 patients in the simple-step maneuver (SSM) group were accelerated twice and rotated 120° per step, whereas 177 patients in the multi-step maneuver (MSM) group were accelerated 4 times and rotated 60° per step. Dix-Hallpike (DH) tests were performed to categorize the treatment outcome as follows: ‘symptom free' if the result was negative, ‘symptom persistent' if the result remained positive after performing the maneuver 3 times or ‘canal conversion' if horizontal nystagmus was evoked. Results: Of the patients in the SSM and MSM groups, 78.4 and 91.5% became symptom free, respectively, while canal conversion occurred in 13.8 and 5.1%, respectively (p = 0.003, χ2 test). The success rate after performing the maneuver once was 57.1% in the MSM and 32.3% in the SSM symptom-free patients (p = 0.001, χ2 test). One month after the treatment, 22.0 and 9.6% of the SSM and MSM patients had symptom relapse, respectively (p = 0.007, χ2 test). Conclusions: More accelerations and a smaller rotation angle improved the effectiveness and efficiency of the repositioning maneuvers and reduced canal conversion.

© 2015 Taylor & Francis Conclusion: This study described objective and subjective evaluations of the Nurotron® Venus™ Cochlear Implant System and indicated that this system produced a satisfactory performance. Objective: To observe the performance of the Nurotron® Venus™ cochlear implant (CI) system via electrophysiological and psychophysical evaluations. Methods: A 26-electrode CI system was specially designed. The performance of MRI in animal and cadaveric head experiments, EABR in cats experiment, the correlation between ESRT and C level, and psychophysics evaluations in clinical trials were observed. Results: In the animal and cadaveric head experiments, magnet dislocation could not be prevented in the 1.5 T MRI without removal of the internal magnet. The EABR was clearly elicited in cat experiment. In the clinical trial, the ESRT was strongly correlated with C level (p

Planar cell polarity (PCP) signaling regulates cochlear extension and coordinates orientation of sensory hair cells in the inner ear. Retroviral-mediated introduction of the Math1 transcription factor leads to the transdifferentiation of some mature supporting cells into hair cells. Testosterone, a gonadal sex steroid hormone, is associated with neuroprotection and regeneration in Central Nervous System (CNS) development. Experiments were performed in vitro using Ad5-EGFP-Math1/Ad5-Math1 in neonatal mouse cochleas. Establishment of ectopic hair-cell like cell(HCLC) polarity in the lesser epithelial ridge (LER) with or without testosterone-3-(O-carboxymethyl) oxime bovine serum albumin (testosterone-BSA) treatment was investigated to determine the role of the PCP pathway in regulating ectopic regenerated (HCLCs) through induction by Math1 and testosterone treatment. After Math1 infection, new ectopic regenerated HCLCs were detected in the LER. After the HCLCs developed actin-rich stereocilia, the basal bodies moved from the center to the distal side. Moreover, the narrower, non-sensory LER region meant that the convergent extension (CE) was also established after transfection with Math1. After 9 days of in vitro testosterone-BSA treatment, more Edu(+), Sox2(+), and HCLC cells were observed in the LER with an accompanying downregulation of E-cadherin. Interestingly, the CE of the Ad5-EGFP-math1 treated LER is altered, but the intrinsic cellular polarity of the HCLCs is not obviously changed. In summary, our results indicate that PCP signaling is involved in the development of ectopic HCLCs and the CE of the ectopic sensory region is altered by testosterone-BSA through downregulation of cell–cell adhesion. Testosterone-BSA and Math1 treatment could promote an increase in HCLCs in the LER through proliferation and transdifferentiation.

Atoh1 overexpression in cochlear epithelium induces new hair cell formation. Use of adenovirus-mediated Atoh1 overexpression has mainly focused on the rat lesser epithelial ridge and induces ectopic hair cell regeneration. The sensory region of rat cochlea is difficult to transfect, thus new hair cells are rarely produced in situ in rat cochlear explants. After culturing rat cochleae in medium containing 10% fetal bovine serum, adenovirus successfully infected the sensory region as the width of the supporting cell area was significantly increased. Adenovirus encoding Atoh1 infected the sensory region and induced hair cell formation in situ. Combined application of the Notch inhibitor DAPT and Atoh1 increased the Atoh1 expression level and decreased hes1 and hes5 levels, further promoting hair cell generation. Our results demonstrate that DAPT enhances Atoh1 activity to promote hair cell regeneration in rat cochlear sensory epithelium in vitro.

Loss of vestibular hair cells is a common cause of balance disorders. Current treatment options for bilateral vestibular dysfunction are limited. During development, atonal homolog 1 (Atoh1) is sufficient and necessary for the formation of hair cells and provides a promising gene target to induce hair cell generation in the mammals. In this study, we used a transgenic mouse line to test the age and cell type specificity of hair cell induction in the postnatal utricle in mice. We found that forced Atoh1 expression in vivo can induce hair cell formation in the utricle from postnatal days 1 to 21, while the efficacy of hair cell induction is progressively reduced as the animals become older. In the utricle, the induction of hair cells occurs both within the sensory region and in cells in the transitional epithelium next to the sensory region. Within the sensory epithelium, the central region, known as the striola, is most subjective to the induction of hair cell formation. Furthermore, forced Atoh1 expression can promote proliferation in an age-dependent manner that mirrors the progressively reduced efficacy of hair cell induction in the postnatal utricle. These results suggest that targeting both cell proliferation and Atoh1 in the utricle striolar region may be explored to induce hair cell regeneration in mammals. The study also demonstrates the usefulness of the animal model that provides an in vivo Atoh1 induction model for vestibular regeneration studies.

The morphological changes that occur in the taste buds after denervation are not well understood in rats, especially in the contralateral tongue epithelium. In this study, we investigated the time course of morphological changes in the taste buds following unilateral nerve transection. The role of the trigeminal component of the lingual nerve in maintaining the structural integrity of the taste buds was also examined. Twenty-four Sprague-Dawley rats were randomly divided into three groups: control, unilateral chorda tympani nerve transection and unilateral chorda tympani nerve transection + lingual nerve transection. Rats were allowed up to 42 days of recovery before being euthanized. The taste buds were visualized using a cytokeratin 8 antibody. Taste bud counts, volumes and taste receptor cell numbers were quantified and compared among groups. No significant difference was detected between the chorda tympani nerve transection and chorda tympani nerve transection + lingual nerve transection groups. Taste bud counts, volumes and taste receptor cell numbers on the ipsilateral side all decreased significantly compared with control. On the contralateral side, the number of taste buds remained unchanged over time, but they were larger, and taste receptor cells were more numerous postoperatively. There was no evidence for a role of the trigeminal branch of the lingual nerve in maintaining the structural integrity of the anterior taste buds.

Otitis media (OM) is a major cause of morbidity in pediatric and adult patients. This inflammatory condition is characterized by mucous cell hyperplasia that is thought to produce mucins from the middle ear mucosa. We are interested in the role of Notch signalling pathway in this inflammatory process. Using an acute otitis media (AOM) mouse model through injection of Streptococcus Pneumoniae into the middle ear, histopathologic examination and quantitative RT-PCR, acute inflammation with the thickness of mucosa, Goblet cell hyperplasia, and cilia loss were determined and gene expression related to the Notch signaling pathway were evaluated. Upregulation of the mucous cell markers, Argr2 and Muc5AC, and downregulation of the cilia cell marker, Foxj1 and Dnai2, were observed in AOM. In addition, genes encoding Notch receptors and ligands (Notch1, Notch2, Notch3, Notch4 and Dll1) and the Notch target genes (Hes1, Hes5, Hey1, NRARP) in AOM decreased significantly. The expression of the Notch1 and Jagged1 also showed down-regulation throughout the mouse middle ear epithelium. Taken together, this study suggests that downregulation of the Notch signaling pathway is involved in the mucosa hyperplasia during AOM.

Patients with mastoiditis and chronic suppurative otitis media which has small mastoids that make them ideal candidates for modified canal wall down mastoidectomy (MCWD) which contributes to a dry and spacious ear and the maintaining and improving hearing.To evaluate surgical outcomes for chronic otitis media underwent MCWD.A clinical retrospective study was performed on 47 ears with chronic otitis media which has relatively limited attic lesions have the small, sclerotic and hypocellular mastoids according to the preoperative high-resolution CT scan of the temporal bone that underwent MCWD and 32 ears with typical canal wall down operation form January 2010 to January 2016.In the MCWD group, the mean preoperative air conduction (AC) threshold of 38.2 ± 1.1 dB was lowered to 31.0 ± 0.8 dB postoperatively (p .01). The mean pre- and postoperative air-bone gaps (ABG) of all patients were 16.0 ± 1.0 dB and 9.6 ± 0.8 dB, respectively. In the canal wall down group, the mean preoperative AC threshold of 37.2 ± 1.0 dB was lowered to 32.8 ± 0.9 dB postoperatively (p .01). The mean pre- and postoperative air-bone gap was reduced with 4.4 ± 0.4 dB (p .01). There was statistical difference in hearing improvement between the modified canal wall down and the canal wall down group (p .05).

Previous reports have suggested that the level and duration of Atoh1 expression are correlated with the survival, arrangement and stereociliary bundle-related morphology of hair cells during development, but whether Atoh1 expression levels are correlated with the arrangement, bundle formation and electrophysiological characteristics of newly formed hair cells is unknown. To address this question, cultured cochlear explants obtained from neonatal rats were treated with different titers of a human adenovirus serotype 5 (Ad5) vector encoding Atoh1 and/or EGFP (EGFP-Atoh1+/-). The results showed that higher EGFP-Atoh1 concentrations led to higher initial Atoh1 mRNA expression levels and induced greater numbers of ectopic hair cell-like cells (EHCLCs) in the lesser epithelial ridge (LER). Furthermore, gradual increases in the number of EHCLCs were associated with the progressive conversion of the LER region similarly to that of hair cells during development. Some of the cilia on EHCLCs with higher Atoh1 expression were regularly arranged in a manner similar to that of normal hair bundles. As demonstrated through patch clamp recordings, high Atoh1 expression was associated with significantly decreased proportions of cells with Ih currents, significantly reduced proportions of transient potassium channel currents, and potassium channel currents with a greatly increased mean amplitude, which indicated that EHCLCs with high Atoh1 expression were more mature than those with low Atoh1 expression. Overall, the evidence suggests that the Atoh1 expression levels affect not only the arrangement and ciliary morphology of hair cells but also the electrophysiological characteristics of Atoh1-induced EHCLCs, and these findings provide important guidance for future therapies aimed at treating deafness.

Objective To investigate the correlation between findings of three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging (3D FLAIR MRI) and baseline as well as outcome variables of idiopathic sudden sensorineural hearing loss (ISSHL). Data sources Publications of all languages listed in PubMed and EMBASE STUDY SELECTION: Studies of ISSHL patients without primary treatment and precontrast 3D FLAIR MRI scan was performed. Data extraction Demographical and clinical characteristics of patients were extracted and the quality of studies was evaluated using the Newcastle-Ottawa Scale. Data synthesis Continuous and dichotomous data was synthesized in Inverse Variance and Mantel-Haenszel models, respectively. The aggregate results were estimated and displayed in forest plots. Conclusions The presence of high signal (HS) in inner ear on 3D FLAIR MRI indicated more severe initial hearing loss, and the existence of HS in inner ear on 3D FLAIR MRI increased the incidence of vertigo by 2.88 times. Meta-analysis of the dichotomous data of hearing recovery rate showed the hazard of recovery in HS group was significantly less than the one in no signal (NS) group. The pooled hearing improvement in decibels also favored NS group, but statistically the difference was not significant.