A New Floating Piezoelectric Microphone for Fully Implantable Cochlear Implants in Middle Ear.

OBJECTIVE: Our team designed a long-lasting, well-sealed microphone, which uses laser welding and vacuum packaging technology. This study examined the sensitivity and effectiveness of this new floating piezoelectric microphone (NFPM) designed for totally implantable cochlear implants (TICIs) in animal experiments and intraoperative testing. METHODS: Different NFPM frequency responses from 0.25 to 10 kHz at 90 dB SPL were analyzed using in vivo testing of cats and human patients. The NFPM was tested in different positions that were clamped to the ossicular chains or placed in the tympanic cavity of cats and human patients. Two volunteers' long incus foot and four cats' malleus neck of the ossicular chain were clamped with the NSFM. The output electrical signals from different locations were recorded, analyzed, and compared. The NFPM was removed after the test without causing any damage to the middle-ear structure of the cats. Intraoperative tests of the NFPM were performed during the cochlear implant surgery and the cochlear implant surgery was completed after all tests. RESULTS: Compared with the results in the tympanic cavity, the NFPM could detect the vibration from the ossicular chain more sensitively in cat experiments and intraoperative testing. We also found that the signal output level of the NFPM decreased as the acoustic stimulation strength decreased in the intraoperative testing. CONCLUSION: The NFPM is effective in the intraoperative testing, making it feasible as an implantable middle-ear microphone for TICIs. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:937-944, 2024.

Chinese Version of the Vestibular Disorders Activities of Daily Living Scale.

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, 132:1446-1451, 2022.

Rab11a Regulates the Development of Cilia and Establishment of Planar Cell Polarity in Mammalian Vestibular Hair Cells.

Vestibular organs have unique planar cell polarity (Figure 1A), and their normal development and function are dependent on the regular polarity of cilia (Figure 1B) requires. Rab11a is a small G protein that participates in the transportation of intracellular and extracellular materials required for polarity formation; however, our understanding of the mechanisms of the actions of Rab11a in vestibular organs is limited. Here, we showed that the general shape of the utricle was abnormal in Rab11a CKO/CKO mice. These mice also showed abnormal morphology of the stereocilia bundles, which were reduced in both length and number, as well as disturbed tissue-level polarity. Rab11a affected the distribution of polarity proteins in the vestibular organs, indicating that the normal development of cilia requires Rab11a and intraflagellar transportation. Furthermore, small G protein migration works together with intraflagellar transportation in the normal development of cilia. FIGURE 1Morphological changes of stereocilia in the extrastriolar hair cells from Rab11a single or Rab11a/IFT88 double-mutant utricles. (A) Medial view of a mouse left inner ear with its five vestibular sensory organs (gray). Enlarged are the utricle showing their subdivisions, LPR (yellow line), and striola (blue). LES, lateral extrastriola; MES, medial extrastriola; LPR, line of polarity reversal. (B) Schematic view of vestibular hair cell. Kinocilium is marked with ace-tubulin. Basal body is marked with γ-tubulin. (C,C1,D,D1) Normal appearance of the stereocilia of extrastriolar hair cells of wild-type controls. (E,E1,F,F1) Altered morphology in Rab11a CKO/CKO animals. (G,G1,H,H1) The changes in the stereocilia morphology were more severe in Rab11a CKO/CKO /IFT 88 CKO/+ mice. (I-L) Higher magnification of confocal images of hair cells. (M-P) Scanning electron microscopy images of hair cells from wild-type controls and Rab11a mutants. (I,M) Morphology of normal. hair cells of wild-type controls. (J,N) The number of stereocilia on a single hair cell was deceased in the Rab11a mutant. (K,O) Stereocilia were shorter in mutants compared to the wild-type controls. (L,P) The staircase-like hair bundle architecture of hair cells was lost in Rab11a mutant mice. (Q) The percentage of hair cells with abnormal development of static cilia bundles in the extrastriola region was counted as a percentage of the total (n = 5). The percentage of abnormal hair cells was higher in Rab11a CKO/CKO , IFT88 CKO/+ mice compared to Rab11a CKO/CKO . The abnormal ratios of single and double knockout hair cells were 42.1 ± 5.7 and 71.5 ± 10.4, respectively. In (A-J), for all primary panels, hair cell stereociliary bundles were marked with phalloidin (green), the actin-rich cuticular plate of hair cells was labeled with ß-spectrin (red), while the basal body of the hair cell was labeled with γ-tubulin (blue). Scale bars: 10 µm (C-H1), 5 µm (J-N). *P < 0.05.

A Predictive Model Development of Hospital Admission during Triage in a Chinese Ear, Nose, and Throat Emergency Department.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

Characteristic manifestation of ocular and cervical vestibular evoked myogenic potentials findings in severe obstructive sleep apnea patients.

BACKGROUND: 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. OBJECTIVES: To investigate otolithic organ function in severe OSA patients who lack vestibular symptoms and systemic disease. MATERIAL AND METHODS: 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. RESULTS: 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 (p = .002), decreased n1-p1 amplitudes (p < .001), prolonged n1 latencies (p < .001) were observed. In cVEMP, the elevation of thresholds (p < .001), decrease in p1-n1 amplitudes (p < .001), and n1-p2 amplitudes (p < .001), prolongation of p1 latencies (p = .003) were observed. No significant difference in the caloric test was found between the two groups. CONCLUSIONS AND SIGNIFICANCE: Disappearance or impairment of VEMPs could be observed in patients with severe OSA, and reflects different degrees of impairment in the utricle and saccule.

Evaluations on the stability and bio-compatibility of a new piezoelectric microphone for the implantable middle ear microphone.

BACKGROUND: A new floating piezoelectric microphone (NFPM), driven by the acoustic vibration of the ossicles, has been manufactured in the lab. OBJECTIVES: This study aimed at exploring the stability and bio-compatibility of this NFPM. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: The NFPM could be implanted in our experimental cats for a long period of time and had good bio-compatibility.

The transcriptome characteristics of vestibular organs from delayed endolymphatic hydrops patients (Meniere's disease).

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 bioinformatic analysis identified 17 genes that were upregulated and eight genes that were downregulated in patients with DEH compared with 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 Ménière's disease and DEH compared with controls. CONCLUSIONS: The protein expression profile of vestibular organs in patients with endolymphatic hydrops exhibited a degree of similarity to that of Ménière's disease. Endolymphatic hydrops is characterised by autoimmune abnormalities. DEH and Ménière'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.

Planar cell polarity governs the alignment of the nasopharyngeal epithelium in mammals.

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.

Modified Translabyrinthine Approach for Massive Petrous Bone Cholesteatoma Removal and Cochlear Preservation Using Latent Spaces Anterior to the Cochlea.

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.

Different findings of morphological changes and functional decline in the vestibule and the semicircular canal in ipsilateral delayed endolymphatic hydrops.

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.

Direct reprogramming adult fibroblast into cells with partial inner ear hair cell characteristics through cell activation and signal directed approach.

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.

Concurrent Occurrence of Congenital Ossicular Anomaly and Localized Cholesteatoma: Series of 10 Cases.

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.

Deep Learning in Automated Region Proposal and Diagnosis of Chronic Otitis Media Based on Computed Tomography.

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.

Endoscopic Tympanoplasty without Mastoidectomy for Active Mucosal Chronic Otitis Media with Mastoid and Tympanic Antrum Lesions: A Prospective Clinical Study.

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.

Petrous bone cholesteatoma: our experience of 51 patients with emphasis on cochlea preservation and use of endoscope.

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.

Neurorrhaphy for Facial Reanimation with Interpositional Graft: Outcome in 23 Patients and the Impact of Timing on the Outcome.

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.

Titanium ossicular chain reconstruction in single stage canal wall down tympanoplasty for chronic otitis media with mucosa defect.

PURPOSE: 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). METHODS: 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. RESULTS: The overall mean AC threshold of 53.4 ±â€¯16.5 dB was lowered to 41.2 ±â€¯15.9 dB postoperatively (p < 0.01). The mean pre- and postoperative ABG of all patients were 27.9 ±â€¯9.9 dB and 17.2 ±â€¯9.3 dB (p < 0.01), respectively, with a mean ABG closure of 10.7 ±â€¯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 ±â€¯9.8 dB and 20.1 ±â€¯9.0 dB (p < 0.01), respectively, with the ABG closure was 8.0 ±â€¯7.9 dB. In the mucosa defect group underwent PORP, the mean pre- and postoperative ABG were 27.9 ±â€¯10.1 dB and 16.5 ±â€¯9.1 dB (p < 0.01), respectively, with the ABG closure was 11.4 ±â€¯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). CONCLUSION: It is revealed PORP in single stage CWD tympanoplasty for the patients suffered from chronic otitis media with mucosa defect is favored.

Mechanisms of Hearing Loss in a Guinea Pig Model of Superior Semicircular Canal Dehiscence.

Defective acoustic transmission in the cochlea is closely related with various auditory and vestibular symptoms. Among them, semicircular canal dehiscence (SCD) with a defective semicircular bone is typical. Currently, the pathogenesis of SCD is usually explained by the third window hypothesis; however, this hypothesis fails to explain the variability in the symptoms and signs experienced by superior SCD (SSCD) patients. We evaluated the mechanism of hearing loss in a guinea pig model of bony dehiscence with various sizes and locations along the superior semicircular canal. Auditory brainstem responses (ABRs) and laser Doppler velocimetry were used to measure hearing loss and vibration changes before and after fenestration, as well as after restorative patching. ABR thresholds at low frequencies (e.g., 1000 Hz) increased after fenestration and decreased back to the normal range after we repaired the defect. Energy leakage from the surgically introduced third window was detected in the range of 300-1500 Hz, accompanied by increased vibration at the umbo, stapes head, and the dehiscence site, while decreased vibration was observed at the round window membrane in the same frequency range. After the patching procedure, the deviant vibrations were recovered. The degree of postfenestration energy leakage was proportional to the size of fenestration and the proximity of the fenestration site to the oval window. These results suggest that the bony fenestration of the superior semicircular canal mimics the hearing loss pattern of patients with SSCD. The decrease in perilymph wave impedance likely accounts for the auditory changes.

Celastrol enhances Atoh1 expression in inner ear stem cells and promotes their differentiation into functional auditory neuronal-like cells.

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.

Cell proliferation during hair cell regeneration induced by Math1 in vestibular epithelia in vitro.

Hair cell regeneration is the fundamental method of correcting hearing loss and balance disorders caused by hair cell damage or loss. How to promote hair cell regeneration is a hot focus in current research. In mammals, cochlear hair cells cannot be regenerated and few vestibular hair cells can be renewed through spontaneous regeneration. However, Math1 gene transfer allows a few inner ear cells to be transformed into hair cells in vitro or in vivo. Hair cells can be renewed through two possible means in birds: supporting cell differentiation and transdifferentiation with or without cell division. Hair cell regeneration is strongly associated with cell proliferation. Therefore, this study explored the relationship between Math1-induced vestibular hair cell regeneration and cell division in mammals. The mouse vestibule was isolated to harvest vestibular epithelial cells. Ad-Math1-enhanced green fluorescent protein (EGFP) was used to track cell division during hair cell transformation. 5-Bromo-2'-deoxyuridine (BrdU) was added to track cell proliferation at various time points. Immunocytochemistry was utilized to determine cell differentiation and proliferation. Results demonstrated that when epithelial cells were in a higher proliferative stage, more of these cells differentiated into hair cells by Math1 gene transfer. However, in the low proliferation stage, no BrdU-positive cells were seen after Math1 gene transfer. Cell division always occurred before Math1 transfection but not during or after Math1 transfection, when cells were labeled with BrdU before and after Ad-Math1-EGFP transfection. These results confirm that vestibular epithelial cells with high proliferative potential can differentiate into new hair cells by Math1 gene transfer, but this process is independent of cell proliferation.