A deep learning approach to the diagnosis of atelectasis and attic retraction pocket in otitis media with effusion using otoscopic images.

BACKGROUND: This study aimed to develop and validate a deep learning (DL) model to identify atelectasis and attic retraction pocket in cases of otitis media with effusion (OME) using multi-center otoscopic images. METHOD: A total of 6393 OME otoscopic images from three centers were used to develop and validate a DL model for detecting atelectasis and attic retraction pocket. A threefold random cross-validation procedure was adopted to divide the dataset into training validation sets on a patient level. A team of otologists was assigned to diagnose and characterize atelectasis and attic retraction pocket in otoscopic images. Receiver operating characteristic (ROC) curves, including area under the ROC curve (AUC), accuracy, sensitivity, and specificity were used to assess the performance of the DL model. Class Activation Mapping (CAM) illustrated the discriminative regions in the otoscopic images. RESULTS: Among all OME otoscopic images, 3564 (55.74%) were identified with attic retraction pocket, and 2460 (38.48%) with atelectasis. The diagnostic DL model of attic retraction pocket and atelectasis achieved a threefold cross-validation accuracy of 89% and 79%, AUC of 0.89 and 0.87, a sensitivity of 0.93 and 0.71, and a specificity of 0.62 and 0.84, respectively. Larger and deeper cases of atelectasis and attic retraction pocket showed greater weight, based on the red color depicted in the heat map of CAM. CONCLUSION: The DL algorithm could be employed to identify atelectasis and attic retraction pocket in otoscopic images of OME, and as a tool to assist in the accurate diagnosis of OME.

Event-Related Potential Evidence of Enhanced Visual Processing in Auditory-Associated Cortex in Adults with Hearing Loss.

OBJECTIVE: The present study investigated the characteristics of visual processing in the auditory-associated cortex in adults with hearing loss using event-related potentials. METHODS: Ten subjects with bilateral postlingual hearing loss were recruited. Ten age- and sex-matched normal-hearing subjects were included as controls. Visual ("sound" and "non-sound" photos)-evoked potentials were performed. The P170 response in the occipital area as well as N1 and N2 responses in FC3 and FC4 were analyzed. RESULTS: Adults with hearing loss had higher P170 amplitudes, significantly higher N2 amplitudes, and shorter N2 latency in response to "sound" and "non-sound" photo stimuli at both FC3 and FC4, with the exception of the N2 amplitude which responded to "sound" photo stimuli at FC3. Further topographic mapping analysis revealed that patients had a large difference in response to "sound" and "non-sound" photos in the right frontotemporal area, starting from approximately 200 to 400 ms. Localization of source showed the difference to be located in the middle frontal gyrus region (BA10) at around 266 ms. CONCLUSIONS: The significantly stronger responses to visual stimuli indicate enhanced visual processing in the auditory-associated cortex in adults with hearing loss, which may be attributed to cortical visual reorganization involving the right frontotemporal cortex.

The miR-34a/Bcl-2 Pathway Contributes to Auditory Cortex Neuron Apoptosis in Age-Related Hearing Loss.

HYPOTHESIS: The miR-34a/Bcl-2 signaling pathway may play a role in the mechanisms related to age-related hearing loss (AHL) in the auditory cortex. BACKGROUND: The auditory cortex plays a key role in the recognition and processing of complex sound. It is difficult to explain why patients with AHL have poor speech recognition, so increasing numbers of studies have focused on its central change. Although micro (mi)RNAs in the central nervous system have recently been increasingly reported to be associated with age-related diseases, the molecular mechanisms of AHL in the auditory cortex are not fully understood. METHODS: The auditory brainstem response was used to assess the hearing ability of C57BL/6 mice, and q-PCR, immunohistochemistry, and Western blotting were used to detect the expression levels of miR-34a and Bcl-2 in the mouse auditory cortex. TUNEL and DNA fragmentation were adopted to detect the apoptosis of neurons in the auditory cortex. To verify the relationship of miR-34a and Bcl-2, we transfected an miR-34a mimic or miR-34a inhibitor into primary auditory cortex neurons. RESULTS: In this study, miR-34a/Bcl-2 signaling was examined in auditory cortex neurons during aging. miR-34a and apoptosis increased in the auditory cortex neurons of C57BL/6 mice with aging, whereas an age-related decrease in Bcl-2 was determined. In the primary neurons of the auditory cortex, miR-34a overexpression inhibited Bcl-2, leading to an increase in apoptosis. Moreover, miR-34a knockdown increased Bcl-2 expression and diminished apoptosis. CONCLUSION: Our results support a link between age-related apoptosis in auditory cortex neurons and miR-34a/Bcl-2 signaling, which may serve as a potential mechanism of the expression of AHL in the auditory cortex.

The Effect of Aging and the High-Frequency Auditory Threshold on Speech-Evoked Mismatch Negativity in a Noisy Background.

Mismatch negativity (MMN) has been widely used to study the function of central auditory processing in the elderly. However, current research has not yet considered the effect of noise and high-frequency hearing threshold on MMN in the elderly. The aim of this study was to evaluate the effect of aging and high-frequency hearing loss on speech-related MMN in noisy backgrounds. Additionally, the possible mechanisms of central auditory processing dysfunction in the elderly were investigated. Fifty people aged 61-80 (70 ± 5.8) years were recruited for this study. They were divided into a 61- to 70-year-old group and a 71- to 80-year-old group. Fifty younger adults aged 21-40 (31 ± 5.3) years were recruited as healthy controls. Pure-tone hearing thresholds were recorded. A speech discrimination score (SDS) and a speech-evoked MMN under white noise with a bandwidth from 125 to 8,000 Hz background condition were recorded. The relationships between SDS and MMN latency and amplitude were analyzed. The effects of age and binaural 2,000-, 4,000- and 8,000-Hz pure-tone hearing thresholds on MMN latency and amplitude were analyzed. We found that the hearing thresholds of 2,000, 4,000 and 8,000 Hz in the 61- to 70-year-old and 71- to 80-year-old groups were higher than those in the control group. The SDS in a noisy background in the 61- to 70-year-old and 71- to 80-year-old groups were lower than those in the control group. Speech-evoked MMN latency was longer in the 61- to 70-year-old and in the 71- to 80-year-old groups than in the control group (215.8 ± 14.2 ms). SDS and speech-evoked MMN latency were negatively correlated. Age and speech-evoked MMN latency were positively correlated, as were the binaural 4,000- to 8,000-Hz pure-tone hearing thresholds and speech-evoked MMN. This study suggests that in elderly subjects, the function of preattentive central auditory processing changes. Additionally, increasing age and high-frequency hearing thresholds create a synergy in neurons that is weakened in the MMN time window, which may be a cause of central auditory processing disorders in elderly subjects in noisy background conditions.

Differential Expression of Bcl-2 in the Cochlea and Auditory Cortex of a Mouse Model of Age-Related Hearing Loss.

Bcl-2, the first gene shown to be involved in apoptosis, is a potent regulator of cell survival and known to have protective effects against a variety of age-related diseases. However, the possible relationship between hearing and Bcl-2 expression in the cochlea or auditory cortex of C57BL/6 mice, a mouse model of age-related hearing loss, is still unknown. Using RT-PCR, immunohistochemistry, and Western blot analysis, our results show that Bcl-2 is strongly expressed in the inner hair cells and spiral ganglion neurons of young mice. In addition, moderate Bcl-2 expression is also detected in the outer hair cells and in the neurons of the auditory cortex. A significant reduction of Bcl-2 expression in the cochlea or auditory cortex is also associated with elevated hearing thresholds and hair cell loss during aging. The expression pattern of Bcl-2 in the peripheral and central auditory systems suggests that Bcl-2 may play an important role in auditory function serving as a protective molecule against age-related hearing loss.

Efficacy of balloon dilation in the treatment of symptomatic Eustachian tube dysfunction: One year follow-up study.

PURPOSE: Eustachian tube balloon dilation (ETBD) has been recently described as feasible treatment for patients with refractory Eustachian tube dysfunction (ETD). The aim of this study was to evaluate the efficacy of ETBD in the treatment of symptomatic Eustachian tube dysfunction (SETD) by subjective and objective analysis. MATERIALS AND METHODS: Forty patients who underwent ETBD were included in the study. Subjects' inclusion criteria were as follows: symptoms of ETD (aural fullness predominantly, with or without otalgia, muffle hearing and tinnitus), normal tympanic membrane, type A or C tympanograms, and without a history of any middle ear diseases. Main outcomes including subjective improvement, otoscopy, pure-tone audiometry, impedance audiometry, R-value in tubomanometry (TMM) at three pressure measurements (30, 40, and 50 mbar), Eustachian Tube Score (ETS) and the ability to perform a Valsalva maneuver were assessed preoperatively, 1 week, 3 months and 12 months postoperatively. RESULTS: All cases were dilated successfully. A significant effect of treatment was documented when measuring subjective improvement, impedance audiometry, R-value in TMM, ETS and the ability to perform a Valsalva maneuver 1 week, 3 months and 12 month postoperatively. Subjective symptoms were not relieved only in one patient. The overall success rate for all patients was 98%. CONCLUSIONS: ETBD can provide both short- and long-term benefits to those who are diagnosed SETD and refractory to medical management. SETD might be an optimal indication for ETBD in the treatment of ETD.

Effect of the combination of balloon Eustachian tuboplasty and tympanic paracentesis on intractable chronic otitis media with effusion.

OBJECTIVE: To evaluate the effect of the combination of balloon Eustachian tuboplasty (BET) and tympanic paracentesis (TP) on intractable chronic otitis media with effusion (COME). METHODS: Ninety patients with intractable COME were included and randomly assigned to three groups: BET only (30 patients), BET+paracentesis (30 patients), and paracentesis only (30 patients). Otic endoscopic findings and tympanograms were recorded before the surgery and at the month 1, month 3, and month 6 follow-up evaluations. RESULTS: Both the BET only and BET+paracentesis groups achieved better outcomes than the paracentesis group. The BET+paracentesis group exhibited better otic endoscopic scores than the BET only group (p<0.05) at 1month post-operation. However, no significant difference was found at month 3 or month 6 post-operation. No significant difference in the tympanograms was observed between these two groups at month 1, month 3, or month 6 post-operation. The otic endoscopic sign scores improved from month 1 to month 6 in the BET only group and from month 1 to month 3 in the BET+paracentesis group. The conversion of type B tympanograms improved from month 1 to month 6 in the BET and BET+paracentesis groups but not in the paracentesis only group. CONCLUSIONS: Our results suggested that the combination of BET and TP was effective for intractable COME and can help shorten the recovery period for middle ear effusion.

The Antioxidant Ergothioneine Alleviates Cisplatin-Induced Hearing Loss through the Nrf2 Pathway.

Aims: Cisplatin (CDDP) is a commonly used chemotherapeutic agent for treating head and neck tumors. However, there is high incidence of ototoxicity in patients treated with CDDP, which may be caused by the excessive reactive oxygen species (ROS) generation in the inner ear. Many studies have demonstrated the strong antioxidant effects of ergothioneine (EGT). Therefore, we assumed that EGT could also attenuate cisplatin-induced hearing loss (CIHL) as well. However, the protective effect and mechanism of EGT on CIHL have not been elucidated as so far. In this study, we investigated whether EGT could treat CIHL and the mechanism. Results: In our study, we confirmed the protective effect of EGT on preventing CDDP-induced toxicity both in vitro and in vivo. The auditory brainstem response threshold shift in the EGT + CDDP treatment mice was 30 dB less than that in the CDDP treatment mice. EGT suppressed production of ROS and proapoptotic proteins both in tissue and cells. By silencing nuclear factor erythroid 2-related factor 2 (Nrf2), we confirmed that EGT protected against CIHL via the Nrf2 pathway. We also found that SLC22A4 (OCTN1), an important molecule involved in transporting EGT, was expressed in the cochlea. Innovation: Our results revealed the role of EGT in the prevention of CIHL by activating Nrf2/HO-1/NQO-1 pathway, and broadened a new perspective therapeutic target of EGT. Conclusion: EGT decreased ROS production and promoted the expression of antioxidative enzymes to maintain redox homeostasis in sensory hair cells. Overall, our results indicated that EGT may serve as a novel treatment drug to attenuate CIHL.

A Multicenter, Single-Arm, Objective Performance Criteria-Controlled Clinical Study of the Safety and Efficacy of the Double-Lumen Eustachian Tube Balloon Catheter.

BACKGROUND: To prospectively evaluate the technical efficacy and safety of the double-lumen eustachian tube (ET) balloon catheter in patients with ET dysfunction. METHODS: Patients who were diagnosed with ET dysfunction and needed balloon eustachian tuboplasty (BET) were prospectively enrolled. A double-lumen ET balloon catheter was used to dilate the ET and inject medicine. Efficacy results were assessed by the injection channel patency (ICP) rate, the injection reached the expected site (IRES) rate, and the improvement in eustachian tube function was evaluated by the seven-item Eustachian Tube Dysfunction Questionnaire (ETDQ-7) score. Safety results were assessed in terms of adverse events and device defects. RESULTS: BET was successfully attempted in 87 patients from April 2022 to August 2022 at two academic medical centers in China (01, 02). The ICP rate was 100%, and the IRES rate was 88.51%. The overall ETDQ-7 score was significantly reduced ( p < 0.001) postsurgically at both centers. There were no major complications or device defects. CONCLUSION: The double-lumen ET balloon catheter is technically effective and safe for the treatment of ET dysfunction.

Hypoxia-inducible factor and vascular endothelial growth factor pathway for the study of hypoxia in a new model of otitis media with effusion.

The hypoxia-inducible factor and vascular endothelial growth factor (HIF-VEGF) pathway in hypoxic conditions of the middle ear due to dysfunction of the eustachian tube is still unknown, but it is considered as one pathogenetic mechanism in otitis media. This study was designed to investigate the possible involvement of the HIF-VEFG pathway in otitis media with effusion induced by dysfunction of the eustachian tube. We adopted a soft palate approach to obstruct the orifice of the eustachian tube to establish otitis media in a rat model. Auditory evoked brainstem response and tympanometry were used as hearing function tests, hypoxia-related factors were examined by reverse transcriptase polymerase chain reaction (RT-PCR). The expression of hypoxia-related proteins was detected by Western blot and immunostaining. The model of otitis media with effusion was successfully induced by cauterizing the orifice of the eustachian tube. RT-PCR showed up-regulation of hypoxia-related factors in cauterized ears. Western blot and immunostaining showed that the expression of hypoxia-related proteins in cauterized ears was increased. Hypoxia-induced vascular proliferation and an increase in permeability may be one pathogenetic mechanism of otitis media due to dysfunction of the eustachian tube.

Surgical treatment of monostotic fibrous dysplasia of the temporal bone: a retrospective analysis.

OBJECTIVE: The aim of this study was to analyze the therapeutic effect of external auditory canal stenosis caused by monostotic fibrous dysplasia of the temporal bone by operation. METHODS: Seven patients who were finally diagnosed as having monostotic fibrous dysplasia of the temporal bone by temporal bone high-resolution computed tomography (CT) and pathological diagnosis after operation underwent surgical reconstruction of the external auditory canal. The follow-up lasted 2 to 6 years, and it included pure-tone audiometry otoendoscopy, and high-resolution CT of the temporal bone. The hearing recovery and formed external auditory meatus results were retrospectively analyzed. The data were obtained from the Department of Otolaryngology in Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, from April 2003 to September 2008. RESULTS: We found 4 ears with combined external auditory canal cholesteatoma intraoperative. The mean pure-tone audiometries (0.5, 1, 2 kHz) and the air-bone gaps for all patients improved after 6 months postoperation. The result was statistically significant. The average air-bone gap was improved, and the external auditory canal restenosis appeared in 1 patient after 4 years. Reconstruction of the external auditory canal was performed in this patient, and no restenosis was found in subsequent 2-year follow-up. All cases were reviewed with CT and otoendoscopy to observe the results and lesion extent, and we found that the lesion was basically stable without significant progress to the periphery major structure. CONCLUSION: The monostotic fibrous dysplasia of the temporal bone and its causative external auditory meatus stenosis must be treated as early as possible to recover its patency of external auditory canal to prevent complicated cholesteatoma. Satisfaction results can be obtained from surgical reconstruction of the external auditory canal. We can excise the pathological change of the external auditory canal simply to restore auditory function and eliminate clinical symptoms such as earache, ear muffled sense, and so on. Because the development of lesions was slow during the follow-up, the complete resection of all lesions was not necessary, the external auditory canal restenosis may be operated again, and the prognosis was optimistic.

[Application of combined ossicular replacement prosthesis and total ossicular replacement prosthesis of type â ¢ tympanoplasty].

Objective:This study investigated the application of combined ossicular replacement prosthesis（The Kurz Omega Connector+TORP） in type Ⅲ tympanoplasty, and compared the surgical effect with traditional TORP. Methods:Twenty patients with unilateral chronic suppurative otitis media diagnosed in the Department of Otorhinolaryngology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University from January 2019 to June 2020 were included in this study.All the patients were treated with intra-auricular incision with a microscopic approach（tympanic exploration, lesion clearance+type Ⅲ tympanoplasty）. According to the placement of different types of ossicular replacement prosthesis in the ossicular chain reconstruction of type Ⅲ tympanoplasty, the patients were divided into two groups: the traditional TORP group（n=10） and the combined ossicular replacement prosthesis（The Kurz Omega Connector+TORP） group（n=10）. All patients underwent pure tone audiometry before and 1 year after the operation, and the average hearing threshold and air-bone conduction difference（ABG） were compared between the two groups before and after the operation. Results:The reconstruction of the ossicular chain was completed successfully in all patients. Endoscopic examination showed that the epithelialization of the operative cavity was good and the repair of the tympanic membrane recovered well one month after the operation. There was no significant difference in preoperative mean airway threshold between the combined ossicular replacement prosthesis and the traditional TORP group （74.13[41.50，80.50] dB vs 74.25[44.81，82.50] dB, P>0.05）, there was no significant difference in preoperative ABG （55.63[21.50，61.25] dB vs 54.13[23.63，60.38] dB, P>0.05）. After the operation, the ABG of the combined auriculus group was significantly lower than that of the traditional operation group （12.00[5.75，24.56] dB vs 34.88[14.19，46.44] dB, P<0.05）. Conclusion: The combined ossicular replacement prosthesis（The Kurz Omega Connector+TORP） can increase the stability of hearing reconstruction and improve hearing in type Ⅲ tympanoplasty.

Metabolomic characterization of congenital microtia: a possible analysis for early diagnosis.

Background: Although metabolic abnormalities have been deemed one of the essential risk factors for growth and development, the relationship between metabolic abnormalities and microtia is still unclear. In this study, we aimed to establish a cell model of microtia and the changes of serum metabolites in patients with microtia. Methods: After constructing a cell model of microtia with low expression of BMP5, we performed integrative metabolomics analysis. For the altered metabolites, the content of glycerophosphocholine (PC), triacylglycerol (TG), and choline in the serum of 28 patients (15 patients with microtia and 13 controls) with microtia was verified by enzyme-linked immunosorbent assay (ELISA). Results: Detailed metabolomic evaluation showed distinct clusters of metabolites between BMP5-low expressing cells and normal control (NC) cells. The cell model of microtia had significantly higher levels of TG, PC, glycerophosphoethanolamine (PE), sphingomyelin, sulfatide, glycerophosphoglycerol, diacylglycerol, and glycosphingolipid. The main abnormal metabolites were mainly concentrated in the glycerophospholipid metabolism pathway, and PC and choline were closely related. In the serum of patients with microtia, the contents of PC, TG, and choline were significantly increased. Conclusions: The individual serum samples confirmed the different metabolites between patients with microtia and controls. In particular, we showed that a newly developed metabolic biomarker panel has a high sensitivity and specificity for separating patients with microtia from controls.

A Deep Learning Approach to Predict Conductive Hearing Loss in Patients With Otitis Media With Effusion Using Otoscopic Images.

Importance: Otitis media with effusion (OME) is one of the most common causes of acquired conductive hearing loss (CHL). Persistent hearing loss is associated with poor childhood speech and language development and other adverse consequence. However, to obtain accurate and reliable hearing thresholds largely requires a high degree of cooperation from the patients. Objective: To predict CHL from otoscopic images using deep learning (DL) techniques and a logistic regression model based on tympanic membrane features. Design, Setting, and Participants: A retrospective diagnostic/prognostic study was conducted using 2790 otoscopic images obtained from multiple centers between January 2015 and November 2020. Participants were aged between 4 and 89 years. Of 1239 participants, there were 209 ears from children and adolescents (aged 4-18 years [16.87%]), 804 ears from adults (aged 18-60 years [64.89%]), and 226 ears from older people (aged >60 years, [18.24%]). Overall, 679 ears (54.8%) were from men. The 2790 otoscopic images were randomly assigned into a training set (2232 [80%]), and validation set (558 [20%]). The DL model was developed to predict an average air-bone gap greater than 10 dB. A logistic regression model was also developed based on otoscopic features. Main Outcomes and Measures: The performance of the DL model in predicting CHL was measured using the area under the receiver operating curve (AUC), accuracy, and F1 score (a measure of the quality of a classifier, which is the harmonic mean of precision and recall; a higher F1 score means better performance). In addition, these evaluation parameters were compared to results obtained from the logistic regression model and predictions made by three otologists. Results: The performance of the DL model in predicting CHL showed the AUC of 0.74, accuracy of 81%, and F1 score of 0.89. This was better than the results from the logistic regression model (ie, AUC of 0.60, accuracy of 76%, and F1 score of 0.82), and much improved on the performance of the 3 otologists; accuracy of 16%, 30%, 39%, and F1 scores of 0.09, 0.18, and 0.25, respectively. Furthermore, the DL model took 2.5 seconds to predict from 205 otoscopic images, whereas the 3 otologists spent 633 seconds, 645 seconds, and 692 seconds, respectively. Conclusions and Relevance: The model in this diagnostic/prognostic study provided greater accuracy in prediction of CHL in ears with OME than those obtained from the logistic regression model and otologists. This indicates great potential for the use of artificial intelligence tools to facilitate CHL evaluation when CHL is unable to be measured.

Cholesterol granuloma of the middle ear in post-irradiated nasopharyngeal carcinoma patients.

BACKGROUND/AIMS: To evaluate the surgical outcome of tympanoplasty with mastoidectomy for cholesterol granuloma of the middle ear in post-irradiated patients with nasopharyngeal carcinoma (NPC). METHODS: Nine post-irradiated NPC patients diagnosed with cholesterol granuloma in a single-sided middle ear were included in this study. The time from radiotherapy termination to surgery ranged from 6 to 14 years (median 9 years). All patients underwent radical tympanoplasty with canal wall down or up mastoidectomy. RESULTS: All the patients with NPC received radiotherapy of 68-75 Gy before surgery. Three ears underwent tympanoplasty with canal wall down mastoidectomy, and 6 ears underwent tympanoplasty with canal wall up mastoidectomy. All the patients were followed up for at least 2 years. Seven ears (77.8%) had an intact tympanic membrane and 2 ears developed re-perforation of the eardrum 3 months after surgery, but otorrhea decreased significantly. All these patients reported improved quality of life after surgery. Before the operation, the pure tone averages (0.25, 0.5, 1, 2 kHz) were 90.5 dB and the air-bone gaps (0.5, 1, 2 kHz) were 45.8 dB (vs. 62.3 and 25.5 dB, respectively, at 6 months after the operation). CONCLUSIONS: Most post-irradiated NPC patients with cholesterol granuloma of the middle ear benefit from this surgery. Chronic otitis media caused by radiotherapy is not a contraindication to tympanoplasty.

[Clinical analysis of 32 cases of facial nerve schwannomas].

Objective:To elucidate the clinical characteristics, surgical strategy, facial nerve repair methods and outcomes of facial nerve schwannomas（FNS）. Methods:The clinical data of patients with FNS treated between January 2010 and December 2018 at Sun Yat-sen Memorial Hospital of Sun Yat-sen University were retrospectively collected, including the sidedness of FNS, clinical manifestations, imaging data, the extent of tumor, clinical management, preoperative and postoperative facial nerve function. Results:The major clinical manifestations of the 32 patients with FNS were facial palsy（27, 84.4%）, hearing loss（27, 84.4%）, tinnitus（22, 68.8%）, ear mass（15, 46.9%）, and stuffy feeling in the ear（13, 40.6%） respectively. Thirty patients were preoperatively diagnosed with FNS and 2 patients were misdiagnosed. 31 patients underwent resection of FNS, except one patient who was selected for long-term follow-up observation. The choice of surgical approach was based on the location, extent and auditory function of the FNS involved as well as the patient's wishes. The surgical approach was decided based on the location and extent of the tumor: 9 patients were operated via the inferior temporal fossa type A（Fisch A） approach; 8 patients were operated via the mastoid approach; 7 patients were operated via the enlarged mastoid approach; 3 patients were operated via the combined mastoid-cranial middle fossa approach; 1 patient was operated via the cranial middle fossa approach; 3 patients were operated via the combined Fisch A-cranial middle fossa approach. 28 patients（87.5%） had FNS with multiple segments of facial nerve involved. The most involved segment was the vertical segment of the facial nerve（26, 81.3%）. 15 patients underwent facial nerve repair simultaneously, including 7 cases of auricular nerve-facial nerve graft and 8 cases of facial nerve-sublingual nerve anastomosis. 4 cases had improved facial nerve function after auricular nerve-facial nerve graft and 2 cases had improved function after facial nerve-sublingual nerve anastomosis. Among patients who underwent facial nerve repair,the best outcome was H-B Ⅲ. Conclusion:The patients with FNS mainly presented with facial palsy and hearing loss. Temporal bone CT and cranial MR plain & enhanced scan served well to confirm the diagnosis. The improvement rate of postoperative facial nerve function was significantly higher in patients who underwent nerve repair than in those who did not. Hence, facial nerve repair should be considered. Compared with facial nerve-sublingual nerve anastomosis, auricular major nerve-facial nerve graft might be a better choice for improving postoperative facial nerve function.

Shape Optimization of Costal Cartilage Framework Fabrication Based on Finite Element Analysis for Reducing Incidence of Auricular Reconstruction Complications.

Skin necrosis is the most common complication in total auricular reconstruction, which is mainly induced by vascular compromise and local stress concentration of the overlying skin. Previous studies generally emphasized the increase in the skin flap blood supply, while few reports considered the mechanical factors. However, skin injury is inevitable due to uneasily altered loads generated by the intraoperative continuous negative suction and uneven cartilage framework structure. Herein, this study aims to attain the stable design protocol of the ear cartilage framework to decrease mechanical damage and the incidence of skin necrosis. Finite element analysis was initially utilized to simulate the reconstructive process while the shape optimization technique was then adopted to optimize the three-pretested shape of the hollows inside the scapha and fossa triangularis under negative suction pressure. Finally, the optimal results would be output automatically to meet clinical requirement. Guided by the results of FE-based shape optimization, the optimum framework with the smallest holes inside the scapha and fossa triangularis was derived. Subsequent finite element analysis results also demonstrated the displacement and stress of the post-optimized model were declined 64.9 and 40.1%, respectively. The following clinical study was performed to reveal that this new design reported lower rates of skin necrosis decrease to 5.08%, as well as the cartilage disclosure decreased sharply from 14.2 to 3.39% compared to the conventional method. Both the biomechanical analysis and the clinical study confirmed that the novel design framework could effectively reduce the rates of skin necrosis, which shows important clinical significance for protecting against skin necrosis.

Mitochondrial dysfunction resulting from the down-regulation of bone morphogenetic protein 5 may cause microtia.

BACKGROUND: Bone morphogenetic protein 5 (BMP5) has been identified as one of the important risk factors for microtia; however, the link between them has yet to be clarified. In this study, we aimed to demonstrate the relationship of BMP5 with mitochondrial function and investigate the specific role of mitochondria in regulating microtia development. METHODS: BMP5 expression was measured in auricular cartilage tissues from patients with and without microtia. The effects of BMP5 knockdown on cellular function and mitochondrial function were also analyzed in vitro. Changes in genome-wide expression profiles were measured in BMP5-knockdown cells. Finally, the specific impact of BMP5 down-regulation on mitochondrial fat oxidation was analyzed in vitro. RESULTS: BMP5 expression was down-regulated in the auricular cartilage tissues of microtia patients. BMP5 down-regulation inhibited various cellular functions in vitro, including cell proliferation, mobility, and cytoactivity. The functional integrity of mitochondria was also damaged, accompanied by a decrease in mitochondrial membrane potential, reactive oxygen species (ROS) neutralization, and reduced adenosine triphosphate (ATP) production. Carnitine O-palmitoyltransferase 2 and diacylglycerol acyltransferase 2, two of the key regulators of mitochondrial lipid oxidation, were also found to be decreased by BMP5 down-regulation. CONCLUSIONS: Down-regulation of BMP5 affects glycerolipid metabolism and fatty acid degradation, leading to mitochondrial dysfunction, reduced ATP production, and changes in cell function, and ultimately resulting in microtia. This research provides supporting evidence for an important role of BMP5 down-regulation in affecting mitochondrial metabolism in cells, and sheds new light on the mechanisms underlying the pathogenesis of microtia.

Characteristics of 43 multiple auricular deformity case families and auricle morphology in 463 microtia patients in South China.

BACKGROUND: Earlier studies have suggested that microtia is a genetic disease with a worldwide incidence of microtia is between 0.83/10,000 and 17.40/10,000. For microtia, auricle morphology is the most crucial characteristic. However, no studies have been performed to characterize the genetic similarity of microtia and auricle morphology similarity. For the sporadic patients, the relationship between the gestational age of parents and the incidence of microtia is unclear. To obtain the characteristics of auricular deformity multiple case family (AD-MCF) and clarify the relationship between genetic similarity and auricle morphology similarity in AD-MCF. METHODS: This study included 463 AD patients who were diagnosed by Sun Yat-sen Memorial Hospital, Sun Yat-sen University, from 2013 to 2019. Among these patients, 116 are from 43 MCF and the other 347 patients are sporadic. For the patients from families, the disease status of the four generations of immediate family members and the family tree map were collected to analyze the similarity of auricle shape in family members. A score evaluated the similarity of auricle shape according to the structure of the residual ear and the similarity in the morphology of each auricle. Moreover, the population distribution of AD and the gestational age of patients were further analyzed. RESULTS: From 2013 to 2019, a total of 463 patients were diagnosed as microtia in our hospital. There were 427 patients with unilateral disease and 36 patients with bilateral disease. Among them, 116 patients were from 34 families and 9 de novo families. The total scores of patients in different genetic difference levels were compared and were found significantly different (P<0.001). Moreover, 58.14% of families were consistent with the law of chromosomal recessive genetic diseases. Importantly, we found that the gestational age of father in microtia de novo families is 30.94±0.75, and mother in de novo is 28.39±0.73 that is significantly higher than the gestational ages of parents from microtia families with P value =0.0001. CONCLUSIONS: The auricle similarity between family members is positively related to the genetic distance between family members. The microtia patients are potentially associated with the gestational ages of parents.

Modulation of miR-34a/SIRT1 signaling protects cochlear hair cells against oxidative stress and delays age-related hearing loss through coordinated regulation of mitophagy and mitochondrial biogenesis.

Mitophagy and mitochondrial biogenesis are 2 pathways that regulate mitochondrial content and metabolism maintaining cellular homeostasis. The imbalance between these opposing processes impairs mitochondrial function and is suggested to be the pathophysiological basis of a variety of neurodegenerative diseases and aging. Here we investigated the role of mitophagy and mitochondrial biogenesis in oxidative damage to the cochlear hair cells and age-related hearing loss. In cultured mouse House Ear Institute-Organ of Corti 1 hair cells, oxidative stress activated mitophagy but inhibited mitochondrial biogenesis and impaired mitochondrial function. Pharmacological inhibition of miR-34a/SIRT1 signaling enhanced mitophagy, mitochondrial biogenesis, and attenuated House Ear Institute-Organ of Corti 1 cell death induced by oxidative stress. In the cochlea of C57BL/6 mice, mitophagy and mitochondrial biogenesis were both upregulated during aging. Long-term supplementation with resveratrol, a SIRT1 activator, not only improved the balance between mitophagy and mitochondrial biogenesis but also significantly reduced age-related cochlear hair cell loss, spiral ganglion neuron loss, stria vascularis atrophy, and hearing threshold shifts in C57BL/6 mice. Moreover, SIRT1 overexpression or miR-34a deficiency both attenuated age-related cochlear hair cell loss and hearing loss in C57BL/6 mice. Our findings reveal that imbalance between mitophagy and mitochondrial biogenesis contributes to cochlea hair cell damage caused by oxidative stress and during aging. Coordinated regulation of these 2 processes by miR-34a/SIRT1 signaling might serve as a promising approach for the treatment of age-related cochlear degeneration and hearing loss.