m^(6)A modification of lncRNA in middle ear cholesteatoma

Objective:Middle ear cholesteatoma is a non-tumorous condition that typically leads to hearing loss,bone destruction,and other severe complications.Despite surgery being the primary treatment,the recurrence rate remains high.Therefore,exploring the molecular mechanisms underlying cholesteatoma is crucial for discovering new therapeutic approaches.This study aims to explore the involvement of N6-methyladenosine(m^(6)A)methylation in long non-coding RNAs(lncRNAs)in the biological functions and related pathways of middle ear cholesteatoma.Methods:The m^(6)A modification patterns of lncRNA in middle ear cholesteatoma tissues(n=5)and normal post-auricular skin tissues(n=5)were analyzed using an lncRNA m^(6)A transcriptome microarray.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were conducted to identify potential biological functions and signaling pathways involved in the pathogenesis of middle ear cholesteatoma.Methylated RNA immunoprecipitation(MeRIP)-PCR was used to validate the m^(6)A modifications in cholesteatoma and normal skin tissues.Results:Compared with normal skin tissues,1525 lncRNAs were differentially methylated in middle ear cholesteatoma tissues,with 1048 showing hypermethylation and 477 showing hypomethylation[fold change(FC)≥3 or<1/3,P<0.05].GO enrichment analysis indicated that hypermethylated lncRNAs were involved in protein phosphatase inhibitor activity,neuron-neuron synapse,and regulation ofα-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid(AMPA)receptor activity.Hypomethylated lncRNAs were associated with mRNA methyltransferase activity,secretory granule membrane,and mRNA methylation.KEGG analysis revealed that hypermethylated lncRNAs were mainly associated with 5 pathways:the Hedgehog signaling pathway,viral protein interaction with cytokines and cytokine receptors,mitogen-activated protein kinase(MAPK)signaling pathway,cytokine-cytokine receptor interaction,and adrenergic signaling in cardiomyocytes.Hypomethylated lncRNAs were mainly involved in 4 pathways:Renal cell carcinoma,tumor necrosis factor signaling pathway,transcriptional misregulation in cancer,and cytokine-cytokine receptor interaction.Additionally,MeRIP-PCR confirmed the changes in m^(6)A methylation levels in NR_033339,NR_122111,NR_130744,and NR_026800,consistent with microarray analysis.Real-time PCR also confirmed the significant upregulation of MAPK1 and NF-κB,key genes in the MAPK signaling pathway.Conclusion:This study reveals the m^(6)A modification patterns of lncRNAs in middle ear cholesteatoma,suggests a direction for further research into the role of lncRNA m^(6)A modification in the etiology of cholesteatoma.The findings provide potential therapeutic targets for the treatment of middle ear cholesteatoma.

Pediatric Middle Ear Congenital Cholesteatoma: A Case Report

Congenital cholesteatoma（CC）is a rarely seen benign tumor of the temporal bone. There are five general sites of extradural occurrence: the middle ear, external auditory meatus, mastoid, squamous portion and the petrous apex of the temporal bone. CC grows slowly and presents no symptoms at the early stage. Delayed and mis-diagnosis are common with this condition. Case report A 10-year-old boy presented with a 3-month history of hearing loss on right side. There was no history of otorrhea, facial palsy, previous otological procedures or trauma. Otoscopy revealed a bulging posterosuperior quadrant in the otherwise intact right tympanic membrane （Fig.1）. Pure tone audiometry showed an average threshold of 51 dB for 500, 1000, 2000 and 4000Hz, with a 40 dB air-bone gap, suggesting a moderate conductive hearing loss（Fig.4）. CT scan of the temporal bone showed an isolated soft tissue density lesion in the middle ear（Fig.2）.

A Novel Surgery Classification for Endoscopic Approaches to Middle Ear Cholesteatoma

This study aimed to develop a novel surgery classification for an endoscopic approach to middle ear cholesteatoma.We retrospectively analyzed the surgical approaches and outcomes of patients with middle ear cholesteatoma.Middle ear cholesteatoma surgeries were divided into four types and two special types as follows:type I,attic retraction pocket,which only requires tympanostomy tube placement or retraction pocket resection and cartilage reconstruction;typeⅡ,cholesteatoma which is limited to the attic or in which endoscopy can confirm complete removal of mastoid cholesteatoma lesions,including type Ⅱa,requiring only use of a curette,and type Ⅱ b,requiring use of an electric drill or chisel;type Ⅲ,cholesteatoma not limited to the attic,in which endoscopy cannot confirm complete removal of mastoid cholesteatoma lesions,requiring the combined use of endoscope and microscope to perform endoscopic tympanoplasty and"Canal Wall Up"mastoidectomy;type Ⅳ,extensive involvement of mastoid cavity cholesteatoma lesions and/or cases with a potential risk of complications,removal of which can only be performed under a microscope for"Canal Wall Down"mastoidectomy.In addition,there were two special types:"difficult external auditory canal"and congenital cholesteatoma in children.In our system,type I and type U middle ear cholesteatoma surgery was completely performed under an endoscope alone.However,estimating the extent of the lesions,determining the choice of mastoid opening and reestablishing ventilation are the key points for an endoscopic approach to middle ear cholesteatoma.The classification of endoscopic middle ear cholesteatoma surgery may benefit the selection of surgical indications.

Congenital cholesteatoma of the middle ear-a report of 10 cases

Objectives To study clinical, imaging features and treatment outcomes of congenital cholesteatoma of middle ear (CCME). Methods This is a retrospective review of 10 CCME cases selected from 952 cholesteatoma cases treated between January 1995 and December 2005 at the Department of Otolaryngology-Head and Neck Surgery, Chinese PLA General Hospital. The main outcome measures were the site of origin, clinical features, surgical findings, imaging characteristics and hearing results. Results The mean age of the 10 patients was 16 years(ranged from 10 to 24 years), with 6 being older than 18 years. There were 7 males and 3 females. The average delay to diagnosis was longer than 2 years. The mean preoperative PTA was 55 dB HL, with a mean ABG of 45 dB. Typical cholesteatomas were seen behind the tympanic membrane in the superoposterior quadrant on otoscopy only in 2 patients. High resolution CT was completed in all patients. Most of the patients(8/10) were diagnosed with otosclerosis or ossicular abnormality before operation. All patients underwent a one-stage tympanoplasty following transmeatal explorative tympanotomy and complete cholesteatoma removal, except one, who underwent a CWU mastoidectomy due to extensive cholesteatoma involvement. The choleasteatoma lesion was confined to the superoposterior mesotympanum in all patients. The mean postoperative PTA was 20 dB HL. All patients were followed-up for at least 1.5 years postoperatively. Revision procedures were performed in 2 patients for hearing deterioration. No residual or recurrence of cholesteatoma was found. Conclusion CCME is a rare disease that often gets delayed diagnosis. Residual lesions and the prognosis mainly depend on the extent of the lesion.

Potential otogenic complications caused by cholesteatoma of the contralateral ear in patients with otogenic abscess secondary to middle ear cholesteatoma of one ear:A case report

BACKGROUND Otogenic brain abscess caused by middle ear cholesteatoma is a potentially serious and life-threatening complication in the ear,nose,and throat clinic.The mortality rate associated with otogenic brain abscesses is 8%–26.3%.Recently,in China,the incidence of brain abscess secondary to middle ear cholesteatoma has started to increase due to antibiotic resistance.CASE SUMMARY A 55-year-old male presented hearing loss in the right ear and headache for 1 mo in 2018.Computed tomography(CT) showed an area of low density in the right middle ear and mastoid and auditory ossicle defects and a small amount of soft tissue density in the left middle ear.The parietal wall of the right tympanic cavity and the posterior wall of the mastoid sinus were thin and less continuous.Cranial magnetic resonance imaging revealed an area of low intensity encapsulated by an area of high intensity in the right temporal lobe.We diagnosed him with a brain abscess secondary to middle ear cholesteatoma.He received surgery to drain the abscess followed by a modified radical mastoidectomy.The patient visited our department 3 years later because of intermittent otorrhea in the left ear.CT revealed that the area of the soft tissue density in the left middle ear and mastoid was significantly increased.The posterior wall of the mastoid sinus was destroyed,leaving the left middle ear connecting with the brain.The patient underwent a modified radical mastoidectomy in the left ear CONCLUSION Regular follow-up and timely treatment of contralateral ear disease are vital for the prevention of otogenic complications in patients with otogenic abscesses secondary to middle ear cholesteatoma in the unilateral ear.

Endoscopic ear surgery in middle ear cholesteatoma

Objective:Endoscope has been used as diagnostic tool for recidivism and as an adjunct to microscopic technique in the management of cholesteatoma.At present transcanal endoscopic ear surgery(TEES)is being used as a minimally invasive alternative for microscopic approach.We aim to evaluate the feasibility,structural,functional and quality of life outcomes of endoscopic technique in middle ear cholesteatoma.Method:This prospective study was conducted at a tertiary care hospital from January 2017 to January 2018 including 32 adult patients who were treated by TEES for middle ear cholesteatoma.Feasibility of endoscopic technique was assessed by the conversion rates,visualization of middle ear structures and complications.Structural outcomes were evaluated in terms of graft uptake at the third month follow-up and presence of residual or recurrent disease.Functional outcomes were evaluated in terms of postoperative air-bone gap closure at third month follow-up.Patient outcomes in terms of post-operative pain,cosmetic score,day of return to daily activities and patient comfort scores were evaluated.The quality of life outcomes were evaluated using chronic ear survey(CES)and short form questionnaire12 version 2(SF-12V2)which are disease specific and general quality of life assessment tools respectively.Result:Out of 32 patients,endoscopic intact canal wall mastoidectomy was done for 28 and endoscopic canal wall down mastoidectomy in 4 patients.One(3.1%)patient had to be converted to microscopic technique.Median follow-up period was 32.8 months(9e46 months).There were no post-operative complications in any of our patients.The mean middle ear structural visibility index score was 8.4±1.4 with the use of zero-degree endoscope.Graft uptake rate at third month follow-up was 100%.Two(6.3%)patients had recurrent disease at 6 months follow-up and were treated by revision endoscopic surgery.The air conduction(51.3±20.2 dB vs.34.5±20.4 dB,p<0.001),and air-bone gap(33.5±11.1 dB vs.16.9±11.8 dB,p<0.001)has been significantly improved.The mean pain score at 0 hours,6 hours and 24 hours after surgery were 2.5/10,1.6/10 and 0.75/10 respectively.At the discharge,the mean patient comfort score was 9.3±0.6 out of 10.Mean cosmetic score was 9.3±0.5 at the third month follow-up.There was significant post-operative improvement in the sub-scale and total scores of CES and SF-12V2.Conclusion:Endoscopic approach to middle ear cholesteatoma is feasible and confers excellent structural,functional as well as patient related quality of life outcomes.

Design of Floating Mass Type Piezoelectric Actuator for Implantable Middle Ear Hearing Devices

To overcome some of the problems inherent in conventional heating aids such as low gain at high fi＇equencies due to acoustic feedback, discomfort in occlusion of the extemal ear canal and so on, implantable middle ear hearing devices （IMEHDs） have been developed over the past two decades. For such kinds of IMEHDs, this paper presents the design of a floating mass piezoelectric actuator using a PMN-30%PT stack as a new type of vibrator. The proposed piezoelectric actuator consists of only three components of a piezoelectric stack, a metal case and a clamp. For the purpose of aiding the design of this actuator, a coupling biomechanics model of human middle ear and the piezoelectric actuator was constructed. This model was built based on a complete set of computerized tomography section images of a healthy volunteer＇s left ear by reverse engineering technology. The validity of this model was confirmed by comparing the motion of the tympanic membrane and stapes footplate obtained by this model with published experimental measurements on human temporal bones. It is shown that the designed actuator can be implanted on the incus long process by a simple surgical operation, and the stapes footplate displacement by its excitation at 10.5 V root-mean-square（RMS） voltage was equivalent to that from acoustic stimulation at 100 dB sound pressure level（SPL）, which is adequate stimulation to the ossicular chain. The corresponding power consumption is 0.04 mW per volt of excitation at 1 kHz, which is low enough for the transducer to be used in an implantable middle ear device.

Application of high resolution computer tomography in external ear canal cholesteatoma diagnosis

Objective: To evaluate High Resolution Computer Tomography(HRCT) in the diagnosis of external ear canal cholesteatoma.Methods: In this retrospective study, HRCTs of 27 patients with external ear canal cholesteatoma were reviewed. The changes in the external ear canal, tympanic membrane(TM), scutum, tympanum and mastoid were measured and categorized.Results: Fourteen patients showed no or mild destruction in the external ear canal(stage Ⅰ group). Eight patients had obvious enlargement in the external ear canal(stage Ⅱ group) but showed limited destructions of the mastoid bone and no damage of the tympanums. Five patients had serious destruction of the mastoid bone and damage of the tympanum(stage Ⅲ group). All patients in the stage Ⅲ group showed a compression of manubriums and TMs, with 3 having damages on ossicular chain. Bone destruction of the vertical section of facial nerve canal was discovered in one case in the stage Ⅲ group.Conclusion: HRCT can provide detail information about the extent of external ear canal cholesteatoma. Such information can be used to identify special situations with serious complications and to differentiate external ear canal cholesteatoma from middle ear cholesteatoma.

Classification of facial nerve aberration in congenital malformation of middle ear:Implications for surgery of hearing restoration

Objectives: Facial nerve aberration is the most troublesome situation in congenital malformations of middle ear.The aim of our study is to investigate its imaging and clinical features as well as relevant choice of surgical techniques for hearing improvement.Methods: A retrospective study involving review of clinical data of 227 patients(256 ears) with congenital middle ear anomaly was undertaken, including preoperative computed tomography(CT) data, surgical records and videos.Results: Aberration involving intratemporal facial nerve was found in 82/256 ears(32.03%) with congenital middle ear anomaly. The most common forms of aberration included overhanging over the oval window(50/82 ears, 60.98%), bifurcation(3/82 ears, 3.66%) and transverse over the promontory(3/82 ears, 3.66%), counting for 68.29%(56/82) of the cases with facial nerve aberration. Concomitant stapes malformation was found in 76/82 ears(92.68%) and atresia or stenosis of the oval window in 27/82 ears(32.93%). In 9/82 ears(10.98%) both stapes and oval window was absent. Elective surgeries for the purpose of hearing improvement included stapodotomy + piston implantation, labyrinthotomy, labyrinthotomy + total ossicular replacement prosthesis(TORP) implantation and Vibrant Soundbridge(VSB) implantation.Conclusion: The majority of facial nerve aberration in congenital malformation of middle ear involves displacement of facial nerve, in addition to concomitant malformations of the stapes and/or oval window, which may influence the choice of surgery for hearing improvement. VSB implantation may be considered as a useful option.

Bacteriolgy before and after total middle ear reconstruction

Objectives To investigate pre-and post-total middle ear reconstruction bacteriological changes in order to facilitate prevention and treatment of surgical infections. Methods Specimens from 128 ears in 124 patients with problematic mastoid cavities who underwent revision total middle ear reconstruction were studied. Results Bacteriological tests were positive in 87(68.0%) pre-operative specimens, despite local treatment, and in 74 (57.8%) specimens collected 10 days after operation. Common organism strains in pre-and post-operative specimens were slightly different and included: coagulase-staphylococcus, GRAM+ rods, staphylococcus aureus, pseudomonas aeruginosa and fungi. At the time of patient discharge(15-20 days post-operative), only 3 ears (2.3%) were tested positive which responded well to and became dry after local treatment. At one year, 4 ears (3.1%) showed recurrent otorrhea which again responded to local treatment. Conclusion For infection of problematic mastoid cavities after an open cavity procedure, revision total middle ear reconstruction is effective in controlling infection and promoting a dry ear. Infection prevention and treatment is important considering the relatively high rates of peri-operative local infections.

Static analysis of tympanic membrane in aero-otitis media by three-dimensional model of the middle ear

The three-dimensional(3D)model of the middle ear is of great significance to the research of middle ear related diseases.The particular focus of this work is to simulate the impact of aircraft altitude and speed changes on the tympanic membrane(TM)during the descent phase,so as to analyze the pathogenesis of aero-otitis media and the mechanical response characteristics of TM under static pressure.The simulations showed that the stress and strain of TM increase as the altitude difference and speed of the aircraft increase,and the maximum stress and strain areas are consistent with the clinical observation of TM hyperemia.Therefore,among many prevention and treatment measures of aero-otitis media,it is a therapeutic method to directly balance the pressure difference between the inner and outer TM.

Capillary Hemangioma of the Middle Ear and External Auditory Canal:a Case Report

We report a case of capillary hemangiomsa that involved the entire middle ear space,external auditory canal(EAC) and tympanic antrum.Symptoms in the case included ear fullness,hearing loss,otalgia and otorrhea.The case was misdiagnosed as recurrent chronic otitis media with granulation preoperatively.A diagnosis of capillary hemangioma was established by postoperative histological examination.The management of capillary hemangioma of the middle ear and external auditory canal is discussed,with a review of the literature.Because of its variable and sometimes misleading clinical presentation,hemangioma can initially be misdiagnosed as other lesions.Therefore,a high index of suspicion is necessary for early and accurate diagnosis.

Adenoma of the middle ear

Adenoma of the middle ear is a primary tumor of the middle ear that can have exocrine (mucinous) and/or neuroendocrine differentiation. It is an uncommon tumor in the practice of otolaryngology. Based on the first description by Hyams and Michael in 1976,

Modification of closed tympanoplasty in middle ear cholesteatoma

Background Classic mastoidectomy and modified mastoidectomy are traditional surgical procedures for middle ear cholesteatoma with goals of eradicating diseases, creating dry ears and preventing severe complications. However, the drawback of these procedures is the lack of hearing improvement. Therefore, our study aimed to investigate the effects and safety of a modification of closed tympanoplasty for middle ear cholesteatoma. Methods Eighty-three patients were recruited in this study based on the following two criteria： each patient had middle ear cholesteatoma in one ear; the affected ears had a functional eustachian tube and had neither intracranial nor extracranial complications. All the patients received a modification of closed tympanoplasty which included ossicular reconstruction with total ossicular replacement prosthesis （TORP） or partial ossicular replacement prosthesis （PORP） and membrane repair with conchal cartilage-perichondral complex. Results All the 83 cases had dry ears with membranes healed within 4-6 postoperative weeks. After 6 postoperative months, there were 3 cases with re-perforation at the tympanic membrane center and after 1.5 postoperative years, there were 5 cases with cholesteatoma recurrence （6.02%）. Function tests after one postoperative year exhibited an improvement of pure tone audiometry （PTA） in 27 cases that was more than 30 dB, in 33 cases between 20-29 dB, 14 cases with improvement between 10-19 dB, and in 9 cases there was no improvement. Conclusions The modified closed tympanoplasty procedure for middle ear cholesteatoma in the present study has all the advantages of both close-cavity and open-cavity procedures. It has low recurrence rate and good hearing improvement.

Clinical characteristics of patients with labyrinthine fistulae caused by middle ear cholesteatoma

Background Labyrinthine fistula （LF） is a very common clinical complication mainly caused by middle ear cholesteatoma. Whether the presence of different degree LF caused by middle ear cholesteatoma aggravates neurosensory hearing loss （NSHL） and what is the degree of the hearing loss caused by LF were still under controversial. This study aimed to investigate whether the LF degree is correlative with the age distribution, disease duration and hearing loss degree for cholesteatomatous patients. Methods The files of 143 patients with middle ear cholesteatoma were selected and reviewed in a retrospective study. Seventy-eight patients with LF were divided into three types according to the degree of destruction of labyrinth. Sixty-five patients without LF were randomly chosen for control. Then, we compared the clinical characteristics of patients with or without labyrinthine fistulae caused by middle ear cholesteatoma. Results According to the study, cholesteatomatous patients with LF were older and suffered longer disease duration than those without LF. Hearing loss is severe with high frequencies both in patients with and without LF. Moreover, inner ear impairment is correlative with the degree of destruction in labyrinth, and more severe destruction in labyrinth follow the more severe symptoms correlative with inner ear impairment. Conclusion Surgical intervention should be performed as early as possible for these cholesteatomatous patients.

Fresh Clues about the Origin of Mammalian Middle Ear Revealed

CAS paleontologists have identified a rod-like bone from two early Cretaceous mammals as ossified Meckel's cartilage (OMC). This clears some doubts on the controversial topic of the origin of definitive mannalian middle ear (DMME).……

Disagreement in middle ear volume estimation between tympanometry and three-dimensional volume reconstruction in the context of tympanic membrane perforation

Introduction: Middle ear volume(MEV) is a clinically relevant parameter across middle ear diseases. MEV values between these techniques have never before been tested for agreement in ears with perforated tympanic membranes(TMs).Methods: Middle ears were identified from 36 patients ranging 18-89 years of age with TM perforations who underwent tympanometry and temporal bone computed tomography(CT) between 2005 and 2015. MEVs calculated by both tympanometry and three-dimensional volume reconstruction(3DVR) were analyzed for agreement using Bland Altman plots. The differences between tympanometric and 3DVR MEV values for each given middle ear were characterized across MEV quartiles(1= smallest; 4= largest) and across increasing states of middle ear disease using Kruskale Wallis and Wilcoxon testing with Bonferroni correction.Results: Bland Altman plots demonstrated significant disagreement between MEV measurement techniques. Differences between tympanometric(T) and 3DVR MEV values were significantly greater with increasing average(i.e.(Tt3DVR)/2)) MEV per linear regression(p < 0.0001). Significance was demonstrated between fourth and first average MEV quartiles(p= 0.0024), fourth and second quartiles(p= 0.0024), third and first quartiles(p= 0.0048), and third and second quartiles(p= 0.048). Absolute MEV difference was not significantly different across varying states of middle ear disease(p= 0.44).Conclusion: Statistically and clinically significant disagreement was demonstrated between tympanometric and 3DVR MEV values. Studies that vary in MEV estimation techniques may be expected to demonstrate significantly different results. These preliminary results suggest that clinicians should endeavor to seek further confirmation when interpreting high tympanometric MEV values.

Tophaceous gout of the middle ear

We present a very rare case of tophaceous gout of the middle ear causing conductive hearing loss,with special emphasis on Computed Tomography presentation.

Intra-operative hearing monitoring methods in middle ear surgeries

Hearing loss is a condition affecting millions of people worldwide. Conductive hearing loss (CHL) is mainly caused by middle ear diseases. The low frequency area is the pivotal part of speech frequencies and most frequently impaired in patients with CHL. Among various treatments of CHL, middle ear surgery is efficient to improve hearing. However, variable success rates and possible needs for prolonged revision surgery still frustrate both surgeons and patients. Nowadays, increasing numbers of researchers explore various methods to monitor the efficacy of ossicular reconstruction intraoperatively, including electrocochleography (ECochG), auditory brainstem response (ABR), auditory steady state response (ASSR), distortion product otoacoustic emissions (DPOAE), subjective whisper test, and optical coherence tomography (OCT). Here, we illustrate several methods used clinically by reviewing the literature.