Surgical management of endolymphatic sac tumor: classification, outcomes and strategy. A single institution's experience.

PURPOSE: To review the resections of endolymphatic sac tumor (ELST) and describe our experience in the surgical management of ELST. METHODS: Retrospective investigation of consecutive patients who underwent resection of ELSTs at our hospital between 1999 and 2019. The symptoms, diagnosis, surgical findings, and outcomes were analyzed to develop a tumor staging system and corresponding surgical strategy. RESULTS: Retrospective review revealed the surgical treatment of 22 ELSTs. Based on intraoperative findings of tumor extent and size, ELSTs were classified into two types. Type-I (n = 6) referred to the small tumors that were locally confined with limited invasion of semicircular canals and dura; type-II (n = 16) referred to the large tumors that presented extensive erosion of at least one anatomic structure apart from the semicircular canals and the dura around endolymphatic sac. In this case series, Type-I ELST is amenable to resection through a transmastoidal approach, and subtotal petrosectomy is appropriate for the resection of type-II ELST. Sensorineural hearing loss (SNHL) is the most commonly preoperative symptom in both two types of cases. Five type-II ELSTs experienced recurrence and underwent reoperation, whereas all type-I ELSTs did not. CONCLUSION: ELST usually results in SNHL (95%) at the time of diagnosis. The surgical strategy and prognosis of ELST resections are different between type-I and type-II: type-I ELST is amenable to transmastoidal approach with the preservation of facial nerve, whereas type-II ELST increase the surgical difficulty and the risk of recurrence, and subtotal petrosectomy is the basic requirement for the resection of type-II ELST.

Evolutionary origin of pathogenic GJB2 alleles in China.

The frequency of the pathogenic allele of the autosomal recessive deafness gene GJB2 varies among different populations in the world, and accumulates to a sufficiently high frequency in certain population. The purpose of this study is to investigate the origin and evolution of GJB2 pathogenic alleles in Chinese deaf patients. Children with non-syndromic hearing loss, and their parents, from 295 families were recruited. Customized capture probes targeted at 943 single nucleotide polymorphisms (SNPs) related to GJB2 gene were designed for sequencing of genomic DNA in blood samples. Haplotypes carrying pathogenic allele were analyzed through linkage disequilibrium block building, ancestry tracing, and extended haplotype heterozygosity calculation. Two pathogenic GJB2 alleles, c.235delC (18.41%) and c.109G > A (15.57%), were observed in 867 donors. For c.235delC allele, three different core haplotypes with one major haplotype (97.32%) were found, and their core SNPs were 100% conserved. For c.109G > A allele, six different haplotypes with one major haplotype (93.28%) were found and the major c.109G > A allele evolved from a specific ancestral haplotype. Geographical origins of donors carrying GJB2 c.109G > A and c.235delC core haplotypes centered between Qinghai and Neimenggu. GJB2 c.235delC has long-range linkage disequilibrium. No positive selection signature was found for GJB2 c.235delC or c.109G > A in the studied population. In conclusion, we discovered a single origin of GJB2 c.235delC allele and multiple independent origins of GJB2 c.109G > A allele. Alternative to positive selection or multiple independent recurrent mutation event, population bottleneck effect might account for the observed high population frequency of these pathogenic alleles.

Petrous bone cholesteatoma: our experience of 20 years and management of two giant cases affecting rhinopharynx.

PURPOSE: To demonstrate our experience in the treatment of petrous bone cholesteatoma (PBC). METHODS: Data of PBC patients in our hospital from January 2000 to December 2019 were collected. Surgical approaches and facial function were mainly discussed and compared with the literature. The management of 2 giant PBC cases affecting rhinopharynx has been demonstrated. RESULTS: The supralabyrinthine type was the most frequent type followed by the massive type. There were 5 cases with cholesteatoma extending into the clivus (2 cases), sphenoid (1 case) and rhinopharynx (2 cases). The translabyrinthine approach (40%) was our most frequently used approach followed by the middle fossa approach (36%) and the transmastoid approach (11%). There were 10 cases managed with the assistance of endoscope, including 3 cases with cholesteatoma extending into clivus, sphenoid and rhinopharynx separately. Obliteration of the cavity was performed in 70.3% (135/192) cases; 3 of them recurred. For the 2 giant PBC cases affecting rhinopharynx, traditional microscopic surgery assisted with transnasal endoscope was performed. The reduced exposure was beneficial for postoperative recovery, and the approach in the nasal cavity provided a permanent drainage for postoperative examination. CONCLUSION: Otologic endoscope combined with traditional microscopic surgery could reduce the exposure in surgery. For extremely extended cases of PBC, supplementary transnasal endoscopic approach deserves to be considered for the traditional temporal bone approach.

Induction and Regulation of the Immunoproteasome Subunit ß5i (PSMB8) in Laryngeal and Hypopharyngeal Carcinoma Cells.

BACKGROUND The ubiquitin-proteasome pathway (UPP) is closely associated with the occurrence and progression of cancer, and the 5i immunoproteasome subunit is an important antitumor target in UPP. This study aimed to characterize the regulation of the immunoproteasome subunit ß5i (PSMB8) in JHU-011 laryngeal carcinoma cells and FaDu hypopharyngeal carcinoma cells to explore a new target for the treatment of laryngeal and hypopharyngeal carcinomas. MATERIAL AND METHODS JHU-011 and FaDu cells were used as effector cells in this study. By means of 6°Co γ-irradiation, the construction of stable cell lines of the silenced proto-oncogene c-Abl, and the addition of exogenous tyrosine kinase inhibitor (TKI) and activator, the transcription and protein expression levels of PSMB8 and its alternatively spliced isoforms in both cell lines were detected by real-time fluorescence quantitative polymerase chain reaction (RT-PCR) and Western blot. RESULTS Ionizing radiation upregulated the transcription level of the alternatively spliced isoform of PSMB8, E2, in both cell lines, thereby upregulating the mRNA and protein levels of PSMB8. The silencing of the proto-oncogene c-Abl and the activation and inhibition of its kinetic kinase product can affect the transcription and protein levels of PSMB8. CONCLUSIONS Ionizing radiation can significantly upregulate the mRNA and protein levels of PSMB8, which happens through the upregulation of its splicing isoform E2. The proto-oncogene c-Abl and its kinetic kinase protein product can regulate the transcription and protein expression levels of PSMB8 and its alternatively spliced isoforms.

Unilateral congenital malformations of middle ear with intact external ear: a review of 64 cases.

OBJECTIVE: To describe the operative findings and surgical results of unilateral congenital middle ear malformations with intact external ear. METHODS: A retrospective review was performed on 64 patients with unilateral congenital middle ear malformations and intact external ear who underwent exploratory tympanotomy from 2011 to 2016. Demographic data, clinical data, high-resolution computed tomography findings, audiometric data and intraoperative findings were collected. Audiological evaluations before and 6 months after surgery were analyzed in 47 patients. RESULTS: The most common malformation were mobile stapes with missing incus long process and stapes suprastructure. The air conduction pure tone average was 58.9 ± 10.5 dB HL (range 34.4-78.1 dB HL) preoperatively and 28.8 ± 10.6 dB HL (range 9.4-55.6 dB HL) postoperatively (P = 0.000). Twenty-five cases (53.2%) acquired an air conduction hearing gain exceeding 30 dB. Mean air-bone gap (ABG) was 44.5 ± 9.4 dB (range 22.5-66.4 dB HL) before surgery and 15.6 ± 9.3 dB (range 0-35.6 dB) after surgery (P = 0.000) for an average gain of 28.8 ± 11.5 dB. Thirty-four cases (72.3%) showed a postoperative ABG of less than 20 dB, 15 had an ABG within 10 dB, and 4 had 0 dB ABG after operation. No significant difference was observed for air conduction hearing gain regarding age (P = 0.261) or types of malformations (mobile stapes footplate with or without a suprastructure anomaly, P = 0.058). CONCLUSION: Unilateral congenital middle ear malformations with intact external ear can be complex and diverse. Functional ossiculoplasty for patients with unilateral congenital middle ear malformations can achieve good hearing outcomes.

Mutation spectra and founder effect of TMC1 in patients with non-syndromic deafness in Xiamen area, China.

To analyze the spectrum and founder effect of TMC1 mutations in patients with non-syndromic deafness in the Xiamen area. Sporadic pedigrees were detected by targeted next-generation sequencing, and 110 unrelated patients from Xiamen Special Education School were analyzed through Sanger sequencing for the TMC1 gene. In total, 53 SNPs were designed to analyze the haplotypes of the TMC1 c.2050G>C mutation. The probands of three families were found to be homozygous for TMC1 c.2050G>C, and their parents were all heterozygous for the TMC1 c.2050G>C mutation. In 110 unrelated patients from Xiamen Special Education School, four were found to carry compound heterozygotes of TMC1 c.2050G>C, which were compound heterozygotes of c.804G>A, c.1127T>C, c.1165C>T, and c.1396_1398delAAC, respectively. Three types of TMC1 polymorphisms (c.45C>T, c.1713C>T, c.2208+49C>T) and two heterozygotes of novel variants (c.1764-4C>A, c.2073G>A[p.K691K]) were found in the remaining 100 patients. In total, four novel variants were detected in this study. These mutations and variants were not detected in 100 normal samples. The haplotypes of the probands of families with TMC1 c.2050G>C were identical. There were unique hotspots and spectra of TMC1 mutations in the Xiamen deaf population. Haplotype analysis is useful to understand the founder effect of the hot spot mutation.

The Advances in Hearing Rehabilitation and Cochlear Implants in China.

Hearing loss (HL) is a common sensory impairment in humans, with significant economic and social impacts. With nearly 20% of the world's population, China has focused on economic development and health awareness to improve the care for its hearing-impaired population. Recently, the Chinese government has initiated national programs such as the China Disabled Persons Federation to fund prevention, treatment, and rehabilitation of hearing impairment. Newborn hearing screening and auditory rehabilitation programs in China have expanded exponentially with government support. While facing many challenges and overcoming obstacles, cochlear implantation (CI) programs in China have also experienced considerable growth. This review discusses the implementation of CI programs for HL in China and presents current HL data including epidemiology, newborn hearing screening, and determination of genetic etiologies. Sharing the experience in Chinese auditory rehabilitation and CI programs will shine a light on the developmental pathway of healthcare infrastructure to meet emerging needs of the hearing-impaired population in other developing countries.

Genetic basis of Y-linked hearing impairment.

A single Mendelian trait has been mapped to the human Y chromosome: Y-linked hearing impairment. The molecular basis of this disorder is unknown. Here, we report the detailed characterization of the DFNY1 Y chromosome and its comparison with a closely related Y chromosome from an unaffected branch of the family. The DFNY1 chromosome carries a complex rearrangement, including duplication of several noncontiguous segments of the Y chromosome and insertion of ∼160 kb of DNA from chromosome 1, in the pericentric region of Yp. This segment of chromosome 1 is derived entirely from within a known hearing impairment locus, DFNA49. We suggest that a third copy of one or more genes from the shared segment of chromosome 1 might be responsible for the hearing-loss phenotype.

Exome sequencing identifies a novel frameshift mutation of MYO6 as the cause of autosomal dominant nonsyndromic hearing loss in a Chinese family.

Autosomal dominant types of nonsyndromic hearing loss (ADNSHL) are typically postlingual in onset and progressive. High genetic heterogeneity, late onset age, and possible confounding due to nongenetic factors hinder the timely molecular diagnoses for most patients. In this study, exome sequencing was applied to investigate a large Chinese family segregating ADNSHL in which we initially failed to find strong evidence of linkage to any locus by whole-genome linkage analysis. Two affected family members were selected for sequencing. We identified two novel mutations disrupting known ADNSHL genes and shared by the sequenced samples: c.328C>A in COCH (DFNA9) resulting in a p.Q110K substitution and a deletion c. 2814_2815delAA in MYO6 (DFNA22) causing a frameshift alteration p.R939Tfs*2. The pathogenicity of novel coding variants in ADNSHL genes was carefully evaluated by analysis of co-segregation with phenotype in the pedigree and in light of established genotype-phenotype correlations. The frameshift deletion in MYO6 was confirmed as the causative variant for this pedigree, whereas the missense mutation in COCH had no clinical significance. The results allowed us to retrospectively identify the phenocopy in one patient that contributed to the negative finding in the linkage scan. Our clinical data also supported the emerging genotype-phenotype correlation for DFNA22.

Functional mutation of SMAC/DIABLO, encoding a mitochondrial proapoptotic protein, causes human progressive hearing loss DFNA64.

SMAC/DIABLO is a mitochondrial proapoptotic protein that is released from mitochondria during apoptosis and counters the inhibitory activities of inhibitor of apoptosis proteins, IAPs. By linkage analysis and candidate screening, we identified a heterozygous SMAC/DIABLO mutation, c.377C>T (p.Ser126Leu, refers to p.Ser71Leu in the mature protein) in a six-generation Chinese kindred characterized by dominant progressive nonsyndromic hearing loss, designated as DFNA64. SMAC/DIABLO is highly expressed in human embryonic ears and is enriched in the developing mouse inner-ear hair cells, suggesting it has a role in the development and homeostasis of hair cells. We used a functional study to demonstrate that the SMAC/DIABLO(S71L) mutant, while retaining the proapoptotic function, triggers significant degradation of both wild-type and mutant SMAC/DIABLO and renders host mitochondria susceptible to calcium-induced loss of the membrane potential. Our work identifies DFNA64 as the human genetic disorder associated with SMAC/DIABLO malfunction and suggests that mutant SMAC/DIABLO(S71L) might cause mitochondrial dysfunction.

Resolving the genetic heterogeneity of prelingual hearing loss within one family: Performance comparison and application of two targeted next generation sequencing approaches.

Here, we report an unconventional Chinese pedigree consisting of three branches all segregating prelingual hearing loss (HL) with unclear inheritance pattern. After identifying the cause of one branch as maternally inherited aminoglycoside-induced HL, targeted next generation sequencing (NGS) was applied to identify the genetic causes for the other two branches. One affected subject from each branch was subject to targeted NGS whose genomic DNA was enriched either by whole-exome capture (Agilent SureSelect All Exon 50 Mb) or by candidate genes capture (Agilent SureSelect custom kit). By NGS analysis, we identified that patients from Branch A were compound heterozygous for p.E1006K and p.D1663V in the CDH23 (DFNB12) gene; and patients from Branch B were homozygous for IVS7-2A>G in the SLC26A4 (DFNB4) gene. Both CDH23 mutations altered conserved calcium binding sites of the extracellular cadherin domains. The co-occurrence of three different genetic causes in this family was exceedingly rare but fully compatible with the mutation spectrum of HL. Our study has also raised several technical and analytical issues when applying the NGS technique to genetic testing.

The Association Between Tinnitus Sensation-Level Loudness and Sleep Quality in Patients With Subjective Consecutive Tinnitus: A Mediation Analysis.

PURPOSE: So far, there have been no in-depth analyses of the connection between tinnitus sensation-level loudness and sleep quality. Accordingly, the present study was formulated as a mediation analysis focused on exploring this relationship. METHOD: Overall, 1,255 adults with consecutive subjective tinnitus who had sought outpatient treatment were enrolled in the present study. RESULTS: Direct effects of tinnitus sensation-level loudness on sleep quality were not statistically significant (95% confidence intervals [CI] include zero), as measured by the point estimate, -0.016. However, the 95% CI for indirect effects did not include zero when assessing the Self-Rating Anxiety Scale (SAS) scores, the Self-Rating Depression Scale (SDS) scores, the visual analogue scale (VAS) scores, and self-reported tinnitus annoyance. CONCLUSIONS: These results suggest that tinnitus sensation-level loudness does not directly have an effect on sleep quality. However, it indirectly impacts sleep quality, mediated by SAS scores, SDS scores, the impact of tinnitus on life measured using the VAS, and self-reported tinnitus annoyance. As such, alleviating anxiety and depression in patients with tinnitus may result in reductions in their insomnia even if there is no reduction in tinnitus loudness. Importantly, otolaryngologists and other clinicians treating tinnitus should refer patients with tinnitus suffering from insomnia with comorbid depression or anxiety for appropriate psychological and/or psychiatric treatment.

[Clinical characteristics and prognosis of two anastomosis techniques in the treatment of facial nerve defects].

Objective:To investigate the characteristics and prognosis of two anastomosis techniques in repairing facial nerve defects. Methods:A retrospective analysis was conducted on 30 patients who underwent facial nerve anastomosis（direct or rerouting） for facial nerve defects in our department from January 2012 to December 2021. Among them, 21 were male and 9 were female, with an average age of（37.53±11.33） years, all with unilateral onset. Preoperative House-Brackmann（H-B） facial nerve function grades were Ⅳ in 2 cases, Ⅴ in 9 cases, and Ⅵin 19 cases. The duration of facial paralysis before surgery was within 6 months in 21 cases, 6-12 months in 6 cases, and over 1 year in 3 cases. The causes of facial paralysis included 14 cases of cholesteatoma, 6 cases of facial neurioma, 6 cases of trauma, and 4 cases of middle ear surgery injury. Surgical approaches included 9 cases of the middle cranial fossa approach, 8 cases of labyrinthine-otic approach, 7 cases of mastoid-epitympanum approach, and 6 cases of retroauricular lateral neck approach. Results:All patients were followed up for more than 2 years. The direct anastomosis was performed in 10 cases: 6 cases with defects located in the extratemporal segment and 4 cases in the tympanic segment. Rerouting anastomosis was performed in 20 cases: 11 cases with defects located in the labyrinthine-geniculate ganglion, 4 cases from the internal auditory canal to the geniculate ganglion, 3 cases in the internal auditory canal, and 2 cases in the horizontal-pyramid segment. Postoperative H-B facial nerve grades were Ⅱ in 2 cases, Ⅲ in 20 cases, and Ⅳ in 8 cases, with 73.3%（22/30） of patients achieving H-B grade Ⅲ or better. Conclusion:Both direct and rerouting anastomosis techniques can effectively repair facial nerve defects, with no significant difference in efficacy between the two techniques. Most patients can achieve H-B grade Ⅲ or better facial nerve function recovery. Preoperative facial nerve function and duration of facial paralysis are the main prognostic factors affecting the outcome of facial nerve anastomosis.

MPZL2-a common autosomal recessive deafness gene related to moderate sensorineural hearing loss in the Chinese population.

BACKGROUND: Mutations in MPZL2, the characteristic genetic etiology of autosomal recessive deafness loci 111 (DFNB111), cause non-syndromic and moderate sensorineural hearing loss. METHODS: In this study, we analyzed the phenotype and genotype of eight pedigrees consisting of 10 hearing loss patients with bi-allelic pathogenic or likely pathogenic variants in MPZL2. These patients were identified from a 3272 Chinese patient cohort who underwent genetic testing. RESULTS: Apart from symmetrical and moderate sensorineural hearing loss, the MPZL2-related phenotype was characterized by progressive hearing loss with variation in the onset age (congenital defect to onset at the young adult stage). We determined that in the Chinese population, the genetic load of MPZL2 defects was 0.24% (8/3272) in patients diagnosed with hearing loss and 7.02% (8/114) in patients diagnosed with hereditary moderate sensorineural hearing loss caused by STRC, OTOA, OTOG, OTOGL, TECTA, MPZL2 and others. Three known MPZL2 variants (c.220C > T (p.Gln74*), c.68delC (p.Pro23Leufs*2), c.463delG (p.Ala155Leufs*10)) and a novel start loss variant (c.3G > T (p.Met1?)) were identified. MPZL2 c.220C > T was identified as the hotspot variant in the Chinese population and even in East Asia compared with c.72delA (p.Ile24Metfs*22) in European and West Asia through allele frequency. CONCLUSIONS: We concluded that apart from moderate HL, progressive HL is another character of MPZL2-related HL. No specified variant was verified for the progression of HL, the penetrance and expressivity cannot be determined yet. A novel MPZL2 variant at the start codon was identified, enriching the variant spectrum of MPZL2. The hotspot variants of MPZL2 vary in different ethnicities. This study provides valuable data for the diagnosis, prognosis evaluation and genetic counseling of patients with moderate sensorineural hearing loss related to MPZL2.

Loss-of-function mutations in the PRPS1 gene cause a type of nonsyndromic X-linked sensorineural deafness, DFN2.

We report a large Chinese family with X-linked postlingual nonsyndromic hearing impairment in which the critical linkage interval spans a genetic distance of 5.41 cM and a physical distance of 15.1 Mb that overlaps the DFN2 locus. Mutation screening of the PRPS1 gene in this family and in the three previously reported DFN2 families identified four different missense mutations in PRPS1. These mutations result in a loss of phosphoribosyl pyrophosphate (PRPP) synthetase 1 activity, as was shown in silico by structural analysis and was shown in vitro by enzymatic activity assays in erythrocytes and fibroblasts from patients. By in situ hybridization, we demonstrate expression of Prps1 in murine vestibular and cochlea hair cells, with continuous expression in hair cells and postnatal expression in the spiral ganglion. Being the second identified gene associated with X-linked nonsyndromic deafness, PRPS1 will be a good candidate gene for genetic testing for X-linked nonsyndromic hearing loss.

Genetic mutations in nonsyndromic deafness patients of Chinese minority and Han ethnicities in Yunnan, China.

BACKGROUND: Each year in China, 30,000 babies are born with congenital hearing impairment. However, the molecular etiology of hearing impairment in the Yunnan Province population where more than 52 minorities live has not been thoroughly investigated. To provide appropriate genetic testing and counseling to these families, we investigated the molecular etiology of nonsyndromic deafness in this population. METHODS: Unrelated students with hearing loss (n = 235) who attended Kunming Huaxia secondary specialized school in Yunnan enrolled in this study. Three prominent deafness-related genes, GJB2, SLC26A4 and mtDNA 12S rRNA, were analyzed. High-resolution temporal bone computed tomography (CT) scan examinations were performed in 100 cases, including 16 cases with SLC26A4 gene variants, and 37 minorities and 47 Han cases without any SLC26A4 gene mutation. RESULTS: The GJB2 mutation was detected in 16.67% (7/42) of minority patients and 17.62% (34/193) of Chinese Han patients (P > 0.05). 235delC was the hotspot mutation in nonsyndromic hearing loss (NSHL) patients, whereas 35delG was not found. The 431_450del19 mutation was detected for the first time in Han NSHL patients, which resulted in a premature stop codon and changed the protein. The SLC26A4 mutation was found in 9.52% (4/42) of minority patients and 9.84% (19/193) of Han Chinese patients (P > 0.05). The frequencies of mtDNA 12S rRNA mutation in minority and Han Chinese patients were 11.90% (5/42) and 7.77% (15/193; P > 0.05), respectively. Sixteen (16/23, 69.57%) patients with SLC26A4 mutations received temporal bone CT scan, and 14 patients were diagnosed with enlarged vestibular aqueducts (EVAs); the other 2 patients had normal inner ear development. The ratio of EVA in the minorities was 14.63% (6/41). CONCLUSIONS: In this study, a total of 35.74% deaf patients showed evidence of genetic involvement, based on either genetic screening or family history; 17.45%, 9.79%, and 8.51% of the patients were determined to have inherited hearing impairment caused by GJB2, SLC26A4, and mtDNA 1555A > G mutations. There was no significant difference in deafness associated gene mutational spectrum and frequency between the Yunnan minority and Han patients.

Tonotopic reorganization and spontaneous firing in inferior colliculus during both short and long recovery periods after noise overexposure.

BACKGROUND: Noise induced injury of the cochlea causes shifts in activation thresholds and changes of frequency response in the inferior colliculus (IC). Noise overexposure also induces pathological changes in the cochlea, and is highly correlated to hearing loss. However, the underlying mechanism has not been fully elucidated. In this study, we hypothesized that overexposure to noise induces substantial electrophysiological changes in the IC of guinea pigs. RESULTS: During the noise exposure experiment, the animals were undergoing a bilateral exposure to noise. Additionally, various techniques were employed including confocal microscopy for the detection of cochlea hair cells and single neuron recording for spontaneous firing activity measurement. There were alterations among three types of frequency response area (FRA) from sound pressure levels, including V-, M-, and N-types. Our results indicate that overexposure to noise generates different patterns in the FRAs. Following a short recovery (one day after the noise treatment), the percentage of V-type FRAs considerably decreased, whereas the percentage of M-types increased. This was often caused by a notch in the frequency response that occurred at 4 kHz (noise frequency). Following a long recovery from noise exposure (11-21 days), the percentage of V-types resumed to a normal level, but the portion of M-types remained high. Interestingly, the spontaneous firing in the IC was enhanced in both short and long recovery groups. CONCLUSION: Our data suggest that noise overexposure changes the pattern of the FRAs and stimulates spontaneous firing in the IC in a unique way, which may likely relate to the mechanism of tinnitus.

Outcomes of cochlear implantation in 75 patients with auditory neuropathy.

Background: Cochlear implantation (CI) outcomes in patients with auditory neuropathy (AN) are variable, which hampers patients' decisions on CI. Objective: This study aims to assess the outcomes of CI in individuals diagnosed with AN and to examine the various factors that may influence the effectiveness of this intervention. Methods: A total of 75 patients diagnosed with AN were included in the study. The hearing threshold, the score of categories of auditory performance (CAP), speech intelligibility rating (SIR), and speech audiometry were tested. Genetic testing was conducted by medical exome sequencing in 46 patients. Results: After CI, the average aided hearing threshold for patients with prelingual and post-lingual onset was 38.25 ± 6.63 dB and 32.58 ± 9.26 dB, respectively; CAP score improved to 5.52 ± 1.64 (p < 0.001) and 6.00 ± 0.96 (p < 0.001), respectively; SIR score increased to 3.57 ± 1.22 (p < 0.001) and 4.15 ± 0.95 (p < 0.001), respectively. Maximum speech recognition ranged from 58 to 93% for prelingual onset patients and 43 to 98% for those with post-lingual onset. Speech outcomes of CI in cases with cochlear nerve (CN) deficiency were significantly poorer (p = 0.008). Molecular etiologies, including TWIST1, ACTG1, m.A7445G, and a copy-number variant (CNV) carrying ACTB, were related to AN here. Conclusion: CI is a viable therapy option for patients with AN; CN deficiency might impact outcomes of CI.

Surgical management and the prognosis of iatrogenic facial nerve injury in middle ear surgery: a 20-year experience.

BACKGROUND: Iatrogenic facial nerve injury is one of the severest complications of middle ear surgery, this study aims to evaluate surgical management and prognosis in the era of improved surgical instruments. METHODS: Patients suffered from facial nerve paralysis after middle ear surgery between January 2000 and December 2019 were retrospectively collected. Demographic characters, primary disease and surgery, details of revision surgery were analyzed. RESULTS: Forty-five patients were collected, of whom 8 were injured at our center and 37 were transferred. For 8 patients injured at our center, seven (87.5%) ranked House-Brackmann (H-B) grade V and one (12.5%) ranked H-B VI before revision surgery; postoperatively, two (25.0%) patients recovered to H-B grade I, four (50.0%) recovered to H-B II, and the other two (25.0%) recovered to H-B III. For 37 patients transferred, thirteen (35.1%) ranked H-B grade V and 24 (64.9%) ranked H-B VI preoperatively, final postoperative grade ranked from H-B grade I to grade V, with H-B I 6 (16.2%) cases, H-B II 6 (16.2%) cases, H-B III 18 (48.6%) cases, H-B IV 5 (13.5%) cases and H-B V 2 (5.4%) cases. The most vulnerable site was tympanic segment (5, 62.5% and 27, 73.0% respectively). Twenty-one (46.7%) patients suffered from mild injury and 24 (53.3%) suffered from partial or complete nerve transection. For surgical management, twenty-one (46.7%) patients received decompression, nineteen (42.2%) received graft and 5 (11.1%) received anastomosis. Those decompressed within 2 months after paralysis had higher possibility of H-B grade I or II recovery (P = 0.026), those received graft within 6 months were more likely to get H-B grade III recovery (P = 0.041), and for patients underwent anastomosis within 6 months, all recovered to H-B grade III. CONCLUSIONS: Tympanic segment is the vulnerable site. If facial nerve paralysis happens, high-resolution computed tomography could help identify the injured site. Timely treatment is important, decompression within 2 months after paralysis, graft and anastomosis within 6 months lead to better recovery.