Facial canal dehiscence, dural exposure, and labyrinthine fistula in middle ear cholesteatoma and mastoiditis.

PURPOSE: To analyze the prevalence and associations of facial canal dehiscence (FCD), dural exposure, and labyrinthine fistula in chronic otitis media (COM) with and without cholesteatoma. METHODS: This was a retrospective study performed in an academic medical center. Patients who received tympanoplasty with mastoidectomy for COM with and without cholesteatoma were included. The prevalence of FCD, dural exposure, and labyrinthine fistula in COM with and without cholesteatoma (mastoiditis) and their relationships were analyzed. RESULTS: A total of 189 patients, including 107 (56.6%) females and 82 (43.4%) males, with 191 ears were included. There were 149 cases (78.0%) of cholesteatoma and 42 patients (22.0%) with mastoiditis. FCD was noted in 27.5% of patients with cholesteatoma and 9.5% of patients with mastoiditis. Dural exposure was found in 21 patients (14.1%) with cholesteatoma and 4 patients (9.5%) with mastoiditis. Eleven patients (7.4%) with cholesteatoma and 1 patient (2.4%) with mastoiditis had labyrinthine fistula. Patients with a labyrinthine fistula had nearly a fivefold greater chance (OR = 4.924, 95% CI = 1.355-17.896, p = 0.015) of having FCD than those without a fistula. There was a positive correlation between dural exposure and labyrinthine fistula (P = 0.011, Fisher's exact test). CONCLUSION: FCD, dural exposure, and labyrinthine fistula are common complications in COM. These complications are more frequently observed in patients with cholesteatoma than in patients with mastoiditis. Surgeons should pay more attention to the treatment of COM.

Higher NAFLD fibrosis score is associated with impaired eGFR.

BACKGROUND/PURPOSE: Chronic kidney disease (CKD) has become a worldwide health problem, leading to high morbidity and mortality, and non-alcoholic fatty liver disease (NAFLD) is considered a risk factor for CKD. The aim of this study was to explore the relationship between NAFLD fibrosis score (NFS) and the estimated glomerular filtration rate (eGFR), and identify possible risk factors related to the NFS among Taiwanese subjects. METHODS: Subjects were enrolled from the database of the Department of Preventive Medicine of Kaohsiung Municipal Hsiao-Kang Hospital. The eGFR was calculated according to the Taiwanese Modification of Diet in Renal Disease (TMDRD) equation, and the NFS was employed to evaluate the fibrotic level. RESULTS: In total, 11,376 subjects were enrolled in this study, with a mean age of 52.0 ± 6.81 years, including 4529 (39.8%) males. A fasting sugar level ≥100 mg/dL (OR = 1.70, 95% CI = 1.52-1.87) and an abnormal waist circumference (OR = 1.81, 95% CI = 1.65-1.99) were significant factors associated with NFS (p < 0.05). Trends of a decreasing TMDRD score and an increasing NFS with increasing age were noted (p < 0.05). The NFS was significantly negatively correlated with the TMDRD score (standard coefficients: -0.067, p < 0.001). CONCLUSION: A higher NFS is associated with an impaired eGFR in Taiwanese subjects. Controlling risk factors, especially fasting sugar level and waist circumference, may be useful in preventing NFS deterioration, which is negatively correlated with the eGFR.

Phosphodiesterase 4D gene polymorphisms in sudden sensorineural hearing loss.

The phosphodiesterase 4D (PDE4D) gene has been reported as a risk gene for ischemic stroke. The vascular factors are between the hypothesized etiologies of sudden sensorineural hearing loss (SSNHL), and this genetic effect might be attributed for its role in SSNHL. We hypothesized that genetic variants of the PDE4D gene are associated with susceptibility to SSNHL. We conducted a case-control study with 362 SSNHL cases and 209 controls. Three single nucleotide polymorphisms (SNPs) were selected. The genotypes were determined using TaqMan technology. Hardy-Weinberg equilibrium (HWE) was tested for each SNP, and genetic effects were evaluated according to three inheritance modes. We carried out sex-specific analysis to analyze the overall data. All three SNPs were in HWE. When subjects were stratified by sex, the genetic effect was only evident in females but not in males. The TT genotype of rs702553 exhibited an adjusted odds ratio (OR) of 3.83 (95 % confidence interval = 1.46-11.18) (p = 0.006) in female SSNHL. The TT genotype of SNP rs702553 was associated with female SSNHL under the recessive model (p = 0.004, OR 3.70). In multivariate logistic regression analysis, TT genotype of rs702553 was significantly associated with female SSNHL (p = 0.0043, OR 3.70). These results suggest that PDE4D gene polymorphisms influence the susceptibility for the development of SSNHL in the southern Taiwanese female population.

Perception of hearing impairment and the willingness to use hearing aids in an elderly population in southern Taiwan: A community-based study.

OBJECTIVES: To estimate the prevalence and severity of hearing impairment (HI), the self-perception of HI, and the willingness to use a hearing aid (HA) in the elderly population in southern Taiwan. DESIGN: This community-based study was performed in a metropolitan hospital. A questionnaire about the perception of HI and the willingness to use a HA was used. The severity of HI in speech-frequency pure-tone average (PTA) was evaluated. The associations between sex, age, severity of HI, self-perception of HI, and the willingness to use a HA were analysed. STUDY SAMPLE: A total of 599 volunteers were recruited from the health management center; 324 (54.1%) males and 275 (45.9%) females, who were 65 years of age or older. RESULTS: The prevalence of HI >25 dBHL in the elderly was 78%. The predicted levels for elderly persons to perceive HI and hearing difficulties were 34.38 dBHL and 54.38 dBHL, respectively. Males and younger participants were more willing to use HA. The primary reasons for refusing HA use were discomfort (25.1%) and a self-perception that the HA was unnecessary (19.7%). CONCLUSIONS: The prevalence of HI was high among the elderly population in southern Taiwan. Age and sex were the determinants of HA use.

Predictive Factors and Audiometric Outcome Comparison Between Titanium Prosthesis and Autologous Incus in Traumatic Ossicular Injury.

OBJECTIVES: To investigate the etiology and ossicular pathology of traumatic ossicular injury in Taiwan and examine the hearing outcomes and predictive factors between the titanium prosthesis and autologous incus groups. METHODS: We retrospectively analyzed patients with traumatic ossicular injury from 2011 to 2020 in Taiwan. Patients were divided into the titanium or autologous group according to the surgical materials used. The audiometric outcomes and predictive factors of ossiculoplasty were analyzed between groups. RESULTS: Twenty patients with ossicular chain discontinuity were enrolled (8 in the titanium group and 12 in the autologous group). The postoperative hearing threshold (26.6 ± 8.9 dB) and air-bone gap (10.3 ± 5.6 dB) improved significantly compared with the preoperative hearing threshold (50.7 ± 13.3 dB) and air-bone gap (29.9 ± 11.0 dB). The improvements in the hearing threshold and air-bone gap were not significantly different between the titanium and autologous groups. Our patients presented an improvement in hearing restoration with 65% closure of the air-bone gap in 0 to 10 dB range and 30% in 11 to 20 dB range, without sensorineural hearing loss during surgery. Univariate regression analysis revealed that vertigo, benign paroxysmal positional vertigo, and temporal bone fracture may serve as negative factors influencing the air-bone gap gain. CONCLUSIONS: Ossiculoplasty with both titanium prosthesis and autologous materials demonstrated favorable hearing recovery in traumatic ossicular injury. Vertigo, benign paroxysmal positional vertigo, and temporal bone fracture may serve as negative predictive factors of the hearing benefit after surgery.

Prognosis Prediction of Sudden Sensorineural Hearing Loss Using Ensemble Artificial Intelligence Learning Models.

OBJECTIVE: We used simple variables to construct prognostic prediction ensemble learning models for patients with sudden sensorineural hearing loss (SSNHL). STUDY DESIGN: Retrospectively study. SETTING: Tertiary medical center. PATIENTS: 1,572 patients with SSNHL. INTERVENTION: Prognostic. MAIN OUTCOME MEASURES: We selected four variables, namely, age, days after onset of hearing loss, vertigo, and type of hearing loss. We also compared the accuracy between different ensemble learning models based on the boosting, bagging, AdaBoost, and stacking algorithms. RESULTS: We enrolled 1,572 patients with SSNHL; 73.5% of them showed improving and 26.5% did not. Significant between-group differences were noted in terms of age ( p = 0.011), days after onset of hearing loss ( p < 0.001), and concurrent vertigo ( p < 0.001), indicating that the patients who showed improving to treatment were younger and had fewer days after onset and fewer vertigo symptoms. Among ensemble learning models, the AdaBoost algorithm, compared with the other algorithms, achieved higher accuracy (82.89%), higher precision (86.66%), a higher F1 score (89.20), and a larger area under the receiver operating characteristics curve (0.79), as indicated by test results of a dataset with 10 independent runs. Furthermore, Gini scores indicated that age and days after onset are two key parameters of the predictive model. CONCLUSIONS: The AdaBoost model is an effective model for predicting SSNHL. The use of simple parameters can increase its practicality and applicability in remote medical care. Moreover, age may be a key factor influencing prognosis.

Normal Weight Central Obesity is a Poor Prognostic Factor for Sudden Sensorineural Hearing Loss.

OBJECTIVES: To investigate the role of normal weight central obesity (NWCO) in the prognosis of sudden sensorineural hearing loss (SSNHL). METHODS: We retrospectively investigated 807 cases of SSNHL from January of 2008 to August of 2019 from the Department of Otorhinolaryngology at Kaohsiung Medical University Hospital in southern Taiwan. We analyzed the association between overweight and obesity, NWCO, and the prognosis of SSNHL. The demographic and clinical characteristics, audiometry results, and outcomes were also reviewed. RESULTS: The nonobese (body mass index [BMI] < 24 kg/m2) and overweight and obese groups (BMI ≥ 24 kg/m2) comprised 343 (42.50%) and 464 (57.50%) patients, respectively. The favorable prognosis rates in the nonobese and the overweight and obese groups were 45.48% and 45.91%, respectively, without a significant difference (P = .9048). Multivariate logistic regression revealed that BMI (adjusted odds ratio [aOR] = 1.00, 95% CI = 0.948-1.062, P = .9165) was not significantly associated with SSNHL recovery. The normal weight noncentral obesity (NWNCO) and NWCO groups comprised 266 (77.55%) and 77 (22.45%) patients, respectively, and had favorable prognosis rates of 48.50% and 35.06%, respectively. The difference between the groups was significant (P = .0371). Multivariate logistic regression analysis revealed that NWCO (aOR = 2.51, 95% CI = 1.292-5.019, P = .0075) was significantly associated with SSNHL recovery. CONCLUSIONS: NWCO may significantly affect the prognosis of SSNHL.

Upregulation of phosphorylated HSP27, PRDX2, GRP75, GRP78 and GRP94 in acquired middle ear cholesteatoma growth.

Cholesteatoma is a destructive and expanding growth of keratinizing squamous epithelium in the middle ear or petrous apex. The molecular and cellular processes of the pathogenesis of acquired middle ear cholesteatoma have not been fully understood. In this study, comparative proteomic analysis was conducted to investigate the roles of specific proteins in the pathways regarding keratinocyte proliferation in cholesteatoma. The differential proteins were detected by comparing the two-dimension electrophoresis (2-DE) maps of the epithelial tissues of 12 attic cholesteatomas with those of retroauricular skins. There were 14 upregulated proteins in the epithelial tissues of cholesteatoma in comparison with retroauricular skin. The modulation of five crucial proteins, HSP27, PRDX2, GRP75, GRP78 and GRP94, was further determined by RT-PCR, Western blot and immunohistochemistry. Phosphorylation of HSP27 at Ser-82 was identified by mass spectroscopy. The results of this study suggested that phosphorylated HSP27 is the end expression of two potential signal-transduction pathways, and together with PRDX2, they are very likely involved in the proliferation of keratinocytes in cholesteatoma. Upregulations of GRP75, GRP78 and GRP94 in keratinocytes may be able to counter endoplasmic reticulum stress, to inhibit cell apoptosis, to prevent protein unfolding and to promote cholesteatoma growth.

Glucocorticoid receptor (NR3C1) genetic polymorphisms and the outcomes of sudden sensorineural hearing loss.

BACKGROUND: The glucocorticoid receptor gene (NR3C1) encodes the receptor to which cortisol and other glucocorticoids bind. Steroids in either oral, intratympanic, or intravascular forms are the treatment of choice for sudden sensorineural hearing loss (SSNHL), but the outcome varies. The outcomes of SSNHL have been investigated for related factors, including age, initial hearing loss severity and pattern, vertigo, genetic variations, and the time between onset and treatment. The objective of the present study was to analyze the association of genetic polymorphisms of NR3C1 with the outcomes of SSNHL. MATERIALS AND METHODS: We conducted a comparison study of 93 cases with a poor outcome (control) and 100 cases with a good outcome (case) in SSNHL patients. Six single nucleotide polymorphisms (SNPs) were selected. The genotypes were determined using TaqMan technology. RESULTS: The heterozygous AT genotype of rs17100289 was associated with a poor outcome in comparison with the major homozygous AA genotype after adjustments for age and sex (OR = 0.50; 95% CI 0.26-0.95; P = 0.035) in SSNHL patients. The CT genotype of rs4912912 was also associated with a poor outcome compared with the major homozygous TT genotype after the adjustments (OR = 0.47; 95% CI 0.24-0.92; P = 0.026). CONCLUSION: These results suggest that NR3C1 genetic polymorphisms may influence the outcomes of SSNHL.

Downregulation of Calreticulin and Annexin A2 Expression in Acquired Middle Ear Cholesteatoma by 2-DE Analysis.

BACKGROUND: Many factors are thought to be associated with the development of cholesteatoma, while the mechanisms of its formation remain unclear. This study aimed to identify the potential mechanisms of the proliferation and growth of cholesteatoma by analysis of the differential expressions of proteins in cholesteatoma and retroauricular skin tissue collected from the same patients. METHODS: The present study is a retrospective study performed in an academic medical center. Comparative proteomics analyses using two-dimensional gel electrophoresis (2-DE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), in addition to immunohistochemical analysis, were conducted to identify differentially-expressed proteins in cholesteatoma tissue as compared with retroauricular skin tissue. Western blotting was also employed to verify the expression patterns of the specific proteins identified by 2-DE and to measure the changes in potential modulators related to cholesteatoma proliferation and growth. RESULTS: Calreticulin (CRT) and annexin A2 (AnxA2) were identified as being differentially-expressed in cholesteatoma by 2-DE and LC-MS/MS, the results of which were in agreement with the results of immunohistochemical analysis and western blotting. Downregulation of CRT and AnxA2 were observed in cholesteatoma. CONCLUSION: Our data suggests that CRT and AnxA2 downregulation are seen in cholesteatoma compared to retroauricular skin. We speculate that the reduced expression of CRT and the persistent inflammatory response play important roles in the epithelial proliferation of cholesteatoma.

Role of interleukin-28B polymorphisms in the treatment of hepatitis C virus genotype 2 infection in Asian patients.

UNLABELLED: Genome-wide association studies have linked single nucleotide polymorphisms (SNPs) near the interleukin-28B gene to the hepatitis C virus genotype 1 (HCV-1) response to peginterferon/ribavirin treatment. We aimed to explore the impact on the treatment outcomes of Asian HCV-2 patients. We determined rs8105790, rs8099917, rs4803219, and rs10853728 to be candidate SNPs in 482 Asian HCV-2 patients treated with the standard of care. Because the first three SNPs were in very strong linkage disequilibrium with one another (r2 = 0.94-0.96), rs8099917 and rs10853728 were selected for an analysis of their influence on the achievement of rapid virological response [RVR; seronegativity for hepatitis C virus (HCV) RNA in treatment week 4] and sustained virological response (SVR; seronegativity for HCV RNA throughout 24 weeks of posttreatment follow-up). The rs10853728 genotype did not predict RVR or SVR in HCV-2 patients. However, patients with the rs8099917 TT genotype, in comparison with patients with GT/GG genotypes, had a significantly higher rate of achieving RVR (85.2% versus 72.0%, P = 0.017) but did have not a significantly higher rate of achieving SVR (89.4% versus 86.0%). Multivariate analysis revealed that a baseline HCV viral load <400,000 IU/mL was the strongest predictor of RVR [odds ratio (OR) = 4.27, 95% confidence interval (CI) = 2.31-7.87, P < 0.001], and this was followed by advanced liver fibrosis (OR = 0.28, 95% CI = 0.15-0.53, P < 0.001), the carriage of the rs8099917 TT genotype (OR = 3.10, 95% CI = 1.34-7.21, P = 0.008), and the pretreatment level of aspartate aminotransferase (OR = 0.996, 95% CI = 0.99-1.00, P = 0.04). Nevertheless, the achievement of RVR was the single predictor of SVR with an OR of 19.37 (95% CI = 8.89-42.23, P < 0.001), whereas the rs8099917 genotypes played no role in achieving SVR with or without RVR. CONCLUSION: The rs8099917 TT genotype is significantly independently predictive of RVR, which is the single best predictor of SVR, in Asian HCV-2 patients.

Heat shock protein 70 gene polymorphisms in sudden sensorineural hearing loss.

BACKGROUND: Heat shock proteins protect cells and tissues against different types of damage. Previous studies have revealed that the serum level of heat shock protein 70 (HSP70) increases in sudden sensorineural hearing loss (SSNHL) patients. We hypothesized that genetic variants of the HSP70 gene are associated with susceptibility to SSNHL. METHODS: We conducted a case-control study with 160 SSNHL cases and 178 controls. Three tagging single nucleotide polymorphisms (SNPs) were selected. The genotypes were determined using TaqMan technology. Hardy-Weinberg equilibrium was tested for each SNP, and genetic effects were evaluated according to three inheritance modes. A haplotype analysis was also performed. RESULTS: All three SNPs were in Hardy-Weinberg equilibrium. The CT genotype of rs2075800 exhibited an adjusted odds ratio of 0.59 (95% confidence interval 0.37-0.94; p = 0.027). The T allele of SNP rs2075800 was associated with SSNHL under the dominant model (p = 0.019; odds ratio 0.59). Haplotype analysis of the three SNPs demonstrated that the haplotype TGC (rs2075800/rs1043618/rs2763979) was statistically significant (p = 0.0137). CONCLUSIONS: These results suggest that HSP70 gene polymorphisms influence the susceptibility to the development of SSNHL in the Taiwanese population.

Safety Parameters of Quantum Molecular Resonance Devices During Thyroid Surgery: Porcine Model Using Continuous Neuromonitoring.

Objectives: Quantum molecular resonance (QMR) devices have been applied as energy-based devices in many head and neck surgeries; however, research on their use in thyroid surgery is lacking. This study aimed to investigate the safety parameters of QMR devices during thyroidectomy when dissection was adjacent to the recurrent laryngeal nerve (RLN). Methods: This study included eight piglets with 16 RLNs, and real-time electromyography (EMG) signals were obtained from continuous intraoperative neuromonitoring (C-IONM). QMR bipolar scissor (BS) and monopolar unit (MU) were tested for safety parameters. In the activation study, QMR devices were activated at varying distances from the RLN. In the cooling study, QMR devices were cooled for varying time intervals, with or without muscle touch maneuver (MTM) before contacting with the RLN. Results: In the activation study, no adverse EMG change occurred when QMR BS and MU were activated at distances of 2 mm or longer from the RLNs. In the cooling study, no adverse EMG change occurred when QMR BS and MU were cooled in 2-second intervals or immediately after MTM. Conclusion: QMR devices should be carefully used when performing RLN dissection during thyroid surgery. According to the activation and cooling safety parameters in this study, surgeons can avoid RLN injury by following standard procedures when using QMR devices.

Association of polymorphisms of heat shock protein 70 with susceptibility to noise-induced hearing loss in the Taiwanese population.

Noise-induced hearing loss (NIHL) is the major cause of adult sensorineural hearing loss. It is a complex disease caused by the interaction of environmental and genetic factors. Previous studies found that heat shock proteins (HSPs) were associated with the development of NIHL. Specifically, polymorphisms in the heat shock protein 70 (HSP70) gene family are associated with a susceptibility to NIHL. In this study, three single nucleotide polymorphisms (SNPs) of the HSP70 family (SNP1: rs2075800; SNP2: rs1043618; SNP3: rs2763979) were genotyped in 349 noise-exposed Taiwanese workers. The subjects were categorized into noise-susceptible (NS; n = 27) and general susceptibility (GS; n = 322) groups by the change of a 4K-weighted audiometric average in an interval of 5 years. The G/C genotype of SNP2 was found to be associated with NIHL susceptibility (adjusted OR = 2.634; 95% CI = 1.096-6.328). No significant association was found for SNP1 and SNP3 with NIHL susceptibility. Analysis of haplotypes composed of these three SNPs revealed a significant association between NIHL susceptibility and haplotype CCC (OR = 2.197; 95% CI = 1.110-4.370). In conclusion, the genetic polymorphisms in the HSP70 genes seem to be associated with the individual's susceptibility to NIHL in the Taiwanese population. These findings could be used as a reference in the understanding and prevention of NIHL.

The association of heat shock protein genetic polymorphisms with age-related hearing impairment in Taiwan.

BACKGROUND: Age-related hearing impairment (ARHI) is a major disability among the elderly population. Heat shock proteins (HSPs) were found to be associated with ARHI in animal studies. The aim of this study was to analyze the associations of single nucleotide polymorphisms (SNPs) of HSP genes with ARHI in an elderly population in Taiwan. METHODS: Participants ≥65 years of age were recruited for audiometric tests and genetic analyses. The pure tone average (PTA) of the better hearing ear was calculated for ARHI evaluation. The associations of HSPA1L (rs2075800 and rs2227956), HSPA1A (rs1043618) and HSPA1B (rs2763979) with ARHI were analyzed in 146 ARHI-susceptible (cases) and 146 ARHI-resistant (controls) participants. RESULTS: The "T" allele of HSPA1B rs2763979 showed a decreased risk of ARHI. The "TT" genotype of rs2763979 also showed a decreased risk of ARHI in the dominant hereditary model. For HSPA1L (rs2075800 and rs2227956) and HSPA1A (rs1043618), the haplotype "CAG" was related to a decreased risk of ARHI. CONCLUSION: These findings suggest that HSP70 polymorphisms are associated with susceptibility to ARHI in the elderly population.

Comparative Study of Endoscopic and Microscopic Type I Tympanoplasty in Terms of Delayed Facial Palsy.

OBJECTIVE: Delayed facial palsy is a complication of otologic surgery. Tympanoplasty is commonly employed in chronic otitis media. We compared the incidence and characteristics of delayed facial palsy and hearing restoration between endoscopic and microscopic tympanoplasty for the treatment of simple chronic otitis media. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary medical center. SUBJECTS AND METHODS: We retrospectively analyzed 468 patients who underwent type I tympanoplasty from January 2009 to April 2017. Patients were divided into transcanal endoscopic ear surgery and microscopic ear surgery groups. Their epidemiological profiles were reviewed and the outcomes of tympanoplasty were analyzed. Blood sample tests for herpes simplex virus and varicella-zoster virus immunoglobulin M and immunoglobulin G were arranged in patients with delayed facial palsy. RESULTS: Transcanal endoscopic ear surgery exhibited similar benefits to microscopic ear surgery in graft-taking rate and hearing restoration but had a shorter operation time (P < .01). Eight patients (1.71%) developed delayed facial palsy, but no statistically significant difference was observed between the 2 surgical approaches. All patients tested negative for varicella-zoster virus and herpes simplex virus immunoglobulin M and positive for immunoglobulin G of the same viruses; however, the titer did not exhibit a 4-fold increase, implying that patients did not have active viral infections. CONCLUSION: Transcanal endoscopic ear surgery is an ideal alternative for simple tympanoplasty. The incidence of delayed facial palsy was not significantly different between the 2 approaches. Because of the favorable prognosis and the absence of direct serological evidence supporting viral reactivation, treatment with antivirals may not be required.

The association of genetic polymorphisms in interleukin-1 receptors type 1 and type 2 with sudden sensorineural hearing loss in a Taiwanese population: a case control study.

BACKGROUND: Sudden sensorineural hearing loss (SSNHL) is a disease with an unknown etiology; damage to the auditory nerve from inflammation due to viral infection or vascular incidents has been implicated. According to several studies, cytokines, including interleukins, are associated with SSNHL in terms of serum expression and genetic polymorphisms. Interleukin-1 (IL-1) plays a key role in inflammation and may be associated with SSNHL. This study analyzed the association of single nucleotide polymorphisms (SNPs) of IL-1 receptor (IL-1R) genes with SSNHL in Taiwan. METHODS: We conducted a case-control study involving 401 patients with SSNHL and 730 healthy controls. Four SNPs (IL-1R type 1 gene [IL1R1] [rs3917225 and rs2234650] and IL-1R type 2 gene [IL1R2] [rs4141134 and rs2071008]) were selected. The genotypes were determined using the TaqMan assay. The Hardy-Weinberg equilibrium (HWE) was tested for each SNP, and genetic effects were evaluated. RESULTS: The TT genotype of rs2234650 had an adjusted odds ratio (OR) of 2.988 (95% confidence interval [95% CI] 1.27-6.82) (P = 0.012) compared with the CC genotype in patients with SSNHL. The SNP rs2234650 was associated with SSNHL in the recessive model (TT vs. CC + CT, P = 0.0206, OR = 2.681). The CT genotype of rs4141134 had an adjusted OR of 3.860 (95% CI 2.01-7.44; P < 0.0001) compared with the TT genotype, in patients with SSNHL. The SNP rs4141134 was associated with SSNHL under the dominant model (CC + CT vs. TT, P < 0.0001, OR = 4.087). CONCLUSION: These findings suggest that IL1R1 and IL1R2 gene polymorphisms may contribute to an increased risk of SSNHL in Taiwan.

The association of genetic polymorphisms in interleukin-1 receptors type 1 and type 2 with age-related hearing impairment in a Taiwanese population: a case control study.

BACKGROUND: Age-related hearing impairment (ARHI) is a major disability among the elder population. Chronic inflammation is an important factor in the development of ARHI. Interleukin-1 (IL-1) plays a key role in inflammation and may be associated with ARHI. The aim of this study is to analyze the associations of single nucleotide polymorphisms (SNPs) of IL-1 receptor genes with ARHI in an elderly population in Taiwan. METHOD: Participants ≥65 years of age were recruited for audiometric tests and genetic analyses. The bilateral pure-tone average (PTA) of high-tone hearing levels was calculated for ARHI evaluation. The associations of SNPs of the IL-1 receptor type 1 gene (IL1R1) (rs3917225 and rs2234650) and type 2 gene (IL1R2) (rs4141134 and rs2071008) with ARHI were analyzed in 182 ARHI-susceptible (case) and 176 ARHI-resistant (control) participants. RESULTS: The G allele of IL1R1 rs3917225 showed a decreased risk of ARHI after adjustments for sex, age, and noise exposure. The GG genotype of IL1R1 rs3917225 in all hereditary models and the TT genotype of IL1R2 rs2071008 in the recessive model also showed decreased risks of ARHI after adjustments. CONCLUSION: These findings suggest that IL1R1 and IL1R2 polymorphisms may contribute to the decreased risk of ARHI in the elderly population.

Autophagy Is Deficient and May be Negatively Regulated by SERPINB3 in Middle Ear Cholesteatoma.

HYPOTHESIS: Whereas autophagy has been linked to various human diseases, whether it also plays a role in cholesteatoma is virtually unknown. This study aimed to investigate the activity and regulation of autophagy in cholesteatoma. BACKGROUND: The treatment of middle ear cholesteatoma has been challenging due to an insufficient understanding of the underlying disease mechanism. METHODS: Expression of microtubule-associated protein 1A/1B-light chain 3 (LC3), the autophagy protein marker, and phosphorylated Akt (p-Akt), and mammalian target of rapamycin (p-mTOR), the known autophagy regulators, in fresh retroauricular skin and cholesteatoma tissue samples was analyzed by immunoblotting. The results were further confirmed by immunohistochemistry and statistical analyses. Cell proliferation of primary retroauricular skin- and cholesteatoma-derived fibroblasts was evaluated by methyl thiazol tetrazolium (MTT) assay. Ectopic expression of serine proteinase inhibitor, clade B, member 3 (SERPINB3) in the fibroblasts was achieved by electroporation and the expression was detected by immunoblotting. RESULTS: LC3 expression was significantly decreased in cholesteatoma in most of the 15 paired retroauricular skin/cholesteatoma tissue samples. However, p-Akt and p-mTOR expression in the cholesteatoma samples was not significantly different from that in the control subjects. Immunohistochemical studies further demonstrated an inverse correlation between LC3 expression and cholesteatoma. The cholesteatoma fibroblasts proliferated faster than the retroauricular skin fibroblasts, and had higher SERPINB3 but lower LC3 expression. Furthermore, overexpression of SERPINB3 in the retroauricular skin fibroblasts enhanced cell proliferation and downregulated LC3 expression. CONCLUSION: Autophagy is significantly suppressed in cholesteatoma tissues, which may not involve the Akt/mTOR signaling pathway. More importantly, SERPINB3 may promote cell proliferation and negatively regulate autophagy in cholesteatoma fibroblasts. Together, these findings warrant further investigation into the pathogenic mechanism of cholesteatoma.

Effect of manganese-superoxide dismutase genetic polymorphisms IVS3-23T/G on noise susceptibility in Taiwan.

PURPOSE: The aim of the study is to investigate the distribution of manganese-superoxide dismutase (SOD2) genetic polymorphisms IVS3-23T/G and their influence on noise susceptibility in Asians. MATERIALS AND METHODS: Questionnaires about history of noise exposure were administered to factory workers, and audiometric data and blood specimens were obtained during their routine annual health examinations. The SOD2 typing was extended with polymerase chain reaction and screened with single-strand conformation polymorphism. The associations of genetic polymorphisms with noise-induced hearing loss (NIHL) were analyzed. RESULTS: The allele frequencies of T and G in the population of this study were 0.868 and 0.132, respectively. In 200 screened participants, individuals with T/G genotype were significantly more vulnerable to noise (adjusted odds ratio, 6.222; 95% confidence interval, 1.498-25.855) than the wild type (ie, T/T) by logistic regressions. CONCLUSIONS: The distributions of SOD2 genetic polymorphisms for Asians are different from those reported on Europeans. Individuals with T/G genotype were more vulnerable to noise. This single nucleotide polymorphism is worthy of more studies for the application to NIHL monitoring.