Ototoxicity among cisplatin, carboplatin, and oxaliplatin in zebrafish model.

Platinum-based antineoplastic drugs, including cisplatin, carboplatin, and oxaliplatin, are widely used in the treatment of various cancers. Ototoxicity is a common adverse effect of platinum-based drugs. Ototoxicity leads to irreversible hearing impairment. We hypothesize that different platinum-based drugs exhibit varying ototoxic concentrations, time effects, and ototoxic mechanisms. We tested this hypothesis by using a zebrafish model (pvalb3b: TagGFP) to assess the viability of hair cells collected from zebrafish larvae. Cisplatin, carboplatin, and oxaliplatin were administered at dosages of 100, 200, or 400 µM, and the ototoxic effects of these drugs were assessed 1, 2, or 3 h after administration. Fm4-64 and a TUNEL assay were used to label the membranes of living hair cells and to detect cell apoptosis, respectively. We observed that >50% of hair cells were damaged at 1 h after cisplatin (100 µM) exposure, and this ototoxic effect increased at higher dosages and over time. Owing to the smaller ototoxic effects of carboplatin and oxaliplatin, we conducted higher-strength and longer-duration experiments with these drugs. Neither carboplatin nor oxaliplatin was obviously ototoxic, even at 1600 µM and after 6 h. Moreover, only cisplatin damaged the membranes of the hair cells. Cell apoptosis and significantly increased antioxidant gene expression were observed in only the cisplatin group. In conclusion, cisplatin significantly damages sensory hair cells and has notable dosage and time effects. Carboplatin and oxaliplatin are less ototoxic than cisplatin, likely due to having different ototoxic mechanisms than cisplatin.

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.

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.

Endoscopic atticotomy for attic cholesteatomas using piezosurgery.

BACKGROUND: Attic cholesteatomas can be exenterated by transcanal endoscopic ear surgery (TEES). In the limited operative field of exclusive transcanal endoscopic atticotomy, surgeons use either a piezosurgery scalpel or a drilling system to remove the posterior lateral bony wall of the epitympanum. We aimed to investigate the feasibility of using piezosurgery or microdrill for endoscopic atticotomy during exenteration of attic cholesteatomas. METHODS: This study is a retrospective chart review of patients diagnosed with attic cholesteatoma, who were treated by exclusive TEES. The superior and posterior external auditory canal bones were excised using a piezosurgery scalpel or microdrill. Preoperative and postoperative hearing thresholds were measured by pure-tone audiometry. RESULTS: The postoperative follow-up duration varied from 6 to 37 months. There were no significant differences in age, sex, laterality of the affected ear, and preoperative bone conduction thresholds between the piezosurgery scalpel and microdrill groups. The operative duration was longer in the piezosurgery group than in the microdrill group (135.6 ± 19.5 minutes vs 117.3 ± 29.1 minutes, p = 0.042). Seven of 30 (23.3%) patients in the microdrill group, but none in the piezosurgery group, had a friction injury from the drilling. Postoperative testing at higher frequencies of 2000, 3000, and 4000 Hz showed no deterioration in the bone conduction threshold in the piezosurgery group. CONCLUSION: Endoscopic atticotomy performed using a piezosurgery scalpel is potentially safer but slower than using a microdrill for exenteration of attic cholesteatomas.

The differential impact of Type D personality on the prognosis of patients with stable coronary artery disease.

OBJECTIVE: This study investigated the association between Type D personality and prognoses in stable coronary artery disease (CAD) patients by mode of endpoints, age, and methodological debates to explain substantial heterogeneity among Type D studies. DESIGN: The prospective study was designed to recruit 590 stable CAD patients in Taiwan. Main outcome measures: Demographic and clinical characteristics, and the 14-item Type D scale-Taiwanese version were recorded at discharge. RESULTS: Hierarchical logistic regression analyses showed, regardless of the methodological debates, Type D personality was significantly associated with MACEs though not non-cardiac outcomes in stable CAD patients after adjusting for possible confounders. Furthermore, Type D personality was especially associated with MACEs in stable CAD patients with younger age (<65 y), rather than older age (≥65 y). Subgroup analysis also showed the adverse effect of Type D personality on MACEs was larger among males, those living in the rural region, those with PTCA or stent, those with heart failure, hypertension, diabetes, and those who were smokers. CONCLUSIONS: Regardless of whether the methodological debate is dichotomous or continuous, Type D personality was significantly associated with MACEs in stable CAD patients, some of whom had younger age, were males, smokers, or had comorbidities.

Growth Regulated Oncogene-α Upregulates TNF-α and COX-2 and Activates NOD1/RIPK2 mediated-MAPK Pathway in Head and Neck Squamous Cell Carcinoma.

Purpose: The long-term prognosis and survival rate of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) are poor, although the identification of specific biomarkers that reveal its nature and aggressiveness has improved it. Growth-related oncogene alpha (Groα) and NOD1 (nucleotide-binding oligomerization domain 1) can be used as prognosis markers to identify subgroups of HNSCC patients with low survival rates and as potential therapeutic targets for HNSCC patients. However, the mechanism associated with the Groα-mediated NOD pathway in HNSCC progression remains unclear. Method: Overall survival analysis and multiple-gene comparison were analyzed using Gene Expression Profiling Interactive Analysis (GEPIA). qRT-PCR and RT-PCR were used to analyze mRNA expression. Microarray, immunofluorescence staining or western blot analyses were carried out to detect protein expression. Results: Groα was significantly higher in the grade 4 HNSCC tumor tissues compared with that in grade 1-3 and healthy subjects. High expression of Groα, NOD1 and RIPK2 (receptor-interacting serine-threonine kinase 2) is correlated with survival rate in HNSCC patients. Treatment of SCC25 and OECM-1 cells with Groα increased the expression of NOD1 and RIPK2 in a concentration-dependent manner. The findings herein reveal the association of Groα, NOD1 and RIPK2 biomarkers with HNSCC carcinogenesis. Moreover, Groα is the major stimulus of inflammatory mediation and promotes TNF-α (tumor necrosis factor-α) and COX-2 (cyclooxygenase-2) expression in HNSCC. Groα induces TNF-α and COX-2 expression through regulation involving ERK (extracellular signal-regulated kinase)-, JNK (C-Jun N-terminal kinase)- and p38 MAPK (mitogen-activated protein kinase)-dependent signaling pathways. Conclusions: Our findings herein constitute the first evidence that Groα is important in HNSCC progression and metastasis via the NOD1-mediated MAPK pathway, suggesting a role for Groα and NOD1 in mediating metastasis and its potential as a therapeutic target.

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.

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.

Growth regulated oncogene-α contribute to EMT/MMPs pathway by binding its receptors in head and neck squamous cell carcinoma.

Squamous cell carcinoma (SCC) is the most common malignant tumor of the head and neck and generally detected in the late stages when the cancer has advanced, and therefore has a poor prognosis and survival rate. A high expression of growth-related oncogene alpha (Groα) is associated with tumor metastasis and invasion and the poor survival rate of patients. Microarray reveals that Groα exhibits a cancer-specific response in HNSCC. Quantitative real-time PCR (qRT-PCR) results concerning the mRNA expression of Groα in HNSCC tissues; indicate that Groα was more highly expressed in HNSCC than in non-cancerous matched tissue (NCMT). The serum of HNSCC patients and healthy subjects demonstrates that the expression of Groα in the HNSCC patients significantly exceeded than in healthy subjects. Furthermore, exposure Groα to stimulated the proliferation, clonogenicity and migration with HNSCC cells (SCC4, SCC9, SCC25 and OECM-1), yielding a stronger response than in non-malignant HaCaT and DOK cells. A high expression of Groα and its receptors CXCR1/2 (chemokine (C-X-C motif) receptor) in HNSCC tissues are highly correlated with tumor progression stage and metastasis. Following the treatment of SCC25 and OECM-1 cells with Groα, ß-catenin, matrix metalloproteinases (MMP)-2, MMP-7 and MMP-9 expressions significantly increased but E-cadherin expression was slightly decreased, suggesting that the EMT and metastasis processes were activated by Groα. These findings constitute the first evidence that Groα promotes epithelial mesenchymal transition (EMT) and MMPs expressions in HNSCC via activating CXCR1/2, suggesting a role for Groα in mediating metastasis and its potential as a therapeutic target.

The impact of sources of perceived social support on readmissions in patients with heart failure.

BACKGROUND: Lower levels of perceived social support have been known as an independent predictor of hospital readmissions in patients with heart failure (HF). However, the impact of sources of perceived social support on readmissions remain unexplored. PURPOSE: The main purpose of this study was to investigate and compare the relative importance of social support from significant other, family, and friends on all-cause readmission and cardiac readmission in patients with HF. METHODS: The prospective cohort study was used to recruit a total of 299 patients with HF in Taiwan between May 2012 and December 2014. Demographic and clinical characteristics, Multidimensional Perceived Social Support Scale (MPSSS), and 18-month follow-up readmissions were recorded during the hospital stay. Univariate and multivariate logistic regressions were constructed to determine the impact of levels and sources of perceived social support with all-cause readmission and cardiac readmission. RESULTS: A total of 158 patients (52.8%) and 118 patients (39.5%), respectively, had all-cause readmission and cardiac readmissions within 18 months. Multivariate logistic regression yielded inverse associations between levels of perceived social support and readmissions by 18-months. Importantly, social support from significant other was significantly associated with a lower risk of readmissions, both of all-cause readmission and cardiac readmission, in patients with HF, even after controlling for possible covariates, social support from family and friends. CONCLUSIONS: Social support from significant other, rather than from family and friends, was relatively and inversely associated with 18-month all-cause readmission and cardiac readmission in patients with HF, which is consistent with the hierarchical compensatory model.

Cochlear Implantation Hearing Outcome in Ménière's Disease.

OBJECTIVE: The aim of this study was to evaluate the hearing outcome of cochlear implantation in patients deafened by Ménière's disease. STUDY DESIGN: Retrospective single-institution study. SETTING: Tertiary medical center. METHODS: Our institutional database of 1400 patients with cochlear implants was reviewed to identify cases with deafness due to Ménière's disease. Twenty-nine patients were identified: 24 with unilateral and 5 with sequential bilateral cochlear implants. Pre- and postoperative speech recognition scores and medical data were extracted from the medical record and analyzed. RESULTS: Overall the mean difference between pre- and postoperative speech recognition after >1 year was 56% (95% CI, 47.08%-64.92%). The mean preoperative monosyllabic word score was 9.5%, and the mean postoperative scores at 1 month, 3 months, 6 months, 1 year, and >1 year were 37.1%, 46.1%, 54.1%, 59.1%, and 66.8%, respectively. Cochlear implantation resulted in improved word scores in all patients regardless of prior medical or surgical treatment (endolymphatic sac, labyrinthectomy). The mean postoperative hearing improvement in patients aged <70 and ≥70 years was 65.26% (95% CI, 54.79%-75.73%) and 40.00% (95% CI, 27.22%-52.77%). Postoperative word scores in patients with bilateral cochlear implants were not significantly different between the first and second implanted ears or between the monoaural and binaural testing conditions. CONCLUSION: Cochlear implant in patients deafened by Ménière's disease significantly improves word recognition scores regardless of whether medical or surgical treatment is used prior to implantation. The potential improvement in word recognition scores decreases after age 70 years.

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 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.

Association of sudden sensorineural hearing loss with dementia: a nationwide cohort study.

BACKGROUND: Impaired cochlear blood perfusion and microvascular damage can cause sudden sensorineural hearing loss (SSHL), which is a potential risk factor for dementia. This study explored the association between SSHL and dementia. METHODS: This retrospective cohort study used a random sample of 1000,000 individuals from Taiwan's National Health Insurance Research Database. We identified 3725 patients newly diagnosed with SSHL between January 1, 2000, and December 31, 2009, and propensity score matching according to age, sex, index year, comorbidities, and medications was used to select the comparison group of 11,175 patients without SSHL. Participants were stratified by age (<65 and ≧65 years) and sex for the subgroup analyses. The outcome of interest was all cause dementia (ICD-9-CM codes 290.0, 290.4, 294.1, 331.0). Both groups were followed up until December 31, 2010, for diagnoses of dementia. Cox regression models were used to estimate the hazard ratio (HR) of dementia. RESULTS: During the average 5-year follow-up period, the incidence rate of dementia in the SSHL cohort was 6.5 per 1000 person-years compared with 5.09 per 10,000 person-years in the comparison group. After adjustment for potential confounders, patients with SSHL were 1.39 times more likely to develop dementia than those without SSHL (95% confidence interval = 1.13-1.71). When stratified by patients' age and sex, the incidence of dementia was 1.34- and 1.64-fold higher in patients with SSHL aged ≥65 years (P = .013) and in women (P = .001), respectively, compared with the comparison group. Women with SSHL who were < 65 years old had the highest risk (2.14, 95% CI = 1.17-4.11, P = .022). In addition, a log-rank test revealed that patients with SSHL had significantly higher cumulative incidence of dementia than those without SSHL (P = .002). CONCLUSIONS: Patients with SSHL, especially women aged < 65 years, were associated with higher risk of dementia than those without SSHL. Thus, clinicians managing patients with SSHL should be aware of the increased risk of dementia.

Endoscopic transcanal removal of external auditory canal osteomas.

BACKGROUND: External auditory canal (EAC) osteomas are rare, slow-growing benign neoplasms. Microscopic surgical excision had been reported for symptomatic osteomas. However, there was no study published on the feasibility of transcanal endoscopic ear surgery (TEES) for EAC osteoma. In this study, we propose two methods of TEES for symptomatic EAC osteomas and report the surgical outcomes of our patients. METHODS: Fifteen patients diagnosed with symptomatic EAC osteoma who underwent TEES were recruited at two otolaryngology referral centers. The extent of osteoma and degree of EAC stenosis was calculated based on high-resolution computed tomography (HRCT) imaging. We divided all the patients into two groups, solitary pedunculated osteoma or broad-based osteomas. The postoperative outcomes and complications were recorded for at least 6 months of outpatient follow-up. RESULTS: In this study, twelve patients with solitary osteoma underwent the first method, a direct transcanal removal procedure. In this approach, only a small bare bony area remained postoperatively, and it healed completely within 1 month. Three patients with broad based osteoma underwent the second method, a transcanal approach involving a skin flap. The degree of stenosis in all patients ranged from 29% to 90%. All of them could be treated completely through a transcanal endoscopic approach. No intraoperative or postoperative complications were noted during follow-up, and no canal stenosis and no recurrences were noted during at least 6 months of follow-up. CONCLUSIONS: This endoscopic transcanal approach to EAC osteomas demonstrated good results for lesion removal without recurrence or intraoperative complications.

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.

Ester-mediated peptide formation promoted by deep eutectic solvents: a facile pathway to proto-peptides.

The ester-amide exchange reaction enables spontaneous formation of prebiotic proto-peptides under mild conditions. However, this reaction also leads to oligomers with a vast sequence diversity of ester and amide linkages. Here, we demonstrate using deep eutectic solvents as a universal strategy to regulate the reaction pathways and promote the formation of amino acid-enriched oligomers with peptide backbones.

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.