Fabrication and Evaluation of Hyaluronidase-Responsive Scaffolds by Electrospinning with Antibacterial Properties for Tympanic Membrane Repair.

Tympanic membrane perforation (TMP) is prevalent in clinical settings. Patients with TMPs often suffer from infections caused by Staphylococcus aureus and Pseudomonas aeruginosa, leading to middle ear and external ear canal infections, which hinder eardrum healing. The objective of this study is to fabricate an enzyme-responsive antibacterial electrospun scaffold using poly(lactic-co-glycolic acid) and hyaluronic acid for the treatment of infected TMPs. The properties of the scaffold were characterized, including morphology, wettability, mechanical properties, degradation properties, antimicrobial properties, and biocompatibility. The results indicated that the fabricated scaffold had a core-shell structure and exhibited excellent mechanical properties, hydrophobicity, degradability, and cytocompatibility. Furthermore, in vitro bacterial tests and ex vivo investigations on eardrum infections suggested that this scaffold possesses hyaluronidase-responsive antibacterial properties. It may rapidly release antibiotics when exposed to the enzyme released by S. aureus and P. aeruginosa. These findings suggest that the scaffold has great potential for repairing TMPs with infections.

Transmastoid Facial Nerve Decompression for Craniometaphyseal Dysplasia.

OBJECTIVE: We document the first successful transmastoid surgical treatment of facial nerve palsy for a patient with craniometaphyseal dysplasia (CMD), a rare genetic disease. PATIENT: A 9-month-old girl with bilateral facial nerve palsies and conductive hearing loss. Genetic testing made a diagnosis of CMD, and imaging showed narrowing of the facial nerve canals and ossicular fixation. INTERVENTION: Right transmastoid facial nerve decompression and ossicular chain reconstruction. MAIN OUTCOME MEASURE: Facial nerve function (House-Brackmann grade). RESULTS: Facial nerve function initially worsened, then improved within 12 months from House-Brackmann grade IV-V to grade III. CONCLUSION: Surgical cranial nerve decompression of and ossicular chain reconstruction may be effective treatments for patients with CMD.

Butterfly Cartilage Tympanoplasty as an Alternative to Conventional Surgery for Tympanic Membrane Perforations: A Systematic Review and Meta-Analysis.

OBJECTIVE: To compare the effectiveness of butterfly cartilage tympanoplasty (BCT) with that of conventional surgical approaches in the treatment of tympanic membrane perforations. METHODS: A systematic search was performed by screening the PubMed, Embase, and Cochrane Library databases up to October 31, 2020. Two coauthors independently identified studies in accordance with the selection criteria. Data were pooled and analyzed via Review Manager version 5.3 and Stata version 12.0 software. The postoperative outcomes were measured and expressed as odds ratios (ORs) and standardized mean differences (SMDs). Additionally, heterogeneity was assessed through the I2 statistic. RESULTS: A total of 15 articles were eligible for final inclusion. The OR values for the graft uptake rate, compared to conventional tympanoplasty, were 1.12 (95%CI: 0.56-2.22, I2 = 52%, P = .75) and 1.22 (95%CI: 0.58-2.59, I2 = 0%, P = .60), and the OR compared to fat plug myringoplasty was 3.02 (95%CI: 1.04-8.77, I2 = 0%, P = .04). The qualitative analysis of the hearing results reflected significant postoperative auditory gains with no significant differences between the BCT and control groups, indicating satisfactory and similar postoperative hearing improvement. Moreover, the operation time was shortened (SMD = -2.19, 95%CI: -2.79 to -1.59, I2 = 82%, P < .05), and the postoperative pain was less with the BCT approach. CONCLUSION: Butterfly cartilage tympanoplasty has satisfactory efficacy in terms of anatomical and functional results in small to medium perforations. It reduces operation time and postoperative pain. However, the effectiveness on large perforation requires further assessment by well-designed studies.

Characterization of otologic symptoms appearing after COVID-19 vaccination.

OBJECTIVES: Anecdotal reports of sudden sensorineural hearing loss (SSNHL) following COVID-19 vaccination have emerged in the otolaryngology community. Studies have demonstrated no association between COVID-19 vaccination and SSNHL. We aim to characterize the spectrum of otologic symptoms following COVID-19 vaccination. METHODS: A cross-sectional study of patients seen in the otology clinic at an academic center was performed. Patients completed a questionnaire on the development of new otologic symptoms within 4 weeks of COVID-19 vaccination. Diagnostic and audiometric data was collected retrospectively for patients reporting otologic symptoms. RESULTS: Between May and July 2021, 500 patients were screened. Median age was 56.6 years old, with 59.4 % female and 40.2 % male. 420 patients (84.0 %) were vaccinated, with 58.4 % receiving Pfizer, 29.1 % receiving Moderna, and 3.8 % receiving Johnson & Johnson. 61 patients (14.5 %) reported one or more otologic symptoms within 4 weeks of vaccination, including 21 (5.0 %) with hearing loss, 26 (6.2 %) with tinnitus, 33 (7.9 %) with dizziness, and 19 (4.5 %) with vertigo. Of the 16 patients (3.2 %) reporting tinnitus with no associated hearing loss, 8 were diagnosed with subjective tinnitus and 4 were diagnosed with temporomandibular joint syndrome. Of the 18 patients reporting hearing loss, 11 had exacerbations of underlying pathologies (e.g. Meniere's disease, presbycusis) and 7 were newly diagnosed with SSNHL (1.4 %). CONCLUSIONS: Patients reporting otologic symptoms following COVID-19 vaccination received various diagnoses of uncertain etiology. The incidence of SSNHL in these patients is comparable to the general otology patient population. Additional studies are required to determine the incidence of specific diagnoses following vaccination.

Risk factors and management outcomes in epistaxis: a tertiary centre experience.

BACKGROUND: Risk factors and outcomes associated with severe epistaxis are not well understood. This study explores the associations between epistaxis severity, comorbidities, use of antiplatelets or anticoagulants and management outcomes. METHODS: This is a retrospective cross-sectional study of all epistaxis cases presenting to the emergency department at a tertiary academic hospital from January 2016 to December 2019. Epistaxis severity was defined as mild (no intervention), moderate (required cautery and/or packing) and severe (clinical instability with reversal products, surgical or radiological intervention). Univariable and multivariable regression analyses were undertaken, with risk factors and management outcomes analysed according to severity. RESULTS: A total of 543 patients with epistaxis (54.2% male, mean age 74.4 ± 15.7 years) were included in this study, with 14.7% (80) having severe epistaxis. Of these presentations 216 (39.8%) were on antiplatelets, while 207 (38.1%) were on anticoagulants. In univariate analyses, clopidogrel use, hereditary haemorrhagic telangiectasia (HHT), haematological malignancy, bleeding disorders and chronic liver disease (CLD) were associated with moderate to severe epistaxis (P < 0.05), while the use of rivaroxaban was inversely associated severity (P = 0.002). Only HHT, haematological malignancy and CLD remained significant in multivariate models. Cautery as first-line management was infrequently utilized while anticoagulation was frequently withheld. A longer length of stay (1.1 days vs. 4.3 days; P < 0.001) and higher 2-week readmission rates (2.2% vs. 12.5%; P < 0.001) were noted with severe epistaxis compared with mild presentations. CONCLUSION: Epistaxis severity is associated with certain clinical conditions and poor outcomes. Despite recommended guidelines, variations in first-line management were evident.

Instrumented insoles for assessment of gait in patients with vestibular schwannoma.

Background: Imbalance and gait disturbances are common in patients with vestibular schwannoma (VS) and can result in significant morbidity. Current methods for quantitative gait analysis are cumbersome and difficult to implement. Here, we use custom-engineered instrumented insoles to evaluate the gait of patients diagnosed with VS. Methods: Twenty patients with VS were recruited from otology, neurosurgery, and radiation oncology clinics at a tertiary referral center. Functional gait assessment (FGA), 2-minute walk test (2MWT), and uneven surface walk test (USWT) were performed. Custom-engineered instrumented insoles, equipped with an 8-cell force sensitive resistor (FSR) and a 9-degree-of-freedom inertial measurement unit (IMU), were used to collect stride-by-stride spatiotemporal gait parameters, from which mean values and coefficients of variation (CV) were determined for each patient. Results: FGA scores were significantly correlated with gait metrics obtained from the 2MWT and USWT, including stride length, stride velocity, normalized stride length, normalized stride velocity, stride length CV, and stride velocity CV. Tumor diameter was negatively associated with stride time and swing time on the 2MWT; no such association existed between tumor diameter and FGA or DHI. Conclusions: Instrumented insoles may unveil associations between VS tumor size and gait dysfunction that cannot be captured by standardized clinical assessments and self-reported questionnaires.

Identification of a cuproptosis-related lncRNA signature to predict the prognosis and immune landscape of head and neck squamous cell carcinoma.

Background: Cuproptosis is considered a novel copper-induced cell death model regulated by targeting lipoylated TCA cycle proteins. In this study, we established a novel signature based on cuproptosis-related lncRNAs (crlncRNAs) to predict the prognosis and immune landscape of head and neck squamous cell carcinoma. Methods: RNA-seq matrix, somatic mutation files, and clinical data were obtained from The Cancer Genome Atlas database. After dividing patients into two sets, a crlncRNA signature was established based on survival related crlncRNAs, which were selected by the univariate Cox analysis and least absolute shrinkage and selection operator Cox regression. To evaluate the model, Kaplan-Meier survival analysis and time-dependent receiver operating characteristic (ROC) were utilized, and a nomogram was established for survival prediction. Immune landscape analysis, drug sensitivity, cluster analysis, tumor mutation burden (TMB) and ceRNA network analysis were conducted subsequently. Results: A crlncRNA related prognosis signature was finally constructed with 12 crlncRNAs. The areas under the ROC curves (AUCs) were 0.719, 0.705 and 0.693 respectively for 1, 3, and 5-year's overall survival (OS). Patients in the low-risk group behaved a better prognosis, lower TMB, higher immune function activity and scores. In addition, patients from cluster 2 were more sensitive to chemotherapy and immunotherapy. Conclusion: In this study, we constructed a novel crlncRNA risk model to predict the survival of HNSCC patients. This reliable and acceptable prognostic signature may guide and promote the progress of novel treatment strategies for HNSCC patients.

Exploration of a predictive model based on genes associated with fatty acid metabolism and clinical treatment for head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent malignant tumors of the head and neck and presents high risks of recurrence and poor prognosis postoperatively. The aim of this study was to establish a predictive model based on fatty acid metabolism (FAM) genes to forecast the prognosis of HNSCC patients and the subsequent treatment strategies. METHODS: We accessed the TCGA and GEO databases for HNSCC genes and clinical data. The FAM risk score model was created and validated using a combination of univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) regression analysis. Combining risk scores and clinical characteristics, a nomogram was established and assessed. Subsequently, the function, gene mutation, immune difference, and chemotherapeutic drug sensitivity of the groups with high- and low-risk scores were analyzed. Consequently, the mode's validity was evaluated comprehensively by combining single gene analysis. RESULTS: The FAM risk score model for predicting HNSCC prognosis had certain validity. Patients in the high- and low-risk groups had genetic mutations, and the prognosis was the poorest for the high-risk groups with high genetic mutations. The patients with low-risk scores were suitable for immunotherapy since they had increased infiltration of immune cells. In contrast, the patients in the other groups were more suitable for chemotherapy. CONCLUSION: The results of this study demonstrated that the FAM risk score model may predict the prognosis of HSNCC and has a certain therapeutic guidance value.

Histopathology of Labyrinthitis Ossificans From an Intralabyrinthine Surgical Specimen.

OBJECTIVE: Histologic characterization of labyrinthitis ossificans (LO) has mostly been limited to postmortem samples. In this report, we describe the histology of LO from a surgical specimen obtained from a patient undergoing labyrinthectomy with simultaneous cochlear implantation. PATIENT: A 38-year-old woman initially presenting to the emergency room with acute vertigo, left-sided hearing loss, tinnitus, and aural fullness. INTERVENTIONS: Contrast-enhanced magnetic resonance imaging (MRI) and computerized tomography (CT) were performed for the patient before labyrinthectomy and cochlear implantation. Audiometric testing was performed before and after surgical intervention. Histologic analysis was performed on a specimen obtained from the left lateral semicircular canal (SCC) during surgery. MAIN OUTCOME MEASURES: Preoperative CT and MRI findings, preoperative and postoperative hearing thresholds via air conduction and bone conduction, hematoxylin and eosin (H&E) stain of the surgical sample, and CD45 immunostain of the surgical sample. RESULTS: Preoperative CT and MRI confirmed the diagnosis of isolated LO of the left lateral SCC. Audiometric testing revealed significant improvement in hearing after labyrinthectomy and cochlear implantation. H&E stain demonstrated fibrosis and ossification in the left lateral SCC, and CD45 immunostain was negative. CONCLUSIONS: Histopathology of LO based on a surgical sample is comparable to heterotopic ossification (HO) seen in other human tissue. Given the similarities between LO and HO, agents effective in preventing HO may have utility in preventing LO.

Construction of a necroptosis-related lncRNA signature to predict the prognosis and immune microenvironment of head and neck squamous cell carcinoma.

BACKGROUND: Previous studies have determined that necroptosis-related genes are potential biomarkers in head and neck squamous cell carcinoma (HNSCC). Herein, we established a novel risk model based on necroptosis-related lncRNAs (nrlncRNAs) to predict the prognosis of HNSCC patients. METHODS: Transcriptome and related information were obtained from TCGA database, and an nrlncRNA signature was established based on univariate Cox analysis and least absolute shrinkage and selection operator Cox regression. Kaplan-Meier analysis and time-dependent receiver operating characteristic (ROC) analysis were used to evaluate the model, and a nomogram for survival prediction was established. Gene set enrichment analysis, immune analysis, drug sensitivity analysis, correlation with N6-methylandenosin (m6A), and tumor stemness analysis were performed. Furthermore, the entire set was divided into two clusters for further discussion. RESULTS: A novel signature was established with six nrlncRNAs. The areas under the ROC curves (AUCs) for 1-, 3-, and 5-year overall survival (OS) were 0.699, 0.686, and 0.645, respectively. Patients in low-risk group and cluster 2 had a better prognosis, more immune cell infiltration, higher immune function activity, and higher immune scores; however, patients in high-risk group and cluster 1 were more sensitive to chemotherapy. Moreover, the risk score had negative correlation with m6A-related gene expression and tumor stemness. CONCLUSION: According to this study, we constructed a novel signature with nrlncRNA pairs to predict the survival of HNSCC patients and guide immunotherapy and chemotherapy. This may possibly promote the development of individualized and precise treatment for HNSCC patients.

Materials used for mastoid obliteration and its complications: a systematic review.

OBJECTIVE: The objectives of this review are to identify the types of materials with their associated complications and respective considerations when used to obliterate the mastoid cavity. METHODS: A systematic search was performed across PubMed, Embase, Medline and Cochrane databases from January 2009 to January 2020 for randomized controlled trials and observational studies of patients that underwent mastoid obliteration. Studies that fulfilled the inclusion criteria were screened and scored according to the MINORS and relevance scores to determine final inclusion. Types of complications were grouped into minor and major complications based on the Clavien-Dindo classification. RESULTS: Two thousand five hundred and seventy-eight ears were evaluated. There were a total of 165 (7.9%) minor and 142 (6.8%) major complications in the autologous group. Overall complication rate is 14.8%. The major complications were largely recurrent and residual disease requiring revision surgery. There were 10 (18.5%) minor complications and three (5.6%) major complications in the allogenic group. The cumulative complications risk is 24%. For the synthetic group, there were 39 (8.0%) minor and 34 (7.6%) major complications. The cumulative complication rate is 16.6%. CONCLUSION: Current evidence on materials for mastoid obliteration has been evolving. Each material has its strengths and limitations. The trend over the last decade favours the use of autologous materials. The principle of using a material remains being cautious of not reimplanting skin that can lead to the development of a cholesteatoma. The choice of materials is dependent on patient factors as well as the surgeons' preference and experience.

The possible mechanism of Hippophae fructus oil applied in tympanic membrane repair identified based on network pharmacology and molecular docking.

OBJECTIVE: This study aimed to explore the mechanisms of Hippophae fructus oil (HFO) in the treatment of tympanic membrane (TM) perforation through network pharmacology-based identification. METHODS: The compounds and related targets of HFO were extracted from the TCMSP database, and disease information was obtained from the OMIM, GeneCards, PharmGkb, TTD, and DrugBank databases. A Venn diagram was generated to show the common targets of HFO and TM, and GO and KEGG analyses were performed to explore the potential biological processes and signaling pathways. The PPI network and core gene subnetwork were constructed using the STRING database and Cytoscape software. A molecular docking analysis was also conducted to simulate the combination of compounds and gene proteins. RESULTS: A total of 33 compounds and their related targets were obtained from the TCMSP database. After screening the 393 TM-related targets, 21 compounds and 22 gene proteins were selected to establish the network diagram. GO and KEGG enrichment analyses revealed that HFO may promote TM healing by influencing cellular oxidative stress and related signaling pathways. A critical subnetwork was obtained by analyzing the PPI network with nine core genes: CASP3, MMP2, IL1B, TP53, EGFR, CXCL8, ESR1, PTGS2, and IL6. In addition, a molecular docking analysis revealed that quercetin strongly binds the core proteins. CONCLUSION: According to the analysis, HFO can be utilized to repair perforations by influencing cellular oxidative stress. Quercetin is one of the active compounds that potentially plays an important role in TM regeneration by influencing 17 gene proteins.

Tympanic membrane regeneration using platelet-rich fibrin: a systematic review and meta-analysis.

PURPOSE: Platelet-rich fibrin (PRF) results in satisfactory wound healing. This analysis focuses on assessing the effectiveness of PRF in the treatment of tympanic membrane (TM) perforations. MATERIALS AND METHODS: The literature was searched using PubMed, Embase, Cochrane Library and Web of Science databases from inception to February 28th, 2021. The following healing and hearing outcomes were measured: closure rate, pre-and postoperative auditory results, and incidence of postoperative infections. Data were pooled and expressed as the odds ratio (OR). RESULTS: Ten studies were eligible for qualitative review, and seven of them were included for the final quantitative comparison. The OR for the closure rate of acute perforations was 4.30 (95% CI 1.35-13.70, I2 = 0%), and the OR in the chronic subgroup was 5.42 (95% CI 2.57-11.43, I2 = 0%). The total OR value for the completed closure rate was 5.10 (95% CI 2.72-9.54, I2 = 0%), indicating that the utilization of PRF can enhance the closure of both acute and chronic perforations. The qualitative review did not find improved hearing results with the use of PRF. In addition to promoting closure, PRF can reduce the incidence of infections (OR = 0.14). The sensitivity analysis did not change the final results, and there was no publication bias in this analysis. CONCLUSION: PRF can increase the closure rate of acute perforations, enhance the survival rate of autografts in TM surgeries and reduce the incidence of infections. However, the literature indicates that PRF does not influence the hearing outcomes. This study shows that PRF is an effective agent for TM regeneration.

An unusual distribution of herpes zoster mandibularis post total parotidectomy.

This case report highlights an unusual presentation of herpes zoster mandibularis in an immunocompromised patient with previous head and neck surgery, with relative sparing of the cheek. It demonstrates the importance of critically considering past medical and surgical history in clinical diagnosis and management of the disease.

Acellular Collagen Scaffold With Basic Fibroblast Growth Factor for Repair of Traumatic Tympanic Membrane Perforation in a Rat Model.

OBJECTIVE: To evaluate the efficacy of acellular collagen scaffold (ACS) in combination with basic fibroblast growth factor (bFGF) for the repair of traumatic tympanic membrane (TM) perforation in a rat model. STUDY DESIGN: A prospective controlled animal study in a rat model of traumatic TM perforation. SETTING: Tertiary medical center. SUBJECTS AND METHODS: Sprague-Dawley rats (N = 84) with unilateral traumatic perforation of the right TMs were randomized to receive ACS, bFGF, ACS in combination with bFGF (ACS/bFGF), or nothing (spontaneous healing without any interventions as a control group). The healing outcomes were evaluated by otoscopy, optical coherence tomography, histology, and transmission electron microscopy at 1, 2, and 4 weeks postoperatively. The hearing outcomes were assessed with auditory brainstem response testing. RESULTS: ACS/bFGF resulted in higher perforation closure rates at an earlier stage than spontaneous healing, ACS, and bFGF. Based on histology, optical coherence tomography, and transmission electron microscopy, a trilaminar structure and uniform thickness with mature, densely packed collagen fibers were seen in the ACS/bFGF group. Auditory brainstem response evaluation also showed that ACS/bFGF treatment promoted faster functional hearing recovery as compared with the control group. CONCLUSIONS: ACS is an effective TM scaffold and a carrier for bFGF. ACS/bFGF improves the TM closure rate, results in better-reconstructed TMs, and improves hearing. ACS/bFGF serves as a potential substitute for TM perforations in clinical settings.

Angiotensin converting enzyme genotypes and mortality from COVID-19: An ecological study.

BACKGROUND: Angiotensin converting enzyme (ACE) genotypes are known to be associated with development of acute respiratory distress syndrome (ARDS) and resultant mortality. In the present study, we examined the association between distribution frequency of ACE genotypes and COVID-19 mortality. METHODS: We undertook an ecological study to examine the association between ACE genotypes and COVID-19 mortality across 25 countries to represent different geographical regions of the world. The population frequencies of ACE genotypes were drawn from previously published reports and data on COVID-19-related mortality were extracted from 'Worldometer'. Multivariable analyses were also undertaken adjusting for age (median age), sex (percentage of females) and the number of COVID-19 tests undertaken. Associations between genotypes deletion/deletion (DD) and insertion/insertion (II) prevalence and COVID-19-related mortality (per million people per day since the first diagnosed case) were evaluated. RESULTS: The frequency of II genotype is highest in east Asian countries and lower among the European and African countries. An inverse geographical distribution frequency was noted for DD genotype. Increasing II genotype frequency was significantly associated with decreased COVID-19 mortality rates (adjusted incident rate ratio [IRR] 0.3, 95% confidence interval [CI]: 0.002-0.7, p = 0.03). However, no association was found between DD genotype frequency and COVID-19 mortality rates (adjusted IRR 4.3, 95% CI: 0.5-41.2, p = 0.2). CONCLUSIONS: Distribution frequency of ACE insertion/insertion (II) genotype may have a significant influence on COVID-19 mortality. This information has potential utility for resource planning at a systemic level, as well as for clinical management.