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.

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.

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.

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.

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.

The Effectiveness of bFGF in the Treatment of Tympanic Membrane Perforations: A Systematic Review and Meta-Analysis.

OBJECTIVE: To investigate the effectiveness of basic fibroblast growth factor (bFGF) versus placebo or no intervention in the treatment of tympanic membrane (TM) perforations from randomized controlled trials (RCTs), prospective and retrospective studies. DATA SOURCES: PubMed, EMBASE, and Cochrane databases were screened from their inceptions to June 2019. STUDY SELECTION: Inclusion criteria: 1) English language; 2) observational (retrospective or prospective) or treatment (RCT) studies; 3) reported the outcomes on the application of bFGF in adult or pediatric population. EXCLUSION CRITERIA: 1) studies without a control group; 2) animal studies, in vitro studies, review studies, and case reports. DATA EXTRACTION: Number of patients, cause of TM perforation, perforation size, treatment, mean age, follow-up time, sex, closure rate, healing time, mean air-bone gap improvement. DATA SYNTHESIS: A total of 14 studies were included, including seven RCTs and seven non-RCTs with a total of 1,072 participants. The odds ratio for closure rate of bFGF treatment was 7.33 (95% confidence interval [CI], 4.65 to 11.53; p < 0.01; I = 44%) and the standardized mean difference (SMD) for healing time was -5.89 (95% CI: -7.85 to -3.93, p < 0.01, I = 98%), suggesting bFGF application has a significant effect on closure of TM perforations. However, no significant change in hearing (SMD: 0.08, 95% CI: -0.11 to 0.27, p = 0.39, I = 0%) was seen as a result of bFGF treatment. CONCLUSIONS: Our meta-analysis has revealed that the application of bFGF can significantly enhance the closure rate as well as shorten the healing time for TM perforations. In terms of hearing, there is as yet no evidence that bFGF has a significant effect. Given its ease, availability, and safety, bFGF can be used effectively for TM repair.

Can endoscopic ear surgery replace microscopic surgery in the treatment of acquired cholesteatoma? A contemporary review.

Acquired cholesteatoma leads to significant morbidities while current surgical options remain a challenge. The principles of surgery include complete removal of disease, prevention of recurrence, and restoration of hearing function when possible. Traditionally, this has been performed using microscopes; however, a novel technique using endoscopes offers a new perspective on our understanding of anatomy, pathogenesis and surgical approaches. In recent years, various studies have demonstrated good outcomes with transcanal endoscopic ear surgery (EES) in cholesteatoma surgery. Nevertheless, the use of EES is not universal and remains controversial due to the efficacy of microscopes, specific limitations of endoscopes and the need to learn new skills. This review focuses on recent advances in EES for the treatment of acquired cholesteatoma, benefits, current challenges, and a discussion on the indications and contraindications of EES.

Tympanic membrane repair using silk fibroin and acellular collagen scaffolds.

OBJECTIVES/HYPOTHESIS: To evaluate the efficacy of silk fibroin scaffolds (SFS) and acellular collagen scaffolds (ACS) for the repair of tympanic membrane (TM) in a guinea pig acute perforation model. STUDY DESIGN: Experimental animal research. METHODS: Seventy-two albino guinea pigs underwent perforation of the right TM and were divided into four experimental groups (n = 18). The perforations were repaired with SFS, ACS, and paper patch using onlay myringoplasty, or they were allowed to heal spontaneously (control). An additional group of 10 guinea pigs without perforation or scaffold was allocated as a normal TM group. Guinea pigs in each experimental group (n = 6) were evaluated at 7, 14, and 28 days following surgery. TM structural healing was evaluated by otomicroscopy and histology, and functional hearing was analyzed by auditory brainstem responses (ABR). Prior to the study, mechanical properties of SFS and ACS were investigated. RESULTS: Tensile strength and elasticity of SFS and ACS were within the known range for human TM. Based on otologic and histologic evaluation, TMs treated with SFS or ACS showed complete closure of the perforation at an earlier stage, with a trilaminar structure and more uniform thickness compared to paper patch and control treated groups. ABR assessment demonstrated that SFS or ACS treatment facilitated a faster restoration of hearing function compared to paper patch and control groups. CONCLUSION: The results of this study show that SFS and ACS are effective graft materials and may be utilized as alternatives to current grafts for TM repair.