No abstract

Tympanic membrane (TM) perforations are common, with current treatments for chronic perforations involving surgery, using various graft materials, from autologous cartilage or fascia through to paper patch. Recent research developments in this field have begun applying the principles of tissue engineering, with appropriate scaffolds, cells, and bioactive molecules (BMs). This has revolutionized the therapeutic approach due to the availability of a wide range of materials with appropriate compatibility and mechanical properties to regenerate the membrane acoustics and may also represent a paradigm shift in the management of TM perforations in an outpatient setting without surgery. However, many factors need to be considered in the fabrication of a bioengineered TM. This review discusses the issues associated with current treatment and examines TM wound healing relevant to the construction of a bioengineered TM. It also describes the tissue-engineering approach to TM regeneration by summarizing currently used scaffolds, BMs, and cells in TM wound healing. Finally, it considers the design of scaffolds, delivery of BMs, and cell engraftment toward potential clinical application.

Tympanic membrane (TM) perforations lead to significant hearing loss and result in possible infection of the middle ear. Myringoplasty is commonly performed to repair chronic perforations. Although various grafts and materials have been used to promote TM regeneration, all have associated limitations. The aim of this study was to evaluate the efficacy and feasibility of two graft materials, silk fibroin scaffold (SFS) and porcine-derived acellular collagen type I/III scaffold (ACS), compared with two commonly used graft materials (paper patch and Gelfoam) for the promotion of TM regeneration. These scaffolds were implanted using on-lay myringoplasty in an acute TM perforation rat model. Surface morphology of the scaffolds was observed with scanning electron microscopy. The morphology of the TM was assessed at various time points postimplantation using otoscopy, light and electron microscopy, and functional outcomes by auditory brainstem responses. We found that SFS and ACS significantly accelerated the TM perforation closure, obtained optimal TM thickness, and resulted in better trilaminar morphology with well-organized collagen fibers and early restoration of hearing. However, paper patch and Gelfoam lost their scaffold function in the early stages and showed an inflammatory response, which may have contributed to delayed healing. This study indicates that compared with paper patch and Gelfoam, SFS and ACS are more effective in promoting an early TM regeneration and an improved hearing, suggesting that these scaffolds may be potential substitutes for clinical use.

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.

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Middle ear packing agents are used in otologic surgery to provide support to the middle ear structures, maintain aeration of the middle ear, and promote hemostasis. However, there is currently a lack of standardization regarding the use of different types of packing agents. The choice of materials and how they are used remain controversial. In fact, some have recently advocated for no packing. In view of this, this review focuses on the types of materials available, a brief historical account of each material, characteristics of an ideal packing agent, and a discussion on the techniques of insertion to optimize surgical outcomes.

The purpose of this study was to investigate the risk factors for central and lateral neck lymph node metastases in papillary thyroid carcinoma (PTC) and multifocal papillary thyroid carcinoma (MPTC), particularly when associated with Hashimoto thyroiditis (HT).A retrospective analysis of 763 consecutive patients who underwent total thyroidectomy with bilateral central neck dissection in the First Affiliated Hospital, College of Medicine, Zhejiang University between October 2011 and October 2014 was conducted. All patients had formal histological diagnoses of HT. Multivariable logistic regression analysis was performed to identify risk factors of neck lymph node metastases.Our study identified 277 PTC patients with HT and showed comparatively low rates of central lymph node metastases (CLNM) compared with the PTC patients without HT (37.2% versus 54.7%, P < 0.001). There were no statistically significant differences in lateral lymph node metastases (LLNM) (P = 0.656). Neck lymph node metastases were histologically proven in 127 (45.8%) patients with PTC with HT, including 103 CLNM and 24 LLNM. There were no significant differences in LLNM between the MPTC-associated HT and classic MPTC cases; however, a significantly reduced risk of CLNM was observed in the MPTC-associated HT compared with the MPTC cases (35.7% versus 72.4%, respectively, P < 0.001). In the multivariate analysis, HT was identified as an independent alleviating factor for CLNM in all PTC patients (odds ratio, 0.369; 95% confidence interval (CI), 0.261 to 0.521; P < 0.001) and in MPTC patients (odds ratio, 0.227; 95% CI, 0.126–0.406; P < 0.001). A cut-off of thyroid peroxidase antibody >140 IU/mL was established as the most sensitive and specific level for the prediction of MPTC based on receiver operating characteristic curve analyses. Thyroid peroxidase antibody, age, tumor size, and multifocality exhibited the ability to predict CLNM in PTC with HT patients with an area under the curve of 81.1% based on a multivariate model.Hashimoto thyroiditis was associated with increased prevalences of multifocality and capsular invasion. In contrast, HT was associated with a reduced risk of CLNM in PTC and MPTC patients, which indicated a potential protective effect. We found that the prognostic prediction model was applicable for predicting multifocality and CLNM in PTC patients with HT.

Benzene is myelotoxic and leukemogenic in humans. The mechanisms leading to these effects, however have not been fully elucidated. One of the underlying mechanisms is believed to be the oxidative damage caused by its metabolites. A comparative study was undertaken to examine the relationships between reactive oxygen species (ROS) production, lipid peroxidation and subse quent cytotoxicity induced by five major benzene meta bolites. The generation of ROS by benzene metabolites was demonstrated by the significant and dose-dependent increase of intracellular ROS formation in HL60 human promyelocytic leukemia cells in vitro. 1,4-Benzoquinone (BQ) was found to be the most potent metabolite in induction of ROS formation, followed by 1,2,4-benzene triol (BT) and to a lesser extent, phenol (PH) and trans, trans-muconaldehyde (MD). No significant effect was observed when the cells were treated with trans, trans-muconic acid (MA). The enhancement of ROS production by BQ was effectively inhibited by the addition of catalase, deferoxamine (DFO) and dimethyl sulfoxide (DMSO), but unchanged by superoxide dismutase (SOD), suggest that hydrogen peroxide (H2O2) and hydroxyl radicals (OH.) are the two major forms of ROS involved. The results also demonstrate that the ability of benzene metabolites in enhancing ROS generation is closely correlated to their capacity in causing lipid peroxidation and subsequent cytotoxicity. These findings together with earlier parallel observations on DNA damage suggest that ROS play an important role in the mechanism of carcinogenesis induced by benzene metabolites.