Opinion statement: Temporal bone paragangliomas (TBPs) are indolent, classically benign and highly vascular neoplasms of the temporal bone. There are two types of TBPs, tympanomastoid paragangliomas (TMPs) and tympanojugular paragangliomas (TJPs). The most common symptoms are hearing loss and pulsatile tinnitus. Diagnostic workup, besides conventional physical and laboratory examinations, includes biochemical testing of catecholamine and genetic testing of SDHx gene mutations as well as radiological examination. Although surgery is traditionally the mainstay of treatment, it is challenging due to the close proximity of tumor to critical neurovascular structures and thus the high risk of complications, especially in patients with advanced lesions. Radiotherapy and active surveillance have been increasingly recommended for selected patients. Decision on treatment should be made comprehensively. Curative effect depends on various factors. Long-term follow-up with clinical, laboratory, and radiological examinations is essential for all patients.

Opinion statement: Malignant tumors of the external auditory canal (EAC) are rare tumors in the head and neck. Delayed diagnosis is not uncommon because the symptoms of early tumors are nonspecific. Various surgical and oncological treatment modalities have been reported. Decision-making depends on pathological feature and stage of the lesions, patient’s general condition and preference, and physician’s experience and skill. Radical surgery is widely accepted as the primary treatment of choice. Postoperative radiotherapy is used more often to improve local and regional control of the disease. Chemotherapy is usually recommended for advanced disease, residual disease, and metastasis. Prognosis is affected by multiple factors such as TNM stage, surgical margin, pathological type and differentiation of tumor, involvement of facial nerve, and so on. Although the survival rate is improved significantly over the past several decades with the development of skull base surgery, neuroradiology, anesthesiology, and oncology, it remains challenging to diagnose and treat EAC malignancies due to the rarity, the local anatomical complexity of temporal bone, and the lack of standard TNM staging system.

It has been demonstrated that the epithelial sodium channel (ENaC) may play critical roles in (re)absorbing Na+ from apical plasma membrane in various tissues and cells. Moreover, the serum glucocorticoid-inducible kinase 1 (SGK1) and the ubiquitin-protein ligase neural precursor cell-expressed, developmentally downregulated isoforms Nedd4 are involved in ENaC regulation in response to hormones such as aldosterone, vasopressin and insulin. The aim of the study was to investigate the cellular localizations of ENaC subunits, SGK1, and Nedd4 isoforms in the cochlea of guinea pig. Ten adult guinea pigs were sacrificed and their cochleas were collected. The expression patterns of ENaC subunits, SGK1 and Nedd4-2 isoforms in the guinea pig cochlea were studied by immunohistochemistry with the specific polyclonal rabbit antibodies against rat α-, β- and γ-ENaC, SGK1, Nedd4-1/2 and Nedd4-2. The results showed that all these proteins were extensively expressed in various regions of the cochlea. They were found in the spiral ligament, organ of Corti, spiral limbus, spiral ganglion and Reissner's membrane with different staining patterns. The results indicated that a Na+ transport system may exist in the cochlea of guinea pig consisting of ENaC, SGK1 and Nedd4, which may work in concert to transport Na+ and to maintain homeostasis in inner ear as it does in other epithelia.

Objective: The etiology of sudden sensorineural hearing loss (SSNHL) is still unknown. It has been demonstrated that normal endolymph metabolism is essential for inner ear function and that epithelial sodium channels (ENaC) may play an important role in the regulation of endolymphatic Na⁺. This study aimed to explore the potential association between αENaC p. Ala663Thr gene polymorphism and SSNHL.Methods: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to examine the genotype and allele frequency of the αENaC p. Ala663Thr polymorphism in 20 cases of low-frequency SSNHL (LF-SSNHL), 19 cases of high-frequency SSNHL (HF-SSNHL), 31 cases of all frequency SSNHL (AF-SSNHL), 42 cases of profound deafness SSNHL (PD-SSNHL), and 115 normal controls.Results: The T663 allele was found to be significantly associated with an increased risk of LF-SSNHL (p = 0.046, OR = 2.16, 95% CI = 1.01–4.62). The TT genotype and T663 allele, on the other hand, conferred a protective effect for PD-SSNHL (AA vs. TT: p = 0.012, OR = 0.25, 95% CI = 0.08–0.74; A vs. T: p = 0.001, OR = 0.36, 95% CI = 0.21–0.61). However, there was no statistically significant difference in genotype or allele frequency between the two groups (HF-SSNHL and AF-SSNHL) and the control group.Conclusion: The αENaC p. Ala663Thr gene polymorphism plays different roles in different types of SSNHL.

Background: Observational studies have indicated a potential association between thyroid dysfunction and the risk of sudden sensorineural hearing loss (SSNHL). However, the precise causal relationship between the two remains uncertain. The objective of our study was to assess the causal influence of thyroid function on SSNHL by employing a bidirectional and multivariable Mendelian randomization (MR) approach.Methods: Single-nucleotide polymorphisms (SNPs) associated with free thyroid (FT4) and thyroid stimulating hormone (TSH) were selected from the summary data of a large genome-wide association study (GWAS) conducted on European individuals. The summary-level data of SSNHL were also obtained from a GWAS, which included 196,592 participants (1,491 cases and 195,101 controls). The MR analysis primarily utilized the inverse variance weighted (IVW) method, with sensitivity analyses performed using the weighted median, MR-Egger, and MR-PRESSO approaches.Results: In the IVW method, an elevated genetically predicted FT4 level was found to effectively reduce the risk of SSNHL (OR = 0.747, 95% CI = 0.565–0.987, P = 0.04). These findings were consistent when conducting multivariate MR analysis, which adjusted for TSH levels (OR = 0.929, 95% CI = 0.867–0.995, P = 0.036). However, genetically predicted TSH levels did not emerge as a risk factor for SSNHL (OR = 1.409, 95% CI = 0.895–1.230, P = 0.547). Furthermore, even after adjusting for FT4 levels in the multivariate MR analysis, no evidence of a direct causal relationship between TSH levels and the risk of SSNHL was observed (OR = 1.011, 95% CI = 0.880–1.161, P = 0.867). The reverse MR analysis showed that there was no evidence of a direct causal relationship between SSNHL and the risk of FT4 level (OR = 1.026, 95% CI = 0.999–1.054, P = 0.056) or TSH level (OR = 1.002, 95% CI = 0.989–1.015, P = 0.702).Conclusion: Within the normal range, genetic variants associated with higher FT4 levels demonstrate a potential protective effect against SSNHL, whereas there is no direct causal relationship between TSH levels and the risk of SSNHL.