Characterization and Clinical Significance of EIF1AX Mutations and Co-Mutations in Cytologically Indeterminate Thyroid Nodules: A 5-Year Retrospective Analysis.

OBJECTIVE: Mutations in the EIF1AX gene have been recently detected in a small percentage of benign and malignant thyroid lesions. We sought to investigate the prevalence and clinical significance of EIF1AX mutations and co-mutations in cytologically indeterminate thyroid nodules at our institution. MATERIALS AND METHODS: A 5-year retrospective analysis was performed on thyroid nodules with a cytologic diagnosis of Bethesda category III or IV, which had undergone testing by our in-house next generation sequencing panel. Surgically resected nodules with EIF1AX mutations were identified, and mutation type and presence of co-mutations were correlated with histopathologic diagnosis. RESULTS: 41/904 (4.5%) cases overall and 26/229 (11.4%) surgically resected nodules harbored an EIF1AX mutation. The most common histologic diagnoses were follicular thyroid carcinoma and follicular variant of papillary thyroid carcinoma. 11/26 (42.3%) of nodules had isolated EIF1AX mutation. Comutations were found in RAS (12/26; 46.2%), TERT (5/26; 19.2%) and TP53 (2/26; 7.7%). EIF1AX mutation alone conferred a 36.4% risk of malignancy (ROM) and 54.5% ROM or noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), while the ROM was significantly higher in nodules with concurrent RAS (71.4%), TERT, TP53 and RAS+TERT (100%) mutations. CONCLUSION: EIF1AX mutations occur in benign and malignant follicular thyroid neoplasms. In our cohort, the majority of mutations occurred at the splice acceptor site between exons 5 and 6. Importantly, the coexistence of EIF1AX mutations with other driver pathogenic mutations in RAS, TERT and TP53 conferred a 100% ROM or NIFTP, indicating that such nodules require surgical removal

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

A Primeval Mechanism of Tolerance to Desiccation Based on Glycolic Acid Saves Neurons in Mammals from Ischemia by Reducing Intracellular Calcium-Mediated Excitotoxicity

Stroke is the second leading cause of death and disability worldwide. Current treatments, such as pharmacological thrombolysis or mechanical thrombectomy, reopen occluded arteries but do not protect against ischemia-induced damage that occurs before reperfusion or neuronal damage induced by ischemia/reperfusion. It has been shown that disrupting the conversion of glyoxal to glycolic acid (GA) results in a decreased tolerance to anhydrobiosis in Caenorhabditis elegans dauer larva and that GA itself can rescue this phenotype. During the process of desiccation/rehydration, a metabolic stop/start similar to the one observed during ischemia/reperfusion occurs. In this study, the protective effect of GA is tested in different ischemia models, i.e., in commonly used stroke models in mice and swine. The results show that GA, given during reperfusion, strongly protects against ischemic damage and improves functional outcome. Evidence that GA exerts its effect by counteracting the glutamate-dependent increase in intracellular calcium during excitotoxicity is provided. These results suggest that GA treatment has the potential to reduce mortality and disability in stroke patients