Multidisciplinary approach in resection of stage IIIA lung cancer with severe aortic stenosis: A case report.

Thoracic surgery in the context of complex multimorbidity and clinical deterioration presents a unique set of challenges when balancing risk and benefit. Advances in anaesthesia, surgical technique, and imaging, have allowed for operative options for patients that were once deemed too high-risk. An effective proactive multi-disciplinary approach is essential for successful outcomes. We report the case of a 65-year-old patient with a background of severe aortic stenosis who underwent lung resection for stage IIIA lung cancer, where pivotal multi-disciplinary team input from the anaesthetic, surgery, critical care and radiology teams, clarified the cause of his clinical deterioration, contributed to decisions over his management and ensured a good clinical outcome.

healthcareCOVID: a national cross-sectional observational study identifying risk factors for developing suspected or confirmed COVID-19 in UK healthcare workers.

OBJECTIVE: To establish the prevalence, risk factors and implications of suspected or confirmed coronavirus disease 2019 (COVID-19) infection among healthcare workers in the United Kingdom (UK). DESIGN: Cross-sectional observational study. SETTING: UK-based primary and secondary care. PARTICIPANTS: Healthcare workers aged ≥18 years working between 1 February and 25 May 2020. MAIN OUTCOME MEASURES: A composite endpoint of laboratory-confirmed diagnosis of SARS-CoV-2, or self-isolation or hospitalisation due to suspected or confirmed COVID-19. RESULTS: Of 6,152 eligible responses, the composite endpoint was present in 1,806 (29.4%) healthcare workers, of whom 49 (0.8%) were hospitalised, 459 (7.5%) tested positive for SARS-CoV-2, and 1,776 (28.9%) reported self-isolation. Overall, between 11,870 and 21,158 days of self-isolation were required by the cohort, equalling approximately 71 to 127 working days lost per 1,000 working days. The strongest risk factor associated with the presence of the primary composite endpoint was increasing frequency of contact with suspected or confirmed COVID-19 cases without adequate personal protective equipment (PPE): 'Never' (reference), 'Rarely' (adjusted odds ratio 1.06, (95% confidence interval: [0.87-1.29])), 'Sometimes' (1.7 [1.37-2.10]), 'Often' (1.84 [1.28-2.63]), 'Always' (2.93, [1.75-5.06]). Additionally, several comorbidities (cancer, respiratory disease, and obesity); working in a 'doctors' role; using public transportation for work; regular contact with suspected or confirmed COVID-19 patients; and lack of PPE were also associated with the presence of the primary endpoint. A total of 1,382 (22.5%) healthcare workers reported lacking access to PPE items while having clinical contact with suspected or confirmed COVID-19 cases. CONCLUSIONS: Suspected or confirmed COVID-19 was more common in healthcare workers than in the general population and is associated with significant workforce implications. Risk factors included inadequate PPE, which was reported by nearly a quarter of healthcare workers. Governments and policymakers must ensure adequate PPE is available as well as developing strategies to mitigate risk for high-risk healthcare workers during future COVID-19 waves.

MESH1 is a cytosolic NADPH phosphatase that regulates ferroptosis.

Critical to the bacterial stringent response is the rapid relocation of resources from proliferation toward stress survival through the respective accumulation and degradation of (p)ppGpp by RelA and SpoT homologues. While mammalian genomes encode MESH1, a homologue of the bacterial (p)ppGpp hydrolase SpoT, neither (p)ppGpp nor its synthetase has been identified in mammalian cells. Here, we show that human MESH1 is an efficient cytosolic NADPH phosphatase that facilitates ferroptosis. Visualization of the MESH1-NADPH crystal structure revealed a bona fide affinity for the NADPH substrate. Ferroptosis-inducing erastin or cystine deprivation elevates MESH1, whose overexpression depletes NADPH and sensitizes cells to ferroptosis, whereas MESH1 depletion promotes ferroptosis survival by sustaining the levels of NADPH and GSH and by reducing lipid peroxidation. The ferroptotic protection by MESH1 depletion is ablated by suppression of the cytosolic NAD(H) kinase, NADK, but not its mitochondrial counterpart NADK2. Collectively, these data shed light on the importance of cytosolic NADPH levels and their regulation under ferroptosis-inducing conditions in mammalian cells.