Fragments of the mitochondrial genome released into the systemic circulation after mechanical trauma, termed mitochondrial DNA damage-associated molecular patterns (mtDNA DAMPs), are thought to mediate the systemic inflammatory response syndrome. The close association between circulating mtDNA DAMP levels and outcome in sepsis suggests that bacteria also might be a stimulus for mtDNA DAMP release. To test this hypothesis, we measured mtDNA DAMP abundance in medium perfusing isolated rat lungs challenged with an intratracheal instillation of 5 × 10(7) colony-forming units of Pseudomonas aeruginosa (strain 103; PA103). Intratracheal PA103 caused rapid accumulation of selected 200-bp sequences of the mitochondrial genome in rat lung perfusate accompanied by marked increases in both lung tissue oxidative mtDNA damage and in the vascular filtration coefficient (Kf). Increases in lung tissue mtDNA damage, perfusate mtDNA DAMP abundance, and Kf were blocked by addition to the perfusion medium of a fusion protein targeting the DNA repair enzyme Ogg1 to mitochondria. Intra-arterial injection of mtDNA DAMPs prepared from rat liver mimicked the effect of PA103 on both Kf and lung mtDNA integrity. Effects of mtDNA and PA103 on Kf were also attenuated by an oligodeoxynucleotide inhibitor of Toll-like receptor 9 (TLR-9) by mitochondria-targeted Ogg1 and by addition of DNase1 to the perfusion medium. Collectively, these findings are consistent with a model wherein PA103 causes oxidative mtDNA damage leading to a feed-forward cycle of mtDNA DAMP formation and TLR-9-dependent mtDNA damage that culminates in acute lung injury.

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SummaryA patient with a twin pregnancy required a Caesarean section for severe pre-eclampsia. Her platelet count was 71 × 10 9 .l À1 . Epidural anaesthesia was performed after platelet transfusion. A spinal epidural haematoma was diagnosed postoperatively. A generalised tonic-clonic seizure sparing the lower limbs enabled early diagnosis to be made. The patient recovered with no permanent neurological damage after laminectomy and clot removal. The risks and benefits of regional techniques require careful consideration, and postoperative monitoring for recovery of neural blockade is essential.

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.

The impact of vaccination and new SARS-CoV-2 variants on peri-operative outcomes is unclear. We aimed to update previously published consensus recommendations on timing of elective surgery after SARS-CoV-2 infection to assist policymakers, administrative staff, clinicians and patients. The guidance remains that patients should avoid elective surgery within 7 weeks of infection, unless the benefits of doing so exceed the risk of waiting. We recommend individualised multidisciplinary risk assessment for patients requiring elective surgery within 7 weeks of SARS-CoV-2 infection. This should include baseline mortality risk calculation and assessment of risk modifiers (patient factors; SARS-CoV-2 infection; surgical factors). Asymptomatic SARS-CoV-2 infection with previous variants increased peri-operative mortality risk three-fold throughout the 6 weeks after infection, and assumptions that asymptomatic or mildly symptomatic omicron SARS-CoV-2 infection does not add risk are currently unfounded. Patients with persistent symptoms and those with moderate-to-severe COVID-19 may require a longer delay than 7 weeks. Elective surgery should not take place within 10 days of diagnosis of SARS-CoV-2 infection, predominantly because the patient may be infectious, which is a risk to surgical pathways, staff and other patients. We now emphasise that timing of surgery should include the assessment of baseline and increased risk, optimising vaccination and functional status, and shared decision-making. While these recommendations focus on the omicron variant and current evidence, the principles may also be of relevance to future variants. As further data emerge, these recommendations may be revised.

AimsThe aim of this study was to determine the relative importance of Ca2+ sensitization, ion channels, and intracellular Ca2+ ([Ca2+]i) in the mixed constrictor/relaxation actions of superoxide anion on systemic and pulmonary arteries.Methods and resultsPulmonary and mesenteric arteries were obtained from rat. Superoxide was generated in arteries and cells with 6-anilino-5,8-quinolinequinone (LY83583). Following pre-constriction with U46619, 10 μmol/L LY83583 caused constriction in pulmonary and relaxation in mesenteric arteries. Both constrictor and relaxant actions of LY83583 were inhibited by superoxide dismutase and catalase. LY83583 caused Rho-kinase-dependent constriction in α-toxin-permeabilized pulmonary but not mesenteric arteries. Phosphorylation of myosin phosphatase-targeting subunit-1 (MYPT-1; as determined by western blot), was enhanced by LY83583 in pulmonary artery only. However, in both artery types, changes in tension were closely correlated with changes in phosphorylation of the 20 kDa myosin light chain as well as changes in [Ca2+]i (as measured with Fura PE-3), with LY83583 causing increases in pulmonary and decreases in mesenteric arteries. When U46619 was replaced by 30 mmol/L K+, all changes in [Ca2+]i were abolished and LY83583 constricted both artery types. The KV channel inhibitor 4-aminopyridine abolished the LY83583-induced relaxation in mesenteric artery without affecting constriction in pulmonary artery. However, LY83583 caused a similar hyperpolarizing shift in the steady-state activation of KV current in isolated smooth muscle cells of both artery types.ConclusionsSuperoxide only causes Rho-kinase-dependent Ca2+ sensitization in pulmonary artery, resulting in constriction, and whilst it opens KV channels in both artery types, this only results in relaxation in mesenteric.

Neuraxial anaesthesia is widely utilised for elective caesarean section, but the prevalence of inadequate intraoperative anaesthesia is unclear. We aimed to determine the prevalence of inadequate neuraxial anaesthesia for elective caesarean section; prevalence of conversion from neuraxial anaesthesia to general anaesthesia following inadequate neuraxial anaesthesia; and the effect of mode of anaesthesia. We searched studies reporting inadequate neuraxial anaesthesia that used ≥ ED95 doses (effective dose in 95% of the population) of neuraxial local anaesthetic agents. Our primary outcome was the prevalence of inadequate neuraxial anaesthesia, defined as the need to convert to general anaesthesia; the need to repeat or abandon a planned primary neuraxial technique following incision; unplanned administration of intra-operative analgesia (excluding sedatives); or unplanned epidural drug supplementation. Fifty-four randomised controlled trials were included (3497 patients). The overall prevalence of requirement for supplemental analgesia or anaesthesia was 14.6% (95%CI 13.3-15.9%); 510 out of 3497 patients. The prevalence of general anaesthesia conversion was 2 out of 3497 patients (0.06% (95%CI 0.0-0.2%)). Spinal/combined spinal-epidural anaesthesia was associated with a lower overall prevalence of inadequate neuraxial anaesthesia than epidural anaesthesia (10.2% (95%CI 9.0-11.4%), 278 out of 2732 patients vs. 30.3% (95%CI 26.5-34.5%), 232 out of 765 patients). Further studies are needed to identify risk factors, optimise detection and management strategies and to determine long-term effects of inadequate neuraxial anaesthesia.

SummaryA patient developed neck swelling following removal of an internal jugular vein cannula. Although tracheal extubation was delayed, severe airway obstruction occurred resulting in a cardiac arrest. He was successfully resuscitated. Doppler ultrasonography revealed a huge cervical haematoma surrounding a carotid artery pseudoaneurysm. The carotid artery pseudoaneurysm was obliterated using radiological intervention.