Continuous positive airway pressure (CPAP) therapy is commonly used for respiratory failure due to severe COVID-19 pneumonitis, including in patients deemed not likely to benefit from invasive mechanical ventilation (nIMV). Little evidence exists demonstrating superiority over conventional oxygen therapy, whilst ward-level delivery of CPAP presents practical challenges. We sought to compare clinical outcomes of oxygen therapy versus CPAP therapy in patients with COVID-19 who were nIMV. This retrospective multi-centre cohort evaluation included patients diagnosed with COVID-19 who were nIMV, had a treatment escalation plan of ward-level care and clinical frailty scale ≤ 6. Recruitment occurred during the first two waves of the UK COVID-19 pandemic in 2020; from 1^st March to May 31^st, and from 1^st September to 31^st December. Patients given CPAP were compared to patients receiving oxygen therapy that required FiO₂ ≥0_.4 for more than 12 hours at hospitals not providing ward-level CPAP. Logistic regression modelling was performed to compare 30-day mortality between treatment groups, accounting for important confounders and within-hospital clustering. Seven hospitals provided data for 479 patients during the UK COVID-19 pandemic in 2020. Overall 30-day mortality was 75.6% in the oxygen group (186/246 patients) and 77.7% in the CPAP group (181/233 patients). A lack of evidence for a treatment effect persisted in the adjusted model (adjusted odds ratio 0.84 95% CI 0.57-1.23, p=0.37). 49.8% of patients receiving CPAP-therapy (118/237) chose to discontinue it. No survival difference was found between using oxygen alone or CPAP to treat patients with severe COVID-19 who were nIMV. A high patient-initiated discontinuation rate for CPAP suggests a significant treatment burden. Further reflection is warranted on the current treatment guidance and widespread application of CPAP in this setting. L Pearmain is supported by the MRC (MR/R00191X/1). TW Felton is supported by the NIHR Manchester Biomedical Research Centre.

Minimally invasive surgical approaches have gained popularity among patients and surgeons. The aim of this project was to assess the safety of initiating aortic valve replacement via an anterior right thoracotomy program. Between May 2015 and May 2019, data of all isolated primary aortic valve replacements were extracted retrospectively from our prospectively collected database and categorized into conventional median sternotomy, hemisternotomy, and anterior right thoracotomy cases. In total, 661 patients underwent isolated primary aortic valve replacement, of whom 429 (65%) had a median sternotomy, 126 (19%) had a hemisternotomy, and 106 (16%) had an anterior right thoracotomy. Preoperative characteristics were similar in each of the three groups. Statistical testing of the surgical groups was undertaken using the chi-square test for categorical variables and one-way analysis of variance with Tukey post-hoc pairwise tests (where appropriate) for continuous variables, to identify differences between pairs of data. Cardiopulmonary bypass and crossclamp times were significantly longer in the anterior right thoracotomy group compared to the hemisternotomy and median sternotomy groups (p < 0.001). Blood loss was significantly less and hospital stay significantly shorter in the hemisternotomy group compared to median sternotomy group but not the anterior right thoracotomy group. Mortality, stroke, renal, gastrointestinal and respiratory complications showed no statistical differences. Surgical aortic valve replacement had a very low mortality and morbidity in our experience, and it is safe to start a minimal access program for aortic valve replacement.

Mutations in the p53 tumor suppressor are found in over 50% of cancers. p53 function is controlled through posttranslational modifications and cofactor interactions. In this study, we investigated the posttranslationally modified p53, including p53 acetylated at lysine 382 (K382), p53 phosphorylated at serine 46 (S46), and the p53 cofactor TTC5/STRAP (Tetratricopeptide repeat domain 5/ Stress-responsive activator of p300-TTC5) proteins in lung cancer. Immunohistochemical (IHC) analysis of lung cancer tissues from 250 patients was carried out and the results were correlated with clinicopathological features. Significant associations between total or modified p53 with a higher grade of the tumour and shorter overall survival (OS) probability were detected, suggesting that mutant and/or modified p53 acts as an oncoprotein in these patients. Acetylated at K382 p53 was predominantly nuclear in some samples and cytoplasmic in others. The localization of the K382 acetylated p53 was significantly associated with the gender and grade of the disease. The TTC5 protein levels were significantly associated with the grade, tumor size, and node involvement in a complex manner. SIRT1 expression was evaluated in 50 lung cancer patients and significant positive correlation was found with p53 S46 intensity, whereas negative TTC5 staining was associated with SIRT1 expression. Furthermore, p53 protein levels showed positive association with poor OS, whereas TTC5 protein levels showed positive association with better OS outcome. Overall, our results indicate that an analysis of p53 modified versions together with TTC5 expression, upon testing on a larger sample size of patients, could serve as useful prognostic factors or drug targets for lung cancer treatment.

Objective To conduct a large-scale, single-centre retrospective cohort study to understand the impact of prior percutaneous coronary intervention (PCI) on long-term survival of patients who then undergo coronary artery bypass graft (CABG). Methods Between 1999 and 2017, a total of 11 332 patients underwent CABG at a hospital in the UK. The patients were stratified into those who received PCI (n=1090) or no PCI (n=10 242) prior to CABG. A total of 1058 patients from each group were matched using propensity score matching. Kaplan-Meier estimates were used to assess risk-adjusted survival in patients with prior PCI. Cox proportional hazards (CoxPH) model was then used to assess the effect of prior PCI and other variables in patients undergoing CABG. Results The immediate postoperative outcome showed no difference in number of grafts per patients, blood transfusion, hospital stay or 30 days mortality between the groups. There was no significant difference in 5 years (90.8% vs 87.9), 10-year (76.5% vs 74.6%) and 15-year (64.4% vs 64.7%) survival between the non-PCI versus PCI groups. The Cox proportional hazards model further supports the null hypothesis as the PCI variable was found to be non-significant (CoxPH=1.03, p=0.75, CI=0.87–1.22) implying there was no difference in hazard of death for CABG patients with or without previous PCI. However, the model did yield information on the covariates that do affect the hazard of death. Conclusion There is no difference in 5-year, 10-year and 15-year survival between patients undergoing CABG with or without prior PCI. However, certain patient, preoperative and intraoperative risk factors were identified with high hazard of death which needs to be investigated further.

(1) Background: Minimal invasive cardiac surgery via right anterolateral thoracotomy for heart valve surgery and other intracardiac procedures proven to have lower postoperative complications. We aim to compare the neurological complications and post-operative outcomes in two cohort groups as well as survival rates up to 5 years postoperatively; (2) Methodology: Retrospective observational study for patients who had minimally invasive cardiac valve surgery with retrograde femoral arterial perfusion between 2007 and 2021 (n = 596) and the categorized patients into two groups based on their age (≥70 years old and below 70). Propensity match analysis was conducted. The primary endpoint consisted of major postoperative complications and the secondary endpoint was the long-term survival rate. (3) Results: There was no difference between the two groups in terms of postoperative outcomes. Patients ≥ 70 years old had no increased risk for neurological complications (p = 0.75) compared with those below 70 years old. The mortality rate was also not significant between the two groups (p = 0.37) as well as the crude survival rates. (4) Conclusions: The use of retrograde femoral arterial perfusion in elderly patients is not associated with increased risk compared to the younger patients’ group for a spectrum of primary cardiac valve procedures. Hence, minimally invasive approaches could be offered to elderly patients who might benefit from it.