Circulating Cell Biomarkers in Pulmonary Arterial Hypertension: Relationship with Clinical Heterogeneity and Therapeutic Response

Background: Endothelial dysfunction is central to PAH. In this study, we simultaneously analysed circulating levels of endothelial microvesicles (EMVs) and progenitor cells (PCs) in PAH and in controls, as biomarkers of pulmonary endothelial integrity and evaluated differences among PAH subtypes and as a response to treatment. Methods: Forty-seven controls and 144 patients with PAH (52 idiopathic, 9 heritable, 31 associated with systemic sclerosis, 15 associated with other connective tissue diseases, 20 associated with HIV and 17 associated with portal hypertension) were evaluated. Forty-four patients with scleroderma and 22 with HIV infection, but without PAH, were also studied. Circulating levels of EMVs, total (CD31+CD42b-) and activated (CD31+CD42b-CD62E+), as well as circulating PCs (CD34+CD133+CD45low) were measured by flow cytometry and the EMVs/PCs ratio was computed. In treatment-naïve patients, measurements were repeated after 3 months of PAH therapy. Results: Patients with PAH showed higher numbers of EMVs and a lower percentage of PCs, compared with healthy controls. The EMV/PC ratio was increased in PAH patients, and in patients with SSc or HIV without PAH. After starting PAH therapy, individual changes in EMVs and PCs were variable, without significant differences being observed as a group. Conclusion: PAH patients present disturbed vascular homeostasis, reflected in changes in circulating EMV and PC levels, which are not restored with PAH targeted therapy. Combined measurement of circulating EMVs and PCs could be foreseen as a potential biomarker of endothelial dysfunction in PAH

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

Heart Rate Recovery After 6-min Walking Test Predicts Acute Exacerbation in COPD

INTRODUCTION: Abnormalities of autonomic function have been reported in patients with chronic obstructive pulmonary disease (COPD). Our objectives were to identify determinants of abnormal heart rate recovery at 1 min (HRR1) following completion of the 6-min walk test (6MWT) in COPD and to establish whether abnormal HRR1 predicts acute exacerbations (AECOPD). METHODS: Hundred one COPD patients (FEV1 (SD) 53 (19) % predicted) were prospectively recruited in a multi-center study. HRR1 after the 6MWT was evaluated as the difference between heart rate at the end of the test and 1 min into the recovery (HRR1). Linear and logistic regression was used to identify predictors of HRR1 and AECOPD, respectively. The best HRR1 cut-off point to predict AECOPD was selected using the receiver operating characteristics (ROC) curves. The follow-up period was 12 months. RESULTS: Distance covered during the 6MWT (m) and DLco (% predicted) were independently associated with HRR1 (r 2 = 0.51, p = 0.001). Among several potential covariates, HRR1 emerged as the most significant predictor of AECOPD (Odds ratio [OR], 0.91 per beat of recovery; 95% confidence interval [CI], 0.85-0.97; p = 0.02). The ROC analysis indicated that subjects with HRR1 less than 14 beats (AUC, 0.71 [CI] 0.60-0.80; p = 0.0001) were more likely to suffer an exacerbation during the follow-up period (for HRR1, p = 0.004 [log-rank test]). CONCLUSIONS: HRR1 after the 6MWT is an independent predictor factor for AECOPD. Further studies are warranted to examine the physiological mechanisms associating a delayed HRR and acute exacerbations in COPD patients

Heart Rate Recovery After 6-min Walking Test Predicts Acute Exacerbation in COPD

INTRODUCTION: Abnormalities of autonomic function have been reported in patients with chronic obstructive pulmonary disease (COPD). Our objectives were to identify determinants of abnormal heart rate recovery at 1 min (HRR1) following completion of the 6-min walk test (6MWT) in COPD and to establish whether abnormal HRR1 predicts acute exacerbations (AECOPD). METHODS: Hundred one COPD patients (FEV1 (SD) 53 (19) % predicted) were prospectively recruited in a multi-center study. HRR1 after the 6MWT was evaluated as the difference between heart rate at the end of the test and 1 min into the recovery (HRR1). Linear and logistic regression was used to identify predictors of HRR1 and AECOPD, respectively. The best HRR1 cut-off point to predict AECOPD was selected using the receiver operating characteristics (ROC) curves. The follow-up period was 12 months. RESULTS: Distance covered during the 6MWT (m) and DLco (% predicted) were independently associated with HRR1 (r 2 = 0.51, p = 0.001). Among several potential covariates, HRR1 emerged as the most significant predictor of AECOPD (Odds ratio [OR], 0.91 per beat of recovery; 95% confidence interval [CI], 0.85-0.97; p = 0.02). The ROC analysis indicated that subjects with HRR1 less than 14 beats (AUC, 0.71 [CI] 0.60-0.80; p = 0.0001) were more likely to suffer an exacerbation during the follow-up period (for HRR1, p = 0.004 [log-rank test]). CONCLUSIONS: HRR1 after the 6MWT is an independent predictor factor for AECOPD. Further studies are warranted to examine the physiological mechanisms associating a delayed HRR and acute exacerbations in COPD patients