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Background: Diagnosis of venous thromboembolism (VTE) requires chest CT angiography for pulmonary embolism and venous ultrasound for deep vein thrombosis. To reduce imaging, guidelines recommend D-dimer levels to rule-out VTE in patients with a low pre-test probability. The most widely used D-dimer cut-off is 500 ng/mL. This cut-off has low specificity, meaning many patients without disease require imaging.Methods: In this retrospective chart review, we evaluated the diagnostic performance of the D-dimer/fibrinogen ratio (DFR) for identifying thromboembolism and compared it to the performance of two different D-dimer cut-offs (500 ng/mL and 1000 ng/mL) in patients who underwent a chest CT angiography or a venous ultrasound in the ED of San Raffaele Hospital, Italy, in 2017. Patients had a retrospective Wells score calculated after chart review, identifying both high-risk and low-risk pre-test probability patients for this study and low probability patients were further stratified into low-risk of deep vein thrombosis or pulmonary embolism.Results: Enrolled patients included 92 with suspected pulmonary embolism and 154 with suspected deep vein thrombosis; of whom 67 (27%) were diagnosed with VTE. The most accurate cut-off for DFR in terms of discriminative power was 2.65. In the whole sample and in low-risk patients, this cut-off had the same sensitivity values of the 500 ng/mL D-dimer cut-off (97% (95% CI: 89.8% to 99.2%)), while slightly lower sensitivity values were found for the 1000 ng/mL D-dimer cut-off (95.5% (95% CI: 87.6% to 98.5%)). Specificity was higher for the 2.65 DFR cut-off (55.3% (95% CI: 48.0% to 62.4%)) in the whole sample compared with both 500 ng/mL D-dimer cut-off (22.9% (95% CI: 17.4% to 29.6%)) and 1000 ng/mL D-dimer cut-off (45.8% (95% CI: 38.7% to 53.1%)). Similar results were found in all subgroups.Conclusion: A DFR, with a cut-off of 2.65, may improve the specificity for VTE patients when compared with D-dimer alone in high-risk VTE emergency medicine populations. This is exploratory information only, needing evaluation in prospective, multicentre studies, prior to consideration for use in routine clinical work. [ABSTRACT FROM AUTHOR]

Objective: It is unclear why activated platelets and platelet‐derived microparticles (MPs) accumulate in the blood of patients with systemic sclerosis (SSc). This study was undertaken to investigate whether defective phagocytosis might contribute to MP accumulation in the blood of patients with SSc. Methods: Blood samples were obtained from a total of 81 subjects, including 25 patients with SSc and 26 patients with stable coronary artery disease (CAD). Thirty sex‐ and age‐matched healthy volunteers served as controls. Studies were also conducted in NSG mice, in which the tail vein of the mice was injected with MPs, and samples of the lung parenchyma were obtained for analysis of the pulmonary microvasculature. Tissue samples from human subjects and from mice were assessed by flow cytometry and immunochemical analyses for determination of platelet–neutrophil interactions, phagocytosis, levels and distribution of P‐selectin, P‐selectin glycoprotein ligand 1 (PSGL‐1), and HMGB1 on platelets and MPs, and concentration of byproducts of neutrophil extracellular trap (NET) generation/catabolism. Results: Activated P‐selectin+ platelets and platelet‐derived HMGB1+ MPs accumulated in the blood of SSc patients but not in the blood of healthy controls. Patients with CAD, a vasculopathy independent of systemic inflammation, had fewer P‐selectin+ platelets and a negligible number of MPs. The expression of the receptor for P‐selectin, PSGL‐1, in neutrophils from SSc patients was significantly decreased, raising the possibility that phagocytes in SSc do not recognize activated platelets, leading to a failure of phagocytosis and continued neutrophil release of MPs. As evidence of this process, activated platelets were not detected in the neutrophils from SSc patients, whereas they were consistently present in the neutrophils from patients with CAD. HMGB1+ MPs elicited generation of NETs, which were only detected in the plasma of SSc patients. In mice, P‐selectin–PSGL‐1 interaction resulted in platelet phagocytosis in vitro and influenced the ability of MPs to elicit NETs, endothelial activation, and migration of leukocytes through the pulmonary microvasculature. Conclusion: The clearance of activated platelets via PSGL‐1 limits the undesirable effects of MP‐elicited neutrophil activation. This balance is disrupted in patients with SSc. Its reconstitution might curb vascular inflammation and prevent fibrosis. [ABSTRACT FROM AUTHOR]

Objective: The use of angiotensin II in invasively ventilated patients with coronavirus disease 2019 (COVID-19) is controversial. Its effect on organ function is unknown. Design: Prospective observational study. Setting: Intensive care unit (ICU) of a tertiary academic hospital in Milan, Italy. Participants: Adult patients receiving mechanical ventilation due to COVID-19. Interventions: Use angiotensin II either as rescue vasopressor agent or as low dose vasopressor support. Main outcome measures: Patients treated before angiotensin II was available or treated in an adjacent COVID-19 ICU served as controls. For data analysis, we applied Bayesian modelling as appropriate. We assessed the effects of angiotensin II on organ function. Results: We compared 46 patients receiving angiotensin II therapy with 53 controls. Compared with controls, angiotensin II increased the mean arterial pressure (median difference, 9.05 mmHg; 95% CI, 1.87-16.22; P = 0.013) and the PaO 2 /FiO 2 ratio (median difference, 23.17; 95% CI, 3.46-42.88; P = 0.021), and decreased the odds ratio (OR) of liver dysfunction (OR, 0.32; 95% CI, 0.09-0.94). However, angiotensin II had no effect on lactate, urinary output, serum creatinine, C-reactive protein, platelet count, or thromboembolic complications. In patients with abnormal baseline serum creatinine, Bayesian modelling showed that angiotensin II carried a 95.7% probability of reducing the use of renal replacement therapy (RRT). Conclusions: In ventilated patients with COVID-19, angiotensin II therapy increased blood pressure and PaO 2 /FiO 2 ratios, decreased the OR of liver dysfunction, and appeared to decrease the risk of RRT use in patients with abnormal baseline serum creatinine. However, all of these findings are hypothesis-generating only. Trial registration: ClinicalTrials.gov NCT04318366., Competing Interests: No relevant disclosures., (© 2021 College of Intensive Care Medicine of Australia and New Zealand.)

Background: Respiratory infections can be complicated by acute brain failure. We assessed delirium prevalence, predictors and outcomes in COVID-19 ED patients., Methods: This was a retrospective observational study conducted at the San Raffaele ED (Italy). Patients age >18 years attending the ED between 26 February 2020 and 30 May 2020 and who had a positive molecular nasopharyngeal swab for SARS-CoV-2 were included. The Chart-Based Delirium Identification Instrument (CHART-DEL) was used to retrospectively assess delirium. Univariable and multivariable logistic regression analyses were used to evaluate delirium predictors. Univariable binary logistic regression analyses, linear regression analyses and Cox regression analyses were used to assess the association between delirium and clinical outcomes. Age-adjusted and sex-adjusted models were then run for the significant predictors of the univariable models., Results: Among the 826 included patients, 123 cases (14.9%) of delirium were retrospectively detected through the CHART-DEL method. Patients with delirium were older (76.9±13.15 vs 61.3±14.27 years, p<0.001) and more frequently living in a long-term health facility (32 (26%) vs 22 (3.1%), p<0.001). Age (OR 1.06, 95% CI 1.04 to 1.09, p<0.001), dementia (OR 17.5, 95% CI 7.27 to 42.16, p<0.001), epilepsy (OR 6.96, 95% CI 2.48 to 19.51, p<0.001) and the number of chronic medications (OR 1.09, 95% CI 1.01 to 1.17, p=0.03) were significant predictors of delirium in multivariable analyses. Delirium was associated with increased in-hospital mortality (adjusted HR 2.16, 95% CI 1.55 to 3.03, p<0.001) and with a reduced probability of being discharged home compared with being institutionalised (adjusted OR 0.39, 95% CI 0.25 to 0.61, p<0.001)., Conclusions: Chart review frequently identified ED delirium in patients with COVID-19. Age, dementia, epilepsy and polypharmacy were significant predictors of ED delirium. Delirium was associated with an increased in-hospital mortality and with a reduced probability of being discharged home after hospitalisation. The findings of this single-centre retrospective study require validation in future studies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Diagnosis of venous thromboembolism (VTE) requires chest CT angiography for pulmonary embolism and venous ultrasound for deep vein thrombosis. To reduce imaging, guidelines recommend D-dimer levels to rule-out VTE in patients with a low pre-test probability. The most widely used D-dimer cut-off is 500 ng/mL. This cut-off has low specificity, meaning many patients without disease require imaging., Methods: In this retrospective chart review, we evaluated the diagnostic performance of the D-dimer/fibrinogen ratio (DFR) for identifying thromboembolism and compared it to the performance of two different D-dimer cut-offs (500 ng/mL and 1000 ng/mL) in patients who underwent a chest CT angiography or a venous ultrasound in the ED of San Raffaele Hospital, Italy, in 2017. Patients had a retrospective Wells score calculated after chart review, identifying both high-risk and low-risk pre-test probability patients for this study and low probability patients were further stratified into low-risk of deep vein thrombosis or pulmonary embolism., Results: Enrolled patients included 92 with suspected pulmonary embolism and 154 with suspected deep vein thrombosis; of whom 67 (27%) were diagnosed with VTE. The most accurate cut-off for DFR in terms of discriminative power was 2.65. In the whole sample and in low-risk patients, this cut-off had the same sensitivity values of the 500 ng/mL D-dimer cut-off (97% (95% CI: 89.8% to 99.2%)), while slightly lower sensitivity values were found for the 1000 ng/mL D-dimer cut-off (95.5% (95% CI: 87.6% to 98.5%)). Specificity was higher for the 2.65 DFR cut-off (55.3% (95% CI: 48.0% to 62.4%)) in the whole sample compared with both 500 ng/mL D-dimer cut-off (22.9% (95% CI: 17.4% to 29.6%)) and 1000 ng/mL D-dimer cut-off (45.8% (95% CI: 38.7% to 53.1%)). Similar results were found in all subgroups., Conclusion: A DFR, with a cut-off of 2.65, may improve the specificity for VTE patients when compared with D-dimer alone in high-risk VTE emergency medicine populations. This is exploratory information only, needing evaluation in prospective, multicentre studies, prior to consideration for use in routine clinical work., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)