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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.)

Background: In Europe, Italy and Lombardy, in autumn 2020, there was a steep increase in reported cases due to the second epidemic wave of SARS-Cov-2 infection. We aimed to evaluate the appropriateness of COVID-19 patients' admissions to the ED of the San Raffaele Hospital., Methods: We compared data between the inter-wave period (IWP, from 1st to 30th September) and the second wave period (WP, 1st October to 15th November) focusing on the ED presentation, discharge priority colour code and outcomes., Results: Out of 977 admissions with a SARS-Cov-2 positive swab, 6% were in the IWP and 94% in the WP. Red, yellow and white code increased (these latter from 1.8% to 5.4%) as well as self-presented in yellow and white code. Discharges home increased from 1.8% to 5.4%, while hospitalizations decreased from 63% to 51%., Discussion: We found a rise in white codes (among self-presented patients), indicating inappropriateness of admissions. The increase in discharges suggests that several patients did not require hospitalization., Conclusions: The pandemic brought out the fundamental role of primary care to manage patients with low-intensity needs. The important increase in ED admissions of COVID-19 patients caused a reduction of NO-COVID-19 patients, with possible inadequate treatment.

Background: Heart involvement confers a poor prognosis in patients affected by systemic sclerosis (SSc). Nevertheless, the prevalence of heart involvement in these patients is not fully known. In this study we analyzed the most frequent manifestations of heart involvement at rest in a cohort of patients with SSc, comparing their prevalence in patients with the limited form (lcSSc) and in patients with the diffuse form (dcSSc) of the disease, taking also into account the duration of the disease., Methods: We thoroughly evaluated with electrocardiographic and echocardiographic examinations 174 patients affected by SSc who were followed at our hospital between 2001 and 2011. They were divided according to the disease subtype (dcSSc vs lcSSc) and information about the disease duration was available for 121 of them (calculated from the onset of the Raynaud's phenomenon)., Results: Patients with dcSSc had a greater prevalence of heart involvement at rest when evaluated within 5 and 10 years after the onset of the Raynaud's phenomenon (p=0.0051 within 5 years and p=0.035 within 10 years). Indeed, patients with dcSSc had a greater prevalence of atrioventricular conduction abnormalities within 20 years after the onset of the Raynaud's phenomenon (p=0.03 within 10 years and p=0.04 within 20 years) and a greater prevalence of valvular abnormalities within 5 years (p=0.04). In dcSSc there was a greater prevalence of rhythm disturbances in patients with a disease duration ≤20 or >20 years (p=0.04 within 20 years and p=0.04 after 20 years), but not in those with a disease duration ≤5 and ≤10 years. Left ventricular hypertrophy had a greater prevalence in dcSSc after 20 years of disease duration (p=0.02)., Conclusions: Cardiac manifestation occurs earlier and more frequently in patients affected by dcSSc than in patients with lcSSc.

Objective: Systemic sclerosis (SSc; scleroderma) is characterized by a unique widespread vascular involvement that can lead to severe digital ischemia, pulmonary arterial hypertension (PAH), or other organ dysfunction. Microthrombotic events and procoagulation factors such as anti-beta2-glycoprotein I (anti-beta2GPI) or anticardiolipin antibodies (aCL) may be implicated in the development of these manifestations. This study was undertaken to investigate whether anti-beta2GPI and aCL are correlated with macrovascular disease, including ischemic digital loss and PAH, in SSc patients., Methods: Seventy-five SSc patients with a history of ischemic digital loss and 75 matched SSc controls were evaluated. Anticentromere antibodies (ACAs), anti-beta2GPI, and aCL were measured, and clinical associations were determined using conditional and simple logistic regression models., Results: Positivity for anti-beta2GPI was significantly more frequent in SSc patients with digital loss than in patients without digital loss (P=0.017), with the IgA isotype of anti-beta2GPI showing the strongest association (odds ratio [OR] 4.0). There was no significant difference in aCL frequency between patients with digital loss and control patients. After adjustment for demographic characteristics, disease type, smoking, and ACA, anti-beta2GPI positivity was significantly associated with active digital ischemia (OR 9.4), echocardiographically evident PAH (OR 4.8), and mortality (OR 2.9). ACA positivity was associated with history of digital loss (OR 3.28), but not with PAH or mortality. History of digital loss was strongly associated with increased mortality (OR 12.5)., Conclusion: Anti-beta2GPI is significantly associated with macrovascular disease in SSc and independently predicts mortality. It is unclear whether it has a pathogenetic role or simply reveals the presence of underlying endothelial injury. The use of anti-beta2GPI as a biomarker of vascular disease in SSc should be further explored.