The PaCO2/FiO2 ratio as outcome predictor in SARS-COV-2 related pneumonia: a retrospective study.

BACKGROUND AND AIM: Respiratory failure in SARS-CoV-2 patients is characterized by the presence of hypoxemia and hypocapnia without relevant dyspnea. To date, the use of respiratory parameters other than PaO2/FiO2 ratio to stratify the risk of worsening of these patients has not been sufficiently studied.  Aim of this work was to evaluate whether the ratio between partial pressure levels of carbon dioxide (PaCO2) and the fraction of inspired oxygen (FiO2) measured at emergency department (ED) admission is predictive of the clinical course of patients suffering from SARS-CoV-2 pneumonia. METHODS: We retrospectively studied 236 patients with SARS-CoV-2 pneumonia evaluated at the ED of the Perugia Hospital. The end-points were: in-hospital mortality, need for invasive mechanical ventilation (IMV) and length of in-hospital stay (LOS). Clinical, blood gas and laboratory data were collected at ED admission. RESULTS: Of the 236 patients 157 were male, the mean age was 64 ± 16. Thirtythree patients (14%) needed IMV, 49 died (21%). In the univariate analysis, the PaCO2/FiO2 ratio was inversely associated with the need for IMV (p <0.001), mortality (p <0.001) and LOS (p = 0.005). At the multivariate analysis the PaCO2/FiO2 ratio was found to be predictive of the need for IMV, independently from age, gender, number of comorbidities, neutrophils, lymphocytes, glomerular filtrate, d-dimer, LDH and CRP. CONCLUSIONS: the PaCO2/FiO2 ratio is predictive of the risk of respiratory failure worsening in patients with SARS-CoV-2 pneumonia, independently from other several confounding factors.

Acute pulmonary embolism: external validation of an integrated risk stratification model.

BACKGROUND: In hemodynamically stable patients with acute pulmonary embolism, risk stratification is essential to drive clinical management. In these patients, risk stratification for in-hospital adverse outcomes based on markers of right ventricular dysfunction and injury has been proposed. METHODS: The aim of this study was to validate a model based on the incremental prognostic value of right ventricular dysfunction and injury in hemodynamically stable patients with acute pulmonary embolism. Patients from the prospective Italian Pulmonary Embolism Registry were included in the study. Study outcomes were in-hospital death and the composite of in-hospital death or clinical deterioration. RESULTS: Among 1,515 hemodynamically stable patients, 869 had both echocardiography and troponin assessments. The risk for in-hospital death or clinical deterioration was higher in patients with right ventricular dysfunction and elevated troponin level (8.8%; hazard ratio [HR], 14.2 [95% CI, 1.94-104.16]; P < .01) and with either right ventricular dysfunction or elevated troponin level (4.7%; HR, 7.9 [95% CI, 1.1-59.9]; P < .05) compared with patients without dysfunction and normal troponin levels. The negative predictive value of the model was 100% for in-hospital death and 99% for death or clinical deterioration. C statistics showed an improvement of the discriminatory power for in-hospital death or clinical deterioration by using the overall model (0.66; 95% CI, 0.60-0.73) over either echocardiography (0.59; 95% CI, 0.53-0.67) or troponin level (0.61; 95% CI, 0.53-0.69) alone. CONCLUSIONS: A model that includes both dysfunction and injury of the right ventricle has an incremental prognostic value for risk stratification in hemodynamically stable patients with acute pulmonary embolism. Patients with no dysfunction or injury have a favorable outcome. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01604538; URL: www.clinicaltrials.gov.

New oral anticoagulants for venous thromboembolism: focus on factor Xa and thrombin inhibitors.

Several oral direct anti-Xa agents and one antithrombin agent are currently under clinical development for the prevention and treatment of venous thromboembolism (VTE). The anti-Xa inhibitors rivaroxaban (10 mg once daily) and apixaban (2.5 mg twice daily) as well as the thrombin inhibitor dabigatran (150 or 220 mg once daily) have been recently licensed for the prevention of VTE in total hip or knee replacement. The publication of the results of studies with rivaroxaban and apixaban in the prevention of VTE in medical patients are awaited. Phase III studies on the treatment of VTE showed the non inferiority of rivaroxaban (15 mg twice daily in the first three weeks and 20 mg once daily thereafter) and dabigatran (150 mg twice daily) to standard treatment. The incidence of major or clinically relevant non-major bleeding was similar in patients receiving standard treatment and rivaroxaban or dabigatran. Clinical trials on VTE treatment are currently ongoing with apixaban and edoxaban. A number of phase II clinical trials are currently ongoing with several other antiXa agents in the prophylaxis and treatment of VTE.

D-dimer for risk stratification in patients with acute pulmonary embolism.

BACKGROUND: Risk stratification is currently recommended for the initial management of patients with acute pulmonary embolism (PE). METHODS: We performed a meta-analysis of studies in patients with acute PE to assess the prognostic value of elevated D-dimer levels for short-term (within 30 days) and 3-month mortality. The association between D-dimer levels and markers of PE severity was also reviewed. Unrestricted searches were performed using the terms D-dimer and pulmonary embolism. Studies reporting on D-dimer levels and mortality and/or markers of PE severity were included in the review. A random-effects model was used to pool study results, funnel-plot inspection to evaluate publication bias and I squared testing to test for heterogeneity. RESULTS: Five studies (2,885 patients) reported on D-dimer levels and short-term mortality. D-dimer levels above a prognostic cut-off were significantly associated with short-term mortality in the overall population (OR: 2.76; 95% CI: 1.83-4.14; I(2) = 0%) and in hemodynamically stable patients (three studies, 874 patients; OR: 4.28; 95% CI: 1.88-9.71; I(2) = 0%). Four studies (1,254 patients) reported on D-dimer levels and 3-month mortality. D-dimer levels above a prognostic cut-off were associated with 3-month mortality (OR: 4.29; 95% IC: 1.70-10.79; I(2) = 0%). Overall, 14 studies assessed the association between D-dimer and markers of PE severity. An association has been observed between D-dimer levels and the degree of pulmonary artery obstruction. CONCLUSION: In patients with acute PE elevated D-dimer is associated with increased short-term and 3-month mortality, suggesting the potential of using this test for both diagnosis and risk stratification.

New anticoagulants for the prevention of venous thromboembolism.

Anticoagulant drugs have an essential role in the prevention and treatment of thromboembolic diseases. Currently available anticoagulants substantially reduce the incidence of thromboembolic events in a number of clinical conditions. However, these agents have limitations that strengthen the case for the development of new anticoagulants. An ideal anticoagulant should be at least as effective as those currently in use, as well as safe, simple to use, and widely applicable.The majority of new anticoagulants currently under investigation are small molecules with a selective and direct anti-Xa or antithrombin action, allowing oral administration in fixed doses. These new agents are in different phases of clinical development. The anti-Xa agent rivaroxaban and the antithrombin agent dabigatran are already available for the prophylaxis of venous thromboembolism in some countries. Apixaban is in an advanced phase of clinical development and several anti-Xa agents are currently approaching phase III clinical trials. Promising results in terms of efficacy and safety profiles have been obtained with these agents in different clinical conditions. Differences in pharmacokinetics and pharmacodynamics could offer the potential for individualized anticoagulant therapies in the near future.