Utility and limitations of patient-adjusted D-dimer cut-off levels for diagnosis of venous thromboembolism-A systematic review and meta-analysis.

PURPOSE: To systematically assess test performance of patient-adapted D-dimer cut-offs for the diagnosis of venous thromboembolism (VTE). METHODS: Systematic review and analysis of articles published in PubMed, Embase, ClinicalTrials.gov, and Cochrane Library databases. Investigations assessing patient-adjusted D-dimer thresholds for the exclusion of VTE were included. A hierarchical summary receiver operating characteristic model was used to assess diagnostic accuracy. Risk of bias was assessed by Quality Assessment of Diagnostic Accuracy Studies 2 score. RESULTS: A total of 68 studies involving 141,880 patients met the inclusion criteria. The standard cut-off revealed a sensitivity of 0.99 (95% confidence interval [CI] 0.98-0.99) and specificity of 0.23 (95% CI 0.16-0.31). Sensitivity was comparable to the standard cut-off for age-adjustment (0.97 [95% CI 0.96-0.98]) and YEARS algorithm (0.98 [95% CI 0.91-1.00]) but lower for pretest probability (PTP)-adjusted (0.95 [95% CI 0.89-0.98) and COVID-19-adapted thresholds (0.93 [95% CI 0.82-0.98]). Specificity was significantly higher across all adjustment strategies (age: 0.43 [95% CI 0.36-0.50]; PTP: 0.63 [95% CI 0.51-0.73]; YEARS algorithm: 0.65 [95% CI 0.39-0.84]; and COVID-19: 0.51 [95% CI 0.40-0.63]). The YEARS algorithm provided the best negative likelihood ratio (0.03 [95% CI 0.01-0.15]), followed by age-adjusted (both 0.07 [95% CI 0.05-0.09]), PTP (0.08 [95% CI 0.04-0.17), and COVID-19-adjusted thresholds (0.13 [95% CI 0.05-0.32]). CONCLUSIONS: This study indicates that adjustment of D-dimer thresholds to patient-specific factors is safe and embodies considerable potential for reduction of imaging. However, robustness, safety, and efficiency vary considerably among different adjustment strategies with a high degree of heterogeneity.

COVID-19-associated acute respiratory distress syndrome (CARDS): Current knowledge on pathophysiology and ICU treatment - A narrative review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces coronavirus-19 disease (COVID-19) and is a major health concern. Following two SARS-CoV-2 pandemic "waves," intensive care unit (ICU) specialists are treating a large number of COVID19-associated acute respiratory distress syndrome (ARDS) patients. From a pathophysiological perspective, prominent mechanisms of COVID19-associated ARDS (CARDS) include severe pulmonary infiltration/edema and inflammation leading to impaired alveolar homeostasis, alteration of pulmonary physiology resulting in pulmonary fibrosis, endothelial inflammation (endotheliitis), vascular thrombosis, and immune cell activation. Although the syndrome ARDS serves as an umbrella term, distinct, i.e., CARDS-specific pathomechanisms and comorbidities can be noted (e.g., virus-induced endotheliitis associated with thromboembolism) and some aspects of CARDS can be considered ARDS "atypical." Importantly, specific evidence-based medical interventions for CARDS (with the potential exception of corticosteroid use) are currently unavailable, limiting treatment efforts to mostly supportive ICU care. In this article, we will discuss the underlying pulmonary pathophysiology and the clinical management of CARDS. In addition, we will outline current and potential future treatment approaches.