Potential of an age adjusted D-dimer cut-off value to improve the exclusion of pulmonary embolism in older patients: a retrospective analysis of three large cohorts

Objectives In older patients, the the D-dimer test for pulmonary embolism has reduced specificity and is therefore less useful. In this study a new, age dependent cut-off value for the test was devised and its usefulness with older patients assessed

Excluding pulmonary embolism in primary care using the Wells-rule in combination with a point-of care D-dimer test: a scenario analysis

ABSTRACT: BACKGROUND: In secondary care the Wells clinical decision rule (CDR) combined with a quantitative D-dimer test can exclude pulmonary embolism (PE) safely. The introduction of point-of-care (POC) D-dimer tests facilitates a similar diagnostic strategy in primary care. We estimated failure-rate and efficiency of a diagnostic strategy using the Wells-CDR combined with a POC-D-dimer test for excluding PE in primary care. We considered ruling out PE safe if the failure rate was <2% with a maximum upper confidence limit of 2.7%. METHODS: We performed a scenario-analysis on data of 2701 outpatients suspected of PE. We used test characteristics of two qualitative POC-D-dimer tests, as derived from a meta-analysis and combined these with the Wells-CDR-score. RESULTS: In scenario 1 (SimpliRed-D-dimer sensitivity 85%, specificity 74%) PE was excluded safely in 23.8% of patients but only by lowering the cut-off value of the Wells rule to <2. (failure rate: 1.4%, 95% CI 0.6-2.6%) In scenario 2 (Simplify-D-dimer sensitivity 87%, specificity 62%) PE was excluded safely in 12.4% of patients provided that the Wells-cut-off value was set at 0. (failure rate: 0.9%, 95% CI 0.2-2.6%) CONCLUSION: Theoretically a diagnostic strategy using the Wells-CDR combined with a qualitative POC-D-dimer test can be used safely to exclude PE in primary care albeit with only moderate efficienc

Rasiowa–Sikorski deduction systems in computer science applications

AbstractA Rasiowa-Sikorski system is a sequence-type formalization of logics. The system uses invertible decomposition rules which decompose a formula into sequences of simpler formulae whose validity is equivalent to validity of the original formula. There may also be expansion rules which close indecomposable sequences under certain properties of relations appearing in the formulae, like symmetry or transitivity. Proofs are finite decomposition trees with leaves having “fundamental”, valid labels. The author describes a general method of applying the R-S formalism to develop complete deduction systems for various brands of C.S and A.I. logic, including a logic for reasoning about relative similarity, a three-valued software specification logic with McCarthy's connectives and Kleene quantifiers, a logic for nondeterministic specifications, many-sorted FOL with possibly empty carriers of some sorts, and a three-valued logic for reasoning about concurrency

High-dimensional phenotyping of the peripheral immune response in community-acquired pneumonia

BackgroundCommunity-acquired pneumonia (CAP) represents a major health burden worldwide. Dysregulation of the immune response plays an important role in adverse outcomes in patients with CAP.MethodsWe analyzed peripheral blood mononuclear cells by 36-color spectral flow cytometry in adult patients hospitalized for CAP (n=40), matched control subjects (n=31), and patients hospitalized for COVID-19 (n=35).ResultsWe identified 86 immune cell metaclusters, 19 of which (22.1%) were differentially abundant in patients with CAP versus matched controls. The most notable differences involved classical monocyte metaclusters, which were more abundant in CAP and displayed phenotypic alterations reminiscent of immunosuppression, increased susceptibility to apoptosis, and enhanced expression of chemokine receptors. Expression profiles on classical monocytes, driven by CCR7 and CXCR5, divided patients with CAP into two clusters with a distinct inflammatory response and disease course. The peripheral immune response in patients with CAP was highly similar to that in patients with COVID-19, but increased CCR7 expression on classical monocytes was only present in CAP.ConclusionCAP is associated with profound cellular changes in blood that mainly relate to classical monocytes and largely overlap with the immune response detected in COVID-19

Thrombolysis for pulmonary embolism and venous thrombosis: is it worthwhile?

Venous thromboembolism is a frequently occurring and potentially fatal disease characterized by short-term and long-term sequelae. Conventional treatment consists of heparin and vitamin K antagonists, but there is an ongoing controversy if more aggressive therapy, such as thrombolytic drugs, should be used in selected patients to achieve faster clot lysis in pursuit of better clinical outcome. A review of the literature shows that thrombolytic therapy is not recommended in the treatment of venous thrombosis. Although in deep vein thrombosis systemically administered and catheter-directed thrombolysis both offer advantages in improving vein patency and reducing the postthrombotic syndrome (PTS), prevention of severe PTS remains unproved while the bleeding risk is high. In pulmonary embolism (PE), thrombolytic therapy is generally recommended for patients with massive PE and hemodynamic instability, despite scarce and inconclusive evidence. There is no evidence that thrombolysis has a benefit over standard anticoagulant treatment in normotensive patients with acute PE, but more research is needed to better identify the subgroup of patients with nonmassive PE in whom the risk-benefit ratio is most favorable. Until this group is defined and the benefit of thrombolytic therapy is demonstrated, thrombolytic therapy should only be considered in patients with signs of massive PE and hemodynamic shoc

Knowledge of the D-dimer test result influences clinical probability assessment of pulmonary embolism

Background: In patients with suspected pulmonary embolism (PE), an unlikely or non-high probability assessment combined with a normal D-dimer test can safely exclude the diagnosis. We studied the influence of early D-dimer knowledge on clinical probability assessment. Methods: A questionnaire was sent to 150 randomly selected pulmonologists and internists in the Netherlands, presenting six hypothetical case-descriptions of patients with suspected PE. Physicians were randomized to receive one of three versions. The version contained a normal, an abnormal or no D-dimer result with each case-description. Each version contained two cases with an abnormal D-dimer result, two cases with a normal D-dimer result and two cases with no D-dimer result. Results: A total of 71 physicians (47%) returned the questionnaire; the three versions were equally represented. Compared to the control cases in which no D-dimer was given, knowledge of an abnormal D-dimer resulted in more "likely" clinical scores using the Wells' score (absolute increase in "likely" of 25-37%, p = 0.005, 0.111 and 0.144), while knowledge of a normal D-dimer resulted in more "unlikely" scores (absolute increase in "unlikely" of 27-44%, p = 0.001 and 0.070). D-dimer knowledge did not influence the probability assessment when the clinical suspicion was very high. Conclusion: Knowledge of the D-dimer test influences the physician in how the clinical probability for PE is scored. This will have direct clinical consequences, such as unnecessary imaging testing or inappropriate exclusion of the diagnosis. Physicians should therefore make sure that they examine the patient before they take notice of the D-dimer test result. (C) 2010 Elsevier Ltd. All rights reserve

Diagnostic Management Strategies in Patients with Suspected Pulmonary Embolism

Adequate diagnosis is essential to prevent pulmonary embolism (PE)-related mortality and morbidity on the one hand and unnecessary treatment on the other. Preferably, excluding the diagnosis is performed using safe, efficient and non-invasive diagnostic methods. Over the last two decades, many new diagnostic methods and strategies for the diagnostic work-up of patients with suspected PE have been introduced and validated. The first step in the approach to patients with suspected PE is a thorough clinical history and physical examination, in order to determine the clinical probability of the presence of PE. The advantage of using pre-test probability in the exclusion of PE is mainly achieved in combination with a D-dimer test result. In patients with a high or likely pre-test clinical probability or patients with an abnormal D-dimer test, additional imaging is required. If the clinical status of the patient permits, the next recommended step is computed tomography (CT) or ventilation-perfusion scintigraphy, followed by additional testing in case of non-diagnostic test results. Selected patients may require a tailored approach, for instance if there is a contraindication for CT scanning. The implementation of diagnostic strategy in clinical practice will increase diagnostic accuracy and reduce costs.</p

Diagnostic Management Strategies in Patients with Suspected Pulmonary Embolism

Adequate diagnosis is essential to prevent pulmonary embolism (PE)-related mortality and morbidity on the one hand and unnecessary treatment on the other. Preferably, excluding the diagnosis is performed using safe, efficient and non-invasive diagnostic methods. Over the last two decades, many new diagnostic methods and strategies for the diagnostic work-up of patients with suspected PE have been introduced and validated. The first step in the approach to patients with suspected PE is a thorough clinical history and physical examination, in order to determine the clinical probability of the presence of PE. The advantage of using pre-test probability in the exclusion of PE is mainly achieved in combination with a D-dimer test result. In patients with a high or likely pre-test clinical probability or patients with an abnormal D-dimer test, additional imaging is required. If the clinical status of the patient permits, the next recommended step is computed tomography (CT) or ventilation-perfusion scintigraphy, followed by additional testing in case of non-diagnostic test results. Selected patients may require a tailored approach, for instance if there is a contraindication for CT scanning. The implementation of diagnostic strategy in clinical practice will increase diagnostic accuracy and reduce costs.</p

Incidental venous thromboembolism in cancer patients: prevalence and consequence

Introduction: Careful re-evaluation of CT-scans for cancer staging frequently reveals unsuspected venous thromboembolism (VTE) on CT-scans. However, it is unknown how often these findings lead to anticoagulant treatment in daily clinical practice. Methods: Reports from thoracic and/or abdominal CT-scans performed in a consecutive series of patients to stage cancer were retrospectively evaluated to determine the prevalence of incidental venous thromboembolism (iVTE). Presence of pre-existing signs of VTE, anticoagulant treatment and 3-month follow-up were analysed in patients with iVTE. Results: A total of 1466 staging scans (838 patients) from the year 2006 were included in the analysis. The prevalence of VTE in patients was 2.5% (21/838 patients, 95% confidence interval 1.6-3.8%); the prevalence of VTE on scans was 1.4% (21/1466 scans, 95% CI 0.9-2.2%). Incidental PE or deep vein thrombosis (DVT) was observed in 11 (1.3%, 0.7-2.3%) and abdominal vein thrombosis in 9 patients (1.1%, 0.6-2.0%; in the portal (5), mesenteric (3) and renal vein (1), respectively). Nine out of eleven patients with PE/DVT were treated with anticoagulants, while none of the patients with thrombosis in other locations received anticoagulants. One of these patients developed symptomatic PE one month later; otherwise, follow up was uneventful in the untreated patients. Conclusion: The prevalence of iVTE in patients with cancer in clinical practice is relatively low and most patients with PE or DVT are treated with anticoagulants. For patients with thrombi in other locations, further research is necessary to understand the natural history of these thrombi in order to develop adequate guidelines. © 2010 Elsevier Ltd. All rights reserved