Diagnosing pulmonary embolism: establishing and consolidating the role of spiral CT

In the Antelope study availability, use and diagnostic accuracy of spiral CT in patients clinically suspected of PE was investigated. This study was divided in two separate phases, starting with a prospective evaluation of available diagnostic techniques part of the diagnostic consensus strategy in The Netherlands in a specifically designed algorithm. Phase I showed that in a direct comparison with the gold standard sensitivity and specificity of spiral CT is too low to endorse its role as a single test to exclude pulmonary embolism. Also spiral CT had a limited added value as a second procedure following ventilation-perfusion scintigraphy. The accuracy of CT was significantly better in cases with interobserver agreement and good image quality. The available data of phase I was used for a cost-effectiveness analysis. Combined with recent literature data two new strategies were proposed and studied independently. Phase II showed in a prospective clinical management study that spiral CT can be used safely as a first line test to rule out pulmonary embolism in clinically suspected patients. It is also possible to reliably determine an alternative diagnosis in 25% of all patients. A new questionnaire showed that since 1997 the use of spiral CT has increased considerably.UBL - phd migration 201

In vitro pharmacokinetics of anti-psoriatic fumaric acid esters

Background: Psoriasis is a chronic inflammatory skin disease that can be successfully treated with a mixture of fumaric acid esters (FAE) formulated as enteric-coated tablets for oral use. These tablets consist of dimethylfumarate (DMF) and salts of monoethylfumarate (MEF) and its main bioactive metabolite is monomethylfumarate (MMF). Little is known about the pharmacokinetics of these FAE. The aim of the present study was to investigate the hydrolysis of DMF to MMF and the stability of MMF, DMF and MEF at in vitro conditions representing different body compartments. Results: DMF is hydrolyzed to MMF in an alkaline environment (pH 8), but not in an acidic environment (pH 1). In these conditions MMF and MEF remained intact during the period of analysis (6 h). Interestingly, DMF was hardly hydrolyzed to MMF in a buffer of pH 7.4, but was rapidly hydrolyzed in human serum having the same pH. Moreover, in whole blood the half-life of DMF was dramatically reduced as compared to serum. The concentrations of MMF and MEF in serum and whole blood decreased with increasing time. These data indicate that the majority of the FAE in the circulation are metabolized by one or more types of blood cells. Additional experiments with purified blood cell fractions resuspended in phosphate buffered saline (pH 7.4) revealed that at concentrations present in whole blood monocytes/lymphocytes, but not granulocytes and erythrocytes, effectively hydrolyzed DMF to MMF. Furthermore, in agreement with the data obtained with the pure components of the tablet, the enteric-coated tablet remained intact at pH 1, but rapidly dissolved at pH 8. Conclusion: Together, these in vitro data indicate that hydrolysis of DMF to MMF rapidly occurs at pH 8, resembling that within the small intestines, but not at pH 1 resembling the pH in the stomach. At both pHs MMF and MEF remained intact. These data explain the observation that after oral FAE intake MMF and MEF, but not DMF, can be readily detected in the circulation of human healthy volunteers and psoriasis patients

Laparoscopic versus percutaneous cryotherapy for renal tumours: a systematic review and meta-analysis

Background: Cryoablation has emerged as an alternative to the more invasive partial nephrectomy for small renal masses. The approach can be carried out by two techniques, either laparoscopic cryoablation (LCA) or percutaneous cryoablation, (PCA) with CT guidance. We aimed to compare between the two procedures. Materials and Methods: A systematic review and meta-analysis was conducted, including studies comparing the two techniques. Outcomes included incomplete ablation, late local recurrence, cancer-specific survival, procedure time, transfusion rates, hospital stay, and complications. Results: A total of 1475 patients were included, 788 patients in the laparoscopic group and 687 patients in the percutaneous group. There was statistical difference favoring the laparoscopic group with regard to having less incomplete ablation (p = 0.0008) and higher cancer-specific survival patients (p = 0.04). However, there was longer hospital stays in the LCA group (p < 0.00001) and was found to be more costly than the PCA group. There was significantly more Clavien-I complications in the PCA group (p = 0.001) and more Clavien-III complications in the LCA group (p = 0.001). Otherwise, there were no differences in any other outcome parameter. Conclusion: LCA was found to have less incomplete tumor ablation rates and higher cancer-specific survival rates, however, higher hospitalization time, more major complications (Clavien III), and was costlier compared with PCA

Small Left Atrium: An Adjunctive Sign of Hemodynamically Compromised Massive Pulmonary Embolism

Pulmonary embolism (PE) is a common disease with a high mortality rate due to right ventricular dysfunction and underfilling of the left ventricle. We present a case of a 33-year-old man with hemodynamically compromised massive PE. His left atrium was collapsed with marked dilatation of the right atrium and ventricle on multi-detector-row CT scans. The patient was treated with an intracatheter injection of a mutant tissue-type plasminogen activator and subsequently showed clinical and radiological improvements. The small left atrial size in combination with a right ventricular pressure overload was considered to be an adjunctive sign of hemodynamically compromised massive PE

Combined chemical genetics and data-driven bioinformatics approach identifies receptor tyrosine kinase inhibitors as host-directed antimicrobials

Immunogenetics and cellular immunology of bacterial infectious disease

Multislice CT Virtual Intravascular Endoscopy for Assessing Pulmonary Embolisms: a Pictorial Review

Multislice CT has been widely used in clinical practice for diagnosing cardiovascular disease due to its reduced invasiveness and its high spatial and temporal resolution. As a reliable alternative to conventional pulmonary angiography, multislice CT angiography has been recognized as the first line technique for detecting and diagnosing pulmonary embolism. A pulmonary embolism located in the main pulmonary artery, as well as being located in the segmental branches, can be accurately detected with multislice CT imaging, and especially with the use of 16- and 64-slice CT scanners. Visualization of pulmonary embolisms has traditionally been limited to 2D, multiplanar reformation and the 3D external surface visualizations. In this pictorial review, we present our experience of using 3D virtual intravascular endoscopy to characterize and evaluate the intraluminal appearance of pulmonary embolisms in a group of patients who were suspected of having pulmonary embolism and who were undergoing multislice CT angiography. We expect that the research findings from this study will provide insight into the extent of disease and the luminal changes to the pulmonary arteries that are due to the presence of thrombus, and so monitoring of the progress of disease and predicting the treatment outcome can well be achieved

Diagnosing pulmonary embolism: establishing and consolidating the role of spiral CT

In the Antelope study availability, use and diagnostic accuracy of spiral CT in patients clinically suspected of PE was investigated. This study was divided in two separate phases, starting with a prospective evaluation of available diagnostic techniques part of the diagnostic consensus strategy in The Netherlands in a specifically designed algorithm. Phase I showed that in a direct comparison with the gold standard sensitivity and specificity of spiral CT is too low to endorse its role as a single test to exclude pulmonary embolism. Also spiral CT had a limited added value as a second procedure following ventilation-perfusion scintigraphy. The accuracy of CT was significantly better in cases with interobserver agreement and good image quality. The available data of phase I was used for a cost-effectiveness analysis. Combined with recent literature data two new strategies were proposed and studied independently. Phase II showed in a prospective clinical management study that spiral CT can be used safely as a first line test to rule out pulmonary embolism in clinically suspected patients. It is also possible to reliably determine an alternative diagnosis in 25% of all patients. A new questionnaire showed that since 1997 the use of spiral CT has increased considerably