The potential of iodinated contrast reduction in dual-energy CT thoracic angiography; an evaluation of image quality.

INTRODUCTION: The purpose of this study was to compare a dual energy CT (DECT) protocol with 50% reduction of iodinated contrast to a single energy CT (SECT) protocol using standard contrast dose in imaging of the thoracic aorta. METHODS: DECT with a 50% reduction in iodinated contrast was compared with SECT. For DECT, monoenergetic images at 50, 55, 60, 65, 68, 70, and 74 keV were reconstructed with adaptive statistical iterative reconstruction (ASiR-V) of 50% and 80%. Objective image quality parameters included intravascular attenuation (HU), image noise (SD), contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR). Two independent radiologists subjectively assessed the image quality for the 55 and 68 keV DECT reconstructions and SECT on a five-point Likert scale. RESULTS: Across 14 patients, the intravascular attenuation at 50-55 keV was comparable to SECT (p > 0.05). The CNRs were significantly lower for DECT with ASIR-V 50% compared to SECT for all keV-values (p < 0.05 for all). For ASIR-V 80%, CNR was comparable to SECT at energies below 60 keV (p > 0.05). The subjective image quality was comparable between DECT and SECT independent of keV level. CONCLUSION: This study indicates that a 50% reduction in iodinated contrast may result in adequate image quality using DECT with monoenergetic reconstructions at lower energy levels for the imaging of the thoracic aorta. The best image quality was obtained for ASiR-V 80% image reconstructions at 55 keV. IMPLICATIONS OF PRACTICE: Dual energy CT with a reduction in iodinated contrast may result in adequate image quality in imaging of the thoracic aorta. However, increased radiation dose may limit the use to patients in which a reduction in fluid and iodinated contrast volume may outweigh this risk.

Patency and Clinical Outcome After Stent Placement for Chronic Obstruction of the Inferior Vena Cava.

OBJECTIVE/BACKGROUND: The objective was to assess the technical success, patency, and clinical outcome after stent placement for chronic obstruction of the inferior vena cava (IVC). METHODS: A retrospective analysis was carried out of patients with chronic IVC obstruction verified with computed tomography and/or magnetic resonance venography, accepted for stent placement at the Norwegian National Unit for Reconstructive Deep Venous Surgery from March 2010 to September 2015. Clinical status was categorized according to the CEAP classification and symptom severity was assessed using venous clinical severity score (VCSS). Stent patency was evaluated by colour duplex ultrasound. Large -diameter Wallstents were placed in the IVC and concurrent iliac and femoral obstructions via right internal jugular and femoral vein access. Sixteen patients presented with symptoms of chronic venous disease. Four patients had symptoms assumed to be related to a reduced cardiac preload. Twelve patients had IVC occlusion and eight had stenosis. Median follow-up was 25 months (range 3-70 months). RESULTS: Stent placement in the IVC was successful in 19 of 20 patients. Primary patency after 24 months was 67% and secondary patency 83%. Fifteen of 19 patients had open stents at final follow-up. Re-interventions were performed in four patients and included catheter directed thrombolysis in all and adjunctive stenting in three. Thirteen of 19 patients (68%) reported a sustained and significant clinical improvement. Mean VCSS improved from 8.5 (range 3-25) at baseline to 7 (range 2-23) at final follow-up (p = .007). There were no peri-procedural or long-term complications. CONCLUSION: The endovascular approach with stent placement for chronic IVC obstruction is a safe treatment option that should be offered to patients who otherwise have little opportunity for sustained clinical improvement.

Cost-effectiveness of additional catheter-directed thrombolysis for deep vein thrombosis.

BACKGROUND: Additional treatment with catheter-directed thrombolysis (CDT) has recently been shown to reduce post-thrombotic syndrome (PTS). OBJECTIVES: To estimate the cost effectiveness of additional CDT compared with standard treatment alone. METHODS: Using a Markov decision model, we compared the two treatment strategies in patients with a high proximal deep vein thrombosis (DVT) and a low risk of bleeding. The model captured the development of PTS, recurrent venous thromboembolism and treatment-related adverse events within a lifetime horizon and the perspective of a third-party payer. Uncertainty was assessed with one-way and probabilistic sensitivity analyzes. Model inputs from the CaVenT study included PTS development, major bleeding from CDT and utilities for post DVT states including PTS. The remaining clinical inputs were obtained from the literature. Costs obtained from the CaVenT study, hospital accounts and the literature are expressed in US dollars ($); effects in quality adjusted life years (QALY). RESULTS: In base case analyzes, additional CDT accumulated 32.31 QALYs compared with 31.68 QALYs after standard treatment alone. Direct medical costs were $64,709 for additional CDT and $51,866 for standard treatment. The incremental cost-effectiveness ratio (ICER) was $20,429/QALY gained. One-way sensitivity analysis showed model sensitivity to the clinical efficacy of both strategies, but the ICER remained < $55,000/QALY over the full range of all parameters. The probability that CDT is cost effective was 82% at a willingness to pay threshold of $50,000/QALY gained. CONCLUSIONS: Additional CDT is likely to be a cost-effective alternative to the standard treatment for patients with a high proximal DVT and a low risk of bleeding.

Long-term quality of life after pregnancy-related deep vein thrombosis and the influence of socioeconomic factors and comorbidity.

BACKGROUND: Little is known about the long-term impact of pregnancy-related deep vein thrombosis (DVT) of the lower limbs. OBJECTIVES: To evaluate the long-term consequences of pregnancy-related DVT by assessment of self-reported, disease-specific quality of life (QOL) and symptom severity using the Venous Insufficiency Epidemiological and Economic Study (VEINES)-QOL/Sym questionnaire, and to investigate the influence of socioeconomic factors and comorbidity. PATIENTS/METHODS: In this cross-sectional case-control study, 313 women with validated pregnancy-related DVT and 353 controls completed a comprehensive questionnaire, including the disease-specific VEINES-QOL/Sym questionnaire. After exclusion of DVT outside the lower limbs and missing scores, the study population comprised 208 patients and 347 controls. A VEINES-QOL/Sym score < the 25th percentile was defined as a clinically relevant reduced outcome compared with scores ≥ the 50th percentile. Predictors for low scores were identified in multivariate logistic regression models. RESULTS: Cases reported lower mean VEINES-QOL/Sym scores than controls, 45.6/45.4 vs. 52.8/52.7, respectively (P < 0.001), and QOL among cases was still reduced compared with controls when adjusted for possible confounders. Low education was an independent predictor for both low VEINES-QOL and VEINES-Sym scores, and in addition being married/cohabitating predicted low VEINES-Sym scores. CONCLUSIONS: Long-term QOL and symptom scores as assessed with the VEINES-QOL/Sym questionnaire were lower in women with previous pregnancy-related DVT than in controls, and also when adjusted for possible confounders. By logistic regression, low education was an independent predictor for low scores. This supports the use of the VEINES-QOL/Sym questionnaire in studies on pregnancy-related DVT.

Catheter-directed thrombolysis vs. anticoagulant therapy alone in deep vein thrombosis: results of an open randomized, controlled trial reporting on short-term patency.

BACKGROUND: Approximately one in four patients with acute proximal deep vein thrombosis (DVT) given anticoagulation and compression therapy develop post-thrombotic syndrome (PTS). Accelerated removal of thrombus by thrombolytic agents may increase patency and prevent PTS. OBJECTIVES: To assess short-term efficacy of additional catheter-directed thrombolysis (CDT) compared with standard treatment alone. PATIENTS AND METHODS: Open, multicenter, randomized, controlled trial. Patients (18-75 years) with iliofemoral DVT and symptoms < 21 days were randomized to receive additional CDT or standard treatment alone. After 6 months, iliofemoral patency was investigated using duplex ultrasound and air-plethysmography assessed by an investigator blinded to previous treatment. RESULTS: One hundred and three patients (64 men, mean age 52 years) were allocated additional CDT (n = 50) or standard treatment alone (n = 53). After CDT, grade III (complete) lysis was achieved in 24 and grade II (50%-90%) lysis in 20 patients. One patient suffered major bleeding and two had clinically relevant bleeding related to the CDT procedure. After 6 months, iliofemoral patency was found in 32 (64.0%) in the CDT group vs. 19 (35.8%) controls, corresponding to an absolute risk reduction (RR) of 28.2% (95% CI: 9.7%-46.7%; P = 0.004). Venous obstruction was found in 10 (20.0%) in the CDT group vs. 26 (49.1%) controls; absolute RR 29.1% (95% CI: 20.0%-38.0%; P = 0.004). Femoral venous insufficiency did not differ between the two groups. CONCLUSIONS: After 6 months, additional CDT increased iliofemoral patency from 36% to 64%. The ongoing long-term follow-up of this study will document whether patency is related to improved functional outcome.

CT pulmonary angiography and suspected acute pulmonary embolism.

PURPOSE: To evaluate the use and quality of CT pulmonary angiography in our department, and to relate the findings to clinical parameters and diagnoses. MATERIAL AND METHODS: A retrospective study of 324 consecutive patients referred to CT pulmonary angiography with clinically suspected pulmonary embolism (PE). From the medical records we registered clinical parameters, blood gases, D-dimer, risk factors and the results of other relevant imaging studies. RESULTS: 55 patients (17%) had PE detected on CT. 39 had bilateral PE, and 8 patients had isolated peripheral PE. 87% of the examinations showing PE had satisfactory filling of contrast material including the segmental pulmonary arteries, and 60% of the subsegmental arteries. D-dimer test was performed in 209 patients, 85% were positive. A negative D-dimer ruled out PE detected at CT. Dyspnea and concurrent symptoms or detection of deep vein thrombosis (DVT), contraceptive pills and former venous thromboembolism (VTE) were associated with PE. The presence of only one clinical parameter indicated a negative PE diagnosis (p < 0.017), whereas two or more suggested a positive PE diagnosis (p < 0.002). CT also detected various ancillary findings such as consolidation, pleural effusion, nodule or tumor in nearly half of the patients; however, there was no association with the PE diagnosis. CONCLUSION: The quality of CT pulmonary angiography was satisfactory as a first-line imaging of PE. CT also showed additional pathology of importance in the chest. Our study confirmed that a negative D-dimer ruled out clinically suspected VTE.

Binding of human factor VIIa to tissue factor induces cytosolic Ca2+ signals in J82 cells, transfected COS-1 cells, Madin-Darby canine kidney cells and in human endothelial cells induced to synthesize tissue factor.

Tissue factor (TF) is the most potent trigger of blood clotting known. It activates factor VII (FVII) thereby initiating a cascade of proteolytic reactions resulting in thrombin production. The cloning of TF revealed its structural characteristics to be those of a receptor related to the class 2 cytokine receptor superfamily, but until now no intracellular signal has been discovered related to binding of the ligand (FVIIa) to the putative receptor. We have studied possible intracellular signaling effects of the FVIIa-TF interaction by measuring cytosolic free Ca2+ in single fura-2-loaded cells and found that 200 nM FVIIa caused Ca2+ transients in about 30% of human umbilical vein endothelial cells treated with interleukin-1 beta to express TF, compared to below 5% in uninduced cells. A gradual increase of the basal Ca2+ level was also caused by binding of FVIIa. In the human bladder carcinoma cell line J82, which has a high constitutive TF activity, similar results were found. An antibody neutralizing TF activity decreased the response rate to control levels. COS-1 cells which do not make TF did not respond to FVIIa as opposed to COS-1 cells expressing TF after transfection with a human TF cDNA construct. The canine kidney cell line MDCK, a constitutive TF producer, responded especially well; up to 100% of the cells examined showed Ca2+ oscillations which were dose dependent with regard to frequency, latency, maximal amplitude, and recruitment of responding cells. The frequency was reduced by inhibition of Ca2+ influx with 100 microM LaCl3. In confluent MDCK cells the Ca2+ oscillations were synchronous, constituting the first evidence of a synchronous cytosolic Ca2+ oscillator generated by global application of agonist. Thus, TF mediates a cytosolic Ca2+ signal upon interaction with its ligand FVIIa, thereby suggesting a more complex biological role for TF.

Polar expression of tissue factor in human umbilical vein endothelial cells.

Endothelial cells grown on filters developed junctional complexes that reduced diffusional transport and increased electrical resistance over the cell layer. Induction of tissue factor by recombinant interleukin-1 beta led to a highly polarized tissue factor expression on the apical cell surface only. After prolonged growth to allow deposition of matrix, removal of the endothelial cells by collagenase or by 0.1 mol/L NH4OH left behind some cellular material as well as tissue factor, which was only detectable in the upper compartment. A human bladder carcinoma cell line, which does not form tight junctions and expresses tissue factor constitutively, showed essentially no polarity. Endothelial cell secretory compounds like von Willebrand factor, tissue plasminogen activator, and plasminogen activator inhibitor-1 were constitutively released to both sides. The added secretion due to recombinant interleukin-1 beta stimulation of the endothelial cells observed for von Willebrand factor and tissue plasminogen activator was, however, localized to the apical surface. The availability of tissue factor on the luminal surface of endothelial cells, ie, allowing contact with factor VII in the flowing blood, has potentially very significant pathophysiological consequences.