Towards a standardization of thrombin generation assessment: The influence of tissue factor, platelets and phospholipids concentration on the normal values of Thrombogram-Thrombinoscope assay

Background

Thrombin generation assay was developed several years ago to mimic physiological coagulation mechanisms but it had important limitations. Thrombogram-Thrombinoscope assay using a fluorogenic substrate, allows obtaining thrombin generation curves in non-defibrinated platelet rich plasma (PRP) in a fully automated manner.

Methods

We standardised the methodology of Thrombogram-Thrombinoscope and we evaluated the precision of thrombin generation parameters (lag-time, maximum concentration of thrombin [Cmax], time required to reach Cmax [Tmax] and endogenous thrombin potential ETP) using different concentrations of recombinant human tissue factor, platelets or phospholipids. Normal values of thrombin generation assay were established in optimal experimental conditions.

Results

In the presence of low TF concentrations (final dilution of thromboplastin in plasma: 1/1000–1/2000) the Thrombogram assay showed intra-assay and inter-assay coefficients of variation lower than 9%. Thrombin generation parameters showed an important inter-individual variability and the coefficients of variation ranged from 18% to 50%. In PRP the lag-time, Cmax and Tmax but not the ETP, were influenced by TF concentration. Thrombin generation parameters were not influenced by variations of platelet concentration from 50 × 10⁹/l to 400 × 10⁹/l. The addition of synthetic procoagulant phospholipids in PPP strongly influenced all the parameters of thrombogram. For all the parameters of thrombogram a threshold effect was observed in the presence of phspholipid concentrations equal or higher to 4 μM. In frozen-thawed PRP the lag-time and the Tmax were significantly reduced and the Cmax was increased compared to the fresh PRP, but the ETP, the intra assay and the inter-assay coefficients of variation were similar in both test-systems.

Conclusion

Thrombogram-Thrombinoscope assay performed in fresh or in frozen-thawed PRP has an acceptable precision, with low inter-assay and intra-assay coefficient of variations. The concentration of TF is determinant for the normal values of the studied parameters of thrombin generation. When the assay is performed in PPP, thrombin generation parameters are influenced by the concentration of procoagulant synthetic phospholipids. The optimal experimental conditions were obtained in the presence of 1/1000 final dilution of thromboplastin, a platelet count higher than 50 × 10⁹/l and a synthetic phospholipid concentration higher than 4 μM.     

Prothrombotic markers in patients with acute myocardial infarction and left ventricular thrombus formation treated with pci and dual antiplatelet therapy

Background

The aim of the present study was to compare circulating levels of selected prothrombotic markers in patients suffering acute myocardial infarction (AMI) with and without left ventricular (LV) thrombus.

Methods

One hundred patients with AMI treated with PCI on the LAD and dual antiplatelet therapy were included. LV thrombus formation was detected by echocardiography and/or MRI in 15 patients. Fasting blood samples were drawn 4–5 days (baseline), 6–7 days, 8–9 days, 2–3 weeks and 3 months after the AMI for determination of haemostatic markers.

Results

We found higher levels of soluble tissue factor (TF) and D-dimer in the LV thrombus group 4–5 days, 8–9 days and 3 months (only TF) after the AMI compared to the patients without thrombus formation (p<0.05). Patients with TF in the upper quartile at baseline had significantly higher risk for LV thrombus (OR 4.2; 95% CI 1.2 -14.5; p=0.02, adjusted for infarct size). The levels of prothrombin fragment 1+2 (F1+2) and endogenous thrombin potential (ETP) were significantly lower in the thrombus group after 8–9 days (only ETP), 2–3 weeks and 3 months. The levels of plasminogen activator inhibitor 1 activity and tissue plasminogen activator antigen did not differ between the groups.

Conclusion

In the acute phase of AMI, we found higher levels of TF and D-dimer in the LV thrombus group, indicating hypercoagulability of possible importance for the generation of mural thrombus. Lower levels of F1+2, ETP and D-dimer in the thrombus group late during follow-up are probably induced by the initiated anticoagulation therapy.     

Thrombotic genetic risk factors and warfarin pharmacogenetic variants in São Miguel's healthy population (Azores)

Objectives and Background

Tissue factor (TF) contributes to thrombosis following plaque disruption in acute coronary syndromes (ACS). Aim of the study was to investigate the impact of plasma TF activity on prognosis in patients with ACS.

Methods and Results

One-hundred seventy-four patients with unstable Angina pectoris (uAP) and 112 patients with acute myocardial infarction (AMI) were included with a mean follow up time of 3.26 years. On admission, plasma TF activity was assessed. Patients were categorized into 2 groups: a high-TF activity group with TF >24 pmol/L and low TF activity group with TF ≤ 24 pmol/L. Fifteen cardiovascular deaths occurred in the uAP group and 16 in the AMI group. In AMI TF activity was 24,9 ± 2,78 pmol/l (mean ± SEM) in survivors and 40,9 ± 7,96 pmol/l in nonsurvivors (P = 0.024). In uAP no differences were observed (25.0 ± 8.04 pmol/L nonsurvivors vs. 25.7 ± 2.14 pmol/L survivors; P = 0.586). Kaplan-Meier estimates of survival at 3.26 years regarding TF activity in AMI were 81.3% and 92.2% with an hazard ratio of 3.02 (95% CI [1.05–8.79], P = 0.03). The Cox proportional hazards model adjusting for correlates of age and risk factors showed that plasma TF activity was an independent correlate of survival (hazard ratio 9.27, 95% CI [1.24–69.12], P = 0.03). In an additional group of patients with uAP and AMI, we identified circulating microparticles as the prevailing reservoir of plasma TF activity in acute coronary syndromes.

Conclusion

Systemic TF activity in AMI has an unfavorable prognostic value and as a marker for dysregulated coagulation may add to predict the atherothrombotic risk.     

Effects of piroximone on the right ventricular function in severe heart failure patients

Objectives

To assess the effects of piroximone, a phosphodiesterase inhibitor, on right ventricular function in patients with heart failure.

Design

Randomized study: patients were randomly assigned to the piroximone infusion rate of 5 or 10 μg/kg/min.

Setting

Cardiologic intensive care unit.

Patients

12 consecutive patients with severe heart failure.

Interventions

Right heart catheterization was performed using a Swan-Ganz ejection fraction thermodilution catheter.

Measurements and results

Measurements of right ventricular ejection fraction (RVEF), end-diastolic and end-systolic right ventricular volumes were obtained using the thermodilution principle. To determine contractility indexes, the relationships between end-systolic pulmonary arterial pressure (ESPAP) over right ventricular end-systolic volume (RVESV) and ESPAP over RVEF were calculated during the infusion of prostacyclin at incremental infusion rates of 2, 4, 6 and 8 ng/kg/min. The slope of the relation between ESPAP over RVESV shifted during piroximone therapy from 7.635±1.632 to 1.975±0.432 (p<0.01) and from 6.092±1.99 to 1.028±0.853 (p<0.05) at 5 and 10 μg/kg/min piroximone infusion, respectively. The slope of the relation between ESPAP over RVEF decreased from ?0.414±0.296 to ?0.821±0.257 (p<0.01) and from ?0.127±0.048 to ?0.533±0.135 (p<0.05) at 5 and 10 μg/kg/min piroximone infusion, respectively.

Conclusions

This study suggests a positive action of piroximone on right ventricular contractility at these 2 dosages. This approach using this type of catheter allowed us to determine right ventricular inotropic indexes.     

Microparticles are new biomarkers of septic shock-induced disseminated intravascular coagulopathy

Purpose

Septic shock-induced disseminated intravascular coagulopathy (DIC) contributes to multiple organ failure. Mechanisms governing vascular responses to open occurrence of DIC have not yet been established. Circulating plasma microparticles (MPs), released upon cell stress, constitute a catalytic procoagulant surface and are surrogates of vascular cell activation/injury. Herein, MPs were assessed as possible markers of haemostatic and vascular dysfunction in the DIC time course.

Methods

One hundred patients with septic shock from three ICUs were enrolled and their haemostatic status evaluated at admission (D1), D2, D3 and D7. Circulating procoagulant MPs were isolated, quantified by prothrombinase assay and their cellular origin determined. DIC diagnosis was made according to the JAAM 2006 score.

Results

Ninety-two patients were analysed and 40 had DIC during the first 24 h. Routine clotting times and factor/inhibitor activity did not allow assessing vascular cell involvement. At admission, thrombin generation and fibrinolysis were observed in both groups while impaired fibrin polymerisation was evidenced only in DIC patients. Sustained thrombin generation persisted over time in both groups at D7. While total microparticle concentrations were in the same range regardless of DIC diagnosis, specific phenotypes were already detected at admission in DIC patients. Endothelial- and leucocyte-derived MPs were higher in DIC while an increased soluble glycoprotein V/platelet ratio was delayed, underscoring the first involvement of endothelial cells and leucocytes whereas platelet activation was delayed. Endothelium-derived CD105-MPs (OR 6.55) and CD31-MPs (OR 0.49) were strongly associated with early DIC in multivariate analysis.

Conclusion

Endothelial-derived microparticles are relevant biomarkers of septic shock-induced DIC and could be used to evaluate early vascular injury.     

Cardiac structure and function during ageing in energetically compromised Guanidinoacetate N-methyltransferase (GAMT)-knockout mice – a one year longitudinal MRI study

Background

In thalassemia major (TM), severe cardiac siderosis can be treated by continuous parenteral deferoxamine, but poor compliance, complications and deaths occur. Combined chelation therapy with deferiprone and deferoxamine is effective for moderate myocardial siderosis, but has not been prospectively examined in severe myocardial siderosis.

Methods

T2* cardiovascular magnetic resonance (CMR) was performed in 167 TM patients receiving standard subcutaneous deferoxamine monotherapy, and 22 had severe myocardial siderosis (T2* < 8 ms) with impaired left ventricular (LV) function. Fifteen of these patients received combination therapy with subcutaneous deferoxamine and oral deferiprone with CMR follow-up.

Results

At baseline, deferoxamine was prescribed at 38 ± 10.2 mg/kg for 5.3 days/week, and deferiprone at 73.9 ± 4.0 mg/kg/day. All patients continued both deferiprone and deferoxamine for 12 months. There were no deaths or new cardiovascular complications. The myocardial T2* improved (5.7 ± 0.98 ms to 7.9 ± 2.47 ms; p = 0.010), with concomitant improvement in LV ejection fraction (51.2 ± 10.9% to 65.6 ± 6.7%; p < 0.001). Serum ferritin improved from 2057 (CV 7.6%) to 666 (CV 13.2%) μg/L (p < 0.001), and liver iron improved (liver T2*: 3.7 ± 2.9 ms to 10.8 ± 7.3 ms; p = 0.006).

Conclusion

In patients with severe myocardial siderosis and impaired LV function, combined chelation therapy with subcutaneous deferoxamine and oral deferiprone reduces myocardial iron and improves cardiac function. This treatment is considerably less onerous for the patient than conventional high dose continuous subcutaneous or intravenous deferoxamine monotherapy, and may be considered as an alternative. Very prolonged tailored treatment with iron chelation is necessary to clear myocardial iron, and alterations in chelation must be guided by repeated myocardial T2* scans.

Trial registration

This trial is registered as NCT00103753     

Mass transfer, clearance and plasma concentration of procalcitonin during continuous venovenous hemofiltration in patients with septic shock and acute oliguric renal failure

Objectives

To measure the mass transfer and clearance of procalcitonin (PCT) in patients with septic shock during continuous venovenous hemofiltration (CVVH), and to assess the mechanisms of elimination of PCT.

Setting

The medical department of intensive care.

Design

A prospective, observational study.

Patients

Thirteen critically ill patients with septic shock and oliguric acute renal failure requiring continuous venovenous postdilution hemofiltration with a high-flux membrane (AN69 or polyamide) and a 'conventional' substitution volume (< 2.5 l/hour).

Measurements and main results

PCT was measured with the Lumitest PCT Brahms^® in the prefilter and postfilter plasma, in the ultrafiltrate at the beginning of CVVH (T0) and 15 min (T15'), 60 min (T60') and 6 hours (T6h) after setup of CVVH, and in the prefilter every 24 hours during 4 days. Mass transfer was determined and the clearance and the sieving coefficient were calculated according to the mass conservation principle. Plasma and ultrafiltrate clearances, respectively, at T15', T60' and T6h were 37 ± 8.6 ml/min (not significant) and 1.8 ± 1.7 ml/min (P < 0.01), 34.7 ± 4.1 ml/min (not significant) and 2.3 ± 1.8 ml/min (P < 0.01), and 31.5 ± 7 ml/min (not significant) and 5 ± 2.3 ml/min (P < 0.01). The sieving coefficient significantly increased from 0.07 at T15' to 0.19 at T6h, with no difference according to the nature of the membrane. PCT plasma levels were not significantly modified during the course of CCVH.

Conclusions

We conclude that PCT is removed from the plasma of patients with septic shock during CCVH. Most of the mass is eliminated by convective flow, but adsorption also contributes to elimination during the first hours of CVVH. The effect of PCT removal with a conventional CVVH substitution fluid rate (<2.5 l/hour) on PCT plasma concentration seems to be limited, and PCT remains a useful diagnostic marker in these septic patients. The impact of high-volume hemofiltration on the PCT clearance, the mass transfer and the plasma concentration should be evaluated in further studies.     

Positron Emission Tomography of 64Cu-DOTA-Rituximab in a Transgenic Mouse Model Expressing Human CD20 for Clinical Translation to Image NHL

Purpose

This study aims to evaluate ⁶⁴Cu-DOTA-rituximab (PETRIT) in a preclinical transgenic mouse model expressing human CD20 for potential clinical translation.

Procedures

⁶⁴Cu was chelated to DOTA-rituximab. Multiple radiolabeling, quality assurance, and imaging experiments were performed. The human CD20 antigen was expressed in B cells of transgenic mice (CD20TM). The mice groups studied were: (a) control (nude mice, n?=?3) that received 7.4?MBq/dose, (b) with pre-dose (CD20TM, n?=?6) received 2?mg/kg pre-dose of cold rituximab prior to PETRIT of 7.4?MBq/dose, and (c) without pre-dose (CD20TM, n?=?6) PETRIT alone received 7.4?MBq/dose. Small animal PET was used to image mice at various time points (0, 1, 2, 4, 24, 48, and 72?h). The OLINDA/EXM software was used to determine the human equivalent dose for individual organs.

Results

PETRIT was obtained with a specific activity of 545?±?38.91?MBq/nmole, radiochemical purity >95%, and immunoreactivity >75%. At 24?h, spleenic uptake of PETRIT%ID/g (mean?±?STD) with and without pre-dose was 1.76?±?0.43% and 16.5?±?0.45%, respectively (P value?=?0.01). Liver uptake with and without pre-dose was 0.41?±?0.51% and 0.52?±?0.17% (P value?=?0.86), respectively. The human equivalents of highest dose organs with and without pre-dose are osteogenic cells at 30.8?±?0.4???Sv/MBq and the spleen at 99?±?4???Sv/MBq, respectively.

Conclusions

PET imaging with PETRIT in huCD20 transgenic mice provided human dosimetry data for eventual applications in non-Hodgkins lymphoma patients.     

Initial Experience with the Radiotracer Anti-1-amino-3-[18F]Fluorocyclobutane-1-Carboxylic Acid (Anti-[18F]FACBC) with PET in Renal Carcinoma

Purpose

Assessment of renal masses with conventional imaging may be challenging. Anti-1-amino-3-[¹⁸F]fluorocyclobutane-1-carboxylic acid (anti-[18F]FACBC) is a synthetic l-leucine analog with relatively little renal excretion. The present study examines anti-[¹⁸F]FACBC positron emission tomography uptake in patients with renal masses.

Procedures

Six patients with seven renal lesions were imaged dynamically for 2 h after injection of 10–10.9 mCi (370–403 MBq) anti-[¹⁸F]FACBC. Lesions were evaluated qualitatively and quantitatively and correlated with histology.

Results

Four clear cell and one Rosai–Dorfman lesion were hypo/isointense to normal cortex; two papillary lesions in the same patient were hyperintense. Mean SUV_max?±?SD at 30 min was 2.8?±?0.24 for clear cell carcinomas and 4.5?±?1.7 for papillary cell lesions. Mean SUV_max/SUV_mean ratios?±?SD of lesion to normal cortex at 30 min was 1.15?±?0.19 for the clear cell carcinomas and 2.3?±?0.84 for papillary cell.

Conclusions

In this small patient sample, relative amino acid transport compared with renal cortex is elevated in renal papillary cell carcinoma but not in clear cell carcinoma.     

Herpes simplex virus type 1 and normal protein permeability in the lungs of critically ill patients: a case for low pathogenicity?

Introduction

The pathogenicity of late respiratory infections with herpes simplex virus type 1 (HSV-1) in the critically ill is unclear.

Methods

In four critically ill patients with persistent pulmonary infiltrates of unknown origin and isolation of HSV-1 from tracheal aspirate or bronchoalveolar lavage fluid, at 7 (1–11) days after start of mechanical ventilatory support, a pulmonary leak index (PLI) for ⁶⁷Gallium (⁶⁷Ga)-transferrin (upper limit of normal 14.1 × 10^-3/min) was measured.

Results

The PLI ranged between 7.5 and 14.0 × 10^-3/min in the study patients. Two patients received a course of acyclovir and all survived.

Conclusions

The normal capillary permeability observed in the lungs argues against pathogenicity of HSV-1 in the critically ill, and favors that isolation of the virus reflects reactivation in the course of serious illness and immunodepresssion, rather than primary or superimposed infection in the lungs.     

In Vitro and In Vivo Characterization of Two C-11-Labeled PET Tracers for Vesicular Acetylcholine Transporter

Purpose

The vesicular acetylcholine transporter (VAChT) is a specific biomarker for imaging presynaptic cholinergic neurons. Herein, two potent and selective ¹¹C-labeled VAChT inhibitors were evaluated in rodents and nonhuman primates for imaging VAChT in vivo.

Procedures

For both (?)-[¹¹C]2 and (?)-[¹¹C]6, biodistribution, autoradiography, and metabolism studies were performed in male Sprague Dawley rats. Positron emission tomography (PET) brain studies with (?)-[¹¹C]2 were performed in adult male cynomolgus macaques; 2 h dynamic data was acquired, and the regions of interest were drawn by co-registration of the PET images with the MRI.

Results

The resolved enantiomers (?)-2 and (?)-6 were very potent and selective for VAChT in vitro (K _i ?35-fold selectivity for VAChT vs. σ receptors); both radioligands, (?)-[¹¹C]2 and (?)-[¹¹C]6, demonstrated high accumulation in the VAChT-enriched striatum of rats. (?)-[¹¹C]2 had a higher striatum to cerebellum ratio of 2.4-fold at 60 min; at 30 min, striatal uptake reached 0.550?±?0.086 %ID/g. Uptake was also specific and selective; following pretreatment with (±)-2, striatal uptake of (?)-[¹¹C]2 in rats at 30 min decreased by 50 %, while pretreatment with a potent sigma ligand had no significant effect on striatal uptake in rats. In addition, (?)-[¹¹C]2 displayed favorable in vivo stability in rat blood and brain. PET studies of (?)-[¹¹C]2 in nonhuman primates indicate that it readily crosses the blood-brain barrier (BBB) and provides clear visualization of the striatum; striatal uptake reaches the maximum at 60 min, at which time the target to nontarget ratio reached ~2-fold.

Conclusions

The radioligand (?)-[¹¹C]2 has high potential to be a suitable PET radioligand for imaging VAChT in the brain of living subjects.     

Fully Automated Radiosynthesis of 2-[18F]Fludarabine for PET Imaging of Low-Grade Lymphoma

Purpose

An efficient and fully automated radiosynthesis of 2-[¹⁸F]fluoro-9-β-d-arabinofuranosyl-adenine (2-[¹⁸F]fludarabine, [¹⁸F]-5) based on a GE TRACERlab? FX-FN module has been developed.

Procedures

A 2-nitro purine derivative 3 was developed as precursor for labeling with fluorine-18. The radiosynthesis of [¹⁸F]-5 was performed in two steps in a single reactor with an intermediary purification on Sep-Pak® silica which involved the addition of a three-way valve on the original module. After hydrolysis, [¹⁸F]-5 was purified by semi-preparative high-pressure liquid chromatography (HPLC) and a quality control was established.

Results

The labeling precursor 3 was obtained in 45 % overall yield. Nucleophilic substitution with K¹⁸F/K_2.2.2 afforded protected 2-[¹⁸F]fludarabine ([¹⁸F]-4) in 73?±?4 % , radiochemical yield (decay corrected to the end of bombardment (EOB)) and based on the initial [¹⁸F]F^? activity. An aqueous ammonia/methanol solution was used for the deprotection reaction and gave the desired [¹⁸F]-5 in 67?±?3 % yield after 20 min at 70 °C based on HPLC profile.

Conclusions

The process afforded pure 2-[¹⁸F]fludarabine in 48?±?3 % yield (decay corrected to the EOB) in 85 min, with a specific activity of 310?±?72 GBq/μmol at the end of synthesis (EOS) and a radiochemical purity up to 99 %.     

Assessment of Airway Distribution of Transnasal Solutions in Mice by PET/CT Imaging

Purpose

Transnasal administration is one of the most common routes for allergen challenge in mouse models of airway diseases. Although this technique is widely used, neither the amount of allergen that reaches the lung nor its airway distribution has been well established. We used positron emission tomography (PET) and computed tomography (CT) to examine the anatomical distribution of a solution containing a tracer immediately after transnasal delivery and to determine the possible influence of age and administered volume.

Procedures

Forty-six female BALB/c mice were divided into three groups according to instillation volume and age: (A) 15 μl, 8–10 weeks old (N?=?10), (B) 30 μl, 8–10 weeks old (N?=?20), and (C) 30 μl, 32 weeks old (N?=?16). Anesthetized animals underwent a dynamic scan in a dedicated small-animal PET scanner immediately after transnasal administration of a solution containing ¹⁸FDG. Regions of interest were used to obtain quantitative data. Animals were also imaged with a small-animal CT scanner to obtain complementary anatomical information.

Results

Mean?±?SD (5.69?±?4.51%) of the solution administered reached the lungs in group A, 41.84?±?8.03% in group B, and 36.65?±?16.15% in group C. A comparable percentage was delivered to the left and right lungs in all the groups. Analysis of variance revealed a significant difference between the groups in the proportion of the solution that reached the lungs depending on the injection volume (P?Conclusions In this first report on quantitative imaging by PET and CT in small animals, we confirmed the suitability of the transnasal route with an instilled volume of 30 μl delivering fluids into the lower airways, although only about 40% of the dose reaches the lungs.     

应用凝血酶生成试验评估肝硬化患者血栓形成风险的研究

目的：研究抗凝血因子和促凝血因子对凝血酶原时间（PT ）、活化部分凝血活酶时间（APTT ）和凝血酶生成试验（TGA）结果的影响,探讨TGA用于评估肝硬化患者血栓形成风险的价值。方法收集93名肝硬化患者和50名健康人群的血液标本,分别进行凝血象、凝血活酶、抗凝因子和抗凝血酶的测定。TGA利用荧光读数仪测定,通过软件监测绘制样本的凝血酶生成曲线。结果 PT受凝血因子（F）Ⅱ、FⅤ、FⅦ、FⅨ和蛋白C浓度的影响,而 APTT 结果主要由 FⅡ、FⅨ和 FⅩ决定。在5 pmol/L组织因子（TF）的TGA反应体系中,凝血酶生成潜力（ETP）比值受FⅡ、抗凝血酶和蛋白C水平的影响,并且肝硬化组与对照组之间没有明显差异;而在1 pmol/L T F反应体系中ET P比值主要由FⅨ和蛋白C决定,肝硬化组与对照组的ET P比值差异有统计学意义（P＜0．05）。结论 PT和 TGA 受凝血和抗凝因子的调控,并且 TGA实验对于蛋白C浓度变化较为敏感;TGA能够在PT延长的情况下,提示肝硬化患者存在血栓形成的风险,TGA可作为临床评估肝硬化患者血液高凝状态的敏感指标。     

Patterns of physical activity participation across the cancer trajectory in colorectal cancer survivors

Purpose

The purpose of the present study was to explore the participation in physical activity (PA) by colorectal cancer survivors across cancer trajectories and based on selected demographic and medical variables.

Methods

A total of 431 participants were surveyed individually at the Shinchon Severance Hospital, Seoul, Korea, to determine their PA levels before diagnosis, during treatment and after completion of cancer treatment.

Results

Percentage of survivors meeting American College of Sports Medicine guideline significantly reduced from 27 % before diagnosis to 10 % during treatment due to reduced strenuous intensity PA (28.8?±?106.2 vs 11.8?±?95.9 min, p?=?0.042), while total PA and mild intensity PA did not change. Total (187.2?±?257.7 vs. 282.6?±?282.0 min, p?<?0.001) and mild (99.1?±?191.5 vs. 175.1?±?231.2 min, p?<?0.001) intensity PA significantly increased after the completion of treatments compared with their PA level before diagnosis. Further analyses showed that age (more vs. equal or less than 60 years) and chemotherapy (chemotherapy vs. no chemotherapy) significantly influenced the level of physical activity (p?=?0.004). Survivors who were older or received chemotherapy increased their total PA and mild intensity PA after the completion of treatment more than those who did not receive chemotherapy.

Conclusions

The level and the pattern of physical activity by colorectal cancer survivors differed across cancer trajectories, which were significantly influenced by age and adjuvant chemotherapy.     

Myocardial tissue tagging with cardiovascular magnetic resonance

Aims

Patients with prior major cardiovascular or cerebrovascular events (MACE) are more likely to have future recurrent events independent of traditional cardiovascular disease risk factors. The purpose of this study was to determine if patients with traditional risk factors and prior MACE had increased cardiovascular magnetic resonance (CMR) plaque burden measures compared to patients with risk factors but no prior events.

Methods and Results

Black blood carotid and thoracic aorta images were obtained from 195 patients using a rapid extended coverage turbo spin echo sequence. CMR measures of plaque burden were obtained by tracing lumen and outer vessel wall contours. Patients with prior MACE had significantly higher MR plaque burden (wall thickness, wall area and normalized wall index) in carotids and thoracic aorta compared to those without prior MACE (Wall thickness carotids: 1.03 ± 0.03 vs. 0.93± 0.03, p = 0.001; SD wall thickness carotids: 0.137 ± 0.0008 vs. 0.102 ± 0.0004, p < 0.001; wall thickness aorta: 1.63 ± 0.10 vs. 1.50 ± 0.04, p = 0.009; SD wall thickness aorta: 0.186 ± 0.035 vs. 0.139 ± 0.012, p = 0.009 respectively). Plaque burden (wall thickness) and plaque eccentricity (standard deviation of wall thickness) of carotid arteries were associated with prior MACE after adjustment for age, sex, and traditional risk factors. Area under ROC curve (AUC) for discriminating prior MACE improved by adding plaque eccentricity to models incorporating age, sex, and traditional CVD risk factors as model inputs (AUC = 0.79, p = 0.05).

Conclusion

A greater plaque burden and plaque eccentricity is prevalent among patients with prior MACE.     

Feasibility and safety of transradial approach for catheter ablation of idiopathic left ventricular tachycardia

Background

The feasibility and safety of the transradial approach for catheter ablation of idiopathic left ventricular tachycardia (ILVT) have not been evaluated. The aim of this study was to investigate the feasibility and safety of transradial approach for catheter ablation in ILVT patients.

Methods

Thirty consecutive ILVT patients with negative Allen??s test undergoing catheter ablation via transradial approach were enrolled to compare the safety and efficacy with 30 other ILVT patients who previously underwent catheter ablation via transfemoral approach.

Results

Ablation was successfully performed in all patients. In the transradial group, the total procedural and the fluoroscopy time (42.8?±?6.9?min and 9.7?±?1.9?min, respectively) were significantly shorter when compared with transfemoral group (52.8?±?8.4?min and 11.5?±?2.1?min, respectively) (both P?<?0.05). The two groups were similar in the number of current applications (4.1?±?0.8 vs. 4.4?±?1.1, P?>?0.05), the power energy (47.3?±?7.3 vs. 49.7?±?6.9?W, P?>?0.05), and the total duration of current application (110.3?±?15.6 vs. 112.3?±?16.5?s, P?>?0.05), respectively. The duration of hospitalization in transradial group was shorter than that in transfemoral group (4.1?±?0.9 vs. 5.8?±?1.1?days, P?<?0.05). During follow-up, there was no recurrence of tachycardia in all patients. One patient in transfemoral group developed access site complications while none occurred in the transradial group.

Conclusions

The transradial approach is feasible and safe for catheter ablation of ILVT.     

Chemotherapy-induced thrombin generation via procoagulant endothelial microparticles is independent of tissue factor activity

BACKGROUND: Cisplatin-based chemotherapy predisposes cancer patients to thromboembolic events. OBJECTIVES: To investigate whether endothelial damage, via formation of procoagulant endothelial microparticles (EMPs), contributes to cisplatin-related hypercoagulability. METHODS: Cell viability and caspase-3/7 activities were assessed in two endothelial cell (EC) lines [human umbilical vein ECs (HUVECs) and human pulmonary microvascular ECs (HMVEC-Ls)] after exposure to cisplatin (1, 2.5, 5, 10 and 20 microm) for up to 120 h. Counts and procoagulant activity of EMPs were measured by flow cytometry and a thrombin generation assay, respectively. Tissue factor (TF) antigen and TF-dependent procoagulant activity of EMP were determined by enzyme-linked immunosorbent assay and a novel functional assay. RESULTS: By inducing apoptosis, cisplatin dose- and time-dependently decreased the viability of confluent HUVECs and HMVEC-Ls. Progression of EC death was accompanied by an increased release of EMPs (relative increase at 20 microm cisplatin for 48 h vs. control: HUVECs 6.5-fold, P < 0.001; HMVEC-Ls 18.4-fold, P < 0.001). EMPs were highly procoagulant (relative increase at 20 microm cisplatin for 48 h vs. control: HUVECs 2.5-fold, P < 0.001; HMVEC-Ls 5.9-fold, P < 0.001). EMP-driven thrombin generation, however, was not dependent on TF: TF expression and TF procoagulant activity levels on microparticles were only marginal and EMP-associated thrombin generation remained unchanged when the extrinsic pathway was blocked by omission of factor VIIa and/or incubation with an anti-human TF antibody. In contrast, blocking of phospholipids by annexin V markedly diminished EMP-associated procoagulant activity. CONCLUSIONS: In vitro, cisplatin induced the release of EMPs that showed TF-independent procoagulant activity.