An MRI Radiomics Approach to Predict the Hypercoagulable Status of Gliomas

Venous thromboembolic events are frequent complications of Glioblastoma Multiforme (GBM) and low-grade gliomas (LGGs). The overexpression of tissue factor (TF) plays an essential role in the local hypercoagulable phenotype that underlies these complications. Our aim was to build an MRI radiomics model for the non-invasive exploration of the hypercoagulable status of LGG/GBM. Radiogenomics data from The Cancer Genome Atlas (TCGA) and REMBRANDT (Repository for molecular BRAin Neoplasia DaTa) cohorts were used. A logistic regression model (Radscore) was built in order to identify the top 20% TF-expressing tumors, considered to be at high thromboembolic risk. The most contributive MRI radiomics features from LGG/GBM linked to high TF were identified in TCGA using Least Absolute Shrinkage and Selection Operator (LASSO) regression. A logistic regression model was built, whose performance was analyzed with ROC in the TCGA/training and REMBRANDT/validation cohorts: AUC = 0.87 [CI95: 0.81–0.94, p 95: 0.56–1.00, p = 0.02], respectively. In agreement with the key role of the coagulation cascade in gliomas, LGG patients with a high Radscore had lower overall and disease-free survival. The Radscore was linked to the presence of specific genomic alterations, the composition of the tumor coagulome and the tumor immune infiltrate. Our findings suggest that a non-invasive assessment of the hypercoagulable status of LGG/GBM is possible with MRI radiomics

Intervention targeted at nurses to improve venous thromboprophylaxis.

International audienceOBJECTIVE: To assess the effectiveness of an intervention targeting both physicians and nurses vs. physicians only in improving venous thromboprophylaxis for older patients. DESIGN: Cluster randomized trial. SETTING: Fifty hospital-based post-acute care departments in France. PARTICIPANTS: Patients aged 65 years or older. INTERVENTION: A multifaceted intervention to implement a clinical practice guideline addressing venous thromboprophylaxis. MAIN OUTCOME MEASURES: The effectiveness outcomes were elastic stocking use, ambulation or mobilization under the supervision of a physical therapist and anticoagulant-based prophylaxis. Patient outcomes included deep vein thrombosis and anticoagulant-related adverse events. RESULTS: One department allocated to the intervention targeted at physicians only and seven departments allocated to the intervention targeted at both physicians and nurses dropped out of the study. Compared with the intervention targeted at physicians only (n = 497 patients), the intervention targeted at both physicians and nurses (n = 315 patients) was associated with a higher rate of mobilization (62 vs. 37%, P < 0.001) and comparable levels of elastic stocking (32 vs. 39%, P = 0.74) and anticoagulant (55 vs. 48%, P = 0.36) use. The rates of deep vein thrombosis (15 vs. 13%, P = 0.50), bleeding (1 vs. 1%, P = 0.99) and thrombocytopaenia (0 vs. 0.2%, P = 0.99) did not differ between the two groups. CONCLUSIONS: A multifaceted intervention targeting nurses in addition to physicians can increase the frequency of mobilization of older patients to prevent venous thromboembolism but does not alter the use of elastic stockings and anticoagulant. A differential drop-out of departments might have contributed to creating imbalances in baseline characteristics and outcomes in this study

Critical limb ischemia: thrombogenic evaluation of two autologous cell therapy products and biologic profile in treated patients

International audienceBackground: Cell therapy has been proposed as a salvage limb procedure in critical limb ischemia (CLI). Autologous cell therapy products (CTP) are obtained from patients with advanced peripheral arterial disease to be injected at the site of ischemia. Thrombogenicity of CTPs has not yet been assessed. The objectives were: 1) to assess thrombotic risk in candidates for cell therapy, 2) to evaluate two different CTPs in terms of thrombogenic potential, and 3) to evaluate clinical thrombotic events.Study design and methods: In this ancillary study of a Phase I and II clinical trial, bone marrow (BM)-CTPs (n = 20) and CTPs obtained by cytapheresis (peripheral blood [PB]-CTPs; n = 20) were compared. Inflammatory and coagulation markers were measured at baseline and 24 hours after CTP implantation. CTP cell content and tissue factor (TF) expression (mRNA and protein) were analyzed. Thrombin generation assessed CTP-related thrombogenicity.Results: All patients presented cardiovascular risk factors. At baseline, the patients' biologic profile was characterized by high levels of fibrinogen, C-reactive protein (CRP), D-dimer, interleukin (IL)-6, and plasmatic TF, whereas IL-10 was low. Although different in terms of cell composition, both BM- and PB-CTPs support low thrombin generation. Twenty-four hours after implantation, biologic markers remained stable in the PB-CTP group, except for IL-6. In the BM-CTP group, a significant increase of IL-6 but also of CRP and D-dimer was observed. Clinically, one single patient developed deep vein thrombosis 24 hours after the implantation of autologous PB-CTP.Conclusion: CTPs supported low thrombin generation and were well tolerated after calf implantation

Risk factors for deep vein thrombosis in older patients: a multicenter study with systematic compression ultrasonography in postacute care facilities in France.

OBJECTIVES: To identify risk factors for deep vein thrombosis (DVT) in older patients with restricted mobility or functional disability. DESIGN: Cross-sectional. SETTING: Forty-two postacute care departments in France. PARTICIPANTS: Eight hundred twelve patients aged 65 and older. MEASUREMENTS: Twenty-two predefined characteristics were investigated, including medical and surgical risk factors, dependence in six basic activities of daily living (ADLs) rated using the Katz index, mobility, the reported value of the Timed Up and Go Test, and pressure ulcers. All patients underwent lower limb ultrasonography on the day of the cross-sectional study. RESULTS: DVT was found in 113 patients (14%, 33 proximal DVTs (4%) and 80 isolated distal DVTs (10%)). A positive trend was found in the odds of DVT for higher values on the Timed Up and Go Test for patients who were not bedridden or confined to a chair (P=.007). In two-level multivariable analysis adjusting for prophylaxis against venous thromboembolism, independent risk factors for DVT were aged 80 and older (adjusted odds ratio (aOR)=1.71, 95% confidence interval (CI)=1.05-2.79), previous history of venous thromboembolism (aOR=2.03, 95% CI=1.06-3.87), regional or metastatic-stage cancer (aOR=2.71, 95% CI=1.27-5.78), dependence in more than three ADLs (aOR=2.18, 95% CI=1.38-3.45), and pressure ulcers (aOR=1.85, 95% CI=1.05-3.24). CONCLUSION: Severe dependence in basic ADLs and higher Timed Up and Go Test score are associated with greater odds of DVT in older patients in postacute care facilities in France

Unresolved questions on venous thromboembolic disease. Therapeutic management of superficial vein thrombosis (SVT). Consensus statement of the French Society for Vascular Medicine (SFMV)

International audienceSuperficial vein thrombosis (SVT), a manifestation of venous thromboembolism (VTE), is a common condition, yet of all the types of VTE, it has been the least well studied. Recent studies have challenged the conception that SVT is a benign disease, showing that its risk factors overlap with those of deep-vein thrombosis (DVT) and that it is frequently associated with DVT or pulmonary embolism (PE). In 2010, the CALISTO trial demonstrated the benefit of treatment with fondaparinux at the dose of 2.5 mg (one injection per day) for 45 days for lower limb SVT. Prior to CALISTO, the treatment of SVT was based on venous compression therapy, nonsteroidal anti-inflammatory drugs (NSAID) and anticoagulation using various therapeutic regimens. Surgery could also be envisaged in certain cases. In CALISTO, the inclusion criteria designed to obtain a homogeneous population meant that numerous questions remained unanswered with respect to SVT occurring in other locations and under other circumstances, notably in pregnant women, patients with renal insufficiency, and patients with recurrent SVT or superficial vein thrombosis less than 5 cm long. The aim of this section is to review the current state of knowledge of SVT and to propose or recommend therapeutic strategies for the management of SVT according to the clinical context, the location of the thrombosis, and the presence of particular risk factors