Safety and efficacy of treatment with vitamin K antagonists in patients managed in a network of anticoagulation services or as routine general care

This is a retrospective, record-linkage study aimed at comparing the effectiveness and safety of two management models of vitamin K antagonists: a Network model (NAS), in which anticoagulation clinics and general practitioners (GP) share the same management software and database, and an individual General Practitioners model. Main outcomes were thromboembolic events (TE), major bleeding (MB) and all-cause mortality. Crude incidence rate and sub-distribution hazard ratio were calculated. Fine and Grey models were used to calculate SHR in multi-variable analysis. 9,418 patients in the NAS and 5,508 in the Routine General Care (RGC) cohort were included. Patients in the NAS cohort had a lower incidence of TE and mortality in respect to the RGC (sHR 0.76%, 95% CI 0.64-0.90 and 0.82%, 95% CI 0.75-0.89, respectively). More patients in the NAS than in the RGC cohort attained a Time in Therapeutic Range >60% (62.2% vs 35.7%, p<0.001). No statistically significant difference was found in MB incidence. This study shows that the NAS model for vitamin K antagonist oral anticoagulants management significantly improves the TTR and reduces the incidence of TE and mortality, without affecting the MB rate

Circulating functional T cells specific to human herpes virus 6 (HHV6) antigens in individuals with chromosomally integrated HHV6

Circulating functional T cells specific to human herpes virus 6 (HHV6) antigens in individuals with chromosomally integrated HHV

The bone marrow represents an enrichment site of specific T lymphocytes against filamentous fungi

Bone marrow has already been described as an enrichment site for several antigen-specific T lymphocytes, but the presence of mould-specific T cells has never been investigated in the bone marrow. We have previously demonstrated that mould-specific T cells emerge in the peripheral blood of patients with invasive fungal infections (IFI) but tend to become undetectable after disease resolution. In seven patients with a history of IFI, we investigated the presence of mould-specific T cells secreting different cytokines in bone marrow and peripheral blood paired samples. The results showed that the frequencies of mould-specific T cells secreting the protective cytokine IFNI3 are significantly higher in bone marrow (BM) and are mainly represented by CD8+ T lymphocytes with effector phenotype. A putative disappearance of such protective BM responses after myeloablative therapy could contribute to the increased risk of IFI in hematologic patients

More About the Risk of Ibrutinib-associated Bleeding

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Pregnancy in PNH: another eculizumab baby.

Pregnancy in PNH: another eculizumab baby

Randomised controlled trial comparing efficacy and safety of high versus low Low-Molecular Weight Heparin dosages in hospitalized patients with severe COVID-19 pneumonia and coagulopathy not requiring invasive mechanical ventilation (COVID-19 HD): a structured summary of a study protocol

To assess whether high doses of Low Molecular Weight Heparin (LMWH) (i.e. Enoxaparin 70 IU/kg twice daily) compared to standard prophylactic dose (i.e., Enoxaparin 4000 IU once day), in hospitalized patients with COVID19 not requiring Invasive Mechanical Ventilation [IMV], are:a)more effective in preventing clinical worsening, defined as the occurrence of at least one of the following events, whichever comes first:1.Death2.Acute Myocardial Infarction [AMI]3.Objectively confirmed, symptomatic arterial or venous thromboembolism [TE]4.Need of either:a.Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) orb.IMV in patients who at randomisation were receiving standard oxygen therapy5.IMV in patients who at randomisation were receiving non-invasive mechanical ventilationb)Similar in terms of major bleeding ris

Safety profile of Erwinia asparaginase treatment in adults with newly diagnosed acute lymphoblastic leukemia: a retrospective monocenter study

Safety profile of Erwinia asparaginase treatment in adults with newly diagnosed acute lymphoblastic leukemia: a retrospective monocenter study

Physical contact with endothelial cells through β1- and β2- integrins rescues chronic lymphocytic leukemia cells from spontaneous and drug-induced apoptosis and induces a peculiar gene expression profile in leukemic cells

Background: Chronic lymphocytic leukemia B-cells display prolonged survival in vivo, but when cultured in vitro rapidly undergo spontaneous apoptosis. We hypothesize that interaction with endothelial cells in infiltrated tissues and during recirculation may have a pathogenetic role in chronic lymphocytic leukemia.Design and Methods: We evaluated apoptosis of leukemic cells after co-culture on HUVEC monolayer with addition of Fludarabine and blocking adhesion antibodies. Then, we compared microarray-based expression profiles between leukemic cells at baseline and after co-culture.\uf9Results: We found that endothelial layer protected leukemic cells from apoptosis inducing a 2-fold mean decrement in apoptotic cells after 2 days co-culture. Moreover, endothelial layer decreased sensitivity of chronic lymphocytic leukemia B-cells to Fludarabine-induced apoptosis. Physical contact with endothelium mediated by both \u3b21- and \u3b22- integrins is essential for survival advantage. In particular, blocking CD106 on endothelial cells or CD18 on leukemic B-cells determined the almost complete abrogation of survival advantage (&gt;70% inhibition of viability). Conversely, a reduction of apoptosis was also measured in leukemic cells cultured in conditioned medium collected after 2 days of co-culture, implying that survival is partially mediated by soluble factors. Overall, the contact with endothelial cells modulated 1,944 genes on chronic lymphocytic leukemia B-cells, establishing a peculiar gene expression profile: up-regulation of angiogenesis-related genes, increase of genes involved in TGF\u3b2 and Wnt signalling pathways, secretion of cytokines recruiting stromal cells and macrophages and increase in anti-apoptotic molecules such as Bcl2 and Survivin. Conclusion: Our study supports the notion that endothelial cells are major players in chronic lymphocytic leukemia microenvironment. Adhesion to endothelium strongly sustains survival, protects from drug-induced apoptosis and widely modifies gene expression profile of leukemic cells