Time-restricted versus standard-duration immunosuppression after allogeneic hematopoietic stem cell transplantation: Results of the prospective randomized HOVON-96 trial.

Cyclosporine A combined with mycophenolate mofetil (CsA/MMF) has become an established regimen for the prevention of graft-versus-host disease (GVHD) following non-myeloablative (NMA) allogeneic hematopoietic stem cell transplantation (alloHSCT). However, the optimal duration of immunosuppression (IS) has not yet been defined and overtreatment is of concern. We hypothesized that time-restricted IS with CsA/MMF would increase the proportion of patients with non-severe GVHD compared to standard-duration IS, thereby resulting in reduction of the relapse rate and improvement of progression-free survival (PFS) and overall survival (OS).

Reactivation of Multidrug-Resistant HSV-1 in a Post-Allogenic Hematopoietic Stem Cell Transplant Patient: Dynamic Detection of the Rare A605V Mutation by Next-Generation Sequencing.

We present an immunocompromised patient with a multiresistant herpes simplex virus-1 reactivation with a rare mutation (A605V) in the viral DNA polymerase gene. Next-generation sequencing suggests the presence of multiple drug-resistant strains before treatment and altered ratios during treatment, affecting the clinical response to aciclovir and foscarnet.

Clinical decision rule and D-dimer have lower clinical utility to exclude pulmonary embolism in cancer patients. Explanations and potential ameliorations.

Patients with malignancy frequently present with clinically suspected pulmonary embolism (PE). However, the safe and efficient combination of a clinical decision rule (CDR) and D-dimer test to rule out PE performs less well in patients with malignancy. We examined potential explanations and analysed whether elevating the D-dimer cut-off could improve the clinical utility.

A low molecular weight heparin inhibits experimental metastasis in mice independently of the endothelial glycocalyx.

Background: Some low molecular weight heparins (LMWHs) prolong survival of cancer patients and inhibit experimental metastasis. The underlying mechanisms are still not clear but it has been suggested that LMWHs (at least in part) limit metastasis by preventing cancer cell-induced destruction of the endothelial glycocalyx.

Methodology/principal Findings: To prove or refute this hypothesis, we determined the net effects of the endothelial glycocalyx in cancer cell extravasation and we assessed the anti-metastatic effect of a clinically used LMWH in the presence and absence of an intact endothelial glycocalyx.

The role of activated protein C in cancer progression.

Activated protein C (APC) is best known as a natural anticoagulant that also has direct cell signaling properties which (among others) enhance vascular barrier function. We recently established the relevance of APC-induced barrier enhancement by showing that endogenous APC limits cancer cell extravasation. In line with this concept, repeated administration of exogenous APC reduced the number of experimental metastasis.

Endogenous activated protein C limits cancer cell extravasation through sphingosine-1-phosphate receptor 1-mediated vascular endothelial barrier enhancement.

Activated protein C (APC) has both anticoagulant activity and direct cell-signaling properties. APC has been reported to promote cancer cell migration/invasion and to inhibit apoptosis and therefore may exacerbate metastasis. Opposing these activities, APC signaling protects the vascular endothelial barrier through sphingosine-1-phosphate receptor-1 (S(1)P(1))activation, which may counteract cancer cell extravasation.