0272: Unfractionated heparin addition during percutaneous coronary intervention in acute coronary syndrome patients previously treated with enoxaparin: biological impact

BackgroundThe benefit of anticoagulants (AC) to prevent thrombotic complications during percutaneous coronary intervention (PCI) is well established. In acute coronary syndrome (ACS) patients previously treated with enoxaparin, an additional bolus of AC is not recommended if the last injection was realized within 8 h. In this setting, many interventional cardiologists use unfractionated heparin (UFH) at the time of sheath insertion.ObjectivesThe aim of our study was to describe local current practices for AC use during PCI in patients already treated with enoxaparin and admitted for ACS and to assess the biological impact of UFH addition at the beginning of the procedure.MethodsA standardized survey was sent to the interventional cardiologists of the southwest of France to investigate their practice in terms of periprocedural AC use. In 2 centers, ACS patients previously treated with subcutaneous injection of enoxaparin within 8 h and who received intravenous UFH at the time of sheath insertion were prospectively included and their plasma anti-Xa activity was assessed at the sheath insertion and 30 min after UFH bolus. In-hospital bleeding and ischemic events were collected. The adequate therapeutic window was defined by anti Xa activity (range 0.5 to 0.9 IU/mL). Results: Among the 41 interventional cardiologists who replied, a large majority (75,6%) considered the addition of UFH in patients who received enoxaparin within 8 h as a valid option. 47 ACS patients were enrolled. The dose of the bolus of UFH was highly variable from 20 to 90 UI / kg. Anti-Xa activities were above 0.9 IU/mL in 14,9% of patients at the sheath insertion and in 72,3% of patients 30 min after UFH injection. 2 bleeding complications occurred, both in over-coagulated patients. No ischemic events were reported.ConclusionThe use of UFH in patients who already received enoxaparin may result in over-anticoagulation and lead to bleeding complications

Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial.

Based on previous findings, we hypothesised that radiotherapy to the prostate would improve overall survival in men with metastatic prostate cancer, and that the benefit would be greatest in patients with a low metastatic burden. We aimed to compare standard of care for metastatic prostate cancer, with and without radiotherapy.This article is freely available via Open Access

Syndecan 4 is required for endothelial alignment in flow and atheroprotective signaling

Atherosclerotic plaque localization correlates with regions of disturbed flow in which endothelial cells (ECs) align poorly, whereas sustained laminar flow correlates with cell alignment in the direction of flow and resistance to atherosclerosis. We now report that in hypercholesterolemic mice, deletion of syndecan 4 (S4(−/−)) drastically increased atherosclerotic plaque burden with the appearance of plaque in normally resistant locations. Strikingly, ECs from the thoracic aortas of S4(−/−) mice were poorly aligned in the direction of the flow. Depletion of S4 in human umbilical vein endothelial cells (HUVECs) using shRNA also inhibited flow-induced alignment in vitro, which was rescued by re-expression of S4. This effect was highly specific, as flow activation of VEGF receptor 2 and NF-κB was normal. S4-depleted ECs aligned in cyclic stretch and even elongated under flow, although nondirectionally. EC alignment was previously found to have a causal role in modulating activation of inflammatory versus antiinflammatory pathways by flow. Consistent with these results, S4-depleted HUVECs in long-term laminar flow showed increased activation of proinflammatory NF-κB and decreased induction of antiinflammatory kruppel-like factor (KLF) 2 and KLF4. Thus, S4 plays a critical role in sensing flow direction to promote cell alignment and inhibit atherosclerosis