Planned use of GP IIb/IIIa inhibitors is safe and effective during implantation of the Absorb Bioresorbable Vascular Scaffold.

Bioresorbable Vascular Scaffolds (BVS) have the potential for adaptive vessel remodeling, restoration of vasomotion, and late luminal enlargement, thus allowing them to circumvent target lesion failures associated with bare metal stents (BMS) and drug-eluting stents (DES). However, recent data has shown a concerning increase in BVS-associated scaffold thrombosis (ScT) compared to DES. Upfront administration of GP IIb/IIIa inhibitors (GPIs) has shown to reduce early stent thrombosis (ST) compared to standard of care in BMS and DES. Since the use of GPIs was limited in BVS studies, the effect of GPIs on the rate of BVS-associated ScT is largely unknown. This is the first study investigating whether a planned use of GPIs during implantation of the Absorb BVS represents a safe and effective strategy in reducing ScT. In a retrospective chart review of 22 patients undergoing PCI with BVS implantation and planned GPI administration, no acute ScT, in-hospital MACE, or in-hospital major/minor bleeding events were observed. Bleeding reduction strategies such as shorter GPI infusion and radial access were implemented. This study provides valuable preliminary evidence on the benefit and safety in using planned GPI administration to reduce the incidence of ScT after implantation of BVS.

An engineered, quantifiable in vitro model for analysing the effect of proteostasis-targeting drugs on tissue physical properties.

Cellular function depends on the maintenance of protein homeostasis (proteostasis) by regulated protein degradation. Chronic dysregulation of proteostasis is associated with neurodegenerative and age-related diseases, and drugs targeting components of the protein degradation apparatus are increasingly used in cancer therapies. However, as chronic imbalances rather than loss of function mediate their pathogenesis, research models that allow for the study of the complex effects of drugs on tissue properties in proteostasis-associated diseases are almost completely lacking. Here, to determine the functional effects of impaired proteostatic fine-tuning, we applied a combination of materials science characterisation techniques to a cell-derived, in vitro model of bone-like tissue formation in which we pharmacologically perturbed protein degradation. We show that low-level inhibition of VCP/p97 and the proteasome, two major components of the degradation machinery, have remarkably different effects on the bone-like material that human bone-marrow derived mesenchymal stromal cells (hMSC) form in vitro. Specifically, whilst proteasome inhibition mildly enhances tissue formation, Raman spectroscopic, atomic force microscopy-based indentation, and electron microscopy imaging reveal that VCP/p97 inhibition induces the formation of bone-like tissue that is softer, contains less protein, appears to have more crystalline mineral, and may involve aberrant micro- and ultra-structural tissue organisation. These observations contrast with findings from conventional osteogenic assays that failed to identify any effect on mineralisation. Taken together, these data suggest that mild proteostatic impairment in hMSC alters the bone-like material they form in ways that could explain some pathologies associated with VCP/p97-related diseases. They also demonstrate the utility of quantitative materials science approaches for tackling long-standing questions in biology and medicine, and could form the basis for preclinical drug testing platforms to develop therapies for diseases stemming from perturbed proteostasis or for cancer therapies targeting protein degradation. Our findings may also have important implications for the field of tissue engineering, as the manufacture of cell-derived biomaterial scaffolds may need to consider proteostasis to effectively replicate native tissues.

Percusurge guardwire balloon-associated thrombus--a limitation of the Percusurge distal protection system.

Saphenous vein graft interventions represent a challenge to interventional cardiologists because of the frequent and unpredictable incidence of distal embolization. Distal embolic protection devices have demonstrated a reduction in the incidence of this phenomenon. As the use of these devices becomes more frequent outside research protocols, the limitations of different devices will become apparent. Thrombus at the site of the distal occlusive balloon of the Percusurge distal embolic protection system was noted in the case described and represents a potential drawback of this form of distal protection.