Device Thrombogenicity Emulation: A Novel Method for Optimizing Mechanical Circulatory Support Device Thromboresistance

Mechanical circulatory support (MCS) devices provide both short and long term hemodynamic support for advanced heart failure patients. Unfortunately these devices remain plagued by thromboembolic complications associated with chronic platelet activation – mandating complex, lifelong anticoagulation therapy. To address the unmet need for enhancing the thromboresistance of these devices to extend their long term use, we developed a universal predictive methodology entitled Device Thrombogenicity Emulation (DTE) that facilitates optimizing the thrombogenic performance of any MCS device – ideally to a level that may obviate the need for mandatory anticoagulation

Life Claiming Anaphylaxis to Intravenous Ceftriaxone after Negative Skin Test

Antibiotic prophylaxis before surgical procedures is commonly practiced. Hypersensitivity reactions to antibacterial drugs are most feared complications; which have varying grades of presentation. Skin testing are commonly applied to detect allergy but that can have false negatives. We report a case of severe anaphylaxis leading ultimately to fatal outcome after negative skin testing. Prior history of allergy of any kind and exposure to ceftriaxone was excluded. Even the best antishock management could not help. This observation clearly demonstrates the limit of screening tests for the diagnosis of sensitization against drugs

Flap versus flapless immediate implants with bone augmentation: A novel study

Background: This study aimed to equate implants placed using a traditional flap elevation technique with implants placed using a flapless process regarding bone healing and success in clinical conditions. Materials and Methods: Sixty subjects were included in this research work. The participants were randomly divided into two groups. Patients in group A underwent implant placement with the flap elevation technique. Similarly, group B patients underwent implant placement without flap reflection. Parameters such as plaque index, wound healing index, crestal bone loss, and radiograph were considered to estimate the effectiveness of the two techniques. Results: Plaque indexes were improved in both groups. The modified gingival index also improved in all the phases of healing. The flapless method showed a better crestal bone. Conclusion: It can be concluded that this study showed that with the right augmentation techniques, implants could be successfully performed immediate extraction sockets, both with and without elevation of the mucoperiosteal flap

Experimental evaluation of the performance of large bore aspiration catheters

Background and purpose: Mechanical thrombectomy using an aspiration catheter (AC) is widely performed in patients with acute ischemic stroke due to large vessel occlusion. AC diameter directly impacts aspiration performance, which has led device companies to develop large bore ACs. The purpose of this study was to evaluate the in vitro performance of several commercially available large bore ACs. Materials and methods: We conceived an experimental set up to assess tracking force, aspiration flow rate, and distal end tensile force pre- and post-thrombectomy of ACs including Sofia 6 (Microvention Inc., California, USA), React 71 (Medtronic Neurovascular, Irvine, California, USA), Jet 7 (Penumbra Inc, Alameda, California, USA), Catalyst 7 (Stryker Neurovascular, Kalamazoo, Michigan, USA) and Embovac 071 (Johnson &amp; Johnson Medical Ltd, UK). Results: React 71 and Sofia 6 had significantly lower trackability force compared to the other ACs tested. Distal AC segment tensile force was highest for React 71 and lowest for Jet 7. Jet 7 had the highest internal diameter and the highest aspiration flow rate. Conclusion: The data from this comparative analysis may assist clinicians in selecting the appropriate AC and highlights the need for key performance criteria during the development of next-generation large-bore ACs for optimal AC performance.</p

Thrombogenicity assessment of Pipeline, Pipeline Shield, Derivo and P64 flow diverters in an in vitro pulsatile flow human blood loop model

Flow diversion is a disruptive technology for the treatment of intracranial aneurysms. However, these intraluminal devices pose a risk for thromboembolic complications despite dual antiplatelet therapy. We report the thrombogenic potential of the following flow diversion devices measured experimentally in a novel human blood in-vitro pulsatile flow loop model: Pipeline™ Flex Embolization Device (Pipeline), Pipeline™ Flex Embolization Device with Shield Technology™ (Pipeline Shield), Derivo Embolization Device (Derivo), and P64 Flow Modulation Device (P64). Thrombin generation (Mean ± SD; μg/mL) was measured as: Derivo (28 ± 11), P64 (21 ± 4.5), Pipeline (21 ± 6.2), Pipeline Shield (0.6 ± 0.1) and Negative Control (1.5 ± 1.1). Platelet activation (IU/μL) was measured as: Derivo (4.9 ± 0.7), P64 (5.2 ± 0.7), Pipeline (5.5 ± 0.4), Pipeline Shield (0.3 ± 0.1), and Negative Control (0.9 ± 0.7). We found that Pipeline Shield had significantly lower platelet activation and thrombin generation than the other devices tested (p  .05). High resolution scanning electron microscopy performed on the intraluminal and cross-sectional surfaces of each device showed the lowest accumulation of platelets and fibrin on Pipeline Shield relative to Derivo, P64, and Pipeline. Derivo and P64 also had higher thrombus accumulation at the flared ends. Pipeline device with Phosphorylcholine surface treatment (Pipeline Shield) could mitigate device material related thromboembolic complications. Keywords: Phosphorylcholine, Flow diversion, Platelet activation, Thrombin, Shield technology, Pipeline, Intracranial aneurysm, Antiplatelet

Simultaneous Tether Extraction from Endothelial Cells and Leukocytes: Observation, Mechanics, and Significance

It has been hypothesized, from earlier studies on single-tether extraction from individual leukocytes and human umbilical vein endothelial cells, that during rolling of leukocytes on the endothelium, simultaneous extraction of membrane nanotubes (tethers) occurs, resulting in enhancement of the force decrease on the adhesive bond. In this study, using the micropipette aspiration technique and fluorescence microscopy, we show that tethers are indeed extracted simultaneously when an endothelial cell and a leukocyte are separated after brief contact and adhesion, and the endothelial cell contributes much more to the composite tether length. In addition, the constitutive relationship for simultaneous tether extraction is determined with neutrophils and T-lymphocytes as force transducers, and cytokine-stimulated human umbilical vein and dermal microvascular endothelial cells as substrates, respectively. This relationship is consistent with that derived theoretically from the constitutive equations for single-tether extraction from either cell alone. Moreover, we show that simultaneous tether extraction was likely terminated by receptor-ligand bond dissociation. With a biomechanical model of leukocyte rolling, we predict the force history of the adhesive receptor-ligand bond and show that it is remarkably similar for different leukocyte-endothelial cell pairs. Simultaneous tether extraction therefore represents a generic mechanism for stabilizing leukocyte rolling on the endothelium

Selectin-like kinetics and biomechanics promote rapid platelet adhesion in flow: the GPIb(alpha)-vWF tether bond.

The ability of platelets to tether to and translocate on injured vascular endothelium relies on the interaction between the platelet glycoprotein receptor Ib alpha (GPIb(alpha)) and the A1 domain of von Willebrand factor (vWF-A1). To date, limited information exists on the kinetics that govern platelet interactions with vWF in hemodynamic flow. We now report that the GPIb(alpha)-vWF-A1 tether bond displays similar kinetic attributes as the selectins including: 1) the requirement for a critical level of hydrodynamic flow to initiate adhesion, 2) short-lived tethering events at sites of vascular injury in vivo, and 3) a fast intrinsic dissociation rate constant, k(0)(off) (3.45 +/- 0.37 s(-1)). Values for k(off), as determined by pause time analysis of transient capture/release events, were also found to vary exponentially (4.2 +/- 0.8 s(-1) to 7.3 +/- 0.4 s(-1)) as a function of the force applied to the bond (from 36 to 217 pN). The biological importance of rapid bond dissociation in platelet adhesion is demonstrated by kinetic characterization of the A1 domain mutation, I546V that is associated with type 2B von Willebrand disease (vWD), a bleeding disorder that is due to the spontaneous binding of plasma vWF to circulating platelets. This mutation resulted in a loss of the shear threshold phenomenon, a approximately sixfold reduction in k(off), but no significant alteration in the ability of the tether bond to resist shear-induced forces. Thus, flow dependent adhesion and rapid and force-dependent kinetic properties are the predominant features of the GPIb(alpha)-vWF-A1 tether bond that in part may explain the preferential binding of platelets to vWF at sites of vascular injury, the lack of spontaneous platelet aggregation in circulating blood, and a mechanism to limit thrombus formation