A Trans-Atlantic Perspective on Stagnation in Clinical Translation of Antimicrobial Strategies for the Control of Biomaterial-Implant-Associated Infection

Current regulatory requirements impede clinical translation and market introduction of many new antimicrobial combination implants and devices, causing unnecessary patient suffering, doctor frustration, and costs to healthcare payers. Regulatory requirements of antimicrobial combination implants and devices should be thoroughly revisited and their approval allowed based on enrichment of benefit demonstrations from high-risk patient groups and populations or device components to facilitate their clinical translation. Biomaterial implant and devices equipped with antimicrobial strategies and approved based on enrichment claims should be mandatorily enrolled in global registry studies supervised by regulatory agencies for a minimum five-year period or until statistically validated evidence for noninferiority or superiority of claims is demonstrated. With these recommendations, this trans-Atlantic consortium of academicians and clinicians takes its responsibility to actively seek to relieve the factors that stagnate downward clinical translation and availability of antimicrobial combination implants and devices. Improved dialogue between the various key players involved in the current translational blockade, which include patients, academicians and doctors, policymakers, regulatory agencies, manufacturers, and healthcare payers, is urgently needed.</p

Heparin interaction with protein-adsorbed surfaces

Albumin and fibrinogen show no binding affinity to varied molecular weights of heparin at physiological pH. Human plasma fibronectin was shown to bind heparins in both the solution and adsorbed states. Fibronectin was shown to have six active binding sites for heparins which may be sterically blocked in some adsorbed states. 125I-Fibronectin monolayer concentrations were shown to be significantly different on polyvinyl chloride surfaces when compared to hydrophilic/hydrophobic silica, Biomer, Silastic, and polystyrene surfaces. Preadsorbing fibronectin to various substrates and then allowing heparins to interact with the protein monolayer made it possible to bind up to 0.2 μg/cm2 heparin in a plasma environment. This fibronectin-heparin complex was at least 85% stable in plasma and buffer solutions for up to 8 h time. The complex was observed to prolong blood clotting times two to three times over that of controls as assayed by Activated Partial Thromboplastin Times. All of the bound heparin was observed to be active by its ability to bind Factor Xa in plasma. Monolayers of blood proteins adsorbed from human serum were not observed to be active in binding heparins. The fibronectin-heparin conjugate showed low activation of blood components compared to protein monolayers preadsorbed from human sera as assayed by Activated Partial Thromboplastin Time

Critical care admission following elective surgery was not associated with survival benefit: prospective analysis of data from 27 countries

This was an investigator initiated study funded by Nestle Health Sciences through an unrestricted research grant, and by a National Institute for Health Research (UK) Professorship held by RP. The study was sponsored by Queen Mary University of London