Consensus statement: minimal criteria for reporting the systemic inflammatory response to cardiopulmonary bypass.

The lack of established cause and effect between putative mediators of inflammation and adverse clinical outcomes has been responsible for many failed anti-inflammatory interventions in cardiopulmonary bypass (CPB). Candidate interventions that impress in preclinical trials by suppressing a given inflammation marker might fail at the clinical trial stage because the marker of interest is not linked causally to an adverse outcome. Alternatively, there exist examples in which pharmaceutical agents or other interventions improve clinical outcomes but for which we are uncertain of any antiinflammatory mechanism. The Outcomes consensus panel made 3 recommendations in 2009 for the conduct of clinical trials focused on the systemic inflammatory response. This panel was tasked with updating, as well as simplifying, a previous consensus statement. The present recommendations for investigators are the following: (1) Measure at least 1 inflammation marker, defined in broad terms; (2) measure at least 1clinical end point, drawn from a list of practical yet clinically meaningful end points suggested by the consensus panel; and(3) report a core set of CPB and perfusion criteria that maybe linked to outcomes. Our collective belief is that adhering to these simple consensus recommendations will help define the influence of CPB practice on the systemic inflammatory response, advance our understanding of causal inflammatory mechanisms, and standardize the reporting of research findings in the peer-reviewed literature.

The sticking point: How integrins bind to their ligands.

The integrin adhesion receptors are alpha beta heterodimers that exist in different ligand-binding states. Because of their large size and conformational lability, it has been difficult to determine how they interact with their ligands. Ligand-binding sites have been identified in the beta subunit, and now more recently in the 'I' domain and EF-hand-like domains V and VI of the alpha subunit. We speculate here about how these various sites might operate together to bind ligand in a stable manner.