In a Fontan circuit the mechanisms involved in control of cardiac output at rest and during exercise differ significantly from normal. The classical model presumes an unlimited preload which is not available in the Fontan circuit. This review critically analyses the role of contractility, heart rate, and afterload and highlights the importance of pulmonary vascular resistance (PVR) in determining adequate preload and, therefore, cardiac output in these patients. A conceptual model of the determinants of cardiac output in Fontan patients is presented.

Key Points• vWbp mediates adhesion of S aureus under flow to activated endothelial cells and the subendothelium via VWF.• vWbp activates prothrombin and triggers the formation of bacteria-fibrin-platelet aggregates, which enhance adhesion to vessels under flow.Adhesion of Staphylococcus aureus to blood vessels under shear stress requires von Willebrand factor (VWF). Several bacterial factors have been proposed to interact with VWF, including VWF-binding protein (vWbp), a secreted coagulase that activates the host's prothrombin to generate fibrin. We measured the adhesion of S aureus Newman and a vWbp-deficient mutant (vwb) to VWF, collagen, and activated endothelial cells in a microparallel flow chamber. In vivo adhesion of S aureus was evaluated in the mesenteric circulation of wild-type (WT) and VWF-deficient mice. We found a sheardependent increase in adhesion of S aureus to the (sub)endothelium that was dependent on interactions between vWbp and the A1-domain of VWF. Adhesion was further enhanced by coagulase-mediated fibrin formation that clustered bacteria and recruited platelets into bacterial microthrombi. In vivo, deficiency of vWbp or VWF as well as inhibition of coagulase activity reduced S aureus adhesion. We conclude that vWbp contributes to vascular adhesion of S aureus through 2 independent mechanisms: shearmediated binding to VWF and activation of prothrombin to form S aureus-fibrin-platelet

The Contegra conduit and Melody valved stents have a significantly higher incidence of IE than homografts. IE is a significant threat for long-term conduit function.

Diagnosis of cancer does not exclude potential benefit from intensive care medicine in these children, although severe complications might affect the prognosis.

Summary:Prognostic scoring systems based on physiological parameters have been established in order to predict the outcome of ICU patients. It has been demonstrated that the predictive value of these scores is limited in patients following hematopoietic stem cell transplantation (HSCT). Therefore, we evaluated patients from the Dü sseldorf pediatric stem cell transplantation center with regard to predisposing factors and prognostic variables for ICU treatment and outcome. Between January 1989 and December 1998, 180 HSCT have been performed. The clinical, laboratory and HSCT-related parameters such as conditioning treatment, engraftment, GVHD, infections and HSCT toxicity were prospectively recorded and retrospectively analyzed. Established pediatric scoring systems (PRISM, TISS, P-TISS) were applied. Twenty-eight patients required intensive care (16 male, 12 female, median age: 10.9 years (range: 0.4 to 18.9 years), five autologous, 13 allogeneic-related and 10 unrelated transplanted patients). Ventilator-dependent respiratory failure was the most frequent cause of admission to the ICU (n ‫؍‬ 23). Fourteen of 28 patients were discharged from ICU, and six of 28 patients achieved a long-term survival (110 to 396 weeks). At admission to the ICU, impaired cardiovascular status, high CRP levels and presence of macroscopic bleeding were each associated with fatal outcome (P Ͻ 0.05). The Pediatric Risk of Mortality (PRISM) score was not prognostically significant at the 0.

Summary. Objective: When establishing endovascular infections, Staphylococcus aureus (S. aureus) overcomes shear forces of flowing blood by binding to von Willebrand factor (VWF). Staphylococcal VWF-binding protein (vWbp) interacts with VWF, but it is unknown how this secreted protein binds to the bacterial cell wall. We hypothesized that vWbp interacts with a staphylococcal surface protein, mediating the adhesion of S. aureus to VWF and vascular endothelium under shear stress. Methods: We studied the binding of S. aureus to vWbp, VWF and endothelial cells in a micro-parallel flow chamber using various mutants deficient in Sortase A (SrtA) and SrtA-dependent surface proteins, and Lactococcus lactis expressing single staphylococcal surface proteins. In vivo adhesion of bacteria was evaluated in the murine mesenteric circulation using real-time intravital vascular microscopy. Results: vWbp bridges the bacterial cell wall and VWF, allowing shear-resistant binding of S. aureus to inflamed or damaged endothelium. Absence of SrtA and Clumping factor A (ClfA) reduced adhesion of S. aureus to vWbp, VWF and activated endothelial cells. ADAMTS-13 and an anti-VWF A1 domain antibody, when combined, reduced S. aureus adhesion to activated endothelial cells by 90%. Selective overexpression of ClfA in the membrane of Lactococcus lactis enabled these bacteria to bind to VWF and activated endothelial cells but only in the presence of vWbp. Absence of ClfA abolished bacterial adhesion to the activated murine vessel wall. Conclusions: vWbp interacts with VWF and with the SrtA-dependent staphylococcal surface protein ClfA. The complex formed by VWF, secreted vWbp and bacterial ClfA anchors S. aureus to vascular endothelium under shear stress.

Surface molecules of Staphylococcus aureus are involved in the colonization of vascular endothelium which is a crucial primary event in the pathogenesis of infective endocarditis (IE). The ability of these molecules to also launch endothelial procoagulant and proinflammatory responses, which characterize IE, is not known. In the present study we investigated the individual capacities of three prominent S. aureus surface molecules; fibronectin-binding protein A (FnBPA) and B (FnBPB) and clumping factor A (ClfA), to promote bacterial adherence to cultured human endothelial cells (ECs) and to activate phenotypic and functional changes in these ECs. Non-invasive surrogate bacterium Lactococcus lactis, which, by gene transfer, expressed staphylococcal FnBPA, FnBPB or ClfA molecules were used. Infection of ECs increased 50- to 100-fold with FnBPA- or FnBPB-positive recombinant lactococci. This coincided with EC activation, interleukin-8 secretion and surface expression of ICAM-1 and VCAM-1 and concomitant monocyte adhesion. Infection with ClfA-positive lactococci did not activate EC. FnBPA-positive L. lactis also induced a prominent tissue factor-dependent endothelial coagulation response that was intensified by cell-bound monocytes. Thus S. aureus FnBPs, but not ClfA, confer invasiveness and pathogenicity to non-pathogenic L. lactis organisms indicating that bacterium-EC interactions mediated by these adhesins are sufficient to evoke inflammation as well as procoagulant activity at infected endovascular sites.

PPVI is safe and feasible in selected patients with an off-label indication. Creating an adequate "landing zone" by prestenting makes the procedure safe and predictable. Updating the indications for PPVI should be considered.