C1-inhibitor in patients with severe sepsis and septic shock: beneficial effect on renal dysfunction

To investigate the efficacy and the safety of the parenteral administration of C1-inhibitor to patients with severe sepsis or septic shock. Double blind, randomized, and placebo-controlled trial. Surgical and medical intensive care units of a tertiary care university hospital. Forty consecutive patients (20 C1-inhibitor/20 placebo) who entered the intensive care unit with severe sepsis or septic shock. C1-inhibitor intravenously in a 1-hr infusion, starting with 6000 IU, followed by 3000 IU, 2000 IU, and 1000 IU at 12-hr intervals, compared with placebo. C1-inhibitor administration significantly increased plasma C1-inhibitor antigen and activity levels during days 1-4 (p <.007). Patients in the C1-inhibitor group had significantly lower serum creatinine concentrations on day 3 (p =.048) and 4 (p =.01) than placebo patients. Multiple organ dysfunction assessed by logistic organ dysfunction and sepsis-related organ failure assessment scores was less pronounced in patients treated with C1-inhibitor. Mortality rate was similar in both groups. There were no C1-inhibitor-related side effects. C1-inhibitor administration attenuated renal impairment in patients with severe sepsis or septic shoc

Factor XIII Substitution in Surgical Cancer Patients at High Risk for Intraoperative Bleeding

Background: Excessive intraoperative bleeding is associated with significant morbidity and mortality. The authors and others have shown that fibrin monomer allows preoperative risk stratification for intraoperative blood loss, likely due to an imbalance between available factor XIII and prothrombin conversion. The authors hypothesized that the use of factor XIII would delay the decrease of clot firmness in high-risk patients. Methods: The concept was tested in a prospective, randomized, double-blind, placebo-controlled trial in elective gastrointestinal cancer surgery. Patients were randomized to receive factor XIII (30 U/kg) or placebo in addition to controlled standard therapy. Results: Twenty-two patients were evaluable for a planned interim analysis. For the primary outcome parameter maximum clot firmness, patients receiving factor XIII showed a nonsignificant 8% decrease, and patients receiving placebo lost 38%, a highly significantly difference between the two groups (P ‫؍‬ 0.004). A reduction in the nonprimary outcome parameters fibrinogen consumption (-28%, P ‫؍‬ 0.01) and blood loss (-29%, P ‫؍‬ 0.041) was also observed in the factor XIII group. Three patients experienced adverse events that seemed unrelated to factor XIII substitution. The trial was stopped early after a planned interim analysis with the primary endpoint reached. Conclusions: This proof of concept study confirms the hypothesis that patients at high risk for intraoperative blood loss show reduced loss of clot firmness when factor XIII is administered early during surgery. Further clinical trials are needed t

From proteomics to systems biology of bacterial pathogens: approaches, tools, and applications.

The hallmark of a systems biology approach is the integration of computational tools with experimental data encompassing multiple classes of biomolecules across different functional levels. Equally important as the availability of reasonably comprehensive information at the gene, protein, and metabolite levels is the development of adequate analysis and visualization tools to reduce the inherent complexity to interpretable dimensions. In this paper, we describe the integration of a 2-D gel-based proteome map of Staphylococcus aureus Mu50 with genomic and transcriptomic information through a customized data integration and user interface built on the Ensembl genome browser. We illustrate its application and potential through the analysis of a defined system perturbation caused by a mutation in the formyltransferase gene. We envision that this software package, which we called Insieme, can support the development of novel antibiotics by allowing a systems-based view of the bacterial response pathways