Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

Background: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). Conclusions: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration: ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015

Ir-LBP, an Ixodes ricinus Tick Salivary LTB4-Binding Lipocalin, Interferes with Host Neutrophil Function

BACKGROUND: During their blood meal, ticks secrete a wide variety of proteins that can interfere with their host's defense mechanisms. Among these proteins, lipocalins play a major role in the modulation of the inflammatory response. METHODOLOGY/PRINCIPAL FINDINGS: We previously identified 14 new lipocalin genes in the tick Ixodes ricinus. One of them codes for a protein that specifically binds leukotriene B4 with a very high affinity (Kd: +/-1 nM), similar to that of the neutrophil transmembrane receptor BLT1. By in silico approaches, we modeled the 3D structure of the protein and the binding of LTB4 into the ligand pocket. This protein, called Ir-LBP, inhibits neutrophil chemotaxis in vitro and delays LTB4-induced apoptosis. Ir-LBP also inhibits the host inflammatory response in vivo by decreasing the number and activation of neutrophils located at the tick bite site. Thus, Ir-LBP participates in the tick's ability to interfere with proper neutrophil function in inflammation. CONCLUSIONS/SIGNIFICANCE: These elements suggest that Ir-LBP is a "scavenger" of LTB4, which, in combination with other factors, such as histamine-binding proteins or proteins inhibiting the classical or alternative complement pathways, permits the tick to properly manage its blood meal. Moreover, with regard to its properties, Ir-LBP could possibly be used as a therapeutic tool for illnesses associated with an increased LTB4 production.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Variability and Action Mechanism of a Family of Anticomplement Proteins in Ixodes ricinus

Background: Ticks are blood feeding arachnids that characteristically take a long blood meal. They must therefore counteract host defence mechanisms such as hemostasis, inflammation and the immune response. This is achieved by expressing batteries of salivary proteins coded by multigene families. Methodology/Principal Findings: We report the in-depth analysis of a tick multigene family and describe five new anticomplement proteins in ixodes ricinus. Compared to previously described Ixodes anticomplement proteins, these segregated into a new phylogenetic group or subfamily. These proteins have a novel action mechanism as they specifically bind to properdin, leading to the inhibition of C3 convertase and the alternative complement pathway. An excess of non-synonymous over synonymous changes indicated that coding sequences had undergone diversifying selection. Diversification was not associated with structural, biochemical o, functional diversity, adaptation to host species or stage specificity but rather to differences in antigenicity. Conclusion/Significance: Anticomplement proteins from I. ricinus are the first inhibitors that specifically target a positive regulator of complement, properdin. They may provide new tools for the investigation of role of properdin in physiological and pathophysiological mechanisms. They may also be useful in disorders affecting the alternative complement pathway, Looking for and detecting the different selection pressures involved will help in understanding the evolution of multigene families and hematophagy in arthropods. © 2008 Couveur et al.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Braudel

566 p., ref. bib. : ref. et notes dissem.Comment devient-on Fernand Braudel, le patron de cette «nouvelle histoire » à laquelle il a su assurer une audience internationale sans précédent ? Le jeune Lorrain né en 1902, agrégé dès 1923, n'avait même pas une vocation d'historien. Il lui fallut d'abord apprendre à regarder la France de loin - dix années en Algérie, trois au Brésil. Il y a gagné l'intuition de ce qu'on appellera, après 1955, le «tiers monde ». La découverte des Annales de Lucien Febvre et Marc Bloch, des explorations neuves dans les archives le conduiront en vingt ans (dont cinq de captivité, après juin 1940) à une thèse révolutionnaire. Délaissant Philippe II et les chancelleries de son sujet initial, il va écrire l'histoire de la Méditerranée comme espace, avec ses dynamiques sociales et économiques. Elle devient grâce à lui un personnage historique inoubliable. Après guerre, écarté par la Sorbonne, Braudel fait de la VIe section de l'Ecole pratique des Hautes Etudes la plus grande institution des sciences humaines, dans l'hostilité d'une université qui ne voit pas venir la catastrophe de 1968. Sa biographie conduit alors à l'histoire, jamais tentée jusqu'ici, du triomphe de la «nouvelle histoire », au coeur de la rénovation des sciences de l'homme. On y trouvera ses débats avec tous les grands historiens, mais aussi avec Claude Lévi-Strauss, Georges Dumézil ou Michel Foucault. Elle s'achève par le récit de l'élaboration des deux chefs-d'œuvre: Civilisation matérielle, économie et capitalisme, et Identité de la France, qui s'ouvrent sur le XXIe siècle

Pour un « aggiornamento » de l’histoire de l’art

Daix Pierre. Pour un « aggiornamento » de l’histoire de l’art. In: Histoire de l'art, N°5-6, 1989. Iconographie. pp. 138-140

Aragon et son journal

Comme je l’ai retracé, à grands traits, dans mon livre de 2004, Les Lettres françaises, Jalons pour l’histoire d’un journal (1941-1972), la Libération avait d’abord mis Aragon, du fait de difficultés avec le Parti communiste, à l’écart des Lettres françaises redevenues légales. Elles étaient dirigées par Claude Morgan qui les avait reprises dans la clandestinité en 1942 après l’arrestation et l’exécution de Jacques Decour. Aragon n’y intervient guère alors que par le biais du Comité national ..

Ce que je sais du xxe siècle / Pierre Daix

Collection : Questions d'actualité ; 8Collection : Questions d'actualité ; 8Contient une table des matièresAvec mode text