Klatsky Endowed Lecture in Human Rights

Catherine Marchi-Uheldiscusses widespread violations of human rights and international humanitarian lawm which the international community should address

Gérer la distance syndicale face à l’« autonomie » des Universités

Si le travail en tant qu’objet scientifique commence à être investi par les géographes, la dimension spatiale du syndicalisme constitue un « angle mort » de la discipline, alors que d’aucuns considèrent l’engagement syndical comme un travail et que surtout le syndicalisme, en défendant les intérêts individuels et collectifs des salarié.es, constitue un acteur majeur des relations professionnelles. En commençant à défricher la géographie du syndicalisme dans le contexte spécifique de l’Université, l’article s’attache à analyser la tension inhérente à la représentation du personnel, prise entre la direction, devenue responsable du budget et de l’emploi depuis la loi sur les Libertés et Responsabilités des Universités (LRU), et les agent.es de l’établissement, subissant les processus d’intensification de l’activité et de fragilisation des collectifs de travail liés au nouvel ordre gestionnaire et managérial. À partir de la position de chercheur engagé syndicalement, il s’agit de restituer la manière dont les militant.es tentent de résister aux logiques de contrôle et d’enrôlement dans les Instances Représentatives du Personnel (IRP), mais aussi de montrer comment il est possible d’expérimenter des modes d’organisation et d’action collectives susceptibles de (re)créer de la co-présence avec les agent.es afin de faire corps et mouvement.If work as a scientific object begins to be invested by geographers, the spatial dimension of unionism constitutes a “blind spot” of the discipline, despite the fact that some consider union involvement as work, and that trade unionism, by defending the individual and collective interests of employees, constitutes a major actor in professional relations. By beginning to explore the geography of trade unionism in the specific context of the University, the article attempts to analyze the tension inherent in staff representation, caught between management, which has become responsible for the budget and employment since the law on University Freedoms and Responsibilities (LRU), and the agents, undergoing the processes of intensification of activity and weakening of work collectives linked to the new managerial order. From the position of a union-committed researcher, the aim is to show how activists attempt to resist the logic of control and enrolment in employee representative body, but also to demonstrate how it is possible to experiment with modes of organization and collective action capable of (re)creating co-presence with agents in order to develop unity and movement

Thrombocytopenia and Acute Renal Failure in Puumala Hantavirus Infections

Low platelet counts are a novel predictive marker suitable for risk-adapted patient management

Immune suppression is associated with enhanced systemic inflammatory, endothelial and procoagulant responses in critically ill patients

Objective: Patients admitted to the Intensive Care Unit (ICU) oftentimes show immunological signs of immune suppression. Consequently, immune stimulatory agents have been proposed as an adjunctive therapy approach in the ICU. The objective of this study was to determine the relationship between the degree of immune suppression and systemic inflammation in patients shortly after admission to the ICU. Design: An observational study in two ICUs in the Netherlands. Methods: The capacity of blood leukocytes to produce cytokines upon stimulation with lipopolysaccharide (LPS) was measured in 77 patients on the first morning after ICU admission. Patients were divided in four groups based on quartiles of LPS stimulated tumor necrosis factor (TNF)-α release, reflecting increasing extents of immune suppression. 15 host response biomarkers indicative of aberrations in inflammatory pathways implicated in sepsis pathogenesis were measured in plasma. Results: A diminished capacity of blood leukocytes to produce TNF-α upon stimulation with LPS was accompanied by a correspondingly reduced ability to release of IL-1β and IL-6. Concurrently measured plasma concentrations of host response biomarkers demonstrated that the degree of reduction in TNF-α release by blood leukocytes was associated with increasing systemic inflammation, stronger endothelial cell activation, loss of endothelial barrier integrity and enhanced procoagulant responses. Conclusions: In patients admitted to the ICU the strongest immune suppression occurs in those who simultaneously display signs of stronger systemic inflammation. These findings may have relevance for the selection of patients eligible for administration of immune enhancing agents.peer-reviewe

Association between age and the host response in critically ill patients with sepsis

Background: The association of ageing with increased sepsis mortality is well established. Nonetheless, current investigations on the influence of age on host response aberrations are largely limited to plasma cytokine levels while neglecting other pathophysiological sepsis domains like endothelial cell activation and function, and coagulation activation. The primary objective of this study was to gain insight into the association of ageing with aberrations in key host response pathways and blood transcriptomes in sepsis.Methods: We analysed the clinical outcome (n=1952), 16 plasma biomarkers providing insight in deregulation of specific pathophysiological domains (n=899), and blood leukocyte transcriptomes (n=488) of sepsis patients stratified according to age decades. Blood transcriptome results were validated in an independent sepsis cohort and compared with healthy individuals. se.Results: Older age was associated with increased mortality independent of comorbidities and disease severity. Ageing was associated with lower endothelial cell activation and dysfunction, and similar inflammation and coagulation activation, despite higher disease severity scores. Blood leukocytes of patients≥70 years, compared to patients<50 years, showed decreased expression of genes involved in cytokine signaling, and innate and adaptive immunity, and increased expression of genes involved in hemostasis and endothelial cell activation. The diminished expression of gene pathways related to innate immunity and cytokine signaling in subjects≥70 years was sepsis-induced, as healthy subjects≥70 years showed enhanced expression of these pathways compared to healthy individuals<50 years.Conclusions: This study provides novel evidence that older age is associated with relatively mitigated sepsis-induced endothelial cell activation and dysfunction, and a blood leukocyte transcriptome signature indicating impaired innate immune and cytokine signaling. These data suggest that age should be considered in patient selection in future sepsis trials targeting the immune system and/or the endothelial cell response.peer-reviewe

Update on neutrophil function in severe inflammation

Neutrophils are main players in the effector phase of the host defense against micro-organisms and have a major role in the innate immune response. Neutrophils show phenotypic heterogeneity and functional flexibility, which highlight their importance in regulation of immune function. However, neutrophils can play a dual role and besides their antimicrobial function, deregulation of neutrophils and their hyperactivity can lead to tissue damage in severe inflammation or trauma. Neutrophils also have an important role in the modulation of the immune system in response to severe injury and trauma. In this review we will provide an overview of the current understanding of neutrophil subpopulations and their function during and post-infection and discuss the possible mechanisms of immune modulation by neutrophils in severe inflammation

Thrombocytopenia and platelet transfusions in ICU patients: an international inception cohort study (PLOT-ICU)

Purpose Thrombocytopenia (platelet count < 150 × 109/L) is common in intensive care unit (ICU) patients and is likely associated with worse outcomes. In this study we present international contemporary data on thrombocytopenia in ICU patients. Methods We conducted a prospective cohort study in adult ICU patients in 52 ICUs across 10 countries. We assessed frequencies of thrombocytopenia, use of platelet transfusions and clinical outcomes including mortality. We evaluated pre-selected potential risk factors for the development of thrombocytopenia during ICU stay and associations between thrombocytopenia at ICU admission and 90-day mortality using pre-specified logistic regression analyses. Results We analysed 1166 ICU patients; the median age was 63 years and 39.5% were female. Overall, 43.2% (95% confidence interval (CI) 40.4–46.1) had thrombocytopenia; 23.4% (20–26) had thrombocytopenia at ICU admission, and 19.8% (17.6–22.2) developed thrombocytopenia during their ICU stay. Non-AIDS-, non-cancer-related immune deficiency, liver failure, male sex, septic shock, and bleeding at ICU admission were associated with the development of thrombocytopenia during ICU stay. Among patients with thrombocytopenia, 22.6% received platelet transfusion(s), and 64.3% of in-ICU transfusions were prophylactic. Patients with thrombocytopenia had higher occurrences of bleeding and death, fewer days alive without the use of life-support, and fewer days alive and out of hospital. Thrombocytopenia at ICU admission was associated with 90-day mortality (adjusted odds ratio 1.7; 95% CI 1.19–2.42). Conclusion Thrombocytopenia occurred in 43% of critically ill patients and was associated with worse outcomes including increased mortality. Platelet transfusions were given to 23% of patients with thrombocytopenia and most were prophylactic.publishedVersio

Thrombocytopenia and platelet transfusions in ICU patients: an international inception cohort study (PLOT-ICU)

Purpose: Thrombocytopenia (platelet count &lt; 150 × 109/L) is common in intensive care unit (ICU) patients and is likely associated with worse outcomes. In this study we present international contemporary data on thrombocytopenia in ICU patients. Methods: We conducted a prospective cohort study in adult ICU patients in 52 ICUs across 10 countries. We assessed frequencies of thrombocytopenia, use of platelet transfusions and clinical outcomes including mortality. We evaluated pre-selected potential risk factors for the development of thrombocytopenia during ICU stay and associations between thrombocytopenia at ICU admission and 90-day mortality using pre-specified logistic regression analyses. Results: We analysed 1166 ICU patients; the median age was 63 years and 39.5% were female. Overall, 43.2% (95% confidence interval (CI) 40.4–46.1) had thrombocytopenia; 23.4% (20–26) had thrombocytopenia at ICU admission, and 19.8% (17.6–22.2) developed thrombocytopenia during their ICU stay. Absence of acquired immune deficiency syndrome (AIDS), non-cancer-related immune deficiency, liver failure, male sex, septic shock, and bleeding at ICU admission were associated with the development of thrombocytopenia during ICU stay. Among patients with thrombocytopenia, 22.6% received platelet transfusion(s), and 64.3% of in-ICU transfusions were prophylactic. Patients with thrombocytopenia had higher occurrences of bleeding and death, fewer days alive without the use of life-support, and fewer days alive and out of hospital. Thrombocytopenia at ICU admission was associated with 90-day mortality (adjusted odds ratio 1.7; 95% CI 1.19–2.42). Conclusion: Thrombocytopenia occurred in 43% of critically ill patients and was associated with worse outcomes including increased mortality. Platelet transfusions were given to 23% of patients with thrombocytopenia and most were prophylactic