Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Excessive production of neutrophil extracellular traps (NETs) in sepsis contributes to vascular occlusion by acting as a scaffold and stimulus for thrombus formation. Removal of extracellular DNA, the major structural component of NETs, by DNase I may reduce host injury. ⋯ Heparin enhances DNA-mediated digestion of DNA–histone complexes in a size-dependent manner that is independent of its anticoagulant properties. Citrullination of histones by PAD4 renders DNA–histone complexes susceptible to DNase I digestion. Endogenous DNase I levels are persistently decreased in septic patients, which supports the potential utility of DNase I as a therapy for sepsis.
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Hemorrhagic shock with tissue trauma (HS/T) leads to the activation of a system-wide immune-inflammatory response that involves all organs and body compartments. Recent advances in single-cell analysis permit the simultaneous assessment of transcriptomic patterns in a large number of cells making it feasible to survey the landscape of immune cell responses across numerous anatomic sites. Here, we used single-cell RNA sequencing of leukocytes from the blood, liver, and spleen to identify the major shifts in gene expression by cell type and compartment in a mouse HS/T model. ⋯ The dominant pattern across all compartments for B and T cells was a suppression of genes associated with cell activation and signaling after HS/T. Using complement factor 3 (C3) knockout mice we unveiled a role for C3 in the suppression of monocyte Major Histocompatibility Complex class II expression and activation of gene expression associated with migration, phagocytosis and cytokine upregulation, and an unexpected role in promoting interferon-signaling in a subset of B and T cells across all three compartments after HS/T. This transcriptomic landscape study of immune cells provides new insights into the host immune response to trauma, as well as a rich resource for further investigation of trauma-induced immune responses and complement in driving interferon signaling.
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Numerous advancements in hemorrhage control and volume replacement that comprise damage control resuscitation (DCR) have been implemented in the last decade to reduce deaths from bleeding. We sought to determine the impact of DCR interventions on mortality over 12 years in a massive transfusion protocol (MTP) population. We hypothesized that mortality would be decreased in later years, which would have used more DCR interventions. ⋯ Despite lower mortality with use of tourniquets and WB, mortality rates due to hemorrhage have not improved at our high MTP volume institution, suggesting implementation of new in-hospital strategies is insufficient to reduce mortality. Future efforts should be directed toward moving hemorrhage control and effective resuscitation interventions to the injury scene.
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Extracorporeal membrane oxygenation (ECMO) use in patients with cardiac arrest is increasing. Utilization remains variable between centers using ECMO as a rescue therapy or early protocolized extracorporeal cardiopulmonary resuscitation. ⋯ mSAVE, BMI, RRT, and tracheostomy are predictors of in-hospital survival and mSAVE and BMI are predictors of favorable neurologic outcome in cardiac arrest with ECMO rescue therapy.