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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Increased thrombin generation in injured patients possibly contributes to early consumption of coagulation factors, exacerbating hemorrhage. Identifying optimal resuscitation products for restoring plasma homeostasis following injury is important for improving management of these patients. ⋯ HS in rats is associated with increased thrombin generation and resuscitation with FFP, not LR, reverses hypercoagulability. Dilution of trauma patient plasma with LR or FFP yielded similar results; however, the modulatory effects of FFP were attenuated when AT was absent. Importantly, FFP reduced thrombin generation in hypercoagulable patient plasma, but slightly increased thrombin generation in hypocoagulable patient plasma. Thus, FFP restores hemostatic balance following trauma and HS which is, in part, by delivering AT.
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Sepsis-induced multiple organ dysfunction syndrome (MODS) is a major cause of morbidity and mortality in critically ill patients and remains impervious to most therapeutic interventions. We utilized a clinically relevant murine model of systemic inflammatory response syndrome (SIRS) during early MODS induced by ventilator-associated pneumonia to systematically delineate pathways dysregulated in lung, liver, and kidney. ⋯ Our analyses led to the identification of several putative drivers of early MODS whose expression was regulated by epidermal growth factor receptor. Our unbiased, integrative method is a promising approach to unravel mechanisms in system-wide disorders afflicting multiple compartments such as sepsis-induced MODS, and identify putative therapeutic targets.
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Sequential insults (hits) may change the inflammatory reaction that develops in response to separate single hits (e.g., injury, infection); however, their effects on the long-term clinical outcome are still only partially elucidated. Double-hit models are typically severe and fatal. We characterized in C57BL/6 mice a moderate double-hit model of hemorrhage (35%-40% of total blood volume) and resuscitation, followed by peritoneal injection of zymosan A that induced local and systemic inflammation with 58% mortality. ⋯ However, this dynamically changed, and by day 7, proinflammatory cytokines were reduced, and anti-inflammatory cytokines were markedly (P < 0.05) elevated in the double-hit group. Mice in the double-hit group that inhaled 100% oxygen intermittently for 6 h every day exhibited markedly reduced serum proinflammatory cytokines as early as day 2 (P < 0.05), inhibited macrophage infiltration into the peritoneum (by 13-fold; P < 0.05), and substantially increased survival rates of 85% (P = 0.00144). Oxygen mitigates the inflammatory response and exerts a beneficial effect on survival in a double-hit model of hemorrhage and zymosan-induced inflammation.
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Danger-associated molecular patterns (DAMPs) that are released by injured, threatened, or dead cells, or that originate from the extracellular matrix, influence the immune system. This is of great relevance in critically ill patients, in whom trauma or surgery-related cell damage, hypoxia, ischemia, and infections can result in extensive release of DAMPs. ⋯ In the present review, we provide an overview of several well known DAMPs (high-mobility group box 1, heat-shock proteins, s100 proteins, nucleic acids, and hyaluronan) and their effects on the immune system. Furthermore, we discuss the role of DAMPs as markers or therapeutic targets in several conditions frequently encountered in critically ill patients, such as sepsis, trauma, ventilator-induced lung injury, and cardiac arrest.
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The pathophysiology of burn injuries is tremendously complex. A thorough understanding is essential for correct treatment of the burned area and also to limit the appearance of organ dysfunction, which, in fact, is a key determinant of morbidity and mortality. ⋯ Research into biomarkers may help to improve the prognosis of patients with severe burn injury. The aim of the present clinical review is to discuss new evidence of the value of biomarkers in this setting.