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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Multiply injured patients (MIPs) in hemorrhagic shock develop oxygen debt which causes organ dysfunction and can lead to death. We developed a noninvasive patient-specific index, Shock Volume (SV), to quantify the magnitude of hypoperfusion. SV integrates the magnitude and duration that incremental shock index values are elevated above known thresholds of hypoperfusion using serial individual vital sign data. ⋯ In addition, SV values corresponded to the magnitude of organ failure determined by Sequential Organ Failure Assessment scores. SV is a patient-specific index that can be quantified in real time in critically injured patients. It is a surrogate for cumulative hypoperfusion and it predicts high-volume transfusions and organ dysfunction.
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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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Refrigeration of platelets (4°C) provides the possibility of improving transfusion practice over the current standard-of-care, room temperature (RT) storage. However, the increased level of platelet activation observed at 4°C in vitro is cause for concern of uncontrolled thrombosis in vivo. In this study, we assessed the safety of 4°C-stored platelets by evaluating their response to physiologic inhibitors prostacyclin (PGI2) and nitric oxide (NO). ⋯ While treatment with inhibitors did not attenuate thrombin generation in stored platelets, activation, aggregation, and adhesion responses were inhibited by both PGI2 and NO in 4°C-stored platelets. In contrast, though RT-stored platelets were activated, they did not adhere or aggregate in response to agonists. Thus, refrigerated platelets maintain their intracellular machinery, are responsive to agonists and platelet function inhibitors, and perform hemostatically better than RT-stored platelets.
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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.
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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.