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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Randomized Controlled Trial
Diagnostic accuracy of left ventricular function for identifying sepsis among emergency department patients with nontraumatic symptomatic undifferentiated hypotension.
The hypothesis of this study states that in emergency department (ED) patients with non-traumatic symptomatic hypotension, the presence of hyperdynamic left ventricular function (LVF) is specific for sepsis as the etiology of shock. We performed a secondary analysis of patients with non-traumatic symptomatic hypotension enrolled in a randomized, clinical diagnostic trial. The study was done in an urban tertiary ED with a census over 100,000 visits per year. ⋯ The sensitivity and specificity of hyperdynamic LVF for predicting sepsis were 33% (95% CI 19%-50%) and 94% (85%-98%), respectively. Hyperdynamic LVF had a positive likelihood ratio of 5.3 for the diagnosis of sepsis and was a strong independent predictor of sepsis as the final diagnosis with an odds ratio of 5.5 (95% CI 1.1-45). Among ED patients with non-traumatic undifferentiated symptomatic hypotension, the presence of hyperdynamic LVF on focused echo is highly specific for sepsis as the etiology of shock.
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Severe trauma induces sustained changes of the immune response, which are thought to be related to secondary organ dysfunction. Despite a similar injury severity, the extent of the inflammatory response may vary between polytraumatized patients. It is unclear whether inflammatory variability is associated with genetic variations. ⋯ A significantly higher incidence of the IL-6-174G allele and the IL-6-174G homozygous genotype in +SIRS patients was observed. The IL-6-174G/C polymorphism was associated with the severity of posttraumatic SIRS. This data points toward a genetic predisposition regarding an enhanced inflammatory response after polytrauma that may be associated with adverse outcome.
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Respiratory dysfunction during sepsis is common. However, although lung function can often be adequately supported, death frequently results from cardiovascular collapse. Despite intense investigation, the mechanism underlying the myocardial dysfunction of sepsis remains unclear. ⋯ Exogenous MIF, instilled into the lungs, increased alveolar keratinocyte-derived chemokine (KC), Macrophage inflammatory protein-2 (MIP2), and tumor necrosis factor alpha (TNFalpha) at 3 h, and plasma KC and MIP2 at 6 h postinstillation. This was associated with an increase in p38 mitogen-activated protein kinase and c-Jun N-terminal kinase phosphorylation. Because changes in mitogen-activated protein kinase activation can lead to myocardial depression, these data suggest that MIF released from the lungs may be responsible, at least in part, for the cardiac dysfunction seen in the late stages of sepsis.
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The release of the immunomodulator, interleukin 18 (IL-18) into sera early in acute pancreatitis (AP) corresponds to disease severity. IL-18 induces nitric oxide (NO), which is involved in the pathophysiology of pancreatitis. The objective of this study was to clarify the role of IL-18 in pathogenesis and NO production during early AP using recombinant mouse (rm) IL-18 protein and IL-18 gene knockout (KO) mice. ⋯ Administration of aminoguanidine, a selective iNOS inhibitor, before AP induction abolished the protective effect of pretreatment with rmIL-18 on pancreatic injury. IL-18 appears to protect the pancreas during early induced-induced AP in mice, probably through induction of NO release from an iNOS source. IL-18 may be a target for new AP therapeutics.
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Calcitonin gene-related peptide (CGRP), a potent vasodilatory peptide present in central and peripheral neurons, is released at inflammatory sites and inhibits several macrophage, dendritic cell, and lymphocyte functions. In the present study, we investigated the role of CGRP in models of local and systemic acute inflammation and on macrophage activation induced by lipopolysaccharide (LPS). Intraperitoneal pretreatment with synthetic CGRP reduces in approximately 50% the number of neutrophils in the blood and into the peritoneal cavity 4 h after LPS injection. ⋯ The protective effect of CGRP correlates with an inhibition of TNF-alpha and an induction of IL-6 and IL-10 in mice sera 90 min after LPS challenge. Finally, CGRP significantly inhibits LPS-induced TNF-alpha released from mouse peritoneal macrophages. These results suggest that activation of the CGRP receptor on macrophages during acute inflammation could be part of the negative feedback mechanism controlling the extension of acute inflammatory responses.