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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Three Forward Aeromedical Evacuation platforms operate in Southern Afghanistan: UK Medical Emergency Response Team (MERT), US Air Force Expeditionary Rescue Squadron (PEDRO), and US Army Medical Evacuation Squadrons (DUSTOFF), each with a different clinical capability. Recent evidence suggests that retrieval by a platform with a greater clinical capability (MERT) is associated with improved mortality in critical patients when compared with platforms with less clinical capability (PEDRO and DUSTOFF). It is unclear whether this is due to en route resuscitation or the dispatch procedure. ⋯ This trend was continued only in the MERT group for the highest ISS bin (1.39 ± 0.62 vs. 1.09 ± 0.42; P = 0.001), whereas a deterioration was identified in the PEDRO group (0.88 ± 0.37 vs. 1.02 ± 0.43; P = 0.440). The use of a Forward Aeromedical Evacuation platform with a greater clinical capability is associated with an improved hemodynamic status in critical casualties. The ideal prehospital triage should endeavor to match patient need with clinical capability.
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The current consensus definition of septic shock requires hypotension after adequate fluid challenge or vasopressor requirement. Some patients with septic shock present with hypotension and hyperlactatemia greater than 2 mmol/L (tissue dysoxic shock), whereas others have hypotension alone with normal lactate (vasoplegic shock). ⋯ In this analysis of patients with septic shock, we found a significant difference in in-hospital mortality between patients with vasoplegic versus tissue dysoxic septic shock. These findings suggest a need to consider these differences when designing future studies of septic shock therapies.
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Severe trauma is characterized by a pronounced immunologic response with both proinflammatory and anti-inflammatory characteristics. The clinical course of trauma patients is often complicated by late-onset (>5 days) sepsis. However, the underlying mechanisms remain poorly defined. Here we studied the kinetics of systemic activation of neutrophils and monocytes following injury in trauma patients in the context of development of sepsis. ⋯ Phenotyping blood PMNs enables identification of the kinetics and magnitude of the initial systemic inflammatory response after injury. The decreased functionality of PMNs and monocytes reaches its minimum before the development of sepsis and could be an important contributing factor. This could support the early identification of patients at risk.
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Oxidative damage and inflammation occur early in the brain after sepsis and are resolved when long-term cognitive impairment occurs. There is no information of a direct relation between acute levels of brain inflammation and oxidative damage and long-term cognitive deficits. We hypothesized that higher levels of early oxidative damage and inflammation are followed by long-term cognitive deficits, and this is related to a decrease in the levels of brain-derived neurotropic factor (BDNF). ⋯ At 6 h, higher CSF levels of thiobarbituric acid-reactive species and TNF-α were observed in septic animals that had a better performance in the IA task and presented higher BDNF levels in the hippocampus. At 24 h, higher CSF levels of IL-1β and TNF-α were observed in septic animals that had a worse performance in the IA task, and this was associated with lower BDNF levels. The persistence of brain inflammation during the acute phase of sepsis is associated with long-term hippocampus levels of BDNF and memory impairment in sepsis survivors.
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It is well established that CD4CD25 regulatory T cells (Tregs) downregulate inflammatory immune responses and help to maintain immune homeostasis. Recent reports have shown that ligation of germline encoded pattern recognition receptors such as Toll-like receptors can stimulate Tregs and therefore implicate Tregs in the pathophysiology of sepsis and other inflammatory diseases. In this report, we show that injection of lipopolysaccharide (LPS) leads to expansion of CD4CD25FoxP3 Tregs, suggesting that these cells may play an important role in immune regulation in LPS-induced acute inflammation. ⋯ Unlike LPS, depletion of Tregs followed by concanavalin A (Con A) challenge does not result in mortality, suggesting that Treg depletion does not globally influence all models of acute inflammation. We authenticate our findings by showing that depletion of Tregs leads to mortality in a nonlethal Escherichia coli challenge accompanied by elevated serum levels of proinflammatory cytokines. Collectively, our results indicate that in addition to regulation of LPS-induced acute inflammation, Tregs help to improve bacterial clearance and promote survival in an acute model of bacterial infection.