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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An overwhelming immune response, particularly from macrophages, plays a critical role in survival and organ damage in sepsis patients. Toll-like receptors (TLRs) are important receptors to recognize the conserved motifs expressed by invading bacteria. The TLRs except TLR3 signal via a MyD88-dependent pathway. ⋯ Moreover, MyD88 KO, but not TRIF KO mice, showed a decreased CD14 expression in the tissue of septic mice, which was associated with a strongly attenuated inflammatory response and increased survival rate. These data suggest that a MyD88-dependent and TRIF-independent pathway of TLR is activated in upregulating CD14 expression under septic conditions. This study deciphers a critical cross-talk between TLRs and CD14.
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The role of intestinal Candida albicans in bacterial sepsis, in the absence of candidemia, was investigated in murine models. Live C albicans or normal saline solution (NSS) was administered orally once, followed by 5 days of daily oral antibiotic-mixtures (ATB). Cecal ligation and puncture (CLP) was then performed to induce sepsis. ⋯ Heat-killed Candida preparations or their supernatants reduced bone marrow-derived macrophage killing activity in vitro but enhanced cytokine production. In conclusion, intestinal abundance of fungi and/or fungal-molecules was associated with increased bacterial sepsis severity, perhaps through cytokine storm induction and/or decreased macrophage killing activity. These observations suggest that further investigation of the potential role of intestinal fungal burdens in sepsis is warranted.
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Patients in the intensive care unit (ICU) who develop chronic critical illness significantly stress the clinical capacity and financial resources of healthcare systems. Although vast improvements have been made in critical care management, outcomes for this ICU subset remain poor. A hallmark for patients who progress to chronic critical illness is the development of persistent inflammation and immunosuppression. ⋯ Interestingly, each of these clinical states bears strikingly similar immune defects, often resulting in the activation of a persistent inflammatory state. Strategies aimed at the prevention or early recognition of this state of immune compromise may help improve outcomes for these individuals and minimize the number who progress to chronic critical illness. This review explores the current knowledge regarding the immune defects associated with the development of persistent inflammation, the ways in which it can manifest clinically, attempted therapeutic interventions to date, and future insights into improving outcomes for this patient population.
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Far from traditional "vital signs," the field of hemodynamic monitoring (HM) is rapidly developing. However, it is also easy to misunderstand hemodynamic therapy as merely HM and some concrete bundles or guidelines for circulation support. Here, we describe the concept of "critical hemodynamic therapy" and clarify the concepts of the "therapeutic target" and "therapeutic endpoint" in clinical practice. ⋯ The flow-directed target for fluid infusion might be a priority, but it remains controversial in resuscitation. The interpretation of these targets is necessary for adequate resuscitation and the correction of tissue hypoxia. The incoherence phenomenon of resuscitation (macrocirculation and microcirculation, tissue perfusion, and cellular oxygen utilization) is gaining increased attention, and early identification of these incoherences might be helpful to reduce the risk of over-resuscitation.
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The release of damage-associated molecular pattern molecules in the extracellular space secondary to injury has been shown to cause systemic activation of the coagulation system and endothelial cell damage. We hypothesized that pediatric trauma patients with increased levels of histone-complexed DNA fragments (hcDNA) would have evidence of coagulopathy and endothelial damage that would be associated with poor outcomes. ⋯ hcDNA is released following injury and correlates with coagulopathy, endothelial glycocalyx damage, and poor clinical outcome early after severe pediatric trauma. These results indicate that hcDNA may play an important role in development of coagulation abnormalities and endothelial glycocalyx damage in children following trauma.