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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Sepsis accounts for a huge number of deaths in intensive care units all over the world. In 2002, Surviving Sepsis Campaign (SSC) was launched, targeting a mortality reduction of 25% in 5 years. Treatment guidelines were developed, published in 2004 and revised in 2007. ⋯ More than 10,000 patients have been enrolled worldwide. However, the SSC and its bundles have been harshly criticized both because of an industry funding and by the presumed fragility of the studies from where they were based. In this review, the main arguments of the SSC critics are discussed and refuted, and the main controversial issues of the resuscitation and management bundles are analyzed, taking into account the new evidence in the literature.
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The release of "neutrophil extracellular traps" (NETs) has been identified as a novel immune response in innate immunity. Neutrophil extracellular traps are composed of neutrophil-derived circulating free DNA (cf-DNA), histones, and neutrophil cytoplasm-derived proteins such as proteases. Here, we studied the putative predictive value of plasma cf-DNA/NETs for the development of sepsis and mortality after multiple trauma. ⋯ Circulating free DNA/NETs kinetics rather followed kinetics of Multiple Organ Dysfunction Score, Sepsis-related Organ Failure Assessment, leukocyte counts, and partially of myeloperoxidase. Circulating free DNA/NETs seems to be a valuable additional marker for the calculation of injury severity and/or prediction of inflammatory second hit on ICU. However, a large clinical trial with severely injured patients should confirm the prognostic value of neutrophil-derived cf-DNA/NETs.
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A promising therapeutic strategy for the management of severe Pseudomonas infection in neutropenic patients may result from the coadministration of colony-stimulating factors (CSFs) that help maintain immune competence and antimicrobial peptides, a novel generation of adjunctive therapeutic agents with antimicrobial and anti-inflammatory properties. A promising peptide with these properties is LL-37, the only member of the cathelicidin family of antimicrobial peptides found in humans. BALB/c male mice were rendered neutropenic by intraperitoneal administration of cyclophosphamide on days -4 and -2 preinfection. ⋯ All regimens were significantly superior to controls at reducing the mouse lethality rate and bacterial burden in organs. Particularly, the combination between LL-37 and G-CSF was the most effective in protecting neutropenic mice from the onset of sepsis and in vitro significantly reduced the apoptosis of neutrophils. Combination therapy between LL-37 and G-CSF is a promising therapeutic strategy for the management of severe Pseudomonas infection complicated by neutropenia.
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Ischemic postconditioning (I-postC) is a newly discovered endogenous protective phenomenon capable of protecting the myocardium from I/R injury. The cardioprotective mechanisms of I-postC involve protein synthesis and preventing an increase in cytosolic calcium. Endoplasmic reticulum (ER) is a principal site for secretory protein synthesis and calcium storage. ⋯ Ischemic postconditioning suppressed I/R-induced ER stress, as shown by a decrease in calreticulin expression and caspase 12 activation. Hypoxic postconditioning up-regulates p38 MAPK phosphorylation and down-regulates JNK phosphorylation in cardiomyocytes subjected to H/R. These results indicate that I-postC protects myocardium from I/R injury by suppressing ER stress, and that p38 MAPK and JNK pathways are associated with the I-postC-induced suppression of ER stress.
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Burn injury has been associated with systemic/compartmental inflammatory responses and myocardial dysfunction. We hypothesized that burn size correlates with the extent of cardiac inflammatory response/contractile dysfunction. Adult male Sprague-Dawley rats were divided to receive anesthesia, a 3-degree burn covering 20%, 30%, 40%, or 60% total body surface area (TBSA) plus fluid resuscitation (lactated Ringer, 4 mL/kg per percent burn); sham burn animals were included as controls. ⋯ However, myocardial contractile depression induced by 60% TBSA burn was similar to that produced by 40% TBSA burn. These data suggest that the degree of inflammatory response, cardiac tissue injury, and myocardial contractile depression were correlated directly with the percent TBSA burn. However, unlike inflammation and cardiac tissue damage, myocardial contractile depression reached a plateau, with maximal myocardial contraction and relaxation defects observed at 40% TBSA burn, which were not further aggravated by a larger (60%) burn.