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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Red blood cell distribution width (RDW) is known to be a predictor of severe morbidity and mortality in some chronic diseases such as congestive heart failure. However, to our knowledge, little is known about RDW as a predictor of mortality in patients with Gram-negative bacteremia, a major nosocomial cause of intra-abdominal infections, urinary tract infections, and primary bacteremia. Therefore, we investigated whether RDW is an independent predictor of mortality in patients with Gram-negative bacteremia. ⋯ In addition, the area under the curve of RDW at the onset of bacteremia, the 72-h RDW, and the Sequential Organ Failure Assessment score for 28-day mortality were 0.764 (P = 0.001), 0.802 (P < 0.001), and 0.703 (P = 0.008), respectively. Red blood cell distribution width at the onset of bacteremia was an independent predictor of mortality in patients with Gram-negative bacteremia. Also, 72-h RDW could be a predictor for all-cause mortality in patients with Gram-negative bacteremia.
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Comparative Study
Adverse effects of resuscitation with lactated ringer compared with ringer solution after severe hemorrhagic shock in rats.
Lactated Ringer (LR) is a widely used resuscitation fluid that is known to mediate beneficial effects on acid-base balance when compared with normal saline. We here compared LR with the more physiological Ringer solution (RS) regarding acid-base status, hemodynamics, survival, and organ injury following fluid resuscitation subsequent to severe hemorrhagic shock. Anesthetized rats were hemorrhaged to a mean arterial blood pressure of 25 to 30 mmHg within 30 min. ⋯ In these blood-resuscitated groups, organ injury, especially of the kidney, was diminished by the use of RS compared with LR. Time-matched acid-base parameters were not different in all shock groups until death of the animals or euthanasia at the end of experimental time. We conclude that, in severe hemorrhagic shock, resuscitation with RS leads to an improved outcome compared with resuscitation with LR, regardless whether blood is coadministered or not.
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Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia-induced sepsis is a common cause of morbidity in the intensive care unit. Although pneumonia is initiated in the lungs, extrapulmonary manifestations occur commonly. In light of the key role the intestine plays in the pathophysiology of sepsis, we sought to determine whether MRSA pneumonia induces intestinal injury. ⋯ To determine if these findings were organism-specific, similar experiments were performed in mice subjected to Pseudomonas aeruginosa pneumonia. Pseudomonas aeruginosa induced gut apoptosis, but unlike MRSA, this was associated with increased Bcl-2 and TNF-R1 and decreased Fas. Methicillin-resistant S. aureus pneumonia thus induces organism-specific changes in intestinal apoptosis via changes in both the mitochondrial and receptor-mediated pathways, although the former may be more functionally significant.
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Glucocorticoids remain a recommended therapy in advanced septic shock despite the often unpredictable response, and our understanding of the mechanisms regulating the steroid and stress response remains limited. Since the initial sequencing of the human glucocorticoid receptor α and β gene (hGRα and hGRβ), only three additional splice variants have been identified--all of which have been postulated to contribute to steroid resistance. During a survey of 97 healthy humans' blood, we identified two novel hGR splice isoforms (hGR-S1 and hGR-S1(-349A) retaining intron H between exons 8 and 9. ⋯ Removal of the 3' untranslated region (3'UTR) of the hGR-S1(-349A) mRNA sequence resulted in a loss of the augmented response. The isoform hGR-S1(-349A) augments the response to steroids, and this significant response appears to be critically regulated by the 3'UTR. The identification and evaluation of these unique hGR isoforms helps further the understanding of the complex genetic regulation of the stress and steroid response.
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More than 50% of severely injured patients have chest trauma. Second insults frequently result in acute lung injury (ALI), with sepsis being the main underlying condition. We aimed to develop a standardized, reproducible, and clinically relevant double-hit mouse model of ALI induced by chest trauma and polymicrobial sepsis and to investigate the pathophysiologic role of activated neutrophils. ⋯ Neutrophil depletion significantly diminished lung interleukin 1β and interleukin 6 concentrations and reduced the degree of septic ALI. Here we have established a novel and highly reproducible mouse model of chest trauma-induced septic ALI characterizing a clinical relevant double-hit scenario. In particular, the depletion of neutrophils substantially mitigated the extent of lung injury, indicating a pathomechanistic role for neutrophils in chest trauma-induced septic ALI.