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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Previous preclinical studies have demonstrated a pathobiome after traumatic injury; however, the impact of post-injury sepsis on gut epithelial permeability and bacterial translocation remains unknown. We hypothesized that polytrauma with post-injury pneumonia would result in impaired gut permeability leading to specific blood microbiome arrays. ⋯ Multicompartmental trauma with post-injury pneumonia results in increased intestinal permeability and bacteremia with a unique blood biome, with sexual dimorphisms evident in the blood biome composition. These findings suggest that post-injury sepsis has clinical significance and could influence outcomes after severe trauma and critical illness.
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Intestinal injury is often caused by systemic ischemia-reperfusion injury early after cardiac arrest (CA) and resuscitation. Artesunate (Art) has been confirmed to protect vital organs against diverse of regional I/R injury. This study aimed to investigate the effect of Art on intestinal injury after CA and cardiopulmonary resuscitation (CPR) in swine. ⋯ Art treatment effectively alleviates post-resuscitation intestinal injury, possibly by inhibiting the caspase-3/GSDME-mediated pyroptosis pathway in a swine CA and CPR model.
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Comparative Study Observational Study
Plasma dynamics of neutrophil extracellular traps and cell-free DNA in septic and non-septic vasoplegic shock: a prospective comparative observational cohort study.
Background: The association between neutrophil extracellular traps (NETs) and the requirement for vasopressor and inotropic support in vasoplegic shock is unclear. This study aimed to investigate the dynamics of plasma levels of NETs and cell-free DNA (cfDNA) up to 48 h after the admission to the intensive care unit (ICU) for management of vasoplegic shock of infectious (SEPSIS) or noninfectious (following cardiac surgery, CARDIAC) origin. Methods: This is a prospective, observational study of NETs and cfDNA plasma levels at 0H (admission) and then at 12H, 24H, and 48H in SEPSIS and CARDIAC patients. ⋯ Conclusion: Plasma levels of NETs and cfDNA correlated with the dose of vasopressors and inotropes administered over 48 h in patients with vasoplegic shock from sepsis or following cardiac surgery. NETs levels also correlated with organ dysfunction. These findings suggest that similar mechanisms involving release of NETs are involved in the pathophysiology of vasoplegic shock irrespective of an infectious or noninfectious etiology.
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Background: Acute kidney injury (AKI) can result from renal ischemia and reperfusion (I/R) and often occurs during surgical procedures in cardiac, liver, kidney transplantation, and trauma-hemorrhage. Milk fat globule epidermal growth factor-factor VIII (MFG-E8) functions as a bridging molecule to promote the removal of dying cells by professional phagocytes. Because MFG-E8 promotes clearance of apoptotic cells, we have explored its therapeutic potential in various organ injury conditions. ⋯ Histologically, at 48 h after AKI, tubular damage, and the number of TUNEL staining cells were increased and treatment markedly decreased these measurements. Administration of tag-free rhMFG-E8 at the time of reperfusion improved survival in a 10-day survival study. Conclusion: Our new human cell-expressed tag-free rhMFG-E8 is protective in I/R-induced AKI and it may have the potential to be further developed as a safe and effective therapy for AKI.
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Background: The recruitment of neutrophils to sites of localized injury or infection is initiated by changes on the surface of endothelial cells located in proximity to tissue damage. Inflammatory mediators, such as TNF-α, increase surface expression of adhesive ligands and receptors on the endothelial surface to which neutrophils tether and adhere. Neutrophils then transit through the activated endothelium to reach sites of tissue injury with little lasting vascular injury. ⋯ Similar findings were demonstrated on fibronectin, collagen I, collagen IV, and laminin, suggesting that neutrophil surface VLA-3 and CD151 are responsible for endothelial damage regardless of substrata and are likely to be operative in all bodily tissues. Conclusion: This report identifies VLA-3 and CD151 on the activated human neutrophil, which are responsible for damage to endothelial function. Targeting these molecules in vivo may demonstrate preservation of organ function during critical illness.