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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Damage-associated molecular patterns (DAMPs) stimulate endothelial syndecan-1 shedding and neutrophil extracellular traps (NET) formation. The role of NETs in trauma and trauma-induced hypercoagulability is unknown. We hypothesized that trauma patients with accelerated thrombin generation would have increased NETosis and syndecan-1 levels. ⋯ Our pilot study demonstrates that trauma patients have increased NETosis, measured by H3NUC and H3Free levels, increased syndecan-1 shedding, and accelerated thrombin generation kinetics early after injury.
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Observational Study
Prognostic Accuracy of Vqsofa for Predicting 28-Day Mortality in Patients with Suspected Sepsis in the Emergency Department.
Sepsis screening in the emergency department (ED) is challenging. The quick Sequential Organ Failure Assessment (qSOFA) score had poor accuracy for predicting mortality in both the intensive care unit and ED. High lactate levels were associated with an increased mortality. However, a previous study using lactate levels in combination with the qSOFA score did not observe a meaningful improvement in predictive accuracy. This study assessed the prognostic accuracy of venous lactate levels plus the qSOFA (VqSOFA) score for predicting 28-day mortality. ⋯ VqSOFA was more predictive of 28-day mortality and vasopressor and mechanical ventilator use than the qSOFA and SOFA scores.
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To evaluate the clinical significance of pro-inflammatory cytokines for disease severity and coagulation in septic patients with bacterial co-infection. ⋯ Septic patients with bacterial co-infection had increased plasma levels of pro-inflammatory cytokines. Furthermore, a positive correlation between high levels of pro-inflammatory cytokines and increased disease severity and depressed blood coagulation function for septic patients with co-infection was identified.
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Angiopoietin-like 4 (ANGPTL4) is a secreted glycoprotein that plays an important role in endothelial injury and the inflammatory response. Experimental models have implicated ANGPTL4 in acute respiratory distress syndrome (ARDS), but its impact on the progression of ARDS is unclear. ⋯ ANGPTL4 levels were elevated in patients with ARDS and significantly correlated with disease severity and mortality. ANGPTL4 may be a novel prognostic biomarker in ARDS.
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IL-33 and WNT1-inducible secreted protein (WISP1) play central roles in acute lung injury (ALI) induced by mechanical ventilation with moderate tidal volume (MTV) in the setting of sepsis. Here, we sought to determine the inter-relationship between IL-33 and WISP1 and the associated signaling pathways in this process. We used a two-hit model of cecal ligation puncture (CLP) followed by MTV ventilation (4 h 10 mL/kg) in wild-type, IL-33-/- or ST2-/- mice or wild-type mice treated with intratracheal antibodies to WISP1. ⋯ This WISP1 upregulation and WNT β-catenin activation were sensitive to inhibition of the β-catenin/TCF/CBP/P300 nuclear pathway. We show that IL-33 drives WISP1 upregulation and ALI during MTV in CLP sepsis. The identification of this relationship and the associated signaling pathways reveals a number of possible therapeutic targets to prevent ALI in ventilated sepsis patients.