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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Multicenter Study Clinical Trial Observational Study
Plasma Neutrophil Elastase and Elafin as Prognostic Biomarker for Acute Respiratory Distress Syndrome: A Multicenter Survival and Longitudinal Prospective Observation Study.
Neutrophil elastase (HNE) is a destructive enzyme and plays crucial roles in the pathophysiology of acute respiratory distress syndrome (ARDS). Endogenous proteinase inhibitors elafin (PI3) is important to protect against lung tissue destruction. We proposed to examine whether HNE and PI3 serve as prognostic biomarkers for ARDS. ⋯ Imbalance between HNE and PI3 levels in ARDS patients was associated with ARDS mortality. By combining these biomarkers with Berlin categories and APACHE II, prognostic power of ARDS was greatly improved. Circulation levels of HNE and PI3 may have the potential to predict ARDS mortality and better inform clinicians about ARDS mortality risk.
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The role of interleukin-6 (IL-6) in physiological processes and disease is poorly understood. The hypothesis tested in this study was that selective alpha7 acetylcholine receptor (α7AChR) agonist, GTS-21, releases IL-6 in association with myonuclear accretion and enhances insulin signaling in muscle cells, and improves survival of burn injured (BI) mice. The in vitro effects of GTS-21 were determined in C2C12 myoblasts and 7-day differentiated myotubes (myotubes). ⋯ The 75% mortality in burned WT mice was reduced to 0% with GTS-21. The in vitro findings suggest that GTS-21-induced IL-6 release from muscle is mediated via α7AChRs upstream of Stat-3 and -5 pathways and is associated with myonuclear accretion, possibly via MyoD and Pax7 expression. GTS-21 in vivo improves survival in burned WT mice and IL6KO mice, suggesting a potential therapeutic application of α7AChR agonists in the treatment of BI.
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Review
Is Coagulopathy an Appropriate Therapeutic Target During Critical Illness Such as Trauma or Sepsis?
Coagulopathy is a common and vexing clinical problem in critically ill patients. Recently, major advances focused on the treatment of coagulopathy in trauma and sepsis have emerged. ⋯ To analyze the state of the science regarding coagulopathy in critical illness, a symposium addressing the problem was organized at the 39th annual meeting of the Shock Society in the summer of 2016. This manuscript synthesizes the viewpoints of the four expert panelists at the debate and presents an overview of the potential positive and negative consequences of targeting coagulopathy in trauma and sepsis.
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To compare the efficacy of hypotensive resuscitation with hypertonic saline dextran 70 (HSD) and lactated Ringer (LR) solutions in a rat model of hemorrhagic shock at a simulated altitude of 4,000 m. ⋯ For hemorrhagic shock at simulated high altitude, resuscitation of rats with a bolus of HSD was associated with reduced blood loss and serum lactate concentration, and superior SaO2, hemoglobin concentration and survival rate, compared with LR solution.
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Several direct oral anticoagulants (DOACs), including direct thrombin and factor Xa inhibitors, have been approved as alternatives to vitamin K antagonist anticoagulants. As with any anticoagulant, DOAC use carries a risk of bleeding. In patients with major bleeding or needing urgent surgery, reversal of DOAC anticoagulation may be required, presenting a clinical challenge. ⋯ We find that in addition to varied species being used, there is variability in the models and assays used between studies; we suggest that blood loss (bleeding volume) is the most clinically relevant measure of DOAC anticoagulation-related bleeding and its reversal. The studies covered indicate that both PCCs and specific reversal agents have the potential to be used as part of a clinical strategy for DOAC reversal. For the future, we advocate the development and use of standardized, clinically, and pharmacologically relevant animal models to study novel DOAC reversal strategies.