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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As activation of the coagulation system is both a consequence and contributor to acute lung injury (ALI), pulmonary coagulopathy has become a potential target for therapeutic intervention in ALI patients. We investigated the effects and possible mechanisms of endothelial cell (EC)-anchored tissue factor pathway inhibitor (TFPI) on lipopolysaccharide (LPS)-induced ALI in mice. To assess the effect of EC-anchored TFPI deletion on ALI indices, TFPI knockout (cKO) mice were generated. ⋯ The number and infiltration of white blood cells (WBCs) from BALF and lung tissue of TFPI cKO mice with LPS-challenged ALI was increased compared to WT mice with LPS-challenged ALI. We also found further increased toll-like receptor 4 and nuclear factor kappa-light-chain-enhancer of activated B cells activation and additional expression of vascular cell adhesion molecule 1 and reduction of angiotensin converting enzyme 2 expression in TFPI cKO+LPS mice compared with WT+LPS mice. Endothelial-specific TFPI deficiency promoted LPS-induced pulmonary inflammation and endothelial barrier permeability possibly via toll-like receptor 4-mediated nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway activation.
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Clinical Trial Observational Study
The Association Between the Neutrophil-to-Lymphocyte Ratio and Mortality in Patients With Acute Respiratory Distress Syndrome: A Retrospective Cohort Study.
Systemic inflammation relates to the initiation and progression of acute respiratory distress syndrome (ARDS). As neutrophil-to-lymphocyte ratio (NLR) has been shown to be a prognostic inflammatory biomarker in various diseases, in this study, we sought to explore whether NLR is a prognostic factor in patients with ARDS. ⋯ High NLR was associated with the poor outcome in critically ill patients with ARDS. The NLR therefore seems to be a prognostic biomarker of outcomes in critically ill patients with ARDS. Further investigation is required to validate this relationship with data collected prospectively.
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Clinical Trial Observational Study
A Novel Implementation of Magnetic Levitation to Quantify Leukocyte Size, Morphology, and Magnetic Properties to Identify Patients with Sepsis.
We have developed a novel, easily implementable methodology using magnetic levitation to quantify circulating leukocyte size, morphology, and magnetic properties, which may help in rapid, bedside screening for sepsis. ⋯ Septic patients had circulating leukocytes with especially increased size parameters, which distinguished sepsis from noninfected patients with promising high accuracy. This portal-device compatible technology shows promise as a potential bedside diagnostic.
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Clinical Trial Observational Study
Clinical Importance of a Cytokine Network in Major Burns.
Major burns elicit an acute inflammatory response including various inflammatory cytokines. Cytokines play mutual interacting roles in inflammatory diseases. There is little evidence of the clinical significance of the cytokine network in patients with major burns. ⋯ Each cytokine showed significant associations with the SOFA score within 5 days and 1 month after burn injury. Cox regression analysis highlighting days 1 and 2 showed significant correlation of IL-6, IL-8, and IL-10 with 28-day mortality. We showed a cytokine network and its relation with prognosis and injury severity on days 1 and 2 and suggest that this cytokine network may play a role in major burns.
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Outer membrane vesicles (OMVs), released by variety of bacteria, are membrane-enclosed entities enriched in microbial components, toxins, and virulent factors. OMVs could deliver lipopolysaccharide (LPS) into the cytosol of host cells and subsequently activate caspase-11, which critically orchestrates immune responses and mediates septic shock. Although it is known that caspase-11 is activated by intracellular LPS, how OMVs deliver LPS into the cytosol remains largely unknown. ⋯ TRIF-mediated cytosolic delivery of LPS from OMVs depends on the production of type 1 interferon and the expression of guanylate-binding proteins (GBPs). Deletion of TRIF or GBPs prevents pyroptosis and lethality induced by OMVs or OMVs-releasing Escherichia coli. Together, these findings provide novel insight into how host coordinates extracellular and intracellular LPS sensing to orchestrate immune responses during gram-negative bacterial infection.