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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To explore the role of Erbin protein and nucleotide-binding oligomerization domain 2/receptor-interacting serine/threonine protein kinases (NOD2/RICK) in GTS-21 activating cholinergic anti-inflammatory pathway. ⋯ GTS-21 could significantly inhibit MDP-induced pro-inflammatory cytokines responses via activating cholinergic anti-inflammatory pathway, and the Erbin might be the key negative regulatory protein in NLR2/RICK signal transduction.
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IFN regulatory factor (IRF)3 plays a detrimental role in the cecal ligation and puncture (CLP) mouse model of sepsis. However, it is unclear which pathway activates IRF3 in this context. In this report, we investigate two pathways that activate IRF3: the Stimulator of Interferon Genes (STING) pathway (that senses cytosolic DNA) and the TIR-domain-containing adapter-inducing interferon-β (TRIF) pathway (that senses dsRNA and LPS via Toll-like receptor 3 and 4). ⋯ Together, our data demonstrate that both the STING and TRIF pathways can promote sepsis pathogenesis; however, their contribution depends on the severity of the disease model. We show that bacteria are abundant in the peritoneum following both severe and moderate CLP, while cell-free DNA is more highly elevated in the serum following severe CLP compared with sham and moderate CLP. Hence, the presence of bacteria and cell-free DNA may explain the variable phenotypes in our severe CLP model (dependent on TRIF and STING) versus our moderate CLP model (dependent on TRIF only).
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Review Meta Analysis
Does Respiratory Variation in Inferior Vena Cava Diameter Predict Fluid Responsiveness: A Systematic Review and Meta-Analysis.
The aim of fluid resuscitation is to increase stroke volume, yet this effect is observed in only 50% of patients. Prediction of fluid responsiveness may allow fluid resuscitation to be administered to those most likely to benefit. The aim of this study was to systematically review the test characteristics of respiratory variation in inferior vena cava (IVC) diameter as a predictor of fluid responsiveness in patients with acute circulatory failure. ⋯ Respiratory variation in IVC diameter has limited ability to predict fluid responsiveness, particularly in spontaneously ventilating patients. A negative test cannot be used to rule out fluid responsiveness. Clinical context should be taken into account when using IVC ultrasound to help make treatment decisions.
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Thrombocytopenia is prevalent in critical care, surgical, and trauma settings. Despite the fact that a significant proportion of these patients receive platelet transfusion during their hospital course, much work remains to be done with regard to development of platelet transfusion guidelines. ⋯ To this end, a literature review was performed utilizing PubMed and Cochrane Central Register of Controlled Trials to select 153 manuscripts that evaluate the current data supporting platelet transfusions in surgical and critical care populations. Advances in transfusion medicine and synthetic platelet substitutes that can be engineered for potential future applications will also be discussed.
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Refractory septic shock is defined as persistently low mean arterial blood pressure despite volume resuscitation and titrated vasopressors/inotropes in patients with a proven or suspected infection and concomitant organ dysfunction. Its management typically requires high doses of catecholamines, which can induce significant adverse effects such as ischemia and arrhythmias. Angiotensin II (Ang II), a key product of the renin-angiotensin-aldosterone system, is a vasopressor agent that could be used in conjunction with other vasopressors to stabilize critically ill patients during refractory septic shock, and reduce catecholamine requirements. ⋯ Here, we review the current literature on this topic to better understand the role of Ang II administration during refractory septic shock, differentiating experimental from clinical studies. We also consider the potential role of exogenous Ang II administration in specific organ dysfunction and possible pitfalls with Ang II in sepsis. Various issues remain unresolved and future studies should investigate important topics such as: the optimal dose and timing of Ang II administration, a comparison between Ang II and the other vasopressors (epinephrine; vasopressin), and Ang II effects on microcirculation.