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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Patients with inflammatory bowel disease have a unique inflammatory response to infection given the pathogenesis of these diseases and the common use of immunosuppressive therapy. ⋯ Sepsis visits with Crohn disease had improved outcomes compared with the control group. Conversely, visits with ulcerative colitis had markedly worsened sepsis-related outcomes. Further investigation is needed to determine the mechanisms underlying these clinical differences.
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Epidermal growth factor (EGF) is a cytoprotective protein that improves survival in preclinical models of sepsis through its beneficial effects on intestinal integrity. Alcohol use disorder worsens intestinal integrity and is associated with increased morbidity and mortality in critical illness. We sought to determine whether chronic alcohol ingestion alters the host response to systemic administration of EGF in sepsis. ⋯ EGF administration resulted in lower levels of both pro- and anti-inflammatory cytokines monocyte chemoattractant protein-1, tumor necrosis factor, and interleukin 10 in alcohol-fed mice. EGF is therefore effective at improving both intestinal integrity and mortality following sepsis in mice with chronic alcohol ingestion. However, the efficacy of EGF in sepsis is blunted in the setting of chronic alcohol ingestion, as intestinal integrity and mortality in alcohol-fed mice given EGF improves animals to levels seen in water-fed mice given vehicle but does not approach levels seen in water-fed mice given EGF.
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Pulmonary injury can be characterized by an increased need for fraction of inspired oxygen or inspired oxygen percentage (FiO2) to maintain arterial blood saturation of oxygenation (SaO2). We tested a smart oxygenation system (SOS) that uses the activity of a closed-loop control FiO2 algorithm (CLC-FiO2) to rapidly assess acute respiratory distress syndrome (ARDS) severity so that rescue ventilation (RscVent) can be initiated earlier. ⋯ Initially, sheep were spontaneously ventilating and then randomized to standard of care (SOC) (n = 6), in which RscVent began when partial pressure of oxygen (PaO2) < 90 mmHg or FiO2 < 0.6, versus SOS (n = 7), software that incorporates and displays SpO2, CLC-FiO2, and SpO2/CLC-FiO2 ratio, at which RscVent was initiated when ratio threshold < 250. RscVent was achieved using a G5 Hamilton ventilator (Bonaduz, Switzerland) with adaptive pressure ventilation and adaptive support ventilation modes for SOC and SOS, respectively.
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Renal ischemia-reperfusion (I/R) injury ranks as the primary cause of acute renal injury with severe morbidity and mortality. Side population (SP) cells have recently drawn increasing attention due to their critical role in injury repair and regeneration. Unfortunately, the underlying mechanism involved in renal I/R remains poorly elucidated. ⋯ Additionally, sonic hedgehog (SHH)-Gli 1 signaling was involved in SDF-1/CXCR4-mediated ABCG2 expression. When SP cells pretreated with AMD3100 were intravenously injected into I/R mice, SP cell-mediated decreases in blood urea nitrogen, serum creatinine, and histological score of kidney were noticeably attenuated, indicating that blocking CXCR4 pathway mitigated the therapeutic function of SP cells in renal I/R injury. Together, this research suggests that SDF-1/CXCR4 axis might act, via Shh-Gli1-ABCG2 signaling, as a positive regulator of SP cell-based therapies for renal I/R by Shh-Gli 1-ABCG2 signaling.
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Red blood cell transfusions in the setting of trauma are a double-edged sword, as it is a necessary component for life-sustaining treatment in massive hemorrhagic shock, but also associated with increased risk for nosocomial infections and immune suppression. The mechanisms surrounding this immune suppression are unclear. ⋯ HMGB1 derived from the supernatant of human-stored RBCs was shown to inhibit bacterial clearance, as neutralizing antibodies to HMGB1 restored the ability of macrophages to clear bacteria. These findings demonstrate that extracellular HMGB1 within stored RBCs could be one factor leading to immune suppression following transfusion in the trauma setting.