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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Observational Study
Time from hospital admission to onset of septic shock is associated with higher in-hospital mortality.
Objective: Several studies have shown septic shock developing later during the hospital stay is associated with higher mortality. However, the precise point at which time from hospital admission to the onset of septic shock (admission-shock-onset-time) becomes an independent prognostic marker of mortality remains unknown. This study evaluated the association between admission-shock-onset-time and in-hospital mortality among patients with septic shock and the optimal cutoff period to categorize early- and late-onset septic shock. ⋯ The adjusted odds ratio exceeded 2 in between 20.1 and 54.6 h, and it surpassed 3 in between 54.6 and 148.4 h of the time from the hospital admission to shock onset. Conclusion: In-hospital mortality continued to rise as admission-shock-onset-time increased in patients with septic shock. No clear dichotomization between early and late septic shock could be ascertained, and this categorization may limit our understanding of the temporal relationship of shock onset to mortality.
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Mitochondrial DNA (mtDNA) acts as a proinflammatory damage-associated molecular pattern that stimulates innate immune activation via Toll-like receptor 9, similarly to bacterial DNA. A number of clinical studies have measured elevated cell-free mtDNA in the plasma of trauma patients, thought to originate from tissue injury and inflammatory processes; however, the magnitude of this increase, the absolute concentration, and the association with poor outcomes varies considerably across studies. Measurements of cell-free mtDNA in healthy individuals have shown that the majority of "cell-free" mtDNA (>95%) can be centrifuged/filtered from plasma in the size range of 0.45 to 5 μm, suggesting that there are larger forms of mtDNA-containing complexes in the plasma that could be considered cell-free. ⋯ These findings from healthy individuals also suggest that the centrifugation speeds used to generate cell-free plasma (which are rarely consistent among studies) could result in mixed populations of cell-free mtDNA that could confound associations with outcomes. We demonstrate in this study of 25 major trauma patients that the majority of the cell-free mtDNA in trauma patient plasma (>95%) is removed after centrifugation at 16,000g. Despite the larger forms of mtDNA being predominant, they do not correlate with outcomes or expected parameters such as injury/shock severity, multiple organ failure, and markers of inflammation, whereas low-molecular-weight cell-free mtDNA correlates strongly with these variables.
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Introduction: Neutrophil extracellular traps (NETs) trigger thrombin generation. We aimed to characterize the effects of deoxyribonuclease (DNAse) on NET components (cell-free DNA [cfDNA] and histones) and thrombin generation after trauma. Methods: Citrated plasma samples were collected from trauma patients and healthy volunteers. ⋯ The effect of DNAse was greater on trauma patients as compared with volunteers for LT (ΔLT, -0.21 vs. -0.02 min, P = 0.007), cfDNA (ΔcfDNA -133.4 vs. -84.9 ng/mL, P < 0.001), and CitH3 (ΔCitH3, -0.65 vs. -0.11 ng/mL, P = 0.004). Conclusion: Deoxyribonuclease treatment accelerates thrombin generation kinetics in trauma patient samples as compared with healthy volunteers. These findings suggest that NETs may contribute to the hypercoagulable state observed in trauma patients.
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Aim: Head and thorax elevation during cardiopulmonary resuscitation improves cerebral hemodynamics and ultimate neurological outcome after cardiac arrest. Its effect during extracorporeal cardiopulmonary resuscitation (E-CPR) is unknown. We tested whether this procedure could improve hemodynamics in swine treated by E-CPR. ⋯ Carotid blood flow and cerebral oxygen saturation were not significantly different among groups. Conclusion: During E-CPR, head and thorax elevation prevents ICP increase. Whether it could improve the ultimate neurological outcome in this situation deserves further investigation.
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Idiopathic pulmonary fibrosis is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause. Interleukin (IL)-11 plays an important role in the pathogenesis of idiopathic pulmonary fibrosis. In this study, we explore whether a potential antifibrotic agent fluorofenidone (FD) exerts its anti-inflammatory and antifibrotic effects through suppressing activation of the IL-11/MEK/ERK signaling pathway in vivo and in vitro. ⋯ Results showed that FD markedly reduced the expressions of IL-8, IL-18, IL-11, monocyte chemotactic protein-1, α-SMA, fibronectin, and collagen I in mice lung tissues. In addition, FD attenuated IL-11-induced expressions of α-SMA, fibronectin, and collagen I and inhibited IL-11RA, gp130, and phosphorylation of the ERK and MEK protein expression, as well as reduced the expressions of IL-8, IL-18, and monocyte chemotactic protein-1 in vitro. This study demonstrated that FD attenuated bleomycin-induced pulmonary inflammation and fibrosis in mice by inhibiting the IL-11/MEK/ERK signaling pathway.