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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Sepsis is a highly prevalent cause of death in intensive care units. Characterized by severe immune cell derangements, sepsis is often associated with multiorgan dysfunction. For many sepsis survivors, these deficits can persist long after clinical resolution of the underlying infection. ⋯ In addition to proportional cell composition changes, acute sepsis induced significant transcriptional alterations in most immune cell types analyzed-changes that failed to completely resolve 1 month after sepsis. Taken together, we report widespread and persistent transcriptional changes in diverse immune cells in response to polymicrobial infection. This study will serve as a valuable resource for future work investigating acute and/or long-term sepsis-associated immune cell derangements.
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Observational Study
Early differentiation between sepsis and sterile inflammation via urinary gene signatures of metabolic dysregulation.
Objective: The aim of this study was to characterize early urinary gene expression differences between patients with sepsis and patients with sterile inflammation and summarize in terms of a reproducible sepsis probability score. Design: This was a prospective observational cohort study. Setting: The study was conducted in a quaternary care academic hospital. ⋯ Functional analyses of probes associated with sepsis demonstrated metabolic dysregulation manifest as reduced oxidative phosphorylation, decreased amino acid metabolism, and decreased oxidation of lipids and fatty acids. Conclusions: Whole-genome transcriptomic profiling of urinary cells revealed focused probe panels that can function as an early diagnostic tool for differentiating sepsis from sterile SIRS. Functional analysis of differentially expressed genes demonstrated a distinct metabolic dysregulation signature in sepsis.
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Resuscitation of trauma patients after hemorrhagic shock causes global I/R, which may contribute to organ dysfunction. Oxidative stress resulting from I/R is known to induce signaling pathways leading to the production of inflammatory molecules culminating in organ dysfunction/injury. Our recent work demonstrated that oxidative stress was able to induce activation of the mitochondrial antiviral signaling protein (MAVS), a protein known to be involved in antiviral immunity, in an in vitro model. ⋯ Further, in vitro silencing of MAVS by specific siRNA in RAW 264.7 and exposure of the cells to H/R caused activation of mitophagy. This may represent a compensatory response to increased liver inflammation. We conclude that activation of MAVS by hypoxia/reoxygenation dampens inflammation, potentially suggesting a novel target for intervention.
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Objective: We previously identified two transcriptomic subtypes (Signature Groups: SG1 vs. SG2) in trauma patients at 12 hours postinjury, with SG1 associated with worse outcomes. In this study, we aimed to further characterize the changes in SG subtype categorization of trauma patients over time after injury and define the corresponding association with outcomes based on the timing of the subtype designation. ⋯ SG1 assignment, regardless of time point, was associated consistently with slower recovery. Further analysis revealed that additional prognostic information could be obtained by assessing SG subtype at both 12 hours and 1 day. Conclusions: This study provides a proof of concept that immune status can worsen after admission and highlights the benefit of longitudinally monitoring SG subtypes in trauma patients.
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Clinical Trial
Value of corrected flow time in common carotid artery in predicting volume responsiveness under mechanical ventilation.
Objective: The present study aimed to investigate whether corrected flow time (FTc) in common carotid artery could predict volume responsiveness under mechanical ventilation and to further explore whether the sensitivity and specificity would be influenced by positive end-expiratory pressure (PEEP). Methods: The first stage of this study included 80 patients from the general surgery department undergoing laparotomy. After induction of general anesthesia, FTc in the common carotid artery was measured when hemodynamic indicators, such as blood pressure, heart rate, and cardiac output (CO), were stabilized. ⋯ The area under the receiver operating characteristic curve for FTc in predicting volume responsiveness was 0.921, 0.805, and 0.719 when PEEP was 0, 5, and 10 cmH 2 O ( P < 0.05), respectively, and the cutoff value of FTc for diagnosing volume responsiveness was 323.42 milliseconds, 326.69 milliseconds, and 312.03 milliseconds, respectively. Conclusion: Corrected flow time in the common carotid artery can predict volume responsiveness under mechanical ventilation, and the predictive performance is not influenced by PEEP. Clinical Trial Registration Clinical register number: ChicTR2000029519.