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
Impaired Lymphocyte Responses in Pediatric Sepsis Vary by Pathogen Type and are Associated with Features of Immunometabolic Dysregulation.
Sepsis is the leading cause of death in hospitalized children worldwide. Despite its hypothesized immune-mediated mechanism, targeted immunotherapy for sepsis is not available for clinical use. ⋯ Pediatric sepsis patients exhibit a complex, dynamic physiologic state characterized by impaired T cell function and immunometabolic dysregulation which varies by pathogen type.
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Oxidation-reduction (redox) reactions, and the redox potential (RP) that must be maintained for proper cell function, lie at the heart of physiologic processes in critical illness. Imbalance in RP reflects systemic oxidative stress, and whole blood RP measures have been shown to correlate with oxygen debt level over time in swine traumatic shock. We hypothesize that RP measures reflect changing concentrations of metabolites involved in oxidative stress. To test this hypothesis, we compared blood and urine RP with concentrations of multiple metabolites in a swine traumatic shock model to identify meaningful RP-metabolite relationships. ⋯ Real-time RP measures demonstrate significant relationships with metabolites attributable to metabolic pathways involved in systemic responses to oxidative stress, as well as those involved in these processes. These data support RP measures as a feasible, biologically relevant marker of oxidative stress. As a direct measure of redox state, RP may be a useful biomarker and clinical tool in guiding diagnosis and therapy in states of increased oxidative stress and may offer value as a marker for organ injury in these states as well.
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Functional Transcriptomic Studies of Immune Responses and Endotoxin Tolerance In early Human Sepsis.
Limited studies have functionally evaluated the heterogeneity in early ex vivo immune responses during sepsis. Our aim was to characterize early sepsis ex vivo functional immune response heterogeneity by studying whole blood endotoxin responses and derive a transcriptional metric of ex vivo endotoxin response. ⋯ An attenuated ex vivo endotoxin response in early sepsis is associated with greater host in vivo inflammation and a worse clinical outcome.
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Observational Study
GROWTH DIFFERENTIATION FACTOR-15 CORRELATES WITH MORTALITY AND SEVERITY IN SEVERE BURNS.
Growth differentiation factor-15 (GDF-15) is expressed in almost all tissues of the body and is necessary for the body's defense response to stress such as inflammation. It has been reported to be associated with incidence and mortality in many diseases, including systemic inflammatory response syndromes. There are no reports on GDF-15 in burns. The purpose of this study was to investigate the trend of GDF-15 in blood in patients with severe burns and to determine its relationship with severity and mortality. ⋯ In the acute phase of severe burn, GDF-15 levels were associated with mortality and SOFA scores.
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Hepcidin Alleviates LPS-Induced ARDS by Regulating The Ferritin-Mediated Suppression of Ferroptosis.
The effects of ferroptosis, an iron-dependent cell death, on acute respiratory distress syndrome (ARDS) remain largely elusive. Hepcidin, encoded by the HAMP gene, affects inflammation, and iron homeostasis. The present study aimed to investigate whether hepcidin protects against ferroptosis in lipopolysaccharide (LPS)-induced ARDS. ⋯ The effects of hepcidin on the A549 cell line were in line with the in vivo results. In addition, we used si-FTH to knock down FTH expression and found that this suppressed the ability of hepcidin to protect against ferroptosis. Collectively, our data suggest that hepcidin inhibits ferroptosis by increasing FTH expression in LPS-induced ARDS; thus, hepcidin may represent a possible treatment targeting ferroptosis.