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
Diagnostic value of mitochondrial DNA and peripheral blood mononuclear cell respirometry for burn-related sepsis.
Background: Sepsis is the leading cause of mortality among burn patients that survive acute resuscitation. Clinical criteria have poor diagnostic value for burn-induced sepsis, making it difficult to diagnose. Protein biomarkers (e.g., procalcitonin) have been examined with limited success. ⋯ A subanalysis revealed a significant mortality difference in PBMC respirometry after sepsis diagnosis, wherein survivors had higher routine respiration ( P = 0.003) and maximal respiration ( P = 0.011) compared with nonsurvivors. Conclusion: Our findings reveal that mtDNA may have diagnostic value for burn sepsis, whereas PBMC respirometry is nonspecifically elevated in burns, but may have value in mortality prognosis. A larger, multisite study is warranted for further validity of the diagnostic value of mtDNA and PBMC respirometry as biomarkers for prognosis of sepsis and outcomes in burn patients.
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This report deals with the advances made in the areas of complement and its role in sepsis, both in mice and in humans. The study relates to work over the past 25 years (late 1990s to October 2022). ⋯ The work in septic humans and mice, along with patients who develop lung dysfunction caused by COVID-19, has taught us that there are many strategies for treatment of humans who are septic or develop COVID-19-related lung dysfunction. To date, treatments in humans with these disorders suggest that we are in the midst of a new and exciting area related to the complement system.
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Aged traumatic brain injury (TBI) patients suffer increased mortality and long-term neurocognitive and neuropsychiatric morbidity compared with younger patients. Microglia, the resident innate immune cells of the brain, are complicit in both. We hypothesized that aged microglia would fail to return to a homeostatic state after TBI and adopt a long-term injury-associated state within aged brains compared with young brains after TBI. ⋯ Notably, aged mice post-injury had a subpopulation of age-specific, immune-inflammatory microglia resembling the gene profile of neurodegenerative disease-associated microglia with enriched pathways involved in leukocyte recruitment and brain-derived neurotrophic factor signaling. Meanwhile, post-injury, aged mice demonstrated heterogeneous T-cell infiltration with gene profiles corresponding to CD8 effector memory, CD8 naive-like, CD8 early active T cells, and Th1 cells with enriched pathways, such as macromolecule synthesis. Taken together, our data showed that the aged brain had an age-specific gene signature change in both T-cell infiltrates and microglia, which may contribute to its increased vulnerability to TBI and the long-term sequelae of TBI.
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Background: Patients with severe coronavirus disease 2019 (COVID-19) are at an increased risk of acute respiratory distress syndrome and mortality. This is due to the increased levels of pro-inflammatory cytokines that amplify downstream pathways that are controlled by immune regulators. Objective: This study aimed to investigate the association between cytokine genetic variants, cytokine serum levels/profiles, and disease severity in critically and noncritically ill COVID-19 patients. ⋯ Conclusion: Data obtained from measuring cytokine levels and genetic variant analyses suggest that IL-6 and CXCL-16 could potentially be used as potential biomarkers for monitoring disease progression of COVID-19 patients. The findings in this study suggest that specific cytokine gene variants correlate with serum levels of the specific cytokine. These genetic variants could be of assistance in the early identification of high-risk patients on admission to the clinic to improve the management of COVID-19 patients and other infectious diseases.
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Background: Severe injury can provoke systemic processes that lead to organ dysfunction, and hemolysis of both native and transfused red blood cells (RBCs) may contribute. Hemolysis can release erythrocyte proteins, such as hemoglobin and arginase-1, the latter with the potential to disrupt arginine metabolism and limit physiologic NO production. We aimed to quantify hemolysis and arginine metabolism in trauma patients and measure association with injury severity, transfusions, and outcomes. ⋯ Conclusions: Severe injury induces intravascular hemolysis, which may mediate postinjury organ dysfunction. In addition to native RBCs, transfused RBCs can lyse and may exacerbate trauma-induced hemolysis. Arginase-1 released from RBCs may contribute to the depletion of l -arginine and the subsequent reduction in the NO necessary to maintain organ perfusion.