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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Sepsis has become the leading cause of death in burn patients. Furthermore, sepsis and septic complications result in significant morbidities and longer hospitalization, which has profound impacts on the healthcare system. Despite this, sepsis in burn patients is surprisingly poorly understood and characterized. ⋯ Applying these definitions, we compared clinical, metabolic, and inflammatory markers in septic and nonseptic burn patients. We found that the Sepsis-3 criteria are the most reliable screening tool used before clinical diagnoses for detecting sepsis trajectories and biochemical patterns. Moreover, we characterized distinct temporal alterations in biomarkers during the pre- and post-septic periods in burn patients, which may be incorporated into future sepsis definitions to improve the accuracy of a sepsis diagnosis in burn patients.
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Sex-related outcome differences in trauma remain controversial. The mechanisms causing sex-biased outcomes are likely to have hormonal and genetic components, in which X-linked genetic polymorphisms may play distinct roles because of X-linked inheritance, hemizygosity in males, and X chromosome mosaicism in females. The study aimed to elucidate the contribution of biological sex and the common X-linked IRAK1 haplotype to posttrauma clinical complications, inflammatory cytokine and chemokine production, and polymorphonuclear cell and monocyte activation. ⋯ Variant IRAK1 decreased IL-6, IL-8, and interferon gamma-induced protein 10 production in male trauma subjects compared to WT, whereas cytokine/chemokine responses were similar in variant IRAK1 and WT female trauma subjects. Trauma-induced and lipopolysaccharide-stimulated polymorphonuclear cell and monocyte activation determined by using a set of cluster of differentiation markers and flow cytometry were not influenced by sex or variant IRAK1. These findings suggest that variant IRAK1 is a potential contributor to sex-based outcome differences, but its immunomodulatory impacts are modulated by biological sex.
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Observational Study
ELEVATED PD-1/CD28 RATIO RATHER THAN PD-1 EXPRESSION IN CD8+ T CELLS PREDICTS NOSOCOMIAL INFECTION IN SEPSIS PATIENTS: A PROSPECTIVE, OBSERVATIONAL COHORT STUDY.
The expression of programmed cell death 1 receptor (PD-1) and CD28 on CD8+ T cells is considered to be related to immune function and prognosis markers in patients with sepsis. However, the relationship between the ratio of PD-1/CD28 and nosocomial infection has not been elucidated. Methods: A prospective, observational cohort study was conducted in a general intensive care unit. ⋯ The area under the receiver operating characteristic curve of PD-1/CD28 ratio in CD8+ T cells was 0.67 (0.52-0.82). The PD-1/CD28 ratio in CD8+ T cells of the nonsurvivors was significantly higher than the survivors (0.23 [0.15-0.52] vs. 0.14 [0.07-0.32]); Cox regression analysis showed that the survival time of patients with PD-1/CD28 ratio in CD8+ T cells of 0.13 or greater was shorter compared with patients with lower levels (hazard ratio, 4.42 [1.29-15.20], χ2 = 6.675; P = 0.010). Conclusions: PD-1/CD28 ratio in CD8+ T cells at admission may serve as a novel prognostic biomarker for predicting nosocomial infection and mortality.