Articles: sepsis.
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Intensive care medicine · Jan 2025
Randomized Controlled TrialSepsis subtypes and differential treatment response to vitamin C: biological sub-study of the LOVIT trial.
We hypothesised that the biological heterogeneity of sepsis may highlight sepsis subtypes with differences in response to intravenous vitamin C treatment in the Lessening Organ Dysfunction with VITamin C (LOVIT) trial. Our aims were to identify sepsis subtypes and to test whether sepsis subtypes have differences in treatment effect to vitamin C and describe putative biological effects of vitamin C treatment. ⋯ We report three sepsis subtypes based on inflammatory response profile. No subtype benefitted from vitamin C treatment in the LOVIT trial, with heterogeneity of treatment effect in the magnitude of harm.
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Background : The interrelation between the plasma proteome and plasma metabolome with sepsis presents a multifaceted dynamic that necessitates further research to elucidate the underlying causal mechanisms. Methods : Our investigation used public genome-wide association study data to explore the relationships among the plasma proteome, metabolome, and sepsis, considering different sepsis subgroup. Initially, two-sample Mendelian randomization established causal connections between the plasma proteome and metabolome with sepsis. ⋯ Further scrutiny revealed that this plasma metabolite notably augments the abundance of ICAM5 protein ( P value = 3.52E-04, OR = 1.11, 95% CI = 1.04-1.17), devoid of any detected heterogeneity, pleiotropy, or reverse causality. Mediated Mendelian randomization revealed ICAM5 mediated 11.9% of 1,2,3-benzenetriol sulfate (2)'s total effect on sepsis progression. Conclusion : This study details the causal link between the plasma proteome and metabolome with sepsis, highlighting the roles of ICAM5 and 1,2,3-benzenetriol sulfate (2) in sepsis progression, both independently and through crosstalk.
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Objective: The Phoenix sepsis criteria define sepsis in children with suspected or confirmed infection who have ≥2 in the Phoenix Sepsis Score. The adoption of the Phoenix sepsis criteria eliminated the Systemic Inflammatory Response Syndrome criteria from the definition of pediatric sepsis. The objective of this study is to derive and validate machine learning models predicting in-hospital mortality for children with suspected or confirmed infection or who met the Phoenix sepsis criteria for sepsis and septic shock. ⋯ For children with Phoenix sepsis and Phoenix septic shock, the multivariable logistic regression, light gradient boosting machine, random forest, eXtreme Gradient Boosting, support vector machine, multilayer perceptron, and decision tree models predicting in-hospital mortality had AUPRCs of 0.48-0.65 (95% CI range: 0.42-0.66), 0.50-0.70 (95% CI range: 0.44-0.70), 0.52-0.70 (95% CI range: 0.47-0.71), 0.50-0.70 (95% CI range: 0.44-0.70), 0.49-0.67 (95% CI range: 0.43-0.68), 0.49-0.66 (95% CI range: 0.45-0.67), and 0.30-0.38 (95% CI range: 0.28-0.40) and AUROCs of 0.82-0.88 (95% CI range: 0.82-0.90), 0.84-0.88 (95% CI range: 0.84-0.90), 0.81-0.88 (95% CI range: 0.81-0.90), 0.84-0.88 (95% CI range: 0.83-0.90), 0.82-0.87 (95% CI range: 0.82-0.90), 0.80-0.86 (95% CI range: 0.79-0.89), and 0.76-0.82 (95% CI range: 0.75-0.85), respectively. Conclusion: Among children with Phoenix sepsis admitted to a PICU, the random forest model had the best AUPRC for in-hospital mortality compared to the light gradient boosting machine, eXtreme Gradient Boosting, logistic regression, multilayer perceptron, support vector machine, and decision tree models or a Phoenix Sepsis Score ≥ 2. These findings suggest that machine learning methods to predict in-hospital mortality in children with suspected infection predict mortality in a PICU setting with more accuracy than application of the Phoenix sepsis criteria.
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Introduction: Gut ischemia and reperfusion (I/R) injury promotes the release of damage-associated molecular patterns (DAMPs) such as extracellular cold-inducible RNA-binding protein (eCIRP). Gut I/R often leads to acute lung injury (ALI), a major contributor to mortality. Milk fat globule-epidermal growth factor-factor VIII-derived oligopeptide-3 (MOP3) is a novel peptide that attenuates sepsis by opsonizing eCIRP and facilitating its phagocytic clearance. ⋯ Finally, mice treated with MOP3 exhibited a significant decrease in mortality ( P < 0.05). Conclusions: Treatment with MOP3 effectively mitigates organ injury induced by gut I/R. This beneficial effect is attributed to the facilitation of eCIRP clearance, directing the potential of MOP3 as an innovative therapeutic approach for this critical and often fatal condition.