ArticleCritical care (London, England)2019
Murine sepsis phenotypes and differential treatment effects in a randomized trial of prompt antibiotics and fluids.
Article in Critical care (London, England), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 30 citations in OpenAlex.
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- Value of animal sepsis research in navigating the translational labyrinth.Frontiers in immunology · 2025Article
- Biological basis of critical illness subclasses: from the bedside to the bench and back again.Critical care (London, England) · 2024Review
- Immune-Related MoleculesInternational journal of molecular sciences · 2024Article
- The Role of Mesenchymal Stem Cell Secretome in the Inflammatory Mediators and the Survival Rate of Rat Model of Sepsis.Biomedicines · 2023Article
- Identifying clinical subtypes in sepsis-survivors with different one-year outcomes: a secondary latent class analysis of the FROG-ICU cohort.Critical care (London, England) · 2022Article
- Renal microvascular endothelial cell responses in sepsis-induced acute kidney injury.Nature reviews. Nephrology · 2022Review
- Article
- Mesenchymal stromal cells expressing a dominant-negative high mobility group A1 transgene exhibit improved function during sepsis.Journal of leukocyte biology · 2021Article
- Characterizing preclinical sub-phenotypic models of acute respiratory distress syndrome: An experimental ovine study.Physiological reports · 2021Article
- PD-1 blockade improves Kupffer cell bacterial clearance in acute liver injury.The Journal of clinical investigation · 2021Article
- Sepsis Biomarkers.Methods in molecular biology (Clifton, N.J.) · 2021Review
- The Effect of Superoxide Dismutase on Inhibition of Acute Kidney Injury Induced by Sepsis Based on Kidney Tissue Histology and Murine Sepsis Score.TheScientificWorldJournal · 2021Article
- Acute respiratory distress syndrome subphenotypes and therapy responsive traits among preclinical models: protocol for a systematic review and meta-analysis.Respiratory research · 2020Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
backgroundClinical and biologic phenotypes of sepsis are proposed in human studies, yet it is unknown whether prognostic or drug response phenotypes are present in animal models of sepsis. Using a biotelemetry-enhanced, murine cecal ligation and puncture (CLP) model, we determined phenotypes of polymicrobial sepsis prior to physiologic deterioration, and the association between phenotypes and outcome in a randomized trial of prompt or delayed antibiotics and fluids.
methodsWe performed a secondary analysis of male C57BL/6J mice in two observational cohorts and two randomized, laboratory animal experimental trials. In cohort 1, mice (n = 118) underwent biotelemetry-enhanced CLP, and we applied latent class mixed models to determine optimal number of phenotypes using clinical data collected between injury and physiologic deterioration. In cohort 2 (N = 73 mice), inflammatory cytokines measured at 24 h after deterioration were explored by phenotype. In a subset of 46 mice enrolled in two trials from cohort 1, we tested the association of phenotypes with the response to immediate (0 h) vs. delayed (2 to 4 h) antibiotics or fluids initiated after physiologic deterioration.
resultsLatent class mixture modeling derived a two-class model in cohort 1. Class 2 (N = 97) demonstrated a shorter time to deterioration (mean SD 7.3 (0.9) vs. 9.7 (3.2) h, p < 0.001) and lower heart rate at 7 h after injury (mean (SD) 564 (55) vs. 626 (35) beats per minute, p < 0.001). Overall mortality was similar between phenotypes (p = 0.75). In cohort 2 used for biomarker measurement, class 2 mice had greater plasma concentrations of IL6 and IL10 at 24 h after CLP (p = 0.05). In pilot randomized trials, the effects of sepsis treatment (immediate vs. delayed antibiotics) differed by phenotype (p = 0.03), with immediate treatment associated with greater survival in class 2 mice only. Similar differential treatment effect by class was observed in the trial of immediate vs. delayed fluids (p = 0.02).
conclusionsWe identified two sepsis phenotypes in a murine cecal ligation and puncture model, one of which is characterized by faster deterioration and more severe inflammation. Response to treatment in a randomized trial of immediate versus delayed antibiotics and fluids differed on the basis of phenotype.
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