ArticleCritical care (London, England)2023
Neutralization of extracellular histones by sodium-Β-O-methyl cellobioside sulfate in septic shock.
Article in Critical care (London, England), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07184593 (Validation of a Point-of-care Device for Rapid Bedside Measurement of Circulating Nucleosome Levels in Critically Ill Patients and Study of Its Relevance to Prognostication), which is not on this map. Cited by 8 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Validation of a Point-of-care Device for Rapid Bedside Measurement of Circulating Nucleosome Levels in Critically Ill Patients and Study of Its Relevance to Prognostication
Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it, 8 citations in OpenAlex.
- Targeting NETosis in Acute Brain Injury: A Systematic Review of Preclinical and Clinical Evidence.Cells · 2024Pooled it
- Research progress on neutrophil extracellular traps in sepsis‑induced coagulopathy (Review).Molecular medicine reports · 2026Review
- Current and future strategies aiming at reducing catecholamine exposure in septic shock.Critical care (London, England) · 2026Review
- A phase I trial evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of intravenously administered low-anticoagulant heparin (M6229) in critically ill sepsis patients.Intensive care medicine experimental · 2025Article
- Circulating Nucleosomes and Histones in the Development of Lung Injury and Sepsis.Current issues in molecular biology · 2025Review
- Neutrophil extracellular traps in sepsis: trade-off between pros and cons.Burns & trauma · 2025Review
- Circulating Nucleosomes as a Novel Biomarker for Sepsis: A Scoping Review.Biomedicines · 2024Article
- Chromatin as alarmins in necrotizing enterocolitis.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundExtracellular histones have been associated with severity and outcome in sepsis. The aim of the present study was to assess the effects of sodium-β-O-Methyl cellobioside sulfate (mCBS), a histone-neutralizing polyanion, on the severity and outcome of sepsis in an experimental model.
methodsThis randomized placebo-controlled experimental study was performed in 24 mechanically ventilated female sheep. Sepsis was induced by fecal peritonitis. Animals were randomized to three groups: control, early treatment, and late treatment (n = 8 each). mCBS was given as a bolus (1 mg/kg) followed by a continuous infusion (1 mg/kg/h) just after sepsis induction in the early treatment group, and 4 h later in the late treatment group. Fluid administration and antimicrobial therapy were initiated 4 h T4 after feces injection, peritoneal lavage performed, and a norepinephrine infusion titrated to maintain mean arterial pressure (MAP) between 65-75 mmHg. The experiment was blinded and lasted maximum 24 h.
resultsDuring the first 4 h, MAP remained > 65 mmHg in the early treatment group but decreased significantly in the others (p < 0.01 for interaction, median value at T4: (79 [70-90] mmHg for early treatment, 57 [70-90] mmHg for late treatment, and 55 [49-60] mmHg for the control group). mCBS-treated animals required significantly less norepinephrine to maintain MAP than controls (p < 0.01 for interaction) and had lower creatinine (p < 0.01), lactate (p < 0.01), and interleukin-6 (p < 0.01) levels, associated with reduced changes in H3.1 nucleosome levels (p = 0.02). Early treatment was associated with lower norepinephrine requirements than later treatment. Two control animals died; all the mCBS-treated animals survived.
conclusionsNeutralization of extracellular histones with mCBS was associated with reduced norepinephrine requirements, improved tissue perfusion, less renal dysfunction, and lower circulating IL-6 in experimental septic shock and may represent a new therapeutic approach to be tested in clinical trials.
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