Evidence map›Paper›PMID 40390092›Full record

Observational studyCritical care (London, England)2025

Plasma H3.1 nucleosomes as biomarkers of infection, inflammation and organ failure.

Daan F L Filippini, Michael Jiang, Lina Kramer, Tom van der Poll, Olaf Cremer, Teddy Tun Win Hla, Andrew Retter, Lieuwe D J Bos, MARS consortium

Registry-linked trialAbstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Critical care (London, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01905033 (Molecular Diagnosis and Risk Stratification of Sepsis), which is not on this map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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.

NCT01905033 unknown statusnot on this map

Molecular Diagnosis and Risk Stratification of Sepsis

Typeobservational_patient_registrySponsorAcademisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)Ran2011 to 2018Enrolled7,500ConditionsSepsis
3 · Its place in the literature

Who cites it

10 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Unraveling NETs in Sepsis: From Cellular Mechanisms to Clinical Relevance.International journal of molecular sciences · 2025
    Review
  7. Review
  8. Review
  9. Review
  10. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Daan F L FilippiniDepartment of Intensive Care Medicine, Amsterdam UMC - location AMC, University of Amsterdam, 1105AZ, Amsterdam, The Netherlands. d.filippini@amsterdamumc.nl.
Michael JiangDepartment of Intensive Care Medicine, Amsterdam UMC - location AMC, University of Amsterdam, 1105AZ, Amsterdam, The Netherlands.
Lina KramerDepartment of Intensive Care Medicine, Amsterdam UMC - location AMC, University of Amsterdam, 1105AZ, Amsterdam, The Netherlands.
Tom van der PollCenter for Infection and Molecular Medicine (C.I.M.M.), Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Olaf CremerDepartment of Intensive Care Medicine, UMC Utrecht, Utrecht University, Utrecht, The Netherlands.
Teddy Tun Win HlaDepartment of Critical Care, St Thomas' Hospital, London, UK.
Andrew RetterDepartment of Critical Care, St Thomas' Hospital, London, UK.
Lieuwe D J BosDepartment of Intensive Care Medicine, Amsterdam UMC - location AMC, University of Amsterdam, 1105AZ, Amsterdam, The Netherlands.
MARS consortium

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNeutrophil extracellular traps (NETs) are a vital part of the innate immune response, while excessive NET formation can cause tissue damage. H3.1 nucleosomes, a component of NETs, have emerged as a potential biomarker. This study aimed to evaluate H3.1 nucleosomes in critical illness, assessing their relationship with sepsis, organ failure, inflammatory subphenotypes and outcomes.

methodsThe MARS cohort was used, comprising of consecutive Intensive Care Unit patients, with plasma samples collected on days 0, 2 and 4. H3.1 nucleosome concentrations were measured using the Nu.Q® NETs Immunoassay. H3.1 nucleosome concentrations were compared across sepsis presence and organ failure, both at baseline and longitudinally. The relationship between H3.1 nucleosome concentrations and clinical outcomes was investigated.

results1713 critically ill patients were included, with a total of 3671 plasma samples. Baseline H3.1 nucleosome concentrations differed between sepsis confirmed by clinical adjudication (740 ng/mL), sepsis unconfirmed by clinical adjudication (416 ng/mL) and non-sepsis (463 ng/mL, P < 0.001). H3.1 concentrations were associated with SOFA score (r = 0.40) and were higher in patients with disseminated intravascular coagulation, acute kidney injury and hyperinflammatory sepsis. H3.1 concentration was highly predictive for the need of renal replacement therapy (hazard ratio 2.00 per log10 increase), correcting for mortality.

conclusionsSepsis and organ failure were closely associated with plasma H3.1 nucleosome concentrations. While individual diagnostic performance for sepsis and organ failure remained low, H3.1 levels predicted the need for renal replacement therapy and disseminated intravascular coagulation, revealing unique insights into the innate immune response.

trial registrationClinicalTrials.gov identifier NCT01905033; IRB number 10-056C, registered June 16, 2010.

Indexed as

InfectionsInflammationMultiple Organ FailureNucleosomesAgedBiomarkersCohort StudiesCritical IllnessFemaleHumansIntensive Care UnitsMaleMiddle AgedOrgan Dysfunction ScoresSepsisBiomarkersNucleosomesCritical careNeutrophil extracellular trapsNucleosomesOrgan failureSepsis

Identifiers

PMID40390092
PMCPMC12090586

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.