Evidence map›Paper›PMID 29261771›Full record

Observational studyPloS one2017

Endotheliopathy is associated with higher levels of cell-free DNA following major trauma: A prospective observational study.

David N Naumann, Jon Hazeldine, Robert J Dinsdale, Jon R Bishop, Mark J Midwinter, Paul Harrison, Sam D Hutchings, Janet M Lord

Registry-linked trialOpen access · goldAbstract readObservational Study
In one paragraph

Observational study in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03682757 (Post-Injury Platelet Biology), which is not on this map. Cited by 22 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 2 pooled it
3.9field-weighted citation impact, top 6% of its field
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.

NCT03682757 completednot on this mapstarted 2018, after this paper: background citation

Post-Injury Platelet Biology: Mechanisms and Outcomes

TypeobservationalSponsorUniversity of California, San FranciscoRan2018 to 2023Enrolled367ConditionsWound and Injuries, Blood Platelets, Endothelium
3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 2 syntheses or guidelines pooled it, 45 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Article
  5. Article
  6. Review
  7. Article
  8. The Polyanionic Drug Suramin Neutralizes Histones and Prevents Endotheliopathy.Journal of immunology (Baltimore, Md. : 1950) · 2023
    Article
  9. Article
  10. Investigation of plasma cell-free DNA as a potential biomarker in horses.Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc · 2022
    Article
  11. Article
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  14. Review
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  20. Noninvasive detection of graft injury after heart transplant using donor-derived cell-free DNA: A prospective multicenter study.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2019
    Observational
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

8 authors at 5 institutions in 2 countries.

David N NaumannAcademic Department of Military Surgery and Trauma, Royal Centre for Defence Medicine, Queen Elizabeth Hospital, Birmingham, United Kingdom.ORCID http://orcid.org/0000-0003-2243-2325
Jon HazeldineNIHR Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital, Birmingham, United Kingdom.
Robert J DinsdaleInstitute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom.
Jon R BishopNIHR Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital, Birmingham, United Kingdom.
Mark J MidwinterDepartment of Surgery, University of Queensland, Rural Clinical School, Bundaberg, Queensland, Australia.
Paul HarrisonInstitute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom.
Sam D HutchingsDepartment of Intensive Care Medicine, Kings College Hospital, Denmark Hill, London, United Kingdom.
Janet M LordInstitute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom.
University of Birmingham · GBQueen Elizabeth Hospital Birmingham · GBKing's College Hospital · GBThe University of Queensland · AUUniversity of Ulster · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCell free deoxyribonucleic acid (cfDNA) has been proposed as a biomarker of secondary complications following trauma. Raised thrombomodulin and syndecan-1 levels have been used to indicate endotheliopathy, and are associated with inflammation, coagulopathy, and mortality. The current study aimed to analyse the association between cfDNA and biomarkers of endotheliopathy in a cohort of trauma patients, and whether raised levels of cfDNA were associated with poorer clinical outcomes.

methodsSerum thrombomodulin and syndecan-1 were used as biomarkers of endotheliopathy and compared to plasma cfDNA in trauma patients from two prospective longitudinal observational studies. Cohort A (n = 105) had a predicted injury severity score (ISS) >8, and had blood sampled within 1h of injury and at 4-12h. Cohort B (n = 17) had evidence of haemorrhagic shock, and had blood sampled at a median time of 3.5h after injury. Relationships between biomarkers were tested using multivariable linear regression models that included the covariates of gender, age, ISS, Glasgow Coma Scale, lactate, systolic blood pressure, and heart rate. A model was fitted to investigate whether changes in cfDNA were associated with similar changes in endothelial biomarkers.

resultsThe mean age was 41 (SD 19), and the median ISS was 25 (IQR 12-34). There was a significant association between cfDNA levels and both syndecan-1 and thrombomodulin levels (both p<0.001). This was independent of all covariates except for ISS, which significantly correlated with cfDNA levels. 50 ng/ml change in syndecan-1 and 1 ng/ml change in thrombomodulin corresponded to 15% and 20% increases in cfDNA levels respectively (both p<0.001). Patients who died had significantly higher prehospital and in-hospital cfDNA levels (both p<0.05).

conclusionsRaised cfDNA levels are associated with markers of endotheliopathy following trauma, and are associated with mortality. This relationship is present within the first hour of injury, and a change in one biomarker level is reflected by similar changes in the others. These findings are in keeping with the hypothesis that circulating DNA and endothelial injury share a common pathway following trauma.

Indexed as

AdultBiomarkersBlood Coagulation DisordersBlood TransfusionCell-Free Nucleic AcidsEndothelium, VascularFemaleHumansLength of StayMaleProspective StudiesSyndecan-1ThrombomodulinTime FactorsTreatment OutcomeWounds and InjuriesBiomarkersCell-Free Nucleic AcidsSyndecan-1THBD protein, humanThrombomodulin

Identifiers

PMID29261771
PMCPMC5736230
OpenAlexW2777097958

What OpenQuestion holds

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LicenceCC BY
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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.