Evidence map›Paper›PMID 31119471›Full record

ArticleIntensive care medicine experimental2019

Comparison of the source and prognostic utility of cfDNA in trauma and sepsis.

Nicholas L Jackson Chornenki, Robert Coke, Andrew C Kwong, Dhruva J Dwivedi, Michael K Xu, Ellen McDonald, John C Marshall, Alison E Fox-Robichaud, Emmanuel Charbonney, Patricia C Liaw

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in Intensive care medicine experimental, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01355042 (DYNAMICS), which is not on this map. Cited by 54 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed, 3 pooled it
3.8field-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.

NCT01355042 completednot on this map

DYNAMICS: DNA as a Prognostic Marker in ICU Patients Study

TypeobservationalSponsorAlison Fox-RobichaudRan2010 to 2016Enrolled792ConditionsSepsis, Shock, Trauma
3 · Its place in the literature

Who cites it

54 citing papers in PubMed, 3 syntheses or guidelines pooled it, 100 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Trial
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Review
  16. Dysregulation of neutrophil in sepsis: recent insights and advances.Cell communication and signaling : CCS · 2025
    Review
  17. Review
  18. Article
  19. Article
  20. Article
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

10 authors at 4 institutions in 1 country.

Nicholas L Jackson ChornenkiDepartment of Medicine, McMaster University, Hamilton, ON, Canada. Nicholas.jacksonchornenki@medportal.ca.
Robert CokeDepartment of Medicine, McMaster University, Hamilton, ON, Canada.
Andrew C KwongThrombosis and Atherosclerosis Research Institute, Hamilton, ON, L8L 2X2, Canada.
Dhruva J DwivediThrombosis and Atherosclerosis Research Institute, Hamilton, ON, L8L 2X2, Canada.
Michael K XuThrombosis and Atherosclerosis Research Institute, Hamilton, ON, L8L 2X2, Canada.
Ellen McDonaldThrombosis and Atherosclerosis Research Institute, Hamilton, ON, L8L 2X2, Canada.
John C MarshallDepartments of Surgery and Critical Care Medicine, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
Alison E Fox-RobichaudDepartment of Medicine, McMaster University, Hamilton, ON, Canada.
Emmanuel CharbonneyDepartment of Critical Care Medicine, Hôpital du Sacré-Coeur de Montreal and Hôpital de Trois-Rivières, University of Montreal, Montreal, QC, Canada.
Patricia C LiawDepartment of Medicine, McMaster University, Hamilton, ON, Canada.
Thrombosis and Atherosclerosis Research Institute · CAMcMaster University · CAHôpital du Sacré-Cœur de Montréal · CASt. Michael's Hospital · CA

Funding

American Society of Hematology Physician Scientist Career Development AwardCIHR MOP-106503CIHR MOP-136878
6 · The paper itself

Abstract

backgroundCirculating cell-free DNA (cfDNA) may contribute to the pathophysiology of post-injury inflammation and coagulation in trauma. However, the source and mechanism of release of cfDNA in trauma is not well understood. One potential source of cfDNA is from Neutrophil Extracellular Traps (NETs), released by activated neutrophils during the process of NETosis. The primary objective of our study was to determine if cfDNA has prognostic utility in trauma. The secondary objective of this study was to determine the source of cfDNA in trauma compared to sepsis.

methodsWe studied trauma patients from two prospective observational cohort studies: the DNA as a Prognostic Marker in ICU Patients (DYNAMICS) study and the Endotoxin in Polytrauma (ENPOLY) study. We also studied septic patients from the DYNAMICS study. Citrated plasma samples were collected longitudinally from the patients (days 1 to 7). The following molecules were measured in the plasma samples: cfDNA, protein C (PC), myeloperoxidase (MPO) (a marker of neutrophil activation), citrullinated Histone H3 (H3Cit, a marker of NETosis), cyclophilin A (a marker of necrosis), and caspase-cleaved K18 (a marker of apoptosis).

resultsA total of 77 trauma patients were included (n = 38 from DYNAMICS and n = 39 from ENPOLY). The median age was 49 years; 27.3% were female, and mortality was 16.9% at 28 days. Levels of cfDNA were elevated compared to healthy values but not significantly different between survivors and non-survivors. There was a positive correlation between MPO and cfDNA in septic patients (r = 0.424, p < 0.001). In contrast, there was no correlation between MPO and cfDNA in trauma patients (r = - 0.192, p = 0.115). Levels of H3Cit, a marker of NETosis, were significantly elevated in septic patients compared to trauma patients (p < 0.01) while apoptosis and necrosis markers did not differ between the two groups.

conclusionOur studies suggest that the source and mechanism of release of cfDNA differ between trauma and sepsis patients. In sepsis, cfDNA is likely primarily released by activated neutrophils via the process of NETosis. In contrast, cfDNA in trauma appears to originate mainly from injured or necrotic cells. Although cfDNA is elevated in trauma and sepsis patients compared to healthy controls, cfDNA does not appear to have prognostic utility in trauma patients.

trial registrationClinicalTrials.gov Identifier: NCT01355042 . Registered May 17, 2011.

Indexed as

Cell-free DNANETosisprotein Ctraumatic injury

Identifiers

PMID31119471
PMCPMC6531595
OpenAlexW2946310508

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.