Evidence map›Paper›PMID 31898953›Full record

Observational studySurgery2020

Persistently increased cell-free DNA concentrations only modestly contribute to outcome and host response in sepsis survivors with chronic critical illness.

Russell B Hawkins, Julie A Stortz, David C Holden, Zhongkai Wang, Steven L Raymond, Michael C Cox, Scott C Brakenridge, Frederick A Moore, Lyle L Moldawer, Philip A Efron

Open access · greenAbstract readObservational Study
In one paragraph

Observational study in Surgery, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 2 pooled it
1.4field-weighted citation impact, top 18% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 2 syntheses or guidelines pooled it, 21 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Cell-Free DNA-Based Theranostics for Inflammatory Disorders.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. STING1 in sepsis: Mechanisms, functions, and implications.Chinese journal of traumatology = Zhonghua chuang shang za zhi · 2022
    Review
  14. Dysregulated Immunity and Immunotherapy after Sepsis.Journal of clinical medicine · 2021
    Review
  15. Article
  16. 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 2 institutions in 1 country.

Russell B HawkinsDepartment of Surgery, University of Florida College of Medicine, Gainesville, FL.
Julie A StortzDepartment of Surgery, University of Florida College of Medicine, Gainesville, FL.
David C HoldenDepartment of Surgery, University of Florida College of Medicine, Gainesville, FL.
Zhongkai WangDepartment of Biostatistics, University of Florida College of Medicine, Gainesville, FL.
Steven L RaymondDepartment of Surgery, University of Florida College of Medicine, Gainesville, FL.
Michael C CoxDepartment of Surgery, University of Florida College of Medicine, Gainesville, FL.
Scott C BrakenridgeDepartment of Surgery, University of Florida College of Medicine, Gainesville, FL.
Frederick A MooreDepartment of Surgery, University of Florida College of Medicine, Gainesville, FL.
Lyle L MoldawerDepartment of Surgery, University of Florida College of Medicine, Gainesville, FL.
Philip A EfronDepartment of Surgery, University of Florida College of Medicine, Gainesville, FL. Electronic address: Philip.Efron@surgery.ufl.edu.
Florida College · USUniversity of Florida · US

Funding

Inflammation and the Response to InjuryU54GM062119 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI TOMPKINS, RONALD GARY · 2001 to 2010
$78.6M
University of Florida Older Americans Independence Center (OAIC)P30AG028740 · NIA · UNIVERSITY OF FLORIDA · PI CHRISTIAAN LEEUWENBURGH · 2007 to 2026
$22.8M
PICS: A New Horizon for Surgical Critical CareP50GM111152 · NIGMS · UNIVERSITY OF FLORIDA · PI MOORE, FREDERICK A · 2014 to 2018
$10.7M
Molecular Biology in Burns and TraumaT32GM008721 · NIGMS · UNIVERSITY OF FLORIDA · PI Philip A Efron · 1999 to 2026
$5.0M
Hematopoietic Stem Cell Dysfunction in the Elderly after Severe InjuryR01GM113945 · NIGMS · UNIVERSITY OF FLORIDA · PI EFRON, PHILIP A · 2015 to 2019
$1.6M
In pursuit of a PICS prognostic: An investigation of the agents activating and perpetuating PICS.F30GM119285 · NIGMS · UNIVERSITY OF FLORIDA · PI HOLDEN, DAVID C · 2016 to 2018
$127k
NIA NIH HHS P30 AG028740NIGMS NIH HHS F30 GM119285NIGMS NIH HHS P50 GM111152NIGMS NIH HHS R01 GM113945NIGMS NIH HHS T32 GM008721NIGMS NIH HHS U54 GM062119
6 · The paper itself

Abstract

backgroundAlthough early survival from sepsis has improved with timely resuscitation and source control, survivors frequently experience persistent inflammation and develop chronic critical illness. We examined whether increased copy number of endogenous alarmins, mitochondrial DNA, and nuclear DNA are associated with the early "genomic storm" in blood leukocytes and the development of chronic critical illness in hospitalized patients with surgical sepsis.

methodsA prospective, observational, cohort study of critically ill septic patients was performed at a United States tertiary health care center. Blood samples were obtained at multiple time points after the onset of sepsis. Droplet Digital polymerase chain reaction (Bio-Rad Laboratories, Hercules, CA) was performed to quantify RHO (nuclear DNA) and MT-CO2 (mitochondrial DNA) copies in plasma. Leukocyte transcriptomic expression of 63 genes was also measured in whole blood.

resultsWe enrolled 112 patients with surgical sepsis. Two experienced early death, 69 recovered rapidly, and 41 developed chronic critical illness. Both mitochondrial DNA and nuclear DNA copy number were increased in all sepsis survivors, but early nuclear DNA, and not mitochondrial DNA, copy number was further increased in patients who developed chronic critical illness. Cell-free DNA copy number was associated with in-hospital but not long-term (180-day and 365-day) mortality and were only weakly correlated with leukocyte transcriptomics.

conclusionIncreased cell-free DNA copy number persists in survivors of sepsis but is not strongly associated with leukocyte transcriptomics. Nuclear DNA but not mitochondrial DNA copy number is associated with adverse, short-term, clinical trajectories and outcomes.

Indexed as

SurvivorsAgedAlarminsCell-Free Nucleic AcidsChronic DiseaseCritical IllnessDNA, MitochondrialFemaleGene DosageHospital MortalityHumansIntensive Care UnitsMaleMiddle AgedProspective StudiesSepsisAlarminsCell-Free Nucleic AcidsDNA, Mitochondrial

Identifiers

PMID31898953
PMCPMC7028489
OpenAlexW2997182663

What OpenQuestion holds

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LicenceTDM
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Registered trials

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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.