Evidence map›Paper›PMID 23979273›Full record

Trial reportAnnals of surgery2013

Elevated levels of plasma mitochondrial DNA DAMPs are linked to clinical outcome in severely injured human subjects.

Jon D Simmons, Yann-Leei Lee, Sujata Mulekar, Jamie L Kuck, Sidney B Brevard, Richard P Gonzalez, Mark N Gillespie, William O Richards

2 registry-linked trialsOpen access · greenAbstract readClinical Trial
In one paragraph

Trial report in Annals of surgery, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 154 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
154citing papers in PubMed, 1 pooled it
10.6field-weighted citation impact, top 1% 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.

NCT04445285 phase2recruitingnot on this mapstarted 2020, after this paper: background citation

Double Blind Randomized Phase 2 Placebo Controlled Trial Using rhDNase to Reduce Mortality in COVID-19 Patients With Respiratory Failure

TypeinterventionalSponsorJon SimmonsRan2020 to 2022Enrolled44ConditionsCovid19ArmsPulmozyme/ Recombinant human deoxyribonuclease (rh-DNase), 0.9%sodium chloride
NCT05441787 completednot on this mapstarted 2022, after this paper: background citation

Comparison of Inflammatory Markers (Serum Mitochondrial DNA, Delta Neutrophil Index, Inflammatory Cytokines) According to the Injury Severity, and Development of Risk Prediction Model Using Inflammatory Markers for Trauma Patients

TypeobservationalSponsorWonju Severance Christian HospitalRan2022 to 2024Enrolled89ConditionsTrauma Injury, Trauma, Multiple
3 · Its place in the literature

Who cites it

154 citing papers in PubMed, 1 synthesis or guideline pooled it, 247 citations in OpenAlex.

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94 more citing papers are in PubMed but not listed here.

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 1 institution in 1 country.

Jon D SimmonsDepartments of *Surgery †Center for Lung Biology ‡Pharmacology, University of South Alabama College of Medicine, Mobile.
Yann-Leei Lee
Sujata Mulekar
Jamie L Kuck
Sidney B Brevard
Richard P Gonzalez
Mark N Gillespie
William O Richards
University of South Alabama · US

Funding

DNA LESIONS AND GENE EXPRESSION IN HYPOXIC LUNG DISEASER01HL058234 · NHLBI · UNIVERSITY OF SOUTH ALABAMA · PI GILLESPIE, MARK N · 1998 to 2018
$5.2M
MtDNA repair: An isolated pharmacologic target in acute lung injuryR01HL113614 · NHLBI · UNIVERSITY OF SOUTH ALABAMA · PI GILLESPIE, MARK N · 2012 to 2021
$3.5M
Training in Cell Signaling and Lung PathobiologyT32HL076125 · NHLBI · UNIVERSITY OF SOUTH ALABAMA · PI RICH, THOMAS C, STEVENS, TROY · 2004 to 2018
$2.7M
NHLBI NIH HHS R01 HL058234NHLBI NIH HHS R01 HL113614NHLBI NIH HHS T32 HL076125
6 · The paper itself

Abstract

objectiveOur objective was to execute a prospective cohort study to determine relationships between plasma mtDNA DAMP levels and the occurrence of systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), and mortality.

backgroundMitochondrial DNA damage-associated molecular patterns (DAMPs) accumulate in the circulation after severe injury. Observations in animal models demonstrate that mtDNA DAMPs contribute to organ dysfunction; however, the link between plasma mtDNA DAMPs and outcome in severely injured human subjects has not been established.

methodsDNA was isolated from plasma samples taken from severely injured patients at hospital days 0, 1, and 2. Real-time PCR was used to quantify selected ≈200 base pair sequences of mtDNA within the COX1, ND1, and ND6 genes, as well as from the D-Loop transcriptional regulatory region. MODS was defined as a Denver Multiple Organ Failure score of 4 or greater.

resultsMtDNA DAMPs were quantified as PCR threshold cycle number. Lower threshold cycles indicate increased mtDNA DAMP content. Patients with SIRS had significantly increased mtDNA DAMP levels in all 4 sequences examined (32.14 ± 0.90 vs 29.00 ± 1.15 for COX1, 31.90 ± 0.47 vs 30.16 ± 1.42 for ND1, 32.40 ± 0.61 vs 28.94 ± 1.13 for ND6, and 33.12 ± 0.83 vs 28.30 ± 1.14 for D-Loop). Patients who developed MODS also had elevated mtDNA DAMP levels compared with those who did not (32.57 ± 0.74 vs 27.12 ± 0.66 for COX1, 32.45 ± 0.65 vs 28.20 ± 0.73 for ND1, 32.52 ± 0.56 vs 27.60 ± 0.79 for ND6, and 32.85 ± 0.75 vs 27.86 ± 1.27 for D-Loop). Patients with above-median mtDNA DAMP levels had a significantly elevated relative risk for mortality. Four patients died secondary to severe MODS.

conclusionsThese findings comprise the first observational evidence that plasma mtDNA DAMPs is associated with the evolution of SIRS, MODS, and mortality in severely injured human subjects.

Indexed as

AdultAgedAged, 80 and overBiomarkersCohort StudiesCyclooxygenase 1DNA, MitochondrialFemaleGenetic MarkersHumansInjury Severity ScoreMaleMiddle AgedMultiple Organ FailureNADH DehydrogenasePrognosisBiomarkersCyclooxygenase 1DNA, MitochondrialGenetic MarkersMT-ND6 protein, humanNADH DehydrogenaseNADH dehydrogenase subunit 1, humanPTGS1 protein, human

Identifiers

PMID23979273
PMCPMC3935616
OpenAlexW2093468893

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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.