Evidence map›Paper›PMID 33106536›Full record

ArticleScientific reports2020

Markers of neutrophil activation and extracellular traps formation are predictive of appendicitis in mice and humans: a pilot study.

Michael Boettcher, Melina Esser, Julian Trah, Stefan Klohs, Nariman Mokhaberi, Julia Wenskus, Madgalena Trochimiuk, Birgit Appl, Konrad Reinshagen, Laia Pagerols Raluy and 1 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.6field-weighted citation impact, top 9% 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, 21 citations in OpenAlex.

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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

11 authors at 2 institutions in 1 country.

Michael BoettcherDepartment of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, UKE Medical School, Martinistrasse 52, 20246, Hamburg, Germany. m.boettcher@uke.de.
Melina EsserDepartment of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, UKE Medical School, Martinistrasse 52, 20246, Hamburg, Germany.
Julian TrahDepartment of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, UKE Medical School, Martinistrasse 52, 20246, Hamburg, Germany.
Stefan KlohsDepartment of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, UKE Medical School, Martinistrasse 52, 20246, Hamburg, Germany.
Nariman MokhaberiDepartment of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, UKE Medical School, Martinistrasse 52, 20246, Hamburg, Germany.
Julia WenskusDepartment of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, UKE Medical School, Martinistrasse 52, 20246, Hamburg, Germany.
Madgalena TrochimiukDepartment of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, UKE Medical School, Martinistrasse 52, 20246, Hamburg, Germany.
Birgit ApplDepartment of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, UKE Medical School, Martinistrasse 52, 20246, Hamburg, Germany.
Konrad ReinshagenDepartment of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, UKE Medical School, Martinistrasse 52, 20246, Hamburg, Germany.
Laia Pagerols RaluyDepartment of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, UKE Medical School, Martinistrasse 52, 20246, Hamburg, Germany.
Michaela KlinkeDepartment of Pediatric Surgery, University Medical Center Hamburg-Eppendorf, UKE Medical School, Martinistrasse 52, 20246, Hamburg, Germany.
Universität Hamburg · DEUniversity Medical Center Hamburg-Eppendorf · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Appendicitis is one of the most frequent emergencies in pediatric surgery, yet current biomarkers for diagnosis are unspecific and have low predictive values. As neutrophils and extracellular traps (ETs) are an essential component of the immune defense against bacterial infections, and appendicitis is considered an inflammation reaction of the appendix, we hypothesized that neutrophil activation and NET formation play an essential role in appendicitis development and maintenance. Therefore, this pilot study aimed to establish a murine model of appendicitis and to evaluate ETs markers to diagnose appendicitis in mice and humans. The study used 20 (12 appendicitis- and 8 controls) 6-week old mice which underwent advanced appendicitis induction using a modified caecal ligation puncture procedure. During the study, cell-free DNA, neutrophil elastase (NE), myeloperoxidase (MPO), and citrullinated Histone H3 (H3cit) were assessed. Additionally, samples of 5 children with histologically confirmed appendicitis and 5 matched controls with catarrhal appendicitis, were examined for the same biomarkers. Moreover, NE, MPO, and H3cit were assessed histologically via immunofluorescence in mice and humans. All mice in the appendicitis group developed an advanced form of appendicitis with focal peritonitis. In mice and humans with appendicitis, markers of neutrophil activation and ETs formation (especially cfDNA, NE and H3cit) were significantly elevated in blood and tissue compared to controls. Ultimately, biomarkers correlated extremely well with tissue expression and thus disease severity. It appears that neutrophil activation and possibly NETs contribute to appendicitis development and biomarkers of neutrophil activation and ET formation reflect disease severity and thus could be used as biomarkers for appendicitis. However, large prospective clinical studies are needed to confirm our findings.

Indexed as

AnimalsAppendicitisBiomarkersCase-Control StudiesCell-Free Nucleic AcidsChildCitrullinationDisease Models, AnimalExtracellular TrapsFemaleHistonesHumansInflammationLeukocyte ElastaseMaleMiceBiomarkersCell-Free Nucleic AcidsHistonesLeukocyte ElastasePeroxidase

Identifiers

PMID33106536
PMCPMC7588418
OpenAlexW3093981948

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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.