Evidence map›Paper›PMID 41574291›Full record

ArticleFrontiers in cellular and infection microbiology2025

Molecular characterization of cell decay in inflammation and topological assignment of released cfDNA for integrative laboratory and radiological outcome assessment.

Catharina Gerhards, Stefanie Nittka, Volker Ast, Osman Evliyaoglu, Maren Hedtke, Jürgen Hench, Marlis Gerigk, Jörg Krebs, Andreas Teufel, Matthias F Froelich and 4 more

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Article in Frontiers in cellular and infection microbiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

14 authors.

Catharina GerhardsInstitute for Clinical Chemistry, Medical Faculty Mannheim of the University of Heidelberg, Mannheim, Germany.
Stefanie NittkaInstitute for Clinical Chemistry, Medical Faculty Mannheim of the University of Heidelberg, Mannheim, Germany.
Volker AstInstitute for Clinical Chemistry, Medical Faculty Mannheim of the University of Heidelberg, Mannheim, Germany.
Osman EvliyaogluInstitute for Clinical Chemistry, Medical Faculty Mannheim of the University of Heidelberg, Mannheim, Germany.
Maren HedtkeInstitute for Clinical Chemistry, Medical Faculty Mannheim of the University of Heidelberg, Mannheim, Germany.
Jürgen HenchDepartment of Pathology, Universitätsspital Basel, Basel, Switzerland.
Marlis GerigkInstitute of Medical Microbiology and Hygiene, Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany.
Jörg KrebsDepartment of Anesthesiology and Critical Care Medicine, Faculty of Medicine, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany.
Andreas TeufelDivision of Hepatology, Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Matthias F FroelichDepartment of Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim of the University of Heidelberg, Mannheim, Germany.
Andreas FischerInstitute for Clinical Chemistry, Medical Faculty Mannheim of the University of Heidelberg, Mannheim, Germany.
Stefan O SchoenbergDepartment of Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim of the University of Heidelberg, Mannheim, Germany.
Michael NeumaierInstitute for Clinical Chemistry, Medical Faculty Mannheim of the University of Heidelberg, Mannheim, Germany.
Alexander HertelDepartment of Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim of the University of Heidelberg, Mannheim, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Integrative biomarkers could aid in the efficient triage of vulnerable patients with systemic infectious diseases. Thus, we investigated cfDNA integrity, cfDNA epigenetics, and radiomics for their potential as prognostic biomarkers for clinical courses in ARDS and systemic involvement. Methods: The cfDNA integrity index was established using automated gel electrophoresis (TapeStation) based on the release of cfDNA induced by apoptosis and necrosis in HEK293 and Jurkat cells (discovery cohort). This method was then used to evaluate cfDNA fragmentation patterns in blood samples from participants with COVID-19 or other acute diseases (validation cohort). In this analysis, various cfDNA size intervals (50-130 bp, 130-270 bp, 270-450 bp, 450-640 bp, 640-800 bp) were considered, and both the classic DNA integrity index (247/50-800 bp) and an adjusted index (450/50-800 bp) were assessed for their clinical potential in respiratory diseases. Infinium Methylation 850K assay was utilized for topological assignment of secondary organ damage via epigenetic analysis of cfDNA via deconvolution. In total, 122 samples, including cell culture and patient samples, were analysed. Results: Participants with ARDS exhibited higher cfDNA concentrations with fragment sizes above 247 bp (p = 0.016). Increased cfDNA fragment sizes were observed in association with ICU admission (p = 0.009) and mortality (p = 0.017). The predominant origin of cfDNA was hematopoietic cells. An elevated epigenetic hepatocyte signal showed a strong correlation with GGT levels (r = 0.79). Hepatocyte-derived cfDNA anticipated later ALT elevation (p = 0.008). ECMO was correlated with selected radiomics parameters (r = -0.84). Conclusion: Implementing the cfDNA integrity index on an automated gel electrophoresis demonstrated promising results in predicting clinical outcomes like ARDS occurrence and mortality. Therefore, integrating laboratory and imaging resources could enhance the allocation of optimal care and may identify secondary systemic complications, especially liver involvement, as our results suggest reduced lead-time for detecting liver injury.

Indexed as

Cell-Free Nucleic AcidsCOVID-19InflammationRespiratory Distress SyndromeAdultAgedBiomarkersDNA FragmentationEpigenesis, GeneticFemaleHumansJurkat CellsMaleMiddle AgedPrognosisRadiomicsBiomarkersCell-Free Nucleic AcidsARDS diagnostics and outcomecell-free nucleic acidCOVID-19DNA-integrityepigeneticsintegrative medicineintensive care unitsradiomics

Identifiers

PMID41574291
PMCPMC12819667

What Socratic holds

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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 Socratic graph.