Evidence map›Paper›PMID 40026254›Full record

Trial reportThe Journal of clinical investigation2025

A multi-analyte blood test for acute spinal cord injury.

Tej D Azad, Kathleen R Ran, Joshua D Materi, Divyaansh Raj, Timour Al-Khindi, Sameer Gabbita, Marvin Li, Elizabeth T Wang, A Karim Ahmed, Megan Parker and 11 more

Abstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. 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

21 authors.

Tej D AzadDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Kathleen R RanDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Joshua D MateriDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Divyaansh RajDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Timour Al-KhindiDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Sameer GabbitaDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Marvin LiDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Elizabeth T WangDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
A Karim AhmedDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Megan ParkerDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Anita L KalluriDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Daniel LubelskiDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Christopher M JacksonDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Daniel M SciubbaDepartment of Neurosurgery, Zucker School of Medicine at Hofstra, Manhasset, New York, USA.
Jon D WeingartDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Ali BydonDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Timothy F WithamDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
David W NauenDepartment of Pathology and.
Srinivasan YegnasubramanianDepartment of Pathology and.
Nicholas TheodoreDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Chetan BettegowdaDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUNDRapid diagnosis to facilitate urgent intervention is critical for treatment of acute spinal cord injury (SCI). We hypothesized that a multi-analyte blood biomarker would support point-of-care SCI diagnosis, correlate with injury severity, and predict long-term neurologic outcomes.METHODSDroplet digital PCR (ddPCR) assays were designed to amplify differentially hypomethylated genomic loci in spinal cord tissue. An optimized ddPCR assay was applied to cell-free DNA (cfDNA) from plasma samples collected from prospectively enrolled acute SCI patients. Targeted proteomic profiling was also performed. Spinal cord-derived cfDNA and plasma proteins were tested for their association with SCI and ability to predict conversion in American Spinal Injury Association (ASIA) score at 6 months.RESULTSA bespoke ddPCR assay detected spinal cord-derived cfDNA in plasma of 50 patients with acute SCI (AUC: 0.89, 95% CI 0.83-0.95, P < 0.0001). Levels of cfDNA were highest in patients with the most severe injury, i.e., ASIA A, compared with those with ASIA B (P = 0.04), ASIA C (P = 0.009), and ASIA D injuries (P < 0.001). Dimensionality reduction identified 4 candidate proteins (FABP3, REST, IL-6, NF-H) that were integrated with spinal cord-derived cfDNA to derive the Spinal Cord Injury Index (SCII), which has high sensitivity and specificity for SCI diagnosis (AUC: 0.91, 95% CI 0.82-0.99, P < 0.0001), correlates with injury severity (P < 0.0001), and predicts 6-month neurologic improvement (AUC: 0.77, 95% CI 0.61-0.93, P = 0.006).CONCLUSIONThe detection of spinal cord-derived cfDNA and plasma protein alterations as part of a multi-analyte blood test can inform SCI diagnosis and prognosis.FUNDINGNorth American Spine Society Young Investigator Award; Morton Cure Paralysis Fund.

Indexed as

Cell-Free Nucleic AcidsSpinal Cord InjuriesAcute DiseaseAdultAgedBiomarkersFemaleHumansMaleMiddle AgedProspective StudiesBiomarkersCell-Free Nucleic AcidsNeurological disordersNeuroscience

Identifiers

PMID40026254
PMCPMC11870727

What OpenQuestion holds

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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.