{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T02:47:42Z","timestamp":1793155662327,"version":"4.5.0"},"reference-count":35,"publisher":"American Society for Clinical Investigation","issue":"5","license":[{"start":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T00:00:00Z","timestamp":1740960000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100003146","name":"Morton Cure Paralysis Fund","doi-asserted-by":"crossref","award":["Morton Cure Paralysis Fund"],"award-info":[{"award-number":["Morton Cure Paralysis Fund"]}],"id":[{"id":"10.13039\/100003146","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100003202","name":"North American Spine Society","doi-asserted-by":"crossref","award":["Young Investigator Award"],"award-info":[{"award-number":["Young Investigator Award"]}],"id":[{"id":"10.13039\/100003202","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,3]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Rapid 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Droplet 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\u2013derived 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      A bespoke ddPCR assay detected spinal cord\u2013derived cfDNA in plasma of 50 patients with acute SCI (AUC: 0.89, 95% CI 0.83\u20130.95,\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.0001). Levels of cfDNA were highest in patients with the most severe injury, i.e., ASIA A, compared with those with ASIA B (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.04), ASIA C (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.009), and ASIA D injuries (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.001). Dimensionality reduction identified 4 candidate proteins (FABP3, REST, IL-6, NF-H) that were integrated with spinal cord\u2013derived 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\u20130.99,\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.0001), correlates with injury severity (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.0001), and predicts 6-month neurologic improvement (AUC: 0.77, 95% CI 0.61\u20130.93,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.006).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>The detection of spinal cord\u2013derived cfDNA and plasma protein alterations as part of a multi-analyte blood test can inform SCI diagnosis and prognosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>North American Spine Society Young Investigator Award; Morton Cure Paralysis Fund.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1172\/jci185463","type":"journal-article","created":{"date-parts":[[2025,3,2]],"date-time":"2025-03-02T14:00:42Z","timestamp":1740924042000},"source":"Crossref","is-referenced-by-count":14,"title":["A multi-analyte blood test for acute spinal cord injury"],"prefix":"10.1172","volume":"135","author":[{"given":"Tej D.","family":"Azad","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen R.","family":"Ran","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua D.","family":"Materi","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Divyaansh","family":"Raj","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timour","family":"Al-Khindi","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sameer","family":"Gabbita","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marvin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth T.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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