Prospective Validation of Glial Fibrillary Acidic Protein, <scp>d</scp> ‐Dimer, and Clinical Scales for Acute Large‐Vessel Occlusion Ischemic Stroke Detection
Bibliographic record
Abstract
Background: Large-vessel occlusion (LVO) ischemic stroke is responsible for significant morbidity and mortality. We have previously described a novel tool for acute LVO detection that combines blood-based biomarkers (glial fibrillary acidic protein and d-dimer) with stroke severity scales to achieve high accuracy. Accordingly, the present study sought to prospectively validate cutoff values that we had previously established for biomarkers and scales. Methods: The TIME (Testing for Identification Markers of Stroke) trial was designed as a prospective observational diagnostic accuracy study. All ambulance-identified stroke code activations <18 hours from symptom onset were recruited at Brandon Regional Hospital (Brandon, FL) between May 2021 and August 2022. Previously determined cutoff concentrations of plasma glial fibrillary acidic protein (213 pg/mL) and d-dimer (600 ng/mL) were used in combination with prehospital stroke scales to detect LVO. We compared rates of LVO detection against a reference standard using computed tomography/magnetic resonance angiography. Results: A total of 382 patients with suspected stroke were recruited. The final cohort was composed of 323 patients with suspected stroke with the following distribution: LVO ischemic stroke (n = 29, 9%), non-LVO ischemic stroke (n = 48, 15%), hemorrhagic stroke (n = 13, 4%), transient ischemic attack (n = 12, 3.9%), and stroke mimics (n = 220, 68.1%). Combining blood-based biomarkers (glial fibrillary acidic protein and d-dimer) with the scale field assessment stroke triage for emergency destination yielded the best performance for LVO detection, with specificity of 94% and sensitivity of 71%. Performance was found to be higher in a subanalysis focusing on patients presenting <6 hours from symptom onset, with 93% specificity and 81% sensitivity. Critically, application of the biomarker and stroke scale algorithms ruled out all patients with hemorrhage. Conclusion: The present work prospectively validated the potential utility of previously defined glial fibrillary acidic protein and d-dimer cutoff levels (ie, 213 pg/mL and 600 ng/mL, respectively), demonstrating their value for discrimination of LVO stroke from differential diagnoses during code stroke workups. (ClinicalTrials.gov number, NCT04292600.).
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".