Association of Serum Brain-Derived Tau With Clinical Outcome and Longitudinal Change in Patients With Severe Traumatic Brain Injury
Notice bibliographique
Résumé
Importance: Blood-based measurements of total tau (T-tau) are commonly used to examine neuronal injury in patients with traumatic brain injury (TBI), but current assays do not differentiate between brain-derived tau (BD-tau) and tau produced in peripheral tissues. A novel assay for BD-tau has recently been reported that selectively quantifies nonphosphorylated tau of central nervous system origin in blood samples. Objectives: To examine the association of serum BD-tau with clinical outcomes in patients with severe TBI (sTBI) and its longitudinal changes over 1 year. Design, Setting, and Participants: This prospective cohort study was conducted at the neurointensive unit at the Sahlgrenska University Hospital, Gothenburg, Sweden, between September 1, 2006, and July 1, 2015. The study included 39 patients with sTBI followed up for up to 1 year. Statistical analysis was performed between October and November 2021. Exposures: Serum BD-tau, T-tau, phosphorylated tau231 (p-tau231), and neurofilament light chain (NfL) measured on days 0, 7, and 365 after injury. Main Outcomes and Measures: Associations of serum biomarkers with clinical outcome and longitudinal change in sTBI. Severity of sTBI was evaluated using the Glasgow Coma Scale at hospital admission, while clinical outcome was assessed with the Glasgow Outcome Scale (GOS) at 1-year follow-up. Participants were classified as having a favorable outcome (GOS score, 4-5) or unfavorable outcome (GOS score, 1-3). Results: Among the 39 patients (median age at admission, 36 years [IQR, 22-54 years]; 26 men [66.7%]) in the study on day 0, the mean (SD) serum BD-tau level was higher among patients with unfavorable outcomes vs those with favorable outcomes (191.4 [190.8] pg/mL vs 75.6 [60.3] pg/mL; mean difference, 115.9 pg/mL [95% CI, 25.7-206.1 pg/mL]), while the other markers had smaller between-group mean differences (serum T-tau, 60.3 pg/mL [95% CI, -22.0 to 142.7 pg/mL]; serum p-tau231, 8.3 pg/mL [95% CI, -6.4 to 23.0 pg/mL]; serum NfL, -5.4 pg/mL [95% CI, -99.0 to 88.3 pg/mL]). Similar results were recorded on day 7. Longitudinally, baseline serum BD-tau concentrations showed slower decreases in the whole cohort (42.2% on day 7 [from 138.6 to 80.1 pg/mL] and 93.0% on day 365 [from 138.6 to 9.7 pg/mL]) compared with serum T-tau (81.5% on day 7 [from 57.3 to 10.6 pg/mL] and 99.0% on day 365 [from 57.3 to 0.6 pg/mL]) and p-tau231 (92.5% on day 7 [from 20.1 to 1.5 pg/mL] and 95.0% on day 365 [from 20.1 to 1.0 pg/mL]). These results did not change when considering clinical outcome, where T-tau decreased twice as fast as BD-tau in both groups. Similar results were obtained for p-tau231. Furthermore, the biomarker levels on day 365 were lower, compared with day 7, for BD-tau but not T-tau or p-tau231. Serum NfL had a different trajectory to the tau biomarkers, with levels increasing by 255.9% on day 7 compared with day 0 (from 86.8 to 308.9 pg/mL) but decreasing by 97.0% by day 365 vs day 7 (from 308.9 to 9.2 pg/mL). Conclusions and Relevance: This study suggests that serum BD-tau, T-tau, and p-tau231 have differential associations with clinical outcome and 1-year longitudinal change in patients with sTBI. Serum BD-tau demonstrated utility as a biomarker to monitor outcomes in sTBI and can provide valuable information regarding acute neuronal damage.
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Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
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