Gene Expression of Proresolving Lipid Mediator Pathways Is Associated With Clinical Outcomes in Trauma Patients
Notice bibliographique
Résumé
OBJECTIVES: Specialized proresolving lipid mediators have emerged as powerful modulators of inflammation and activators of resolution. Animal models show significant benefits of specialized proresolving lipid mediators on survival and wound healing after major burn trauma. To date, no studies have investigated specialized proresolving lipid mediators and their relation to other lipid mediator pathways in humans after trauma. Here we determine if patients with poor outcomes after trauma have dysregulated lipid mediator pathways. DESIGN: We studied blood leukocyte expression of 18 genes critical to the synthesis, signaling, and metabolism of specialized proresolving lipid mediators and proinflammatory lipid mediators, and we correlated these expression patterns with clinical outcomes in trauma patients from the Inflammation and the Host Response to Injury study. SETTING: Seven U.S. medical trauma centers. SUBJECTS: Ninety-six patients enrolled in the Inflammation and Host Response to Injury study, after blunt trauma and unambiguously classified as having uncomplicated or complicated recoveries. Twenty-eight healthy volunteers were enrolled as controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Within each patient, the 18 genes of interest were used to calculate scores for distinct families of lipid mediators, including resolvins, lipoxins, prostaglandins, and leukotrienes, as well as leukotriene to resolvin score ratios. Scores were built using a simple weighting scheme, taking into consideration both dependent and independent activities of enzymes and receptors responsible for lipid mediator biosynthesis and function. Individually, ALOX12, PTGS2, PTGES, PTGDS, ALOX5AP, LTA4H, FPR2, PTGER2, LTB4R, HPGD, PTGR1, and CYP4F3 were expressed differentially over 28 days posttrauma between patients with uncomplicated and complicated recoveries (p < 0.05). When all genes were combined into scores, patients with uncomplicated recoveries had differential and higher resolvin scores (p < 0.001) and lower leukotriene scores (p < 0.001). A final combined ratio was calculated for each patient, and posttrauma leukotriene score to resolvin score ratios were significantly lower in patients with uncomplicated clinical courses (p < 0.001). CONCLUSIONS: proresolving lipid mediator lipidomics and/or protein expression, and identifying associated therapeutic targets, may influence the clinical management of trauma patients.
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Comment cette classification a été obtenuedéplier
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 | 0,001 | 0,019 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| 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.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».