title: Inflammatory and metalloproteinases profiles predict three-month poor outcomes in ischemic stroke treated with thrombolysis.
abstract: Inflammatory mediators and metalloproteinases are altered in acute ischemic stroke (AIS) and play a detrimental effect on clinical severity and hemorrhagic transformation of the ischemic brain lesion. Using data from the Italian multicenter observational MAGIC (MArker bioloGici nell'Ictus Cerebrale) Study, we evaluated the effect of inflammatory and metalloproteinases profiles on three-month functional outcome, hemorrhagic transformation and mortality in 327 patients with AIS treated with intravenous thrombolys in according to SITS-MOST (Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy) criteria. Circulating biomarkers were assessed at baseline and 24 h after thrombolysis. Adjusting for age, sex, baseline glycemia and National Institute of Health Stroke Scale, history of atrial fibrillation or congestive heart failure, and of inflammatory diseases or infections, baseline alpha-2macroglobulin (A2M), baseline serum amyloid protein (SAP) and pre-post tissue-plasminogen activator (tPA) variations (Δ) of metalloproteinase 9, remained significantly and independently associated with three-month death [OR (95% CI):A2M:2.99 (1.19-7.53); SAP:5.46 (1.64-18.74); Δmetalloproteinase 9:1.60 (1.12-2.27)]. The addition of baseline A2M and Δmetalloproteinase 9 or baseline SAP and Δmetalloproteinase 9 (model-2 or model-3) to clinical variables (model-1) significantly improved the area under curve for prediction of death [model-2 with A2M: p = 0.0205; model-3 with SAP: p = 0.001]. In conclusion, among AIS patients treated with thrombolysis, circulating A2M, SAP and Δmetalloproteinase 9 are independent markers of poor outcome. These results may prompt controlled clinical research about agents antagonizing their effect.
authors.affiliation: 1 Department of Experimental and Clinical Medicine, University of Florence, Atherothrombotic Diseases Center, Careggi Hospital, Florence, Italy.|2 Don Gnocchi Foundation, IRCCS, Florence, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Gori
authors.affiliation: 1 Department of Experimental and Clinical Medicine, University of Florence, Atherothrombotic Diseases Center, Careggi Hospital, Florence, Italy.
authors.forename: Betti
authors.initials: B
authors.lastname: Giusti
authors.affiliation: 3 Stroke Unit, Careggi University Hospital, Florence, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Piccardi
authors.affiliation: 3 Stroke Unit, Careggi University Hospital, Florence, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Nencini
authors.affiliation: 3 Stroke Unit, Careggi University Hospital, Florence, Italy.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Palumbo
authors.affiliation: 3 Stroke Unit, Careggi University Hospital, Florence, Italy.
authors.forename: Mascia
authors.initials: M
authors.lastname: Nesi
authors.affiliation: 4 Department of Clinical Neurological Sciences, London Health Sciences Centre, Western University, London, Ontario, Canada.
authors.forename: Antonia
authors.initials: A
authors.lastname: Nucera
authors.affiliation: 3 Stroke Unit, Careggi University Hospital, Florence, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pracucci
authors.affiliation: 3 Stroke Unit, Careggi University Hospital, Florence, Italy.
authors.forename: Paolina
authors.initials: P
authors.lastname: Tonelli
authors.affiliation: 3 Stroke Unit, Careggi University Hospital, Florence, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Innocenti
authors.affiliation: 1 Department of Experimental and Clinical Medicine, University of Florence, Atherothrombotic Diseases Center, Careggi Hospital, Florence, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Sereni
authors.affiliation: 1 Department of Experimental and Clinical Medicine, University of Florence, Atherothrombotic Diseases Center, Careggi Hospital, Florence, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Sticchi
authors.affiliation: 5 Emergency Department Stroke Unit and Department of Neurological Sciences, Sapienza University of Rome, Rome, Italy.
authors.forename: Danilo
authors.initials: D
authors.lastname: Toni
authors.affiliation: 6 DAI di Neuroscienze, Azienda Ospedaliera Integrata, Verona, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bovi
authors.affiliation: 7 Neurology Unit, Valduce General Hospital, Como, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Guidotti
authors.affiliation: 8 Azienda Ospedaliera-Universitaria S. Anna, Ferrara, Italy.
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Tola
authors.affiliation: 9 U.O. Neurologia, G. Jazzolino Hospital, Vibo Valentia, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Consoli
authors.affiliation: 10 Istituto Neurologico Nazionale C. Mondino, Pavia, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Micieli
authors.affiliation: 11 U.O.C. Stroke Unit, Dipartimento di Scienze Neurologiche e Neurosensoriali, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
authors.forename: Rossana
authors.initials: R
authors.lastname: Tassi
authors.affiliation: 12 Department of Neurosciences, Neurological Clinic, University of Pisa, Pisa, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Orlandi
authors.affiliation: 13 Department of Neurology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Sessa
authors.affiliation: 14 UOC di Neurologia e "Stroke Unit", Ospedale San Bortolo, Vicenza, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Perini
authors.affiliation: 15 U.O. Neurologia e Stroke Unit, Ospedale di Circolo e Fondazione Macchi di Varese.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Delodovici
authors.affiliation: 16 Neurology Unit, Arcispedale Santa Maria Nuova, Reggio Emilia, Italy.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Zedde
authors.affiliation: 17 Neurology Unit, Misericordia e Dolce Hospital, Prato, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Massaro
authors.affiliation: 18 Centro Studi Medicina Avanzata (CESMAV) Florence, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Abbate
authors.affiliation: 3 Stroke Unit, Careggi University Hospital, Florence, Italy.|19 Institute of Neuroscience, Italian National Research Council (CNR), Florence, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Inzitari
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D045726:Metalloproteases / Q000097:blood*; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D012372:ROC Curve; D020521:Stroke / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D015912:Thrombolytic Therapy; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D016207:Cytokines; D045726:Metalloproteases
keywords: Hemorrhagic transformation; inflammation; ischemic stroke; metalloproteinase; thrombolysis