title: Serum osteopontin levels are upregulated and predict disability after an ischaemic stroke.
abstract: BACKGROUND
  After an acute ischaemic stroke (AIS), several inflammatory biomarkers have been investigated, but their predictive role on functional recovery remains to be validated. Here, we investigated the prognostic relevance of biomarkers related to atherosclerotic plaque calcification, such as osteopontin (OPN), osteoprotegerin (OPG) and the receptor activator of nuclear factor kappa-B ligand (RANKL) in a cohort of patients with AIS (n = 90) during 90-day follow-up.
  
  
  METHODS
  Radiological and clinical examinations as well as blood sampling were performed at admission and at days 1, 7 and 90 from the event. Validated scores [such as modified Rankin scale (mRS) and the National Institutes of Health Stroke Scale (NIHSS)] were used to assess poststroke outcome. Serum levels of OPN, OPG and RANKL were measured by colorimetric enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  When compared to the admission, OPN serum levels increased at day 7. Serum OPN levels at this time point were positively correlated with both ischaemic lesion volume and NIHSS at days 7 and 90. A cut-off of 30.53 ng/mL was identified for serum OPN by receiver operating characteristic (ROC) curve analysis. Adjusted logistic regression showed that serum OPN levels at day 7 predicted worse mRS at day 90 [OR 4.13 (95% CI 1.64-10.36); P = 0.002] and NIHSS [1.49 (95% CI 1.16-1.99); P = 0.007], independently of age, gender, hypertension and thrombolysis.
  
  
  CONCLUSIONS
  Serum levels of OPN, but not OPG and RANKL, peaked at day 7 after AIS and predicted worse neurological scores. Therefore, OPN might have a pathophysiological and clinical relevance after AIS.
authors.affiliation: First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa School of Medicine, IRCCS Azienda Ospedaliera Universitaria San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.|Division of Cardiology, Department of Medical Specialties, Foundation for Medical Researches, University of Geneva, Geneva, Switzerland.
authors.forename: Federico
authors.initials: F
authors.lastname: Carbone
authors.affiliation: Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Vuilleumier
authors.affiliation: Division of Cardiology, Department of Medical Specialties, Foundation for Medical Researches, University of Geneva, Geneva, Switzerland.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Burger
authors.affiliation: Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, Ferrara, Italy.
authors.forename: Gloria
authors.initials: G
authors.lastname: Roversi
authors.affiliation: Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, Ferrara, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Tamborino
authors.affiliation: Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, Ferrara, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Casetta
authors.affiliation: Section of Infectious Diseases, Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
authors.forename: Silva
authors.initials: S
authors.lastname: Seraceni
authors.affiliation: Section of Medical Biochemistry, Molecular Biology and Genetics, Department of Biomedical and Specialist Surgical Sciences University of Ferrara, Ferrara, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Trentini
authors.affiliation: Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, Ferrara, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Padroni
authors.affiliation: First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa School of Medicine, IRCCS Azienda Ospedaliera Universitaria San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Dallegri
authors.affiliation: Division of Cardiology, Department of Medical Specialties, Foundation for Medical Researches, University of Geneva, Geneva, Switzerland.
authors.forename: François
authors.initials: F
authors.lastname: Mach
authors.affiliation: Section of Neurology, Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, Ferrara, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Fainardi
authors.affiliation: First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa School of Medicine, IRCCS Azienda Ospedaliera Universitaria San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.|Division of Cardiology, Department of Medical Specialties, Foundation for Medical Researches, University of Geneva, Geneva, Switzerland.|Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Montecucco
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D002545:Brain Ischemia / Q000097:blood*; D006233:Persons with Disabilities; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D053495:Osteopontin / Q000378:metabolism*; D053244:Osteoprotegerin / Q000378:metabolism; D011379:Prognosis; D011446:Prospective Studies; D053245:RANK Ligand / Q000378:metabolism; D020521:Stroke / Q000097:blood*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D015415:Biomarkers; D053244:Osteoprotegerin; D053245:RANK Ligand; C506030:TNFRSF11B protein, human; D053495:Osteopontin
keywords: Ischaemic stroke; osteopontin; osteoprotegerin; receptor activator of nuclear factor kappa-B ligand