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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 (?) 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); ?metalloproteinase 9:1.60 (1.12-2.27)]. The addition of baseline A2M and ?metalloproteinase 9 or baseline SAP and ?metalloproteinase 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 ?metalloproteinase 9 are independent markers of poor outcome. These results may prompt controlled clinical research about agents antagonizing their effect.

SUBMITTER: Gori AM

PROVIDER: S-EPMC5584701 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Inflammatory and metalloproteinases profiles predict three-month poor outcomes in ischemic stroke treated with thrombolysis.

Gori Anna Maria AM Giusti Betti B Piccardi Benedetta B Nencini Patrizia P Palumbo Vanessa V Nesi Mascia M Nucera Antonia A Pracucci Giovanni G Tonelli Paolina P Innocenti Eleonora E Sereni Alice A Sticchi Elena E Toni Danilo D Bovi Paolo P Guidotti Mario M Tola Maria Rosaria MR Consoli Domenico D Micieli Giuseppe G Tassi Rossana R Orlandi Giovanni G Sessa Maria M Perini Francesco F Delodovici Maria Luisa ML Zedde Maria Luisa ML Massaro Francesca F Abbate Rosanna R Inzitari Domenico D

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20170307 9

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 intrav ...[more]

PMID: 28266892

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Project description:Background: Evidence for the effect of subclinical thyroid dysfunction on the prognosis of patients suffering from acute ischemic stroke and receiving reperfusion therapy remains controversial. We aimed to investigate the association between subclinical thyroid dysfunction and the outcomes of patients with acute ischemic stroke who were treated with reperfusion therapy. Methods: One hundred fifty-six consecutively recruited patients with acute ischemic stroke receiving reperfusion therapy (intravenous thrombolysis, intraarterial thrombectomy and combined intravenous thrombolysis and intraarterial thrombectomy) were included in this prospective observational study. We divided patients with subclinical thyroid dysfunction into the following 2 groups and defined a euthyroid group: subclinical hyperthyroidism (a thyroid-stimulating hormone level <0.35 μU/mL), subclinical hypothyroidism (a thyroid-stimulating hormone level >4.94 μU/mL), and a euthyroid state (0.35 μU/mL ≤ thyroid-stimulating hormone level ≤ 4.94 μU/mL). Patients with overt thyroid dysfunction were excluded. The primary outcome was functional disability at 3 months (modified Rankin Scale, mRS), and the secondary outcome was successful reperfusion. A multivariate analysis was performed to evaluate the associations between subclinical thyroid dysfunction and the primary and secondary outcomes. Results: The subclinical hyperthyroidism group appeared to have poor functional outcomes, but the differences were not significant. However, compared with patients in the euthyroid state, patients with subclinical hyperthyroidism had an increased risk of poor functional outcomes at 3 months after a stroke (adjusted odds ratio [OR] 2.50, 95% confidence interval [CI] 1.01-6.14 for a mRS score of 3 to 6) and a decreased rate of successful reperfusion after reperfusion therapy (OR 0.13, 95% CI 0.04-0.43). Conclusion: Subclinical hyperthyroidism may be independently associated with a poor prognosis at 3 months and unsuccessful reperfusion in patients with acute ischemic stroke receiving reperfusion therapy.

Project description:Tenecteplase is a fibrinolytic drug with higher fibrin specificity and longer half-life than the standard stroke thrombolytic, alteplase, permitting the convenience of single bolus administration. Tenecteplase, at 0.5 mg/kg, has regulatory approval to treat ST-segment-elevation myocardial infarction, for which it has equivalent 30-day mortality and fewer systemic hemorrhages. Investigated as a thrombolytic for ischemic stroke over the past 15 years, tenecteplase is currently being studied in several phase 3 trials. Based on a systematic literature search, we provide a qualitative synthesis of published stroke clinical trials of tenecteplase that (1) performed randomized comparisons with alteplase, (2) compared different doses of tenecteplase, or (3) provided unique quantitative meta-analyses. Four phase 2 and one phase 3 study performed randomized comparisons with alteplase. These and other phase 2 studies compared different tenecteplase doses and effects on early outcomes of recanalization, reperfusion, and substantial neurological improvement, as well as symptomatic intracranial hemorrhage and 3-month disability on the modified Rankin Scale. Although no single trial prospectively demonstrated superiority or noninferiority of tenecteplase on clinical outcome, meta-analyses of these trials (1585 patients randomized) point to tenecteplase superiority in recanalization of large vessel occlusions and noninferiority in disability-free 3-month outcome, without increases in symptomatic intracranial hemorrhage or mortality. Doses of 0.25 and 0.4 mg/kg have been tested, but no advantage of the higher dose has been suggested by the results. Current clinical practice guidelines for stroke include intravenous tenecteplase at either dose as a second-tier option, with the 0.25 mg/kg dose recommended for large vessel occlusions, based on a phase 2 trial that demonstrated superior recanalization and improved 3-month outcome relative to alteplase. Ongoing randomized phase 3 trials may better define the comparative risks and benefits of tenecteplase and alteplase for stroke thrombolysis and answer questions of tenecteplase efficacy in the >4.5-hour time window, in wake-up stroke, and in combination with endovascular thrombectomy.

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Inflammatory and metalloproteinases profiles predict three-month poor outcomes in ischemic stroke treated with thrombolysis.

Publications

Inflammatory and metalloproteinases profiles predict three-month poor outcomes in ischemic stroke treated with thrombolysis.

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