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Nuclear Magnetic Resonance-Based Metabolomics to Predict Early and Late Adverse Outcomes in Ischemic Stroke Treated with Intravenous Thrombolysis.

ABSTRACT: Metabolic perturbations and inflammatory mediators play a fundamental role in both early and late adverse post-acute ischemic stroke outcomes. Using data from the observational MAGIC (MArker bioloGici nell'Ictus Cerebrale) study, we evaluated the effect of 130 serum metabolic features, using a nuclear magnetic spectroscopy approach, on the following outcomes: hemorrhagic transformation at 24 h after stroke, non-response to intravenous thrombolytic treatment with the recombinant tissue plasminogen activator (rt-PA), and the 3 month functional outcome. Blood circulating metabolites, lipoproteins, and inflammatory markers were assessed at the baseline and 24 h after rt-PA treatment. Adjusting for the major determinants for unfavorable outcomes (i.e., age, sex, time onset-to-treatment, etc.), we found that acetone and 3-hydroxybutyrate were associated with symptomatic hemorrhagic transformation and with non-response to rt-PA; while 24 h after rt-PA, levels of triglycerides high-density lipoprotein (HDL) and triglycerides low-density lipoprotein (LDL) were associated with 3 month mortality. Cholesterol and phospholipids levels, mainly related to smaller and denser very low-density lipoprotein (VLDL) and LDL subfractions were associated with 3 month poor functional outcomes. We also reported associations between baseline 24 h relative variation (Δ) in VLDL subfractions and ΔC-reactive protein, Δinterleukin-10 levels with hemorrhagic transformation. All observed metabolic changes reflect a general condition of energy failure, oxidative stress, and systemic inflammation that characterize the development of adverse outcomes.

SUBMITTER: Licari C

PROVIDER: S-EPMC9830637 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Nuclear Magnetic Resonance-Based Metabolomics to Predict Early and Late Adverse Outcomes in Ischemic Stroke Treated with Intravenous Thrombolysis.

Licari Cristina C Tenori Leonardo L Di Cesare Francesca F Luchinat Claudio C Giusti Betti B Kura Ada A De Cario Rosina R Inzitari Domenico D Piccardi Benedetta B Nesi Mascia M Sarti Cristina C Arba Francesco F Palumbo Vanessa V Nencini Patrizia P Marcucci Rossella R Gori Anna Maria AM Sticchi Elena E

Journal of proteome research 20221205 1

Metabolic perturbations and inflammatory mediators play a fundamental role in both early and late adverse post-acute ischemic stroke outcomes. Using data from the observational MAGIC (MArker bioloGici nell'Ictus Cerebrale) study, we evaluated the effect of 130 serum metabolic features, using a nuclear magnetic spectroscopy approach, on the following outcomes: hemorrhagic transformation at 24 h after stroke, non-response to intravenous thrombolytic treatment with the recombinant tissue plasminoge ...[more]

PMID: 36469426

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Project description:BackgroundHemorrhagic transformation (HT) is the most serious complication of ischemic stroke patients after intravenous thrombolysis and leads to a poor clinical prognosis. This study aimed to determine the independent predictors associated with HT in stroke patients with intravenous thrombolysis and to establish and validate a nomogram that combines with predictors to predict the probability of HT after intravenous thrombolysis in patients with ischemic stroke.MethodThis study enrolled ischemic stroke patients with intravenous thrombolysis from December 2016 to June 2022. All the patients were divided into training and validation cohorts. The nomogram was composed of the significant predictors for HT in the training cohort as obtained by the multivariate logistic regression analysis. The area under the receiver operating characteristic curve was used to assess the discriminative performance of the nomogram. The calibration performance of the nomogram was assessed by the Hosmer-Lemeshow goodness-of-fit test and calibration plots. Decision curve analysis was used to test the clinical validity of the nomogram.ResultsA total of 394 patients with intravenous thrombolysis were enrolled in the study. In the training cohort (n = 257), 45 patients had HT after intravenous thrombolysis. Multivariate logistic regression analysis demonstrated early infarct signs (OR, 7.954; 95% CI, 3.553-17.803; P < 0.001), NIHSS scores (OR, 1.110; 95% CI, 1.054-1.168; P < 0.001), uric acid (OR, 0.993; 95% CI, 0.989-0.997; P = 0.001), and albumin-to-globulin ratio (OR, 0.109; 95% CI, 0.023-0.508; P = 0.005) were independent predictors for HT and constructed the nomogram. In the training and validation cohorts, the AUC of the nomogram was 0.859 and 0.839, respectively. The Hosmer-Lemeshow goodness-of-fit test and calibration plot showed good concordance between predicted and observed probability in the training and validation cohorts. Decision curve analysis indicated that the nomogram was significantly useful for predicting HT in the training and further confirmed in the validation cohort.ConclusionThis study proposes a novel and practical nomogram based on early infarct signs, NIHSS scores, uric acid, and albumin-to-globulin ratio that can well predict the probability of HT after intravenous thrombolysis in patients with ischemic stroke.

Project description:IntroductionThe optimal timing for decompressive hemicraniectomy (DHC) after intravenous thrombolysis (IVT) remains unclear. This study in patients with acute ischemic stroke treated with IVT aimed to assess the safety of DHC and patient outcome.MethodsData was extracted from the Tabriz stroke registry from June 2011 up to September 2020. In all, 881 patients were treated with IVT. Among these, 23 patients underwent DH. Six patients were excluded due to symptomatic intracranial hemorrhage (parenchymal hematoma type 2 based on SITS-MOST definition) after IVT, but other types of bleeding after venous thrombolysis, including HI1, HI2, and PH1 were not excluded; so the remaining 17 patients were enrolled in the study. Functional Outcome was defined as the proportion of patients who achieved mRS score of 2-3 (moderate disability), 4-5 (severe disability), or 6 (mortality) at 90 days after stroke. mRSwas assess by trained neurologist at the hospital clinic with direct interview Safety outcome was assessed by comparison of two scans just prior to and after craniectomy. Any new hemorrhage or worsening of previous hemorrhage was reported. Parenchymal hematoma type 2, based on ECASS II definition, was considered as major surgical complication. This study was approved by the local ethics committee of the Tabriz University of Medical Sciences (Ethics Code: IR.TBZMED.REC.1398.420).ResultsAt the three-month mRS follow up, six patients (35%) had moderate and five (29%) had severe disability. The outcome of death was observed in six patients (35%).Nine of 15 patients (60%) underwent surgery in the first 48 hours after onset of symptoms. No patient over 60 years of age survived to the three-month follow up; 67% of those who were under60 years and underwent DH in the first 48 hours had favorable outcome. Hemorrhagic complication was seen in 64% of patients but none was major.ConclusionResults of this study showed that the rate of major bleeding and outcome of acute ischemic stroke patients who underwent DHC after IVT is comparable with the reported data in the literature and intentionally waiting for the fibrinolytic effects of IVT to disappear may not outweigh the benefits of DHC. Although the findings of the study should be interpreted with caution and larger studies are needed to confirm the results.

Dataset Information

Nuclear Magnetic Resonance-Based Metabolomics to Predict Early and Late Adverse Outcomes in Ischemic Stroke Treated with Intravenous Thrombolysis.

Publications

Nuclear Magnetic Resonance-Based Metabolomics to Predict Early and Late Adverse Outcomes in Ischemic Stroke Treated with Intravenous Thrombolysis.

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