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Metabolome of Cerebral Thrombi Reveals an Association between High Glycemia at Stroke Onset and Good Clinical Outcome.

ABSTRACT: Despite the fact that glucose is the main fuel of the brain, hyperglycemia at hospital admission is generally associated with a poor functional outcome in stroke patients. This paradox may be explained by the lack of information about the blood glucose level at stroke onset. Here, we analyzed the metabolome of blood cells entrapped in cerebral thrombi to gain insight into their metabolism at stroke onset. Fourty-one consecutive stroke patients completely recanalized by mechanical thrombectomy within 6 h were included. The metabolome of retrieved thrombi was analyzed by liquid chromatography tandem with mass spectrometry. Discriminant Analysis (sparse Partial Least Squares Discriminant Analysis (sPLS-DA)) was performed to identify classification models and significant associated features of favorable clinical outcome at 3 months (modified Rankin Scale (mRS) < 2). sPLS-DA of the metabolomes of cerebral thrombi discriminated between stroke patients with a favorable or poor clinical outcome (Area Under the Curve (AUC) = 0.992 (0.931-1)). In addition, our results revealed that high sorbitol and glucose levels in the thrombi positively correlated with favorable clinical outcomes. Sorbitol, a short-term glycemic index reflecting a high blood glucose level at stroke onset, was found to be an independent predictor of good outcome (AUC = 0.908 (0.807-0.995)). This study demonstrates that a high blood glucose level at stroke onset is beneficial to the clinical outcome of the patient.

SUBMITTER: Suissa L

PROVIDER: S-EPMC7760729 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Metabolome of Cerebral Thrombi Reveals an Association between High Glycemia at Stroke Onset and Good Clinical Outcome.

Suissa Laurent L Guigonis Jean-Marie JM Graslin Fanny F Doche Emilie E Osman Ophélie O Chau Yves Y Sedat Jacques J Lindenthal Sabine S Pourcher Thierry T

Metabolites 20201125 12

Despite the fact that glucose is the main fuel of the brain, hyperglycemia at hospital admission is generally associated with a poor functional outcome in stroke patients. This paradox may be explained by the lack of information about the blood glucose level at stroke onset. Here, we analyzed the metabolome of blood cells entrapped in cerebral thrombi to gain insight into their metabolism at stroke onset. Fourty-one consecutive stroke patients completely recanalized by mechanical thrombectomy wi ...[more]

PMID: 33255770

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Project description:It is important to understand the microbial features of the cerebral thrombus and its clinical relevance in stroke patients, of which data were scarce. We aimed to investigate the microbial features of cerebral thrombi retrieved via thrombectomy in stroke patients with large vessel occlusion (LVO) and their correlations with 3-month mortality. In a prospective cohort study, thrombus samples were collected during mechanical thrombectomy in LVO stroke patients with successful revascularization at a tertiary hospital. Oral, fecal, and isolated plasma samples were collected within 12 h of admission. The microbial compositions of all samples were compared using 16S rRNA gene amplicon next-generation sequencing. Fluorescent in situ hybridization (FISH) was used to detect bacteria in thrombus samples. The primary outcome was 3-month mortality. Perioperative adverse events (AEs) within 48 h were also recorded. Bacterial DNA was detected in 96.2% of thrombus samples from 104 patients, and clusters of bacterial signals were seen in the thrombi with FISH. Compared with fecal and oral samples, the thrombus microbiota was mainly characterized by excessive enrichment of Proteobacteria, mainly originating from plasma. The bacterial concentrations, dominant bacteria, and distribution patterns differed in thrombi obtained from cardioembolic and large-artery atherosclerotic strokes. Higher abundances of Acinetobacter and Enterobacteriaceae were associated with a higher risk of perioperative AEs, and a higher abundance of Acinetobacter was independently associated with a higher risk of 90-day mortality. This study demonstrated the presence of bacteria in cerebral thrombi retrieved with thrombectomy in LVO strokes, with some bacteria associated with patients' prognoses. IMPORTANCE In this study, we (i) checked for the presence of bacteria in cerebral thrombi in over 95% of the LVO stroke patients using 16S rRNA sequencing, in contrast with periprocedural control samples that are bacteria negative; (ii) visualized clusters of bacterial signals in the thrombi using FISH; and (iii) cultivated Lactobacillus vaginalis, Bacillus cereus, and Kocuria marina in the bacterial culture of the tissue fragment solution of thrombus aspirates. We found excessive enrichment of Proteobacteria in the thrombi, mainly originating from plasma, as indicated with fast expectation-maximization microbial source tracking (FEAST). Different bacterial concentrations, dominant bacteria, and distribution patterns were found in thrombi obtained from cardioembolic and large-artery atherosclerotic LVO strokes. There was an association between higher abundances of Acinetobacter and Enterobacteriaceae in the thrombi and a higher risk of perioperative adverse events and an association between a higher abundance of Acinetobacter in the thrombi and a higher risk of 90-day mortality.

Project description:Successful recanalization after endovascular stroke therapy (EVT) did not translate into a good clinical outcome in randomized trials. The goal of the study was to identify the predictors of a good outcome after mechanical thrombectomy with stent retrievers.A retrospective analysis of a prospectively collected database included consecutive patients treated with stent retrievers. We evaluated the influence of risk factors for stroke, baseline NIHSS score, Alberta Stroke Program Early CT (ASPECT) score, recanalization rate, onset-to-recanalization and onset-to-groin puncture time, and glucose levels at admission on good outcomes. The number of stent passes during procedure and symptomatic hemorrhage rate were also recorded. A modified Rankin Scale (mRS) score of 0-2 at 90 days was considered as a good outcome.From January 2011 to 2014, 70 consecutive patients with an acute ischemic stroke underwent EVT with stent retrievers. The absence of a medical history of diabetes was associated with good outcomes. Apart from diabetes, the baseline demographic and clinical characteristics of patients were similar between subjects with poor outcome versus those with good outcomes. Median time from onset to recanalization was significantly shorter in patients with good outcomes 245 (IQR: 216-313 min) compared with poor outcome patients (315 (IQR: 240-360 min); P = 0.023). Symptomatic intracranial hemorrhage was observed in eight (21.6%) of 37 patients with poor outcomes and no symptomatic hemorrhage was seen in patients with good outcomes (P = 0.006). In multivariate stepwise logistic regression analysis, a favorable ASPECT score (ASPECT > 7) and successful recanalization after EVT were predictors of good outcomes. Every 10-year increase was associated with a 3.60-fold decrease in the probability of a good outcome at 3 months. The probability of a good outcome decreases by 1.43-fold for each 20 mg/dL increase in the blood glucose at admission.To achieve a good outcome after EVT with stent retrievers, quick and complete recanalization and better strategies for patient selection are warranted. We need randomized trials to identify the significance of tight blood glucose control in clinical outcome during or after EVT.

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Metabolome of Cerebral Thrombi Reveals an Association between High Glycemia at Stroke Onset and Good Clinical Outcome.

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Metabolome of Cerebral Thrombi Reveals an Association between High Glycemia at Stroke Onset and Good Clinical Outcome.

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