Dataset Information

CCL11 (Eotaxin-1) Levels Predict Long-Term Functional Outcomes in Patients Following Ischemic Stroke.

ABSTRACT: Circulating levels of the pro-inflammatory cytokine C-C motif chemokine 11 (CCL11, also known as eotaxin-1) are increased in several animal models of neuroinflammation, including traumatic brain injury and Alzheimer's disease. Increased levels of CCL11 have also been linked to decreased neurogenesis in mice. We hypothesized that circulating CCL11 levels would increase following ischemic stroke in mice and humans, and that higher CCL11 levels would correlate with poor long-term recovery in patients. As predicted, circulating levels of CCL11 in both young and aged mice increased significantly 24 h after experimental stroke. However, ischemic stroke patients showed decreased CCL11 levels compared to controls 24 h after stroke. Interestingly, lower post-stroke CCL11 levels were predictive of increased stroke severity and independently predictive of poorer functional outcomes in patients 12 months after ischemic stroke. These results illustrate important differences in the peripheral inflammatory response to ischemic stroke between mice and human patients. In addition, it suggests CCL11 as a candidate biomarker for the prediction of acute and long-term functional outcomes in ischemic stroke patients.

SUBMITTER: Roy-O'Reilly M

PROVIDER: S-EPMC5648599 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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CCL11 (Eotaxin-1) Levels Predict Long-Term Functional Outcomes in Patients Following Ischemic Stroke.

Roy-O'Reilly Meaghan M Ritzel Rodney M RM Conway Sarah E SE Staff Ilene I Fortunato Gilbert G McCullough Louise D LD

Translational stroke research 20170621 6

Circulating levels of the pro-inflammatory cytokine C-C motif chemokine 11 (CCL11, also known as eotaxin-1) are increased in several animal models of neuroinflammation, including traumatic brain injury and Alzheimer's disease. Increased levels of CCL11 have also been linked to decreased neurogenesis in mice. We hypothesized that circulating CCL11 levels would increase following ischemic stroke in mice and humans, and that higher CCL11 levels would correlate with poor long-term recovery in patien ...[more]

PMID: 28634890

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Project description:Early treatment of acute ischemic stroke with intravenous thrombolysis therapy (ITT) followed by intra-arterial thrombectomy (IAT) is a promising new treatment option for improving functional outcomes. Identifying patients who will benefit from this treatment combination is important.A total of 92 acute ischemic stroke patients who received ITT and IAT with a minimum of 1-year follow-up were included in the study. All parameters of clinical and imaging examinations at baseline were examined which parameters were significantly correlated with the 1-year functional outcomes (modified Rankin scale [mRS], National Institute of Health Stroke Scale [NIHSS], and Barthel Index) after stroke. Receiver-operating characteristic (ROC) curves analysis was performed to estimate the diagnostic performance of each significantly related parameter. Youden index was used to determine the optimal threshold value. Multivariate logistic regression model analyses were applied to verify the results of predicting the favorable functional outcomes.Immediate postoperation outcome with modified thrombolysis in cerebral infarction grading showed that total of 62 patients qualified for satisfactory result (2b or 3). In predicting NIHSS improvement, ROC curve analysis showed that a cutoff point of vertebral artery pulsatility index (VA PI)-ipsilateral ?2.3 yields the best diagnostic performance (area under the ROC curve [AUC]?=?0.728); in predicting mRS improvement, VA PI-ipsilateral ?1.92 and internal carotid artery resistance index (ICA RI)-ipsilateral ?0.71 yield good diagnostic performance (AUC?=?0.697 and 0.672, respectively); and ICA RI-contralateral ?0.70 or plaque index-ipsilateral ?2 had better diagnostic accuracy (AUC?=?0.764 and 0.689, respectively) than other indices to predict Barthel index improvement. The multivariate analysis also showed that these 5 indices were those more powerful and highly significant favorable functional outcomes predictors.Parameters of pulsatility and resistance index from carotid duplex could be easily accessed and noninvasive. The outcome of ischemic stroke patients receiving ITT followed by IAT can be forecasted by these 2 crucial predictors that hint the patients' functional outcomes as well as guiding first line in-charge clinician in terms of decision making.

Project description:BACKGROUND:Intravenous thrombolysis therapy (IVT) bridged with intra-arterial thrombectomy (IAT) has recently been recommended as favorable treatment option to ensure that the thrombolytic effect is delivered to the affected region for acute ischemic stroke patients. However, there remains a lack of studies reporting outcome prediction in this group of patients. In this study, we aimed to identify indicators from baseline data that could be used for early prediction of long-term functional outcomes. METHODS:This retrospective single center cohort study included acute ischemic stroke (AIS) patients (n?=?92) who received IVT and IAT. Functional outcomes were assessed by the National Institute of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS) and Barthel Index. We investigated the relationship between functional outcomes at one-year post-procedure and potential predictors such as occlusion site, modified thrombolysis in cerebral infarction (mTICI) score following the IVT/IAT procedure, and degree of stenosis measured by carotid duplex. RESULTS:67.4% of the studied patients had satisfactory outcomes with mTICI grades of 2b or 3. From baseline to one-year post-procedure, the NIHSS score improved in 88.0%, the mRS score improved in 69.6%, and the Barthel index improved with 59.8%. Patients with internal carotid artery (ICA) or vertebral artery (VA) stenosis detected by carotid duplex had significantly poorer functional outcomes, measured by the mRS score and Barthel index. In patients with a satisfactory mTICI grade, improvement in the mRS score was only observed in 60.0% of patients with ICA stenosis, compared to 93.8% without ICA stenosis. The VA stenosis was the most significant factor associated with the improvement of mRS (OR?=?0.08; 95% CI: 0.01-0.63; P?=?0.017) and Barthel Index (OR?=?0.06; 95% CI: 0.01-0.47; P?=?0.008) in multiple regression analysis. CONCLUSIONS:ICA or VA stenosis detected by carotid duplex could serve as predictors of significantly poorer functional outcomes in stroke patients treated with bridging therapy; they might be useful clinical markers, particularly as stenosis could be detected by a non-invasive and portable method.

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Project description:BackgroundSince the complication of diabetes mellitus (DM) is a risk for adverse cardiovascular outcomes in patients with coronary artery disease (CAD), appropriate risk estimation is needed in diabetic patients following percutaneous coronary intervention (PCI). However, there is no useful biomarker to predict outcomes in this population. Although stromal cell derived factor-1α (SDF-1α), a circulating chemokine, was shown to have cardioprotective roles, the prognostic impact of SDF-1α in diabetic patients with CAD is yet to be fully elucidated. Moreover, roles of SDF-1α isoforms in outcome prediction remain unclear. Therefore, this study aimed to assess the prognostic implication of three forms of SDF-1α including total, active, and inactive forms of SDF-1α in patients with DM and after PCI.MethodsThis single-center retrospective analysis involved consecutive patients with diabetes who underwent PCI for the first time between 2008 and 2018 (n = 849). Primary and secondary outcome measures were all-cause death and the composite of cardiovascular death, non-fatal myocardial infarction, and ischemic stroke (3P-MACE), respectively. For determining plasma levels of SDF-1α, we measured not only total, but also the active type of SDF-1α by ELISA. Inactive isoform of the SDF-1α was calculated by subtracting the active isoform from total SDF-1α.ResultsUnadjusted Kaplan-Meier analyses revealed increased risk of both all-cause death and 3P-MACE in patients with elevated levels of inactive SDF-1α. However, plasma levels of total and active SDF-1α were not associated with cumulative incidences of outcome measures. Multivariate Cox hazard analyses repeatedly indicated the 1 higher log-transformed inactive SDF-1α was significantly associated with increased risk of all-cause death (hazard ratio (HR): 2.64, 95% confidence interval (CI): 1.28-5.34, p = 0.008) and 3P-MACE (HR: 2.51, 95% CI: 1.12-5.46, p = 0.02). Moreover, the predictive performance of inactive SDF-1α was higher than that of total SDF-1α (C-statistics of inactive and total SDF-1α for all-cause death: 0.631 vs 0.554, for 3P-MACE: 0.623 vs 0.524, respectively).ConclusionThe study results indicate that elevated levels of plasma inactive SDF-1α might be a useful indicator of poor long-term outcomes in diabetic patients following PCI.Trial registrationThis study describes a retrospective analysis of a prospective registry database of patients who underwent PCI at Juntendo University Hospital, Tokyo, Japan (Juntendo Physicians' Alliance for Clinical Trials, J-PACT), which is publicly registered (University Medical Information Network Japan-Clinical Trials Registry, UMIN-CTR 000035587).

Dataset Information

CCL11 (Eotaxin-1) Levels Predict Long-Term Functional Outcomes in Patients Following Ischemic Stroke.

Publications

CCL11 (Eotaxin-1) Levels Predict Long-Term Functional Outcomes in Patients Following Ischemic Stroke.

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