High red blood cell composition in clots is associated with successful recanalization during intra-arterial thrombectomy - Fig 1

<p>Measurement of RBC, fibrin/platelet, and WBC composition using the Positive Pixel Count (PPC) algorithm of the ImageScope program in an RBC-rich clot (A), a mixed clot (B), and a fibrin/platelet-rich clot (C). To measure the area of RBC and fibrin/platelet in a digitized clot image, hue value (0.05), hue width (0.4), saturation (0.04), the intensity of strong positive pixels (I_sp, 100), and the intensity of weak positive pixels (I_wp, 215) were set to the fixed values. The intensity of positive pixels (I_p) was only adjusted in a best image of the 10 clot images differently digitized from 135 to 180 of I_p values to obtain the clearest discrimination of RBC and fibrin/platelet in the individual clot images.</p

High red blood cell composition in clots is associated with successful recanalization during intra-arterial thrombectomy

<div><p>We evaluated the composition of individual clots retrieved during intra-arterial thrombectomy in relation to recanalization success, stroke subtype, and the presence of clot signs on initial brain images. We analyzed clot and interventional data from 145 retrieval trials performed for 37 patients (69.5±14.0 years, 20 men, large artery atherosclerosis, n = 7; cardioembolism, n = 22; undetermined etiology, n = 8) who had undergone intra-arterial thrombectomy. Rates of clot retrieval and successful recanalization (Arterial Occlusive Lesion score of 2–3) for separate retrieval trials were evaluated. The area occupied by red blood cell (RBC), fibrin/platelets, and white blood cell (WBC) was measured from digitized images of hematoxylin-eosin stained clots. Compositional differences were compared according to recanalization success, stroke subtype, and the presence of hyperdense clot sign on initial computed tomography and/or blooming artifact on magnetic resonance image. Of the 145 total retrieval trials (3.4±2.4 times per patient), clot was retrieved in 93 trials (64%), while recanalization was successful in 73 (50%). Fibrin/platelets (63%) occupied the greatest area in retrieved clots, followed by RBCs (33%) and WBCs (4%). Clots retrieved from successful recanalization exhibited higher RBC composition (37%) than those retrieved from non-recanalization trials (20%, p = 0.001). RBC composition was higher in cardioembolic stroke (38%) rather than large artery atherosclerosis (23%) and undetermined etiology (26%, p = 0.01). Clots exhibiting clot signs (40%) had higher RBC composition than those without clot signs (19%, p = 0.001). RBC-rich clots were associated with successful recanalization of intra-arterial thrombectomy, cardioembolic stroke, and the presence of clot-signs on initial brain images.</p></div

Number of trials for clot retrieval and successful recanalization.

<p>Number of trials for clot retrieval and successful recanalization.</p

High red blood cell composition in clots is associated with successful recanalization during intra-arterial thrombectomy - Fig 3

<p>Comparison of clot composition (red blood cells [RBCs], fibrin/platelets, white blood cells [WBCs]) according to recanalization status (A), the presence of clot signs (hyperdense MCA sign on initial computed tomography and/or blooming artifact on initial gradient-echo magnetic resonance images) (B), and the retrieval devices (C).</p

High red blood cell composition in clots is associated with successful recanalization during intra-arterial thrombectomy - Fig 2

<p>Comparison of clot composition (red blood cells [RBCs], fibrin/platelets, white blood cells [WBCs]) in total retrieved clots (A) and in total included patients according to stroke subtype. LAA: Large artery atherosclerosis.</p

Frequencies of clot types by the stroke subtypes in all retrieved clots.

<p>Frequencies of clot types by the stroke subtypes in all retrieved clots.</p

Synergy of circulating miR-212 with markers for cardiovascular risks to enhance estimation of atherosclerosis presence

<div><p>Synergy of specific microRNAs (miRNAs) with cardiovascular risk factors to estimate atherosclerosis presence in ischemic stroke patients has not been investigated. The present study aimed to identify atherosclerosis-related circulating miRNAs and to evaluate interaction with other cardiovascular markers to improve the estimation of atherosclerosis presence. We performed a miRNA profiling study using serum of 15 patients with acute ischemic stroke who were classified by the presence of no (n = 8) or severe (n = 7) stenosis on intracranial and extracranial vessels, which identified miR-212, -372, -454, and -744 as miRNAs related with atherosclerosis presence. Of the 4 miRNAs, only miR-212 showed a significant increase in expression in atherosclerosis patients in a validation study (atherosclerotic patients, n = 32, non-atherosclerotic patients, n = 33). Hemoglobin A1c, a high-density lipoprotein cholesterol, and lipoprotein(a), both established risk markers, were independently related with atherosclerosis presence in the validation population. miR-212 enhanced the accuracy of atherosclerosis presence by the three existing markers (three markers, 78.5%; three markers+miR-212, 84.6%, <i>P</i><0.05) and significantly added to the area under the receiver operating characteristic curve (three markers, 0.8258; three markers+miR-212, 0.8646, <i>P</i><0.05). The inclusion of miR-212 increased the reclassification index calculated using net reclassification improvement (0.4527, <i>P</i><0.05) and integrated discrimination improvement (0.0737, <i>P</i><0.05). We identified circulating miR-212 as a novel marker of atherosclerosis. miR-212 enhanced the estimation of atherosclerosis presence in combination with hemoglobin A1c, high-density lipoprotein cholesterol, and lipoprotein(a). Thus, miR-212 is expected to improve the estimation of atherosclerosis using peripheral blood of patients.</p></div

Synergy of circulating miR-212 with markers for cardiovascular risks to enhance estimation of atherosclerosis presence

<div><p>Synergy of specific microRNAs (miRNAs) with cardiovascular risk factors to estimate atherosclerosis presence in ischemic stroke patients has not been investigated. The present study aimed to identify atherosclerosis-related circulating miRNAs and to evaluate interaction with other cardiovascular markers to improve the estimation of atherosclerosis presence. We performed a miRNA profiling study using serum of 15 patients with acute ischemic stroke who were classified by the presence of no (n = 8) or severe (n = 7) stenosis on intracranial and extracranial vessels, which identified miR-212, -372, -454, and -744 as miRNAs related with atherosclerosis presence. Of the 4 miRNAs, only miR-212 showed a significant increase in expression in atherosclerosis patients in a validation study (atherosclerotic patients, n = 32, non-atherosclerotic patients, n = 33). Hemoglobin A1c, a high-density lipoprotein cholesterol, and lipoprotein(a), both established risk markers, were independently related with atherosclerosis presence in the validation population. miR-212 enhanced the accuracy of atherosclerosis presence by the three existing markers (three markers, 78.5%; three markers+miR-212, 84.6%, <i>P</i><0.05) and significantly added to the area under the receiver operating characteristic curve (three markers, 0.8258; three markers+miR-212, 0.8646, <i>P</i><0.05). The inclusion of miR-212 increased the reclassification index calculated using net reclassification improvement (0.4527, <i>P</i><0.05) and integrated discrimination improvement (0.0737, <i>P</i><0.05). We identified circulating miR-212 as a novel marker of atherosclerosis. miR-212 enhanced the estimation of atherosclerosis presence in combination with hemoglobin A1c, high-density lipoprotein cholesterol, and lipoprotein(a). Thus, miR-212 is expected to improve the estimation of atherosclerosis using peripheral blood of patients.</p></div

Stability values of candidate reference miRNAs calculated with NormFinder.

<p>Stability values of candidate reference miRNAs calculated with NormFinder.</p

Multivariate analysis using 4 target miRNAs and markers for cardiovascular risk factors.

<p>Multivariate analysis using 4 target miRNAs and markers for cardiovascular risk factors.</p