High glycemic albumin representing prestroke glycemic variability is associated with hemorrhagic transformation in patients receiving intravenous thrombolysis.
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ABSTRACT:
SUBMITTER: Lee SH
PROVIDER: S-EPMC8755722 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background: Clinical and biological risk factors for hemorrhagic transformation (HT) after intravenous thrombolysis (IT) have been well-established in several registries. The added value of magnetic resonance imaging (MRI) variables has been studied in small samples, and is controversial. We aimed to assess the added value of MRI variables in HT, beyond that of clinical and biological factors. Methods: We enrolled 474 consecutive patients with brain infarction treated by IT alone at our primary stroke center between January 2011 and August 2017. Baseline demographic, clinical, biological, and imaging characteristics were collected. MRI variables were: brain infarction volume in cm3; parenchymal fluid attenuated inversion recovery (FLAIR) hyperintensity; FLAIR hyperintense vessel signs; number of microbleeds; subcortical white matter hyperintensity; and thrombus length. Results: Overall, 301 patients were included out of 474 (64%). The main causes of exclusion were combined thrombectomy (n = 98) and no MRI before IT (n = 44). In the bivariate analysis, HT was significantly associated with the presence of more FLAIR hyperintense vessel signs, thrombus length (>8 mm), and larger brain infarction volume (diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) < 500 × 10-6 mm2/s). In the multivariable analysis, only brain infarction volume was significantly associated with HT. The discrimination value of the multivariable model, including both the DWI volume and the clinical model (area under the receiver operating characteristic curve, 0.80; 95% confidence interval 0.74-0.86), was improved significantly compared with the model based only on clinical variables (P = 0.012). Conclusions: Brain infarction volume on DWI was the only MRI variable that added value to clinico biological variables for predicting HT after IT.
| S-EPMC6719609 | biostudies-literature
Project description:Previous studies have identified a diverse set of predisposing factors for the occurrence of hemorrhagic transformation (HT), but the independent clinical predictors of HT after intraarterial thrombolysis have not been determined. In this retrospective study, we investigated the characteristics of patients with or without HT who had received intra-arterial thrombolysis therapy, using biochemical analysis, renal function test, routine blood test, blood lipid test, coagulation blood test, liver function test, random blood glucose test, time-window for intra-arterial thrombolysis, recanalization, National Institutes of Health Stroke Scale (NIHSS) score and systolic blood pressure before intra-arterial thrombolysis. The mortality rates were similar in the HT and non-HT groups (P = 0.944). In the single-factor analysis, patients with a higher globulin level (P <0.002), prothrombin time activity percentage (PTA; P = 0.026), and NIHSS score (P = 0.002), had a significantly increased risk of developing HT. In the multifactor logistic regression model involving globulin level, PTA, white blood cell count, and NIHSS score, the globulin level (P <0.001; OR, 1.185; 95% confidence interval [CI], 1.090-1.288), PTA (P = 0.018; OR, 1.016; 95% CI, 1.003-1.029), white blood cell count (P = 0.025; OR, 1.097; 95% CI, 1.012-1.190) and NIHSS score (P = 0.003; OR, 1.097; 95% CI, 1.031-1.166) were significantly increased in the HT group. The increase in globulin level is an independent risk factor for HT in patients receiving intra-arterial thrombolysis. The possible mechanisms may involve inflammatory cytokines, matrix metalloproteinase 9, and positive acute-phase reactants synthesized by the liver.
| S-EPMC5562614 | biostudies-other
Project description:AimsThe canonical Wnt signaling pathway plays an essential role in blood-brain barrier integrity and intracerebral hemorrhage in preclinical stroke models. Here, we sought to explore the association between canonical Wnt signaling and hemorrhagic transformation (HT) following intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients as well as to determine the underlying cellular mechanisms.Methods355 consecutive AIS patients receiving IVT were included. Blood samples were collected on admission, and HT was detected at 24 hours after IVT. 117 single-nucleotide polymorphisms (SNPs) of 28 Wnt signaling genes and exon sequences of 4 core cerebrovascular Wnt signaling components (GPR124, RECK, FZD4, and CTNNB1) were determined using a customized sequencing chip. The impact of identified genetic variants was further studied in HEK 293T cells using cellular and biochemical assays.ResultsDuring the study period, 80 patients experienced HT with 27 parenchymal hematoma (PH). Compared to the non-PH patients, WNT7A SNPs (rs2163910, P = .001, OR 2.727; rs1124480, P = .002, OR 2.404) and GPR124 SNPs (rs61738775, P = .012, OR 4.883; rs146016051, P < .001, OR 7.607; rs75336000, P = .044, OR 2.503) were selectively enriched in the PH patients. Interestingly, a missense variant of GPR124 (rs75336000, c.3587G>A) identified in the PH patients resulted in a single amino acid alteration (p.Cys1196Tyr) in the intracellular domain of GPR124. This variant substantially reduced the activity of WNT7B-induced canonical Wnt signaling by decreasing the ability of GPR124 to recruit cytoplasmic DVL1 to the cellular membrane.ConclusionVariants of WNT7A and GPR124 are associated with increased risk of PH in patients with AIS after intravenous thrombolysis, likely through regulating the activity of canonical Wnt signaling.
| S-EPMC7804912 | biostudies-literature
Project description:Background: Hemorrhagic transformation (HT) is an important complication of intravenous thrombolysis with alteplase. HT can show a wide range from petechiae to parenchymal hematoma with mass effect with varying clinical impact. We studied clinical and imaging characteristics of patients with HT and evaluated whether different types of HT are associated with functional outcome. Methods: We performed a post-hoc analysis of WAKE-UP, a multicenter, randomized, placebo-controlled trial of MRI-guided intravenous alteplase in unknown onset stroke. HT was assessed on follow-up MRI or CT and diagnosed as hemorrhagic infarction type 1 and type 2 (HI1 and HI2, combined as HI), and parenchymal hemorrhage type 1 and type 2 (PH1 and PH2, combined as PH). Severity of stroke symptoms was assessed using the National Institutes of Health Stroke Scale (NIHSS) at baseline. Stroke lesion volume was measured on baseline diffusion weighted imaging (DWI). Primary endpoint was a favorable outcome defined as a modified Rankin Scale score 0-1 at 90 days. Results: Of 483 patients included in the analysis, 95 (19.7%) showed HI and 21 (4.4%) had PH. Multiple logistic regression analysis identified treatment with alteplase (OR, 2.08 [95% CI, 1.28-3.40]), baseline NIHSS score (OR, 1.11 [95% CI, 1.05-1.17]), DWI lesion volume (OR, 1.03 [95% CI, 1.01-1.05]), baseline glucose levels (OR, 1.01 [95% CI, 1.00-1.01]) and atrial fibrillation (OR, 3.02 [95% CI, 1.57-5.80]) as predictors of any HT. The same parameters predicted HI. Predictors of PH were baseline NIHSS score (OR, 1.11 [95% CI, 1.01-1.22]) and as a trend treatment with alteplase (OR, 2.40 [95% CI, 0.93-6.96]). PH was associated with lower odds of favorable outcome (OR 0.25, 95% [CI 0.05-0.86]), while HI was not. Conclusion: Our results indicate that HI is associated with stroke severity, cardiovascular risk factors and thrombolysis. PH is a rare complication, more frequent in severe stroke and with thrombolysis. In contrast to HI, PH is associated with worse functional outcome. The impact of HT after MRI-guided intravenous alteplase for unknown onset stroke on clinical outcome is similar as in the trials of stroke thrombolysis within a known early time-window.
| S-EPMC7483750 | biostudies-literature
Project description:Background: We investigated whether prestroke glycemic variability, represented by glycated albumin (GA), affects the initial stroke severity and infarct volume in diabetic patients presenting with acute ischemic stroke. Methods: We evaluated a total of 296 acute ischemic stroke patients with diabetes mellitus who were hospitalized within 48 h of stroke onset. GA was measured in all acute ischemic stroke patients consecutively during the study period. The primary outcome was the initial National Institute Health Stroke Scale (NIHSS) score. The secondary outcome was infarct volume on diffusion-weighted imaging, which was performed within 24 h of stroke onset. Higher GA (?16.0%) was determined to reflect glycemic fluctuation prior to ischemic stroke. Results: The number of patients with higher GA was 217 (73.3%). The prevalence of a severe initial NIHSS score (>14) was higher in patients with higher GA than in those with lower GA (3.8% vs. 15.7%, p = 0.01). The proportion of participants in the highest quartile of infarct volume was higher in the higher GA group (11.4% vs. 36.4%, p < 0.001). A multivariable analysis showed that higher GA was significantly associated with a severe NIHSS score (odds ratio, [95% confidence interval], 7.99 [1.75-36.45]) and large infarct volume (3.76 [1.05-13.45]). Conclusions: Prestroke glucose variability estimated by GA was associated with an increased risk of severe initial stroke severity and large infarct volume in acute ischemic stroke patients with diabetes mellitus.
| S-EPMC7186307 | biostudies-literature
Project description:About 30%-40% of stroke patients are taking antiplatelet at the time of their strokes, which might increase the risk of symptomatic intracranial hemorrhage (SICH) with intravenous tissue plasminogen activator (IV-TPA) therapy. We aimed to assess the effect of prestroke antiplatelet on the SICH risk and functional outcome in Koreans treated with IV-TPA.From a prospective stroke registry, we identified patients treated with IV-TPA between October 2009 and November 2014. Prestroke antiplatelet use was defined as taking antiplatelet within 7 days before the stroke onset. The primary outcome was SICH. Secondary outcomes were discharge modified Rankin Scale (mRS) score and in-hospital mortality.Of 1,715 patients treated with IV-TPA, 441 (25.7%) were on prestroke antiplatelet. Prestroke antiplatelet users versus non-users were more likely to be older, to have multiple vascular risk factors. Prestroke antiplatelet use was associated with an increased risk of SICH (5.9% vs. 3.0%; adjusted odds ratio [OR] 1.79 [1.05-3.04]). However, at discharge, the two groups did not differ in mRS distribution (adjusted OR 0.90 [0.72-1.14]), mRS 0-1 outcome (34.2% vs. 33.7%; adjusted OR 1.27 [0.94-1.72), mRS 0-2 outcome (52.4% vs. 52.9%; adjusted OR 1.21 [0.90-1.63]), and in-hospital mortality (6.1% vs. 4.2%; adjusted OR 1.19 [0.71-2.01]).Despite an increased risk of SICH, prestroke antiplatelet users compared to non-users had comparable functional outcomes and in-hospital mortality with IV-TPA therapy. Our results support the use of IV-TPA in eligible patients taking antiplatelet therapy before their stroke onset.
| S-EPMC5066428 | biostudies-other
Project description:BACKGROUND:A reliable scoring tool to detect the risk of intracerebral hemorrhage (ICH) after intravenous thrombolysis for ischemic stroke is warranted. The present study was designed to develop and validate a new nomogram for individualized prediction of the probability of hemorrhagic transformation (HT) in patients treated with intravenous (IV) recombinant tissue plasminogen activator (rt-PA). METHODS:We enrolled patients who suffered from acute ischemic stroke (AIS) with IV rt-PA treatment in our emergency green channel between August 2016 and July 2018. The main outcome was defined as any type of intracerebral hemorrhage according to the European Cooperative Acute Stroke Study II (ECASS II). All patients were randomly divided into two cohorts: the primary cohort and the validation cohort. On the basis of multivariate logistic model, the predictive nomogram was generated. The performance of the nomogram was evaluated by Harrell's concordance index (C-index) and calibration plot. RESULTS:A total of 194 patients with complete data were enrolled, of whom 131 comprised the primary cohort and 63 comprised the validation cohort, with HT rate 12.2, 9.5% respectively. The score of chronic disease scale (CDS), the global burden of cerebral small vascular disease (CSVD), National Institutes of Health Stroke Scale (NIHSS) score???13, and onset-to-treatment time (OTT)???180 were detected important determinants of ICH and included to construct the nomogram. The nomogram derived from the primary cohort for HT had C- Statistics of 0.9562 and the calibration plot revealed generally fit in predicting the risk of HT. Furthermore, we made a comparison between our new nomogram and several other risk-assessed scales for HT with receiver operating characteristic (ROC) curve analysis, and the results showed the nomogram model gave an area under curve of 0.9562 (95%CI, 0.9221-0.9904, P?<?0.01) greater than HAT (Hemorrhage After Thrombolysis), SEDAN (blood Sugar, Early infarct and hyper Dense cerebral artery sign on non-contrast computed tomography, Age, and NIHSS) and SPAN-100 (Stroke Prognostication using Age and NIHSS) scores. CONCLUSIONS:This proposed nomogram based on the score of CDS, the global burden of CSVD, NIHSS score???13, and OTT???180 gives rise to a more accurate and more comprehensive prediction for HT in patients with ischemic stroke receiving IV rt-PA treatment.
| S-EPMC7685652 | biostudies-literature
Project description:Serum albumin levels has been shown to predict outcome in ischemic stroke patients. We aimed to investigate the relationship between serum albumin levels and hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) in patients with acute stroke. 428 patients receiving intravenous rt-PA therapy were included from 2013 to 2016 and were categorized into two groups: low level (<35 mmol/L) and normal level (35-55 mmol/L) group. Demographic, clinical and laboratory information, HT and functional outcomes were analyzed. Hemorrhagic transformation was comfirmed by CT scan or MRI within 7 days. The functional outcome was measured by modified Barthel Index and modified Rankin Scale (mRS) at 7 days and 90 days. Patients with lower albumin had significantly higher risk of HT (15.3% vs. 4.2%, P = 0.002) and sICH (6.2% vs. 1.4%, P = 0.03) than those with normal level of albumin. In univariate analysis for HT, atrial fibrillation and level of albumin were identified as significant factors (P < 0.001, P = 0.001 respectively). On multivariate logistic regression analysis, serum albumin level remained independent predictor of HT (OR = 4.369, 95% CI = 1.626-11.742, P = 0.003). No significantly difference were found in the clinical outcome at 7 days and 90 days between two groups (P > 0.05). Low level of serum albumin within 24 hours may be an independent predictor of post-thrombolytic HT.
| S-EPMC5552877 | biostudies-other
Project description:Intravenous thrombolysis using recombinant tissue plasminogen activator (tPA) remains the primary treatment for patients with acute ischemic stroke (AIS). However, the mechanism of tPA-related hemorrhagic transformation (HT) remains poorly understood. Elevation of histidine-rich glycoprotein (HRG) expression was detected by nano-liquid chromatography tandem mass spectrometry at 1 h following tPA infusion as compared to baseline prior to tPA infusion (discovery cohort, n=10), which was subsequently confirmed in a validation cohort (n=157) by ELISA. Surprisingly, no elevation of HRG was detected in individuals who subsequently developed HT. During in vitro experiments, HRG reduced neutrophil NETosis, inflammatory cytokine production, and migration across the blood-brain barrier induced by tPA. In a photothrombotic murine AIS model, HRG administration ameliorated HT with delayed thrombolysis, by inhibiting neutrophil immune infiltration and downregulating proinflammatory signaling pathways. Neutrophil depletion or NETosis inhibition also alleviated HT, whereas HRG siRNA treatment exacerbated HT. In conclusion, fluctuations in HRG levels may reflect tPA therapy and its associated HT. The inhibitory effect of HRG on neutrophils may counteract tPA-induced immune abnormalities and HT in patients with AIS.
| S-SCDT-10_1038-S44321-024-00117-Y | biostudies-other
Project description:Background and purposePatients with low estimated glomerular filtration rate (eGFR) and proteinuria may be at increased risk for stroke. This study investigated whether low eGFR and proteinuria are outcome predictors in stroke patients treated with intravenous thrombolysis.MethodsWe studied 432 consecutive stroke patients who received thrombolysis from January 2006 to December 2012, in Taiwan. Unfavorable outcome was defined as modified Rankin scale ?2 at 3 months after stroke. Proteinuria was classified as negative or trace, mild, and moderate to severe. Using logistic regression analysis, we identified independent factors for unfavorable outcome after thrombolysis.ResultsOf all patients, 32.7% had proteinuria. Patients with proteinuria were older, had higher frequencies of diabetes mellitus, hyperlipidemia, atrial fibrillation, lower eGFR, and greater severity of stroke upon admission than those without proteinuria. Proteinuria, not low eGFR, was an independent predictor for unfavorable outcome for stroke (OR?=?2.00 for mild proteinuria, p?=?0.035; OR?=?2.54 for moderate to severe proteinuria, p?=?0.035). However, no clear relationship was found between proteinuria and symptomatic hemorrhage after thrombolysis.ConclusionsProteinuria is an independent predictor of unfavorable outcome for acute ischemic stroke in patients treated with intravenous thrombolysis, indicating the crucial role of chronic kidney disease on the effectiveness of thrombolysis.
| S-EPMC3838417 | biostudies-literature