Elevated glucose is associated with hemorrhagic transformation after mechanical thrombectomy in acute ischemic stroke patients with severe pretreatment hypoperfusion.
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ABSTRACT:
SUBMITTER: Laredo C
PROVIDER: S-EPMC7324383 | biostudies-literature | 2020 Jun
REPOSITORIES: biostudies-literature
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Elevated glucose is associated with hemorrhagic transformation after mechanical thrombectomy in acute ischemic stroke patients with severe pretreatment hypoperfusion.
Laredo Carlos C Renú Arturo A Llull Laura L Tudela Raúl R López-Rueda Antonio A Urra Xabier X Macías Napoleón G NG Rudilosso Salvatore S Obach Víctor V Amaro Sergio S Chamorro Ángel Á
Scientific reports 20200629 1
Several pretreatment variables such as elevated glucose and hypoperfusion severity are related to brain hemorrhage after endovascular treatment of acute stroke. We evaluated whether elevated glucose and severe hypoperfusion have synergistic effects in the promotion of parenchymal hemorrhage (PH) after mechanical thrombectomy (MT). We included 258 patients MT-treated who had a pretreatment computed tomography perfusion (CTP) and a post-treatment follow-up MRI. Severe hypoperfusion was defined as ...[more]
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Project description:Serum biomarkers are associated with hemorrhagic transformation and brain edema after cerebral infarction. However, whether serum biomarkers predict hemorrhagic transformation in large vessel occlusion stroke even after mechanical thrombectomy, which has become widely used, remains uncertain. In this prospective study, we enrolled patients with large vessel occlusion stroke in the anterior circulation. We analyzed 91 patients with serum samples obtained on admission. The levels of matrix metalloproteinase-9 (MMP-9), amyloid precursor protein (APP) 770, endothelin-1, S100B, and claudin-5 were measured. We examined the association between serum biomarkers and hemorrhagic transformation within one week. Fifty-four patients underwent mechanical thrombectomy, and 17 patients developed relevant hemorrhagic transformation (rHT, defined as hemorrhagic changes ≥ hemorrhagic infarction type 2). Neither MMP-9 (no rHT: 46 ± 48 vs. rHT: 15 ± 4 ng/mL, P = 0.30), APP770 (80 ± 31 vs. 85 ± 8 ng/mL, P = 0.53), endothelin-1 (7.0 ± 25.7 vs. 2.0 ± 2.1 pg/mL, P = 0.42), S100B (13 ± 42 vs. 12 ± 15 pg/mL, P = 0.97), nor claudin-5 (1.7 ± 2.3 vs. 1.9 ± 1.5 ng/mL, P = 0.68) levels on admission were associated with subsequent rHT. When limited to patients who underwent mechanical thrombectomy, the level of claudin-5 was higher in patients with rHT than in those without (1.2 ± 1.0 vs. 2.1 ± 1.7 ng/mL, P = 0.0181). APP770 levels were marginally higher in patients with a midline shift ≥ 5 mm than in those without (79 ± 29 vs. 97 ± 41 ng/mL, P = 0.084). The predictive role of serum biomarkers has to be reexamined in the mechanical thrombectomy era because some previously reported serum biomarkers may not predict hemorrhagic transformation, whereas the level of APP770 may be useful for predicting brain edema.
| S-EPMC8366990 | biostudies-literature
Project description:Managing endovascular thrombectomy (ET) in diabetic ischemic stroke (IS) with novel anticoagulants is challenging due to putative risk of intracerebral hemorrhage. The study evaluates increased hemorrhagic transformation (HT) risk in Rivaroxaban-treated diabetic rats post ET. Diabetes was induced in male Sprague-Dawley rats by intraperitoneal injection of 60 mg/kg streptozotocin. After 4-weeks, rats were pretreated orally with 30 mg/kg Rivaroxaban/saline; prothrombin time was monitored. IS and ET was induced after 1 h, by thread-induced transient middle cerebral artery occlusion (tMCAO) that mimicked mechanical ET for proximal MCA occlusion at 60 min. After 24 h reperfusion, infarct volumes, HT, blood-brain barrier (BBB) permeability, tight junction at peri-ischemic lesion and matrix metalloproteinase-9 (MMP-9) activity was measured. Diabetic rats seemed to exhibit increased infarct volume and HT at 24 h after ET than normal rats. Infarct volumes and functional outcomes did not differ between Rivaroxaban and diabetic control groups. A significant increase in HT volumes and BBB permeability under Rivaroxaban treatment was not detected. Compared to diabetic control group, neither the occludin expression was remarkably lower in the Rivaroxaban group nor the MMP-9 activity was higher. Together, Rivaroxaban does not increase HT after ET in diabetic rats with proximal MCA occlusion, since Rivaroxaban has fewer effects on post-ischemic BBB permeability.
| S-EPMC5943582 | biostudies-literature
Project description:BackgroundElevated International Normalized Ratio (INR) is a marker of coagulopathy, but its impact on outcomes following mechanical thrombectomy (MT) in patients with stroke is unclear. This study investigates the impact of mild INR elevations on clinical outcomes following MT.MethodsIn this retrospective cohort study, consecutive patients with stroke treated with MT were identified from 2015 to 2020 at a Comprehensive Stroke Center. Demographic information, past medical history, INR, National Institutes of Health Stroke Scale score, use of tissue plasminogen activator, and last known normal to arteriotomy time were recorded. Outcome measures included modified Thrombolysis in Cerebral Infarction (mTICI) score, modified Rankin Scale (mRS) score at 90 days, and intracerebral hemorrhage (ICH). Patients were divided into two groups: normal INR (0.8-1.1) and mildly elevated INR (1.2-1.7).ResultsA total of 489 patients were included for analysis, of which 349 had normal INR and 140 had mildly elevated INR. After multivariable adjustments, mildly elevated INR was associated with lower odds of excellent outcomes (mRS 0-1, OR 0.24, p=0.009), lower odds of functional independence (mRS 0-2, OR 0.38, p=0.038), and higher odds of 90-day mortality (OR 3.45, p=0.018). Elevated INR was not associated with a higher likelihood of ICH, and there were no differences in rates of HI1, HI2, PH1, or PH2 hemorrhagic transformations; however, elevated INR was associated with significantly higher odds of 90-day mortality in patients with ICH (OR 6.22, p=0.024). This effect size was larger than in patients without ICH (OR 3.38, p<0.001).ConclusionIn patients with stroke treated with MT, mildly elevated INR is associated with worse clinical outcomes after recanalization and may worsen the mortality risk of hemorrhagic transformations.
| S-EPMC10593142 | biostudies-literature
Project description:Although intravenous thrombolysis increases the probability of a good functional outcome in carefully selected patients with acute ischemic stroke, a substantial proportion of patients who receive thrombolysis do not have a good outcome. Several recent trials of mechanical thrombectomy appear to indicate that this treatment may be superior to thrombolysis. We therefore conducted a systematic review and meta-analysis to evaluate the clinical effectiveness and safety of new-generation mechanical thrombectomy devices with intravenous thrombolysis (if eligible) compared with intravenous thrombolysis (if eligible) in patients with acute ischemic stroke caused by a proximal intracranial occlusion. We systematically searched seven databases for randomized controlled trials published between January 2005 and March 2015 comparing stent retrievers or thromboaspiration devices with best medical therapy (with or without intravenous thrombolysis) in adults with acute ischemic stroke. We assessed risk of bias and overall quality of the included trials. We combined the data using a fixed or random effects meta-analysis, where appropriate. We identified 1579 studies; of these, we evaluated 122 full-text papers and included five randomized control trials (n=1287). Compared with patients treated medically, patients who received mechanical thrombectomy were more likely to be functionally independent as measured by a modified Rankin score of 0-2 (odds ratio, 2.39; 95% confidence interval, 1.88-3.04; I2=0%). This finding was robust to subgroup analysis. Mortality and symptomatic intracerebral hemorrhage were not significantly different between the two groups. Mechanical thrombectomy significantly improves functional independence in appropriately selected patients with acute ischemic stroke.
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Project description:Disability or death occurs more frequently in patients with hemorrhagic transformation (HT) after ischemic stroke. In rat models of stroke, sulfonylurea (SU) drugs such as glibenclamide (adopted US name, glyburide) confer protection against swelling and HT through actions on the novel SUR1-regulated NC(Ca-ATP) channel. Here, we sought to determine whether the use of SU drugs in patients with diabetes mellitus (DM) presenting with acute ischemic stroke might influence the incidence of HT.We retrospectively analyzed data on 220 patients with DM who presented with acute ischemic stroke, 43 of whom were managed with and continued to receive SU drugs, and 177 of whom were managed without (controls).During a median length of stay in hospital of 11 days, 20 control patients (11%) experienced symptomatic HT (sHT), whereas no patient in the SU group experienced sHT (p = 0.016). No patient in the SU group died, compared to 18 (10%) in the control group (p = 0.027). Similarly favorable outcomes were observed after matching for baseline imbalances and excluding outliers. In support of the proposed mechanism, we present a case of sHT in which an analysis of brain tissues obtained intraoperatively showed prominent upregulation of SUR1, the target of SU drugs, in microvessels and neurons.We conclude that, in diabetic patients with acute ischemic stroke, prior and continued use of SU drugs is associated with reduced sHT compared to those whose treatment regimen does not include SU drugs.
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Project description:Glucose and platelet are two easily obtained clinical indicators; the present research aimed to demonstrate their association with hemorrhagic transformation (HT) in acute ischemic stroke (AIS) patients without thrombolytic or thrombectomy therapy. This was a single-center retrospective study. Patients who were diagnosed with HT after AIS were included in the HT group. Meanwhile, using the propensity score matching (PSM) approach, with a ratio of 1:2, matched patients without HT were included in the non-HT group. Serum G/P levels were measured on the first morning after admission (at least eight hours after the last meal). Characteristics were compared between the two groups. Multivariate logistic regression was used to determine the independent relationship between G/P and HT after AIS, with G/P being divided into quartiles. From January 2013 to March 2022, we consecutively included 643 AIS patients with HT (426/643 [66.25%] with HI and 217/643 [33.75%] with PH), and 1282 AIS patients without HT, at the First Affiliated Hospital of Wenzhou Medical University. The HT group had higher G/P levels than the non-HT group (0.04 ± 0.02 vs. 0.03 ± 0.02, p < 0.001). However, there was no difference in G/P levels between HI and PH subgroups (0.04 ± 0.02 vs. 0.04 ± 0.02, p > 0.05). Moreover, the G/P levels were divided into quartiles (Q1 ≤ 0.022; Q2 = 0.023–0.028; Q3 = 0.029–0.039; Q4 ≥ 0.040), with Q1 being settled as the reference layer. After controlling the confounders, multivariate regression analyses showed that the Q4 layer (Q4: G/P ≥ 0.040) was independently associated with elevated HT risk (odds ratio [OR] = 1.85, 95% CI = 1.31–2.63, p < 0.001). G/P levels on admission were independently associated with HT risk in AIS patients. In clinical practice, adequate attention should be paid to AIS patients with elevated G/P levels (G/P ≥ 0.040).
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Project description:Background and purposeEarly differentiation of contrast staining from hemorrhagic transformation in patients with acute ischemic stroke who have undergone endovascular treatment is critical in preventing the delayed administration of antiplatelet agents. We aimed to demonstrate the usefulness of an immediate postinterventional DWI protocol including B0 and gradient recalled-echo sequences to discriminate those 2 conditions through phantom and preliminary retrospective patient studies.Materials and methodsOn 3T MR imaging, the signal intensities of the phantom models consisting of iodinated contrast agents diluted with normal saline and arterial blood were compared using T1WI, T2WI, and gradient recalled-echo sequences. A total 17 patients (8 with hemorrhagic transformation and 9 with contrast staining; 8 men and 9 women; mean age, 72.00 ± 10.91 years; range, 52-90 years) who underwent mechanical thrombectomy for acute ischemic stroke and showed newly appearing hyperdense lesions on immediate (<24 hours) postinterventional nonenhanced CT scans were included in this study. Immediate postinterventional DWI of patients were compared.ResultsIn the phantom study, iodinated contrast agents diluted with normal saline showed minimal signal drop, while those diluted with arterial blood demonstrated dark signal intensity in the T2WI and gradient recalled-echo sequences. In the patient study, all hemorrhagic transformations and none of the contrast staining demonstrated dark or low signal (<gray matter) intensities similar to those of the vessel in the B0-DWI and gradient recalled-echo images.ConclusionsAccording to our preliminary results, contrast staining might be differentiated from hemorrhagic transformation using an immediate postinterventional DWI protocol including gradient recalled-echo sequences. It might be possible to expedite establishment of postinterventional medical treatment strategy.
| S-EPMC7655397 | biostudies-literature
Project description:Background and Purpose- We aimed to compare functional and procedural outcomes of patients with acute ischemic stroke with none-to-minimal (modified Rankin Scale [mRS] score, 0-1) and moderate (mRS score, 2-3) prestroke disability treated with mechanical thrombectomy. Methods- Consecutive adult patients undergoing mechanical thrombectomy for an anterior circulation stroke were prospectively identified at 2 comprehensive stroke centers from 2012 to 2018. Procedural and 90-day functional outcomes were compared among patients with prestroke mRS scores 0 to 1 and 2 to 3 using χ2, logistic, and linear regression tests. Primary outcome and significant differences in secondary outcomes were adjusted for prespecified covariates. Results- Of 919 patients treated with mechanical thrombectomy, 761 were included and 259 (34%) patients had moderate prestroke disability. Ninety-day mRS score 0 to 1 or no worsening of prestroke mRS was observed in 36.7% and 26.7% of patients with no-to-minimal and moderate prestroke disability, respectively (odds ratio, 0.63 [0.45-0.88], P=0.008; adjusted odds ratio, 0.90 [0.60-1.35], P=0.6). No increase in the disability at 90 days was observed in 22.4% and 26.7%, respectively. Rate of symptomatic intracerebral hemorrhage (7.3% versus 6.2%, P=0.65), successful recanalization (86.7% versus 83.8%, P=0.33), and median length of hospital stay (5 versus 5 days, P=0.06) were not significantly different. Death by 90 days was higher in patients with moderate prestroke disability (14.3% versus 40.3%; odds ratio, 4.06 [2.82-5.86], P<0.001; adjusted odds ratio, 2.83 [1.84, 4.37], P<0.001). Conclusions- One-third of patients undergoing mechanical thrombectomy had a moderate prestroke disability. There was insufficient evidence that functional and procedural outcomes were different between patients with no-to-minimal and moderate prestroke disability. Patients with prestroke disability were more likely to die by 90 days.
| S-EPMC7367056 | biostudies-literature
Project description:Intravenous recombinant tissue plasminogen activator (IV-rtPA) is given in acute ischemic stroke patients to achieve reperfusion. Hemorrhagic transformation (HT) is a serious complication of IV-rtPA treatment and related to blood-brain barrier (BBB) injury. It is unclear whether HT occurs secondary to reperfusion in combination with ischemic BBB injury or is caused by the negative effect of IV-rtPA on BBB integrity. The aim of this study was to establish the association between reperfusion and the occurrence of HT.From the DUST study, patients were selected with admission and follow-up non-contrast CT (NCCT) and CT perfusion (CTP) imaging, and a perfusion deficit in the middle cerebral artery territory on admission. Reperfusion was categorized qualitatively as reperfusion or no-reperfusion by visual comparison of admission and follow-up CTP. Occurrence of HT was assessed on follow-up NCCT. The association between reperfusion and occurrence of HT on follow-up was estimated by calculating odds ratios (ORs) and 95 % confidence intervals (CIs) with additional stratification for IV-rtPA treatment.Inclusion criteria were met in 299 patients. There was no significant association between reperfusion and HT (OR 1.2 95%CI 0.5-3.1). In patients treated with IV-rtPA (n?=?203), the OR was 1.3 (95%CI 0.4-4.0), and in patients not treated with IV-rtPA (n?=?96), the OR was 0.8 (95%CI 0.1-4.5). HT occurred in 14 % of the IV-rtPA patients and in 7 % of patients without IV-rtPA (95%CI of difference -1 to 14 %).Our results suggest that the increased risk of HT after acute ischemic stroke treatment is not dependent on the reperfusion status.
| S-EPMC4648971 | biostudies-literature
Project description:BackgroundsThere have been neither appropriate guidelines nor clinical studies about the use of antithrombotics after hemorrhagic transformation (HT). We sought to find whether the use of antithrombotics after hemorrhagic infarction might be associated with aggravation of HT and neurological deterioration.MethodsThis retrospective study included prospectively registered consecutive patients with acute ischemic stroke and HT in our tertiary stroke center. We focused on the hemorrhagic infarction. Aggravation of HT was defined as either enlargement of the original HT or newly developed HT within the infarcted area by visual analysis. We analyzed relationships between antithrombotics and HT, and neurological deterioration after HT in patients with hemorrhagic infarction. In addition, we assessed composite outcomes including neurological deterioration, vascular events, and death at 1 month after HT. We analyzed relationships between antithrombotics after discharge and composite outcomes within 1 month after HT.Results222 patients were finally analyzed. Of the 150 patients with hemorrhagic infarction, 75 (50.0%) were type 1. The use of warfarin after detection of hemorrhagic infarction more frequently increased aggravation of HT than did the use of antiplatelets (4 of 24 vs 3 of 69; p = 0.094), but neither warfarin nor antiplatelets caused more HT than no medication. In addition, the use of antithrombotics after hemorrhagic infarction was not significantly associated with neurological deterioration after HT. The frequency of composite events at 1 months was significantly lower in patients treated with antithrombotics than those treated without (p = 0.041).ConclusionIn conclusion, the results of this study suggest that antithrombotics can safely be used after hemorrhagic infarction and may not be associated with neurological deterioration and aggravation of HT. Further studies are needed to confirm our results.
| S-EPMC3938534 | biostudies-literature