Deviation From Personalized Blood Pressure Targets Correlates With Worse Outcome After Successful Recanalization.

BACKGROUND: Personalized blood pressure (BP) management for patients with acute ischemic stroke after successful endovascular thrombectomy lacks evidence. We aimed to investigate whether the deviation of BP from cerebral autoregulation limits is associated with worse outcomes. METHODS AND RESULTS: We determined autoregulation by measuring mean velocity index and calculated the percentage of time and the burden (defined as the time-BP area) with BP outside the autoregulatory limits of each subject within 48 hours after endovascular thrombectomy. In total, 91 patients with large vessel occlusion stroke who had achieved successful recanalization were prospectively enrolled between May 2020 and February 2022. The burden with BP outside the autoregulatory limits was associated with poor outcome (modified Rankin Scale score 3-6) at 90 days (adjusted odds ratio, 1.28 [95% CI, 1.03-1.59]). The percentage of time with BP out of the autoregulatory limits was correlated with early neurological deterioration (National Institute of Health Stroke Scale scores increased ≥2 at 7 days) (adjusted odds ratio, 1.38 [95% CI, 1.04-1.83]). The burden of BP that decreased below the autoregulatory lower limit was associated with significant infarct growth (volume of infarct growth >11.6 mL) at 7 days (adjusted odds ratio, 1.21 [95% CI, 1.01-1.44]). The percentage of time that BP exceeded the autoregulatory upper limit was associated with symptomatic intracranial hemorrhage within 48 hours (adjusted odds ratio, 1.55 [95% CI, 1.02-2.34]). CONCLUSIONS: Both the percentage of time and the burden of BP that deviates from the autoregulation-preserved range are associated with unfavorable clinical outcomes. This study highlights the potential benefits of autoregulation-guided BP management strategy after successful recanalization.

Detailed phenotype of RNF213 p.R4810K variant identified by the Chinese patients with acute ischaemic stroke or transient ischaemic attack.

BACKGROUND AND PURPOSE: The ring finger protein 213 gene (RNF213) p.R4810K variant increased the risk of acute ischaemic stroke (AIS) attributable to intracranial arterial stenosis (ICAS) in the Japanese and Korean populations. In this study, we aimed to examine the prevalence of the RNF213 p.R4810K variant in Chinese patients with AIS or transient ischaemic attack and identify the phenotype of the carriers. METHODS: We analysed data from the Third China National Stroke Registry. All included participants were divided into two groups by carrier status of the p.R4810K variant. The aetiological classification was conducted according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. The presence of ICAS and extracranial arterial stenosis (ECAS) was defined as 50%-99% stenosis or occlusion of any intracranial and extracranial artery. Logistic regression models and Cox regression models were used to evaluate the association of the p.R4810K variant with TOAST classification, stenosis phenotypes and clinical outcomes. RESULTS: A total of 10 381 patients were enrolled, among which 56 (0.5%) had the heterozygote GA genotype for p.R4810K. The variant carriers were younger (p=0.01), and more likely to suffer from peripheral vascular disease (p=0.04). The p.R4810K variant was associated with large-artery atherosclerosis (LAA) (adjusted OR=1.94, 95% CI 1.13 to 3.33), anterior circulation stenosis (adjusted OR=2.12, 95% CI 1.23 to 3.65) and ECAS (adjusted OR=2.29, 95% CI 1.16 to 4.51). Nevertheless, the p.R4810K variant was not associated with recurrence, poor functional outcome and mortality at 3 months and 1 year. CONCLUSIONS: The RNF213 p.R4810K variant was associated with LAA, anterior circulation stenosis and ECAS in Chinese patients. Given the low carrying rate and only 1-year follow-up information, caution should be taken to interpret our findings in no statistically significant association between the p.R4810K variant and stroke prognosis in Chinese patients.

Brain symmetry index predicts 3-month mortality in patients with acute large hemispheric infarction.

Quantitative electroencephalography data are helpful to predict outcomes of cerebral infarction patients. The study was performed to evaluate the value of brain symmetry index by quantitative electroencephalography in predicting 3-month mortality of large hemispheric infarction. We studied a prospective, consecutive series of patients with large supratentorial cerebral infarction confirmed within 3 days from the onset in 2 intensive care units from August 2017 to February 2020. The electroencephalography was recorded once admission. The brain symmetry index (BSI) which is divided into BSIfast and BSIslow were calculated for each electrodes pair. The outcome was mortality at 3 months after the onset. A total of 38 patients were included. The subjects were divided into the mortality group (15 patients) and survival group (23 patients). Of the BSIfast and BSIslow at each electrodes pair, higher BSIfastC3-C4, higher BSIslowC3-C4, and higher BSIslowO1-O2 were noticed in the mortality group than that in the survival group at 3 months (P = .001; P = .010; P = .009). Multivariable analysis indicated that BSIfastC3-C4 was an independent predictor of 3-month mortality (odds ratio = 1.059, 95%CI 1.003, 1.119, P = .039). BSIfastC3-C4 could significant predict 3-month mortality (area under curve = 0.805, P = .005). And when we combined BSIfastC3-C4, Glasgow Coma Scale and infarct volume together to predict the 3-month mortality, the predicted value increased (area under curve = 0.840, P = .002). BSIfastC3-C4 could independently predict the 3-month mortality of large hemispheric infarction. The combination marker which includes Glasgow Coma Scale, infarct volume, and BSIfastC3-C4 has a better diagnostic value. Further clinical trials with a large sample size are still needed.

Increased serum uric acid level is associated with better outcome after endovascular treatment for acute ischemic stroke-a prospective cohort study.

Background: The role of serum uric acid (SUA) in affecting outcomes after endovascular treatment (EVT) in patients with ischemic stroke remains unclear. This study investigated the association of SUA with outcomes of patients with acute large vessel occlusion (LVO) who had received EVT. Methods: Patients with acute LVO stroke who underwent EVT within 24 hours were enrolled from a prospective, nationwide registry study. Baseline characteristics and SUA level within 24 hours of EVT were collected. The primary outcome was an excellent 90-day functional outcome [modified Rankin Scale (mRS) score 0-1]. Secondary outcomes included a favorable 90-day outcome (mRS score 0-2), symptomatic intracranial hemorrhage (sICH), and 90-day mortality. The SUA level was analyzed in quartiles and as a continuous variable. We investigated the independent association of SUA with the primary outcome using multivariable logistic regression. Results: Among 780 patients (mean age 64 years; 66.28% males), 230 (29.49%) had an excellent 90-day outcome. A higher SUA level was significantly associated with an excellent outcome in univariate logistic regression (P=0.045) and after adjusting for confounders in multivariate analysis [adjusted odds ratio (aOR), 0.998; 95% confidence interval (CI), 0.996-1.000; P=0.018]. Multivariate logistic regression analysis showed patients with SUA level in the fourth quartile had an excellent 90-day outcome (aOR, 0.367; 95% CI, 0.154-0.876; P=0.024). There was no significant association for SUA level with favorable 90-day outcome, sICH, or 90-day mortality (P>0.05). Conclusions: Among patients with acute LVO type of stroke who received EVT, baseline high SUA level may predict a better 90-day functional outcome.

LC-MS and Transcriptome Analysis of Lipopeptide Biosynthesis by Bacillus velezensis CMT-6 Responding to Dissolved Oxygen.

Dissolved oxygen (DO) is an key factor for lipopeptide fermentation. To better understand the link between oxygen supply and lipopeptide productivity in Bacillus velezensis CMT-6, the mechanism of DO on the synthesis of antimicrobial lipopeptides by Bacillus velezensis CMT-6 was examined. The production of surfactin and iturin of CMT-6 was detected by liquid chromatography-mass spectrometer (LC-MS) under different DO conditions and transcriptome analysis was performed. At 100 and 200 rpm, the lipopeptides productions were 2753.62 mg/L and 3452.90 mg/L, respectively. There was no significant change in the yield of iturin but that of surfactin increased by 64.14%. Transcriptome analysis revealed that the enriched differential genes were concentrated in the GO term of oxidation-reduction process. The marked enrichment of the lipopeptides synthesis pathway, including microbial metabolism in diverse environments and carbon metabolism in the two-component system, were observed. More importantly, the expression levels of the four surfactin synthetase genes increased at higher DO, however, the iturin synthetase gene expression did not. Furthermore, modular surfactin synthetase was overexpressed (between 9- and 49-fold) at 200 rpm but not at 100 rpm, which is suggestive of efficient surfactin assembly resulting in surfactin overproduction. This study provides a theoretical basis for constructing engineering strains with high lipopeptide production to adapt to different DO.

Posterior circulation stroke due to intracranial artery disease in the Chinese population.

BACKGROUND: Little is known about the distribution of the intracranial arteries that are responsible for noncardiogenic posterior circulation stroke (PCS) in the Chinese population. Furthermore, few studies have compared the imaging manifestations and outcomes across PCS due to the disease of different intracranial arteries. Therefore, our aim was to demonstrate the distribution of the intracranial arteries that were responsible for noncardiogenic PCS and to compare the imaging manifestations and outcome across PCS due to the disease of different intracranial arteries. METHODS: We prospectively enrolled 690 patients from 22 Chinese centers with noncardiogenic PCS due to intracranial artery disease. Intracranial artery disease was classified as intracranial vertebral artery disease (IVAD) and intracranial nonvertebral artery disease (INVAD). Clinical-radiologic patterns and outcomes were compared between IVAD and INVAD. RESULTS: INVAD was more frequent than IVAD. Compared to the INVAD group, the IVAD group more frequently had hypertension, coronary heart disease, multiple infarcts, border zone infarcts, territorial infarcts, small cortical infarcts, multilevel infarcts, multisector infarcts, and more often had severe stenosis of the responsible artery, more often presented with decreased alertness, gaze palsy, bilateral limb weakness, ataxia, dysphagia, diplopia, vertigo, and headache. In addition, the IVAD group had a higher National Institutes of Health stroke scale score and modified Rankin Scale score at discharge and more deaths and recurrent ischemic cerebrovascular disease within 1 year of onset. Multivariable Cox regression identified IVAD as an independent predictor of recurrent ischemic cerebrovascular disease. CONCLUSIONS: PCS due to INVAD was more common in the Chinese population. However, PCS due to IVAD had more serious clinical-radiologic patterns and worse outcomes.

Small vessel disease burden may not portend unfavorable outcome after thrombectomy for acute large vessel occlusion.

OBJECTIVES: We aimed to investigate the correlation between an overall cerebral small vessel disease (CSVD) burden and outcomes after endovascular treatment (EVT) for patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). METHODS: In a multicenter registry study, we enrolled patients with EVT for anterior-circulation LVO-stroke. In 3.0-T MR imaging, we assessed 4 CSVD imaging markers, lacunes, white matter hyperintensities, cerebral microbleeds, and enlarged perivascular spaces, each assigned a score of 0 or 1 and summed up to an overall CSVD burden score of 0-4. We dichotomized the overall CSVD severity as none to mild (score 0-2) and moderate to severe (3-4). Primary outcome was 90-day functional dependence or death (modified Rankin Scale (mRS) 3-6). Secondary outcomes included increase in NIH Stroke Scale ≥ 4 within 24 h (early neurological deterioration (END)) and within 7 days, symptomatic intracranial hemorrhage, 90-day mRS 2-6, and 90-day mortality. RESULTS: Among 311 patients (63.0% male; mean age 65.1 ± 12.7 years), 260 (83.6%) had none-to-mild and 51 (16.4%) had moderate-to-severe overall CSVD burden. Moderate-to-severe CSVD burden was not significantly associated with the primary outcome (47.1% versus 45.4%; p > 0.05 in univariate and multivariate logistic regression), or the secondary outcomes except for a higher risk of END (11.8% versus 3.1%; p < 0.05 in multivariate analyses). Sensitivity analyses with 0-1 versus 2-4 of the CSVD burden score, and the score as an ordinal variable, showed similar results. CONCLUSIONS: An overall moderate-to-severe CSVD burden was not associated with 90-day functional dependence or death, after EVT for anterior-circulation LVO. TRIAL REGISTRATION: ChiCTR1900022154 KEY POINTS: • Moderate-to-severe cerebral small vessel disease burden on MRI should not be an exclusion indicator in determining the eligibility of an acute ischemic stroke patient for endovascular treatment.

The role of hypertension and diabetes mellitus on the etiology of middle cerebral artery disease.

BACKGROUND: Ischemic stroke (IS) caused by middle cerebral artery (MCA) disease is the most common type of IS caused by intracranial artery disease in the Chinese population. Hypertension and diabetes mellitus are the common risk factors of cerebral small vessel disease and large artery atherosclerosis (LAA). However, little is known about whether hypertension and diabetes mellitus had different correlations with the small artery occlusion (SAO) and LAA etiology of MCA disease. Therefore, our aim was to identify the predictors of the etiology of MCA disease. METHODS: We consecutively enrolled 967 patients with noncardiogenic IS in unilateral MCA territory. Vascular risk factors and the clinical-radiologic features of IS were analyzed. The etiology of IS were classified as SAO or LAA according to the Stop Stroke Study Trial of Org 10172 in Acute Stroke Treatment classification criteria. Multivariable logistic regression was used to identify the differences in the predictors between SAO and LAA etiology of MCA disease. RESULTS: Multivariable logistic regression identified male and hypertension as the predictors of the SAO etiology of MCA disease, however diabetes mellitus, repeated transient ischemic attack before the stroke, gaze palsy, aphasia, headache at admission, and disability at discharge as the predictors of the LAA etiology of MCA disease. CONCLUSION: Hypertension and diabetes mellitus are related with the different etiology of MCA disease.

Altered Expression of Specific MicroRNAs in Plasma of Aneurysmal Subarachnoid Hemorrhage Patients.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening condition with high disability and mortality. MicroRNAs (miRNAs) are reported to play a modulating role in aSAH. We investigated specific plasma microRNAs (miRNAs) associated with aSAH and gained comprehensive insight into its pathological mechanisms. METHODS: This is a prospective case-control study. We used a two-stage approach, with primary screening and ensuing two-step validation stages. Significantly differentially expressed plasma miRNAs between aSAH patients and neurologically healthy controls were initially screened by microarray analysis. These miRNAs were then validated in two groups of independent cohorts using reverse transcription quantitative real-time polymerase chain reaction assays. Functional annotation of these miRNA targets was performed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. RESULTS: In the primary screening stage, 14 miRNAs were identified as differentially expressed at a significance level of P < 0.05 and fold change >2 between 5 aSAH patients and 5 neurologically healthy controls. In the two validation steps (20 patients vs. 20 control; 40 patients vs. 30 controls), miR-23b-3p, miR-590-5p, miR-20b-5p, miR-142-3p, and miR-29b-3p were found to be significantly down-regulated in patients with aSAH compared with controls. Through these 5 miRNAs, we obtained 32 overlapping target genes, including TGM2, EREG, EDN1, and COL4A1, in three databases that may affect the progression of aSAH. The results of functional annotation revealed mechanisms mainly related to inflammation, smooth muscle cell proliferation and cell adhesion, potentially contributing to the occurrence of aSAH. CONCLUSION: We demonstrate that specific miRNAs in plasma, including miR-23b-3p, miR-590-5p, miR-20b-5p, miR-142-3p, and miR-29b-3p, are significantly down-regulated in aSAH patients and may play a modulating role in its progression.

Posterior circulation stroke due to vertebral artery disease in the Chinese population.

BACKGROUND AND PURPOSE: Little is known about the distribution of the arteries responsible for noncardiogenic posterior circulation stroke due to vertebral artery disease in the Chinese population. Furthermore, few studies have compared the risk factors, imaging manifestations, and outcomes across different types of vertebral artery disease. Therefore, our aim was to compare the differences in the risk factors, imaging manifestations, and outcome across various types of vertebral artery disease. METHODS: We prospectively enrolled 228 patients from 22 Chinese centers with noncardiogenic posterior circulation stroke due to vertebral artery disease. Vertebral artery disease was classified by the involved segments of the responsible vertebral artery, and basilar artery (BA) involvement or not. Risk factors, clinical-radiologic patterns, and outcomes were compared across different types of vertebral artery disease. RESULTS: The intracranial vertebral artery (ICVA) was more frequently involved than was the extracranial vertebral artery (ECVA). The ICVA/ICVA + ECVA group more often presented with hypertension and higher systolic blood pressure than did the ECVA group. Compared with the single-segment-of-vertebral-artery group (SSVA), the group with multiple-segments-of-vertebral-artery (MSVA) involvement or SSVA with BA involvement had more serious clinical-radiologic patterns and worse outcomes. Multivariable Cox regression identified MSVA/SSVA + BA involvement as an independent predictor of recurrent ischemic cerebrovascular events. CONCLUSIONS: The risk factors for ICVA/ICVA + ECVA were different from those of ECVA, and the MSVA/SSVA + BA group had more serious clinical-radiologic patterns and worse outcomes.

Endovascular treatment with or without intravenous alteplase for acute ischaemic stroke due to basilar artery occlusion.

BACKGROUND AND PURPOSE: It remains controversial if endovascular treatment (EVT) can improve the outcome of patients with acute basilar artery occlusion (BAO). This study aims to compare the functional outcomes between EVT with and without intravenous thrombolysis (IVT) first in patients who had acute ischaemic stroke (AIS) due to BAO. METHODS: Patients who had AIS with BAO who underwent EVT within 24 hours of onset were enrolled in this multicentre cohort study, and the efficacy and safety were compared between IVT+EVT and direct EVT. The primary outcome was 90-day functional independence. All outcomes were assessed with adjusted OR (aOR) from the multivariable logistic regression. In addition, a meta-analysis was performed on all recently published pivotal studies on functional independence after EVT in patients with BAO. RESULTS: Of 310 enrolled patients with BAO, 241 (78%) were treated with direct EVT and 69 (22%) with IVT+EVT. Direct EVT was associated with a worse functional outcome (aOR, 0.46 (95% CI 0.24 to 0.85), p=0.01). IVT+EVT was associated with a lower percentage of patients who needed ≥3 passes of stent retriever (10.14% vs 20.75%). The meta-analysis regression revealed a potential positive correlation between bridging with IVT first and functional independence (r=0.14 (95% CI 0.05 to 0.24), p<0.01). CONCLUSIONS: This study showed that compared with direct EVT, EVT with IVT first was associated with better functional outcomes in patients with BAO treated within 24 hours of onset. The meta-analysis demonstrated similar favourable efficacy of IVT first followed by EVT in patients with BAO.

Prior Antithrombotic Therapy is Associated with Increased Risk of Death in Patients with Intracerebral Hemorrhage: Findings from the Chinese Stroke Center Alliance (CSCA) Study.

The association of preceding antithrombotic therapy with outcomes of patients with intracerebral hemorrhage (ICH) has not been well clarified. We investigated the characteristics and associations of prior antithrombotic therapy (oral anticoagulants, antiplatelet therapy or both) in outcomes of in-hospital patients with ICH. Data were derived from the Chinese Stroke Center Alliance (CSCA) database. Enrolled patients were categorized by the different types of preceding antithrombotic therapy: antiplatelet therapy (APT), oral coagulants (OAs), both OAs and APT use and no-antithrombotic therapy (no-ATT). Among 85705 patients enrolled, 4969 (5.8%), 720 (0.8%), 905 (1.1%) and 79111 (92.3%) patients were on APT, OAs, both OAs and APT, and non-ATT respectively prior to their admission. Crude in-hospital death was 149(3.0%), 41(5.7%), 46(5.1%) and 1781(2.3%) in APT, OAs, both OAs and APT, and non-ATT groups, respectively (P<0.0001). Multivariate analysis revealed that patients in prior OAs (adjusted odds ratio [aOR], 1.95; 95% confidence interval [CI], 1.18-3.21; P=0.0091) and both OAs and APT groups (aOR 1.92, 95% CI 1.17-3.15, P=0.0094) were associated with an increased risk of in-hospital mortality compared with the non-ATT group, but not in those who were on APT (aOR 1.12, 95% 0.93-1.36, P=0.2372). In the subgroup analysis, a stronger association between prior OAs and in-hospital death was found among patients who were older ≥ 65 years (P for interaction is 0.0382). In this nationwide prospective study, prior OAs and concomitant use of OAs and APT but not prior ATP were associated with increased odds of in-hospital mortality compared with ICH patients who were on no-ATT.

The change index of quantitative electroencephalography for evaluating the prognosis of large hemispheric infarction.

A growing number of studies have demonstrated the role of quantitative electroencephalography in assessing brain function in neuro-intensive care units. Still, few studies have examined patients with large hemisphere infarction. Thirty patients with large hemisphere infarction were included in this preliminary study, and the patients were divided into the death group (twelve patients) and survival group (eighteen patients). Electroencephalography monitored the patients, and a computerized tomography inspection was performed. The quantitative electroencephalography of the alpha-beta/delta-theta ratio change index was calculated and used to predict the prognosis of early large hemisphere infarction patients. The relationship between three months modified Rankin Scale, and alpha-beta/delta-theta ratio change index was analyzed. The death group had negative changes for alpha-beta/delta-theta ratio change index (-0.0140 ± 0.0193), while there was an opposite trend in the survival group, the median is 0.004 (-0.0067, 0.0137). The death group's brain function decreased more severely and rapidly than the survival group (P = 0.004). The highest diagnostic value (AUC value 0.815, P < 0.001) was observed when the alpha-beta/delta-theta ratio change index dropped and exceeded -0.008. The area under the GCS curve was 0.674, but its predictive ability was low (P = 0.094). The correlation analysis result showed that the 3-month modified Rankin Scale was negatively correlated with the alpha-beta/delta-theta ratio change index (r = -0.489, P = 0.006). The alpha-beta/delta-theta ratio change index is considered an indicator for predicting the prognosis of large hemisphere infarction. Therefore, the alpha-beta/delta-theta ratio change index may be a reliable quantitative EEG parameter that predicts the early prognosis of patients with acute large hemispheric infarction.

Matrix metallopeptidase 9 and placental growth factor may correlate with collateral status based on whole-brain perfusion combined with multiphase computed tomography angiography.

OBJECTIVE: The aim of this study was to find out the relationship between serum biomarkers and cerebral collateral status in acute ischemic stroke with cerebral large artery atherosclerosis. METHODS: We enrolled patients with ischemic stroke due to large artery atherosclerosis within 7 days of symptom onset, age 18-80 years, from August 2016 to December 2017. Twelve biomarkers representing different pathophysiological mechanisms were tested after admission. Whole-brain perfusion combined with multiphase computed tomography angiography was performed to assess cerebral collateral structure and function. RESULTS: Fifty-two patients completed the test of candidate biomarkers and recruited in this study. The mean age was 55.0 (11.1) years, 42 (80.8%) patients were male, 20 (38.5%) had poor collateral, 36 (69.2%) patients had anterior circulation stenosis or occlusion. Compared with poor collateral group, the level of MMP-9 (135,475.00 pg/ml vs. 103,612.00 pg/ml, p = 0.040) and PGF (5.75 pg/ml vs. 3.46 pg/ml, p = 0.046) was significantly higher in good collateral group. The adjusted OR (95%CI) of MMP-9 and PGF were 5.533 (1.10-27.74, p = 0.038), 7.73 (1.41-42.39, p = 0.018), respectively. sTie-2 level had a positive correlation with proportion of Tmax 4-6 (r = 0.302, p = 0.033) and HMW-KGN had negative correlation with proportion of Tmax 6-8 (r = -0.338, p = 0.02). After adjustment, the correlation of sTie-2 level and proportion of Tmax 4-6 was statistically significant (p = 0.003), and correlation of HMW-KGN and Tmax6-8 was not statistically significant (p = 0.056). DISCUSSION: Serum PGF and MMP-9 levels may correlate with collateral status based on MP-CTA in acute ischemic stroke patients with cerebral large artery atherosclerosis. Higher PGF and MMP-9 concentration associated with good collateral status.

Tranexamic acid for acute intracerebral haemorrhage growth based on imaging assessment (TRAIGE): a multicentre, randomised, placebo-controlled trial.

BACKGROUND: Studies show tranexamic acid can reduce the risk of death and early neurological deterioration after intracranial haemorrhage. We aimed to assess whether tranexamic acid reduces haematoma expansion and improves outcome in intracerebral haemorrhage patients susceptible to haemorrhage expansion. METHODS: We did a prospective, double-blind, randomised, placebo-controlled trial at 10 stroke centres in China. Acute supratentorial intracerebral haemorrhage patients were eligible if they had indication of haemorrhage expansion on admission imaging (eg, spot sign, black hole sign or blend sign), and were treatable within 8 hours of symptom onset. Patients were randomly assigned (1:1) to receive either tranexamic acid or a matching placebo. The primary outcome was intracerebral haematoma growth (>33% relative or >6 mL absolute) at 24 hours. Clinical outcomes were assessed at 90 days. RESULTS: Of the 171 included patients, 124 (72.5%) were male, and the mean age was 55.9±11.6 years. 89 patients received tranexamic acid and 82 received placebo. The primary outcome did not differ significantly between the groups: 36 (40.4%) patients in the tranexamic acid group and 34 (41.5%) patients in the placebo group had intracranial haemorrhage growth (OR 0.96, 95% CI 0.52 to 1.77, p=0.89). The proportion of death was lower in the tranexamic acid treatment group than placebo group (8.1% vs 10.0%), but there were no significant differences in secondary outcomes including absolute intracranial haemorrhage growth, death and dependency. CONCLUSIONS: Among patients susceptible to haemorrhage expansion treated within 8 hours of stroke onset, tranexamic acid did not significantly prevent intracerebral haemorrhage growth. Larger studies are needed to assess safety and efficacy of tranexamic acid in intracerebral haemorrhage patients.

Haemostatic therapy in spontaneous intracerebral haemorrhage patients with high-risk of haematoma expansion by CT marker: a systematic review and meta-analysis of randomised trials.

BACKGROUND AND PURPOSE: Current randomised controlled trials (RCTs) showed an uncertain benefit of haemostatic therapy on preventing haematoma expansion and improving the outcome in patients with intracerebral haemorrhage (ICH). This meta-analysis aims to systematically evaluate the effect of haemostatic agents on the prevention of haemorrhage growth in patients with high-risk spontaneous ICH predicted by CT signs in RCTs. METHODS: A comprehensive search of PubMed, EMBASE and Cochrane library from 1 January 2005 to 30 June 2021 was conducted. RCTs that compared haemostatic agents with placebo for the treatment of spontaneous patients with ICH with high-risk haemorrhage growth were included. The primary endpoint was haematoma expansion at 24 hours. Other major endpoints of interest included 90-day functional outcome and mortality. RESULTS: The meta-analysis included four RCTs that randomised 2666 patients with ICH with high-risk haemorrhage growth. Haemostatic therapy reduced the rate of haematoma expansion at a marginally statistically significant level when compared with placebo (OR 0.84; 95% CI 0.70 to 1.00; p=0.051). Subgroup analysis for patients with black hole sign on CT revealed a significant reduction of haematoma expansion with haemostatic therapy (OR 0.61; 95% CI 0.39 to 0.94; p=0.03). However, both the primary analysis and subgroup analyses showed that haemostatic therapy could not reduce the rate of poor functional outcome (modified Rankin Scale >3) or death. CONCLUSIONS: Haemostatic therapy showed a marginally significant benefit in reducing early haematoma expansion in patients with high-risk spontaneous ICH predicted by markers on CT scan. However, no significant improvement in functional outcome or reduction of mortality was observed.

Intraluminal Thrombus and Outcomes of Patients With Acute Large Vessel Occlusive Stroke Undergoing Endovascular Treatment.

BACKGROUND AND PURPOSE: Intraluminal thrombus (ILT) is an emerging imaging marker in acute ischemic stroke. We aimed to investigate the association of ILT with outcomes of acute large vessel occlusion (LVO) patients receiving endovascular treatment. METHODS: Acute LVO stroke patients who underwent endovascular treatment within 24 hours, in a prospective, nationwide registry were enrolled. Pretreatment digital subtraction angiography was reviewed for the presence of ILT. The primary outcome was 90-day functional dependence (modified Rankin Scale scores, 3-6). Secondary outcomes included 24-hour LVO, 90-day death, and symptomatic intracranial hemorrhage. RESULTS: Among 711 patients enrolled, 75 (10.5%) with ILT were less likely to have 90-day functional dependence compared with those without ILT (adjusted odds ratio, 0.53 [95% CI, 0.31-0.90]; P=0.021). The same trend was found among those with successful reperfusion (modified Thrombolysis in Cerebral Infarction 2b-3; P=0.008) but not in those without successful reperfusion (P=0.107). Presence of ILT was also independently associated with a lower rate of 24-hour LVO (adjusted odds ratio 0.34 [95% CI, 0.13-0.89]; P=0.028). However, those with or without ILT had similar risks of symptomatic intracranial hemorrhage and 90-day death. CONCLUSIONS: Among acute LVO patients receiving endovascular treatment, pretreatment ILT-positive patients may have a better 90-day functional outcome (versus ILT-negative) but similar risk of death and symptomatic intracranial hemorrhage. The possibly favorable effect of ILT patients remained in those with successful reperfusion. Registration: URL: http://www.chictr.org.cn; Unique identifier: ChiCTR1900022154.

Adverse Outcomes Associated With Higher Mean Blood Pressure and Greater Blood Pressure Variability Immediately After Successful Embolectomy in Those With Acute Ischemic Stroke, and the Influence of Pretreatment Collateral Circulation Status.

Background To investigate whether collateral status could modify the associations between post-thrombectomy blood pressure (BP) measures and outcomes. Methods and Results Patients with anterior-circulation large-vessel-occlusion successfully recanalized in a multicenter endovascular thrombectomy registry were enrolled. Pretreatment collateral status was graded and dichotomized (good/poor) in angiography. Maximum, minimum, and mean systolic BP (SBP) and BP variability (assessed by the SD, coefficient of variation) during the initial 24 hours after endovascular thrombectomy were obtained. The primary outcome was unfavorable 90-day outcome (modified Rankin Scale score 3-6). Secondary outcomes included symptomatic intracranial hemorrhage and 90-day mortality. Adjusted odds ratios (aOR) of BP parameters over the outcomes were obtained in all patients and in patients with good/poor collaterals. Among 596 patients (mean age 66 years; 59.9% males), 302 (50.7%) patients had unfavorable 90-day outcome. In multivariable analyses, higher mean SBP (aOR, 1.59 per 10 mm Hg increment; 95% CI, 1.26-2.02; P<0.001), mean SBP >140 mm Hg (versus ≤120 mm Hg; aOR, 4.27; 95% CI, 1.66-10.97; P=0.002), and higher SBP SD (aOR, 1.08 per 1-SD increment; 95% CI, 1.01-1.16; P=0.02) were respectively associated with unfavorable 90-day outcome in patients with poor collateral but not in those with good collateral. A marginal interaction between SBP coefficient of variation tertiles and collaterals on 90-day functional outcome (P for interaction, 0.09) was observed. A significant interaction between SBP coefficient of variation tertiles and collaterals on 90-day mortality (P for interaction, 0.03) was observed. Conclusions Higher postprocedural BP is associated with 90-day unfavorable outcomes after successful endovascular thrombectomy in patients with poor collateral. Registration URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1900022154.