Prevalence and clinical features of carotid artery web in patients undergoing endovascular thrombectomy for acute ischemic stroke.

PURPOSE: Carotid artery web (CaW) is a rare focal fibromuscular dysplasia that can lead to embolic strokes with large vessel occlusion. This condition can be effectively treated with endovascular thrombectomy (EVT). Our study aims to assess the prevalence of CaW among patients with acute ischemic stroke (AIS) who underwent EVT and to compare the clinical characteristics of CaW with other carotid artery pathologies. METHODS: We enrolled consecutive patients with AIS who underwent EVT at a single medical center and two regional teaching hospitals in Taiwan from September 2014 to December 2021. We compared CaW with carotid dissection (CaD) and carotid large artery atherosclerosis (CaLAA) in terms of patient demographics and thrombus histological findings. RESULTS: Of the 576 AIS patients who underwent EVT, four (mean age: 50 years) were diagnosed with CaW, resulting in a prevalence of 0.69%. Among these four patients, three experienced successful reperfusion after EVT and achieved functional independence (defined as a modified Rankin Scale score ≤2) three months post-stroke. Importantly, none of the CaW patients suffered a recurrent stroke within one year. Patients with CaW were younger than those with CaD or CaLAA, and exhibited fewer vascular risk factors. Additionally, CaW was associated with distal occlusion sites. The thrombus composition in CaW patients was similar to that in CaD patients. CONCLUSIONS: In conclusion, CaW is a rare finding among Asian patients with carotid artery disease who undergo for AIS. It is more prevalent in younger patients with a limited number of vascular risk factors.

Association between modifiable vascular risk factors and rapid progression of postradiation carotid artery stenosis.

BACKGROUND: Postradiotherapy carotid vasculopathy is a clinically relevant complication in patients with head and neck cancer receiving radiotherapy. In this study, we investigated the factors associated with the development and progression of carotid artery stenosis (CAS) in such patients. METHODS: Patients who received radiotherapy for head and neck cancers between October 2011 and May 2019 at a medical center in Taiwan were eligible for inclusion in this study. This study included patients who underwent two consecutive carotid duplex examinations within an interval of 1 to 3 years. The factors associated with ≥50% CAS at baseline and follow-up were analyzed. RESULTS: In total, 694 patients (mean age, 57.8 ± 9.9 years; men, 75.2%; nasopharyngeal cancer, 73.3%) were included. The mean interval between radiotherapy and carotid duplex examination was 9.9 ± 5.9 years. At baseline, 103 patients had ≥50% CAS, which was significantly associated with tobacco smoking, hypercholesterolemia, and a prolonged interval between radiotherapy and carotid duplex examination. A total of 586 patients did not have CAS at baseline; of them, 68 developed ≥50% CAS during follow-up. Hypertension and hypercholesterolemia were identified as independent risk factors for CAS progression. CONCLUSION: Modifiable vascular risk factors, such as hypertension and hypercholesterolemia, appear to be significantly associated with the rapid progression of postradiotherapy CAS in patients with head and neck cancer.

Serum amyloid A predicts poor functional outcome in patients with ischemic stroke receiving endovascular thrombectomy: a case control study.

BACKGROUND: Post-stroke inflammation contributes to poor outcomes, but its impact on patients with stroke receiving endovascular thrombectomy (EVT) remains unknown. METHODS: We enrolled adult patients with stroke who received EVT, with blood sampling immediately before (T1) and after EVT (T2), and at 24 hours after EVT (T3). Non-stroke controls and patients with non-EVT stroke were also enrolled. The medical information, image findings and levels of serum amyloid A (SAA) and C-reactive protein (CRP) were analyzed to clarify the association with poor functional outcome (modified Rankin Scale 4-6) at 3 months after stroke. RESULTS: A total of 93 patients with stroke receiving EVT, 51 non-stroke controls, and 64 with non-EVT stroke were enrolled in this study. The SAA and CRP levels at T1 to T3 in patients with stroke receiving EVT were higher compared with those in controls (all p<0.001), and their levels at T3 were significantly higher than those at T1 (both p<0.0001) while similar to those in patients with non-EVT stroke. The SAA levels at the three time points were significantly associated with poor functional outcome (p=0.003 to 0.009). Furthermore, adding SAA level at T3 significantly improved the basic prediction model for 3-month poor functional outcome by receiver operating characteristic (ROC) analysis (areas under ROC curves from 0.803 to 0.878, p=0.03). CONCLUSIONS: Our findings demonstrate that plasma levels of SAA at an early stage are significant predictors for poor functional outcomes at 3 months in patients with stroke receiving EVT, indicating the substantial role of systemic inflammation in shaping stroke outcomes following EVT.

Outcome of endovascular thrombectomy in patients with end-stage renal disease undergoing dialysis.

BACKGROUND: Patients with end-stage renal disease (ESRD) are often excluded from clinical trials of endovascular thrombectomy (EVT). This study investigated the outcome in these patients. METHODS: From September 2014 to July 2021, all patients undergoing EVT for anterior circulation stroke in two stroke centers in Taiwan were included. They were divided into no renal dysfunction (non-RD, estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2), RD (eGFR <60 mL/min/1.73 m2 but no dialysis), and ESRD undergoing dialysis (ESRD-dialysis). The clinical features and outcomes were compared. RESULTS: Of 482 patients included, there were 20 ESRD-dialysis, 110 RD, and 352 non-RD patients. The Alberta Stroke Program Early CT Score (ASPECTS), National Institutes of Health Stroke Scale (NIHSS), use of intravenous thrombolysis, EVT-related time metrics, and successful recanalization rates were comparable among the three groups. However, the ESRD-dialysis patients had more symptomatic intracerebral hemorrhage (ICH, 15% vs 3.6% vs 3.7%), more contrast-induced encephalopathy (15% vs 1.8% vs 0.9%), and a higher mortality at 90 days (35% vs 18% vs 11%) than the other groups. Multivariable analysis revealed that ESRD-dialysis was associated with a less favorable outcome (OR 0.21, 95% CI 0.04 to 0.77) and more severe disability or mortality (modified Rankin Scale 5 or 6; OR 13.1, 95% CI 3.93 to 48.1) at 90 days. In the ESRD-dialysis group, the patients with premorbid functional dependence had a significantly higher mortality than those without (75% vs 8.3%; P=0.004). CONCLUSION: ESRD-dialysis patients were associated with symptomatic ICH and less favorable outcome at 90 days. Patients with premorbid functional dependency had an excessively high mortality.

Postoperative vascular event prediction using angiography and ultrasonography in patients with Moyamoya disease.

OBJECTIVE: Indirect revascularization surgery reduce the risk of recurrent vascular events in patients with moyamoya disease (MMD), but the roles of postoperative angiography and ultrasonography in predicting these events remain unclear. METHODS: This prospective study enrolled patients with MMD who would undergo their first unilateral indirect revascularization surgery. They received preoperative and postoperative ultrasound examination at 1, 3, and 6 months and conventional cerebral angiography. On ultrasonography, postoperative emerging flow (PEF) in an intracranial artery was defined as emerging flow postoperatively with absence of flow preoperatively. Predictors of vascular event frequency reduction were identified from angiographic and ultrasonographic parameters. RESULTS: In total, 52 patients (including 24 pediatric and 24 male patients), who underwent 52 preoperative and 82 postoperative ultrasound examinations, were enrolled. Significant postoperative changes were noted in all the ultrasonographic parameters of ipsilateral superficial temporal artery (STA) and the end-diastolic velocity and flow volume in contralateral STA. During a median follow-up of 5.3 years, indirect revascularization surgery significantly reduced the occurrence of ipsilateral vascular events. Predictors of vascular event frequency reduction included Matsushima grade A or B on the ipsilateral side on angiography (odds ratio [OR] = 22.00, P = 0.002) and lower resistance index (RI) in ipsilateral STA (OR = 0.0001, P = 0.012) but no PEF pattern in ipsilateral middle cerebral artery (OR = 0.14, P = 0.029) on ultrasonography performed within 6 months. CONCLUSIONS: Reduction of long-term vascular event frequency probably can be predicted through postoperative angiography and ultrasonography within 6 months after indirect revascularization surgery.

An Effective Strategy to Activate Physicians to Promote High Cardiovascular Risk Patients to Quit Smoking.

Background: Adult patients cared for by cardiologists, neurologists, and diabetologists are highly vulnerable to cardiovascular diseases (CVDs), which are worsened by smoking. In the past, physicians of these three specialties at major hospitals in Taiwan always referred patients to family medicine and chest medicine departments for smoking cessation programs. However, the participation rate in these programs was unsatisfactory. Objectives: To encourage cardiologists, neurologists, and diabetologists to provide smoking cessation treatment services (SCTSs) to their patients through an annual contest. Methods: Sequential expert meetings, group training, a contest to reward service quantity and abstinence rate, and an annual awards ceremony were held over the past 3 years. Results: More than 350 cardiologists, neurologists, and diabetologists were certified to provide SCTSs, and in the second half of 2020, 3716 high CVD risk patients entered smoking cessation treatment programs, with an abstinence rate exceeding 30% at 3 months. Conclusions: The strategy used in this study was effective in overcoming physician inertia to provide SCTSs and encourage high CVD risk smokers to quit smoking.

Genetic analysis of a family presenting with coexisting cerebral cavernous malformations and polycystic kidney disease.

Hereditary cerebral cavernous malformations (CCMs) are characterized by clustered dilated capillary-like vessels in the brain. Autosomal dominant polycystic kidney disease (PKD) is characterized by renal cysts and extra-renal abnormalities. We report a Taiwanese family in which the index case exhibited coexisting phenotypes of both CCMs and PKD. The index case was a 55-year-old woman with known PKD who developed an intracerebral hemorrhage (ICH) in the right medulla. Neuroimaging revealed numerous microbleeds in the bilateral cerebrum and cerebellum. Radiological CCMs were suspected given the absence of other imaging markers of small vessel disease. A comprehensive panel of 183 cerebral vascular malformation genes were investigated through genome sequencing. A novel CCM2 frameshift variant (c.607_608delCT, p.Leu203Valfs∗53) causing a pathogenic premature stop codon, and a known PKD2 nonsense variant (c.2407C > T, p.Arg803∗), were found. Segregation analysis revealed that four siblings were affected by either isolated aforementioned PKD2 or CCM2 variant. Notably, radiological CCMs were exclusively found in siblings who had this CCM2 variant, and bilateral internal carotid artery aneurysms were restricted to one sibling who had the PKD2 variant but not the CCM2 variant. Our study expands the genetic spectrum of CCM2 and demonstrates unambiguous cosegregation of CCM2 and PKD2 variants with their respective phenotypes.

Does tranexamic acid affect intraventricular hemorrhage growth in acute ICH? An analysis of the STOP-AUST trial.

Background: Trials of tranexamic acid (TXA) in acute intracerebral hemorrhage (ICH) have focused on the imaging outcomes of intraparenchymal hematoma growth. However, intraventricular hemorrhage (IVH) growth is also strongly associated with outcome after ICH. Revised definitions of hematoma expansion incorporating IVH growth have been proposed. Aims: We sought to evaluate the effect of TXA on IVH growth. Methods: We analyzed data from the STOP-AUST trial, a prospective randomized trial comparing TXA to placebo in ICH patients presenting ≤ 4.5 h from symptom onset with a CT-angiography spot sign. New IVH development at follow-up, any interval IVH growth, and IVH growth ≥ 1 mL were compared between the treatment groups using logistic regression. The treatment effect of TXA against placebo using conventional (> 6 mL or 33%), and revised definitions of hematoma expansion (> 6 mL or 33% or IVH expansion ≥ 1 mL, > 6 mL or 33%, or any IVH expansion, and > 6 mL or 33% or new IVH development) were also assessed. Treatment effects were adjusted for baseline ICH volume. Results: The analysis population consisted of 99 patients (50 placebo, 49 TXA). New IVH development at follow-up was observed in 6/49 (12%) who received TXA and 13/50 (26%) who received placebo (aOR: 0.38 [95% CI: 0.13-1.13]). Any interval IVH growth was observed in 12/49 (25%) who received TXA versus 26/50 (32%) receiving placebo (aOR: 0.69 [95% CI: 0.28-1.66]). IVH growth ≥ 1 mL did not differ between the two groups. Using revised definitions of hematoma expansion, no significant difference in treatment effect was observed between TXA and placebo. Conclusions: IVH may be attenuated by TXA following ICH; however, studies with larger cohorts are required to investigate this further. Registration: http://www.clinicaltrials.gov; Unique identifier: NCT01702636.

Application of hyperglycemia/diabetes-derived polygenic risk scores on the risk of poor outcomes after an ischemic stroke.

BACKGROUND: Unfavorable prognoses are often accompanied for hyperglycemic stroke patients. This study aimed to construct a hyperglycemia/diabetes-derived polygenic risk score (PRS) to improve the predictive performance for poor outcome risks after a stroke and to evaluate its potential clinical application. METHODS: A hospital-based cohort study was conducted including 1320 first-ever acute ischemic stroke (AIS) patients and 1210 patients who completed the follow-up at 3 months. PRSs were calculated for hyperglycemia/diabetes mellitus using results from genome-wide association studies in Asians. An unfavorable functional outcome was defined as a modified Rankin Scale score of ≥3 at 3, 6, and 12 months of follow-up. The prediction of a poor prognosis was evaluated using measures of model discrimination, calibration, and net reclassification improvement (NRI). RESULTS: The second to fourth PRS quartiles (≥Q2) were significantly associated with higher risks of unfavorable outcomes at 3 months compared with the first quartile as the reference group after adjusting for age, baseline stroke severity, hypertension, diabetes, dyslipidemia, smoking, heart disease, and ischemic stroke subtype (p for trend <0.0001). The addition of the PRS to traditional risk predictors of poor outcomes after an AIS significantly improved the model fit (likelihood ratio test p < 0.0001) and enhanced measures of reclassification (NRI, 0.245; 95% confidence interval [CI], 0.195-0.596). The corrected C-index for the PRS combining traditional risk factors at 3 months after a stroke was 0.899 (95% CI, 0.878-0.980). Among hyperglycemic AIS patients, those who did not take an antidiabetic drug and whose PRS was ≥Q2 had higher risks of an unfavorable outcome at 3 months compared with patients who took the medicine. CONCLUSION: The hyperglycemia/diabetes-derived PRS was associated with poor outcomes after an AIS, but further studies are needed to validate its use for clinical applications.

Impact of different renal function equations on direct oral anticoagulant concentrations.

The purpose of this study is to investigate the correlation between glomerular filtration rate (GFR) estimated by different renal function equations and non-vitamin K antagonist oral anticoagulant concentration. Atrial fibrillation patients who aged ≥ 20 years and used dabigatran, rivaroxaban, or apixaban for thromboembolism prevention were enrolled to collect blood samples and measure drug concentrations using ultra-high-performance liquid chromatography with tandem mass spectrometry. The GFR was estimated using the Cockroft-Gault formula (abbreviated as creatinine clearance, CrCL), Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI) featuring both creatinine and cystatin C, and the Modification of Diet in Renal Disease Study equation (MDRD). Multivariate regression was used to investigate the associations of different renal function estimates with drug concentrations. A total of 511 participants were enrolled, including 146 dabigatran users, 164 rivaroxaban users and 201 apixaban users. Compared to clinical trials, 35.4% of dabigatran, 4.9% of rivaroxaban, and 5.5% of apixaban concentrations were higher than the expected range (p < 0.001). CKD-EPI and MDRD estimates classified fewer patients as having GFR < 50 mL/min than CrCL in all 3 groups. Both CrCL and CKD-EPI were associated with higher-than-expected ranges of dabigatran or rivaroxaban concentrations. Nevertheless, none of the renal function equations was associated with higher-than-expected apixaban concentrations. For participants aged ≥ 75 years, CKD-EPI may be associated with higher-than-expected trough concentration of dabigatran. In conclusion, CrCL and CKD-EPI both can be used to identify patients with high trough concentrations of dabigatran or rivaroxaban. Among elderly patients who used dabigatran, CKD-EPI may be associated with increased drug concentration.

Determinants for Control of Status Epilepticus in Patients with Anti-N-Methyl-D-Aspartate Receptor Encephalitis.

BACKGROUND: Treatment guideline for status epilepticus (SE) specifically in patients with anti-N-methyl- D-aspartate receptor (anti-NMDAR) encephalitis is insufficient. This study aimed to clarify the determinants for the control of SE in adult patients with anti-NMDAR encephalitis. METHODS: Medical records of all patients with anti-NMDAR encephalitis hospitalized between Jan. 2010 and Sep. 2019 were analyzed for the time sequence of seizures and treatments, and antiepileptic drug (AED) regimens related to SE. The outcomes were control of SE and seizures, and the discharge score of modified Rankin Scale (mRS). RESULTS: All eight patients had seizures and seven (87.5%) suffered from SE which lasted for 3.6 ± 3.9 days. Five patients (71.4%) had SE earlier than using IT, whose SE was controlled by AEDs alone (n = 4) or combined with teratomas resection (n = 1). Another two patients suffered from SE after receiving IT, and one of them had SE only for 1 hour. Moreover, all SE patients received increased types and dosages of AEDs at SE end. A shorter duration of refractory SE was associated with its later occurrence after seizure onset (p = 0.005) and longer duration of AEDs use before SE (p = 0.026). All cases achieved seizure freedom after receiving AEDs and IT. CONCLUSIONS: In these patients with anti-NMDAR encephalitis, all the SE which occurred before initiating IT was successfully controlled by AEDs alone or combined with teratoma resection, and later onset of refractory SE was associated with a shorter SE duration.

Measurement of Dabigatran Concentration Using Finger Prick Dried Blood Spot Sample Collection.

Background and Purpose: Real-world laboratory monitoring of dabigatran activity is challenging. The purpose of the present study was to demonstrate the feasibility and accuracy of finger prick sampling with dried blood spot (fpDBS) cards in measuring the dabigatran concentration. Material and Methods: Patients >20 years of age with atrial fibrillation and receiving dabigatran therapy for more than 7 days were included in the study. Peak and trough dabigatran concentrations were collected by simultaneous finger prick and venous puncture. The dabigatran concentration was measured by ultra-high performance liquid chromatography with tandem mass spectrometry. Our previously developed post-column infused internal standard (PCI-IS) method was applied to estimate the blood spot volume on fpDBS and to calibrate the drug concentration. Deming regression was used to analyze the correlation between dabigatran concentration on fpDBS cards and in plasma samples, followed by Bland-Altman analysis to compare the bias between two sampling techniques. Results: A total of 33 patients were enrolled and contributed 66 plasma and 55 fpDBS dabigatran samples. The average patient age was 74.6 ± 7.9 years, mean creatinine clearance 58.1 ± 18.3 mL/min, and CHA2DS2-VASc score 3.5 ± 1.6 points. The dabigatran concentration ranged from 41.8-1421.7 ng/mL. The plasma and DBS dabigatran concentrations correlated well (r = 0.98), and the conversion factor for fpDBS to plasma dabigatran concentration was 1.28. The Bland-Altman analysis showed that 94.5% of the fpDBS-predicted concentration fell within 20% of bias. Conclusions: The study showed that fpDBS measurement of dabigatran concentration is reliable and can be applied in clinical scenarios.

Prognostic impact of renal dysfunction on embolic stroke of undetermined source-Role beyond CHA2 DS2 -VASc score: Results from Taiwan Stroke Registry.

BACKGROUND AND PURPOSE: The CHA2 DS2 -VASc score has immense prognostic value in patients with embolic stroke of undetermined source (ESUS). We aimed to determine the usefulness of advanced renal dysfunction and its addition to the CHA2 DS2 -VASc score in improving predictive accuracy. METHODS: In total, 3775 ESUS patients were enrolled from a nationwide hospital-based prospective study. Advanced renal dysfunction was defined as estimated glomerular filtration rate <30 ml/min per 1.73 m2 or patients under dialysis. Clinical outcomes included recurrent stroke and 1-year all-cause mortality. Poor functional outcome was defined as a modified Rankin Scale >2 at first-, third-, and sixth-month post-stroke. The renal (R)-CHA2 DS2 -VASc score was derived by including advanced renal dysfunction in the CHA2 DS2 -VASc score. Risk stratification improvement after including advanced renal dysfunction was assessed using C statistic, integrated discrimination improvement (IDI), and category-free net reclassification index (NRI). RESULTS: After adjusting for confounding factors and CHA2 DS2 -VASc score, advanced renal dysfunction showed significant associations with all-cause mortality (HR: 2.88, 95% CI: 1.92-4.34) and poor functional outcome at third- (OR: 2.69, 95% CI: 1.47-4.94) and sixth-month post-stroke (OR: 2.67, 95% CI: 1.47-4.83). IDI and NRI showed that incorporating advanced renal dysfunction significantly improved risk discrimination over the original CHA2 DS2 -VASc score. R-CHA2 DS2 -VASc score ≥2 increased risk by 1.94-fold (95% CI: 1.15-3.27) for all-cause mortality, and ≥4 increased risk by 1.62-fold (95% CI: 1.05-2.50) of poor functional outcome at third-month post-stroke and by 1.81-fold (95% CI: 1.19-2.75) at sixth-month post-stroke. CONCLUSIONS: Advanced renal dysfunction was significantly associated with clinical and functional outcomes in ESUS patients and may improve prognostic impact of the CHA2 DS2 -VASc score.

Fibrin and Platelet-Rich Composition in Retrieved Thrombi Hallmarks Stroke With Active Cancer.

BACKGROUND AND PURPOSE: We aim to investigate whether histopathologic examination of thrombi retrieved from acute ischemic stroke patients undergoing endovascular treatment could distinguish cancer-related stroke from other etiologies. METHODS: Thrombi from patients undergoing endovascular treatment were analyzed. The etiology of stroke was divided into cardioembolism, large artery atherosclerosis, and active cancer groups. All selected thrombi were subjected to hematoxylin and eosin staining. The percentages of fibrin/platelets, red blood cells, and white blood cells within a thrombus were quantified. RESULTS: One-hundred fifty-two patients (active cancer, 19; cardioembolism, 107; large artery atherosclerosis, 26) were included. Thrombi from the active cancer group exhibited a higher fibrin/platelet composition than did those from the cardioembolism and large artery atherosclerosis groups (median, 85.7% versus 43.9% and 42.5%; P<0.001). Fibrin/platelet composition was the only independent factor (odds ratio, 1.05 [95% CI, 1.02-1.08]) in differentiating cancer-related stroke from stroke caused by cardioembolism and large artery atherosclerosis. A fibrin/platelet proportion of ≥65% accurately predicted cancer-related stroke (area under the curve, 0.84; P<0.001). CONCLUSIONS: In thrombi retrieved from patients undergoing endovascular treatment, a high fibrin/platelet composition was a probable indicator of cancer-related stroke.

Tranexamic acid in patients with intracerebral haemorrhage (STOP-AUST): a multicentre, randomised, placebo-controlled, phase 2 trial.

BACKGROUND: Despite intracerebral haemorrhage causing 5% of deaths worldwide, few evidence-based therapeutic strategies other than stroke unit care exist. Tranexamic acid decreases haemorrhage in conditions such as acute trauma and menorrhoea. We aimed to assess whether tranexamic acid reduces intracerebral haemorrhage growth in patients with acute intracerebral haemorrhage. METHODS: We did a prospective, double-blind, randomised, placebo-controlled, investigator-led, phase 2 trial at 13 stroke centres in Australia, Finland, and Taiwan. Patients were eligible if they were aged 18 years or older, had an acute intracerebral haemorrhage fulfilling clinical criteria (eg, Glasgow Coma Scale score of >7, intracerebral haemorrhage volume <70 mL, no identified or suspected secondary cause of intracerebral haemorrhage, no thrombotic events within the previous 12 months, no planned surgery in the next 24 h, and no use of anticoagulation), had contrast extravasation on CT angiography (the so-called spot sign), and were treatable within 4·5 h of symptom onset and within 1 h of CT angiography. Patients were randomly assigned (1:1) to receive either 1 g of intravenous tranexamic acid over 10 min followed by 1 g over 8 h or matching placebo, started within 4·5 h of symptom onset. Randomisation was done using a centralised web-based procedure with randomly permuted blocks of varying size. All patients, investigators, and staff involved in patient management were masked to treatment. The primary outcome was intracerebral haemorrhage growth (>33% relative or >6 mL absolute) at 24 h. The primary and safety analyses were done in the intention-to-treat population. The trial is registered at ClinicalTrials.gov (NCT01702636). FINDINGS: Between March 1, 2013, and Aug 13, 2019, we enrolled and randomly assigned 100 participants to the tranexamic acid group (n=50) or the placebo group (n=50). Median age was 71 years (IQR 57-79) and median intracerebral haemorrhage volume was 14·6 mL (7·9-32·7) at baseline. The primary outcome was not different between the two groups: 26 (52%) patients in the placebo group and 22 (44%) in the tranexamic acid group had intracerebral haemorrhage growth (odds ratio [OR] 0·72 [95% CI 0·32-1·59], p=0·41). There was no evidence of a difference in the proportions of patients who died or had thromboembolic complications between the groups: eight (16%) in the placebo group vs 13 (26%) in the tranexamic acid group died and two (4%) vs one (2%) had thromboembolic complications. None of the deaths was considered related to study medication. INTERPRETATION: Our study does not provide evidence that tranexamic acid prevents intracerebral haemorrhage growth, although the treatment was safe with no increase in thromboembolic complications. Larger trials of tranexamic acid, with simpler recruitment methods and an earlier treatment window, are justified. FUNDING: National Health and Medical Research Council, Royal Melbourne Hospital Foundation.

Asymptomatic Striatocapsular slit-like Hemorrhage as a Severity Marker in Patients with Hypertensive Angiopathy.

BACKGROUND: Concomitant asymptomatic striatocapsular slit-like hemorrhage (SSH) is occasionally found in patients of spontaneous intracerebral hemorrhage (ICH), but was seldomly described in the literature. In this study, we described the clinico-radiological features of asymptomatic SSH in ICH patients with hypertensive microangiopathy. METHODS AND RESULTS: 246 patients with strictly deep or mixed deep and lobar ICH/microbleeds were included. SSH was defined as hypointense lesions involving the lateral aspect of lentiform nucleus or external capsule in slit shape (>1.5 cm) on susceptibility-weighted imaging without history of associated symptoms. Demographics and neuroimaging markers were compared between patients with SSH and those without. Patients with SSH (n=24, 10%) and without SSH had comparable age (62.0 ± 12.6 vs. 62.3 ± 13.5, p = 0.912) and vascular risk factor profiles including the diagnosis of chronic hypertension, diabetes, and dyslipidemia (all p>0.05). SSH was associated with more common lobar microbleeds (79.2% vs 48.2%, p = 0.005), lacunes (75% vs. 41.4%, p = 0.002) and higher white matter hyperintensity (WMH) volumes (24.1 [10.4-46.3] vs. 13.9 [7.0-24.8] mL, p = 0.012) on MRI, as well as more frequent left ventricular hypertrophy (LVH) (50.0% vs. 20.5%, p = 0.004) and albuminuria (41.7% vs. 19.4%, p = 0.018). In multivariable analyses, SSH remains independently associated with LVH (p = 0.017) and albuminuria (p = 0.032) after adjustment for age, sex, microbleed, lacune and WMH volume. CONCLUSIONS: Asymptomatic SSH is associated with more severe cerebral small vessel disease-related change on brain MRI, and hypertensive cardiac and renal injury, suggesting a more advanced stage of chronic hypertension.

Factors for recurrent stroke among Asian patients with non-valvular atrial fibrillation under non-vitamin K antagonist oral anticoagulant therapy.

BACKGROUND/PURPOSE: Atrial fibrillation (AF) patients with a history of ischemic stroke or transient ischemic attack (TIA) carry excessive risk of recurrent stroke. Real-world data for the Asian population is scarce. This study aimed to investigate the thromboembolism and major bleeding risk of non-vitamin K antagonist oral anticoagulant (NOAC) therapy among Asian patients, and to identify the risk factors of recurrent stroke. METHODS: This retrospective study recruited AF patients aged over 20 years, who had a previous stoke or TIA, and received NOAC therapy. Thromboembolic events were recurrent ischemic stroke or TIA, and the major bleeding events were classified according to the PLATO (Platelet Inhibition and Patient Outcomes) criteria. RESULTS: A total of 361 patients (61.2% male) were enrolled for data analysis. The incidence rate for recurrent ischemic stroke or TIA was 3.6 (95% CI = 2.5 to 5.5) per 100 person-years, and 0.9 (95% CI = 0.4 to 1.7) per 100 person-years for major bleeding. Patients with recurrent ischemic stroke or TIA were more likely to have malignancy (hazard ratio [HR] for malignancy = 4.4, 95% CI = 1.9 to 10.3, p = 0.001) and concomitantly take enzyme inducing antiepileptic drugs (EIAED, HR = 8.1, 95% CI = 2.7 to 24.1, p < 0.001). CONCLUSION: Atrial fibrillation patients with underlying malignancy or concurrently use of EIAED may have increased risk of treatment failure in secondary stroke prevention.

Using G-FAST to recognize emergent large vessel occlusion: a training program for a prehospital bypass strategy.

INTRODUCTION: The shorter the time between the onset of symptoms and reperfusion using endovascular thrombectomy, the better the functional outcome of patients. A training program was designed for emergency medical technicians (EMTs) to learn the gaze-face-arm-speech-time test (G-FAST) score for initiating a prehospital bypass strategy in an urban city. This study aimed to evaluate the effect of the training program on EMTs. METHODS: All EMTs in the city were invited to join the training program. The program consisted of a 30 min lecture and a 20 min video which demonstrated the G-FAST evaluation. The participants underwent tests before and after the program. The tests included (1) a questionnaire of knowledge, attitudes, confidence, and behaviors towards stroke care; and (2) watching 10 different scenarios in a video and answering questions, including eight sub-questions of G-FAST parameters, and choosing a suitable receiving hospital. RESULTS: In total, 1058 EMTs completed the training program. After the program, significant improvement was noted in knowledge, attitudes, and confidence, as well as scenario judgement. The performance of the EMTs in evaluating G-FAST criteria in comatose patients was relatively poor in the pre-test and improved significantly after the training course. Although the participants answered the G-FAST items correctly, they tended to overtriage the patients and refer them to higher-level hospitals. CONCLUSIONS: A short training program can improve the ability to identify stroke patients and choose a suitable receiving hospital. A future training program could put further emphasis on how to evaluate comatose patients and choose a suitable receiving hospital.

Redistributing medical resources for a bypass strategy for large vessel occlusion: a community-based study.

BACKGROUND: A bypass strategy for large vessel occlusion (LVO) benefits patients receiving endovascular thrombectomy (EVT), but may delay some patients from receiving IV thrombolysis. However, patient centralization has been shown to improve outcomes. OBJECTIVE: To understand the current coverage of medical services for patients with stroke, and to identify the best coverage under different medical resource redistribution to help balance medical equality and patient centralization. METHODS: This 6-year geographic study of 7679 on-scene patients with suspected stroke with a positive Cincinnati Prehospital Stroke Scale (CPSS) score identified 4037 patients with all three CPSS items who were suspected as having an LVO. Geographic, population, and patient coverage rates for hospitals providing IV thrombolysis and those providing EVT were identified according to hospital service areas, defined as geographic districts with access to a hospital within a ≤15 min off-peak driving time estimated using Google Maps. Moreover, we estimated the effects on resource redistribution when implementing a bypass strategy. RESULTS: Geographic coverage rates for hospitals providing IV thrombolysis and those providing EVT were 64.75% and 56.62%, respectively, and population coverage rates were 97.30% and 92.72%, respectively. The service areas of hospitals providing IV thrombolysis covered 93.77% of patients with suspected stroke, and those of hospitals providing EVT covered 87.89% of patients with suspected LVO. The number of hospitals providing IV thrombolysis and those providing EVT could be reduced to six and two hospitals, respectively, without affecting hospital arrival time when implementing a bypass strategy. CONCLUSION: Hospitals providing IV thrombolysis and EVT could be reduced without reducing medical equality.

Similar outcomes between vitamin K and non-vitamin K antagonist oral anticoagulants associated intracerebral hemorrhage.

BACKGROUND: The application of non-vitamin K antagonist oral anticoagulant (NOAC) reduces the risk of intracerebral hemorrhage (ICH) in comparison with vitamin K antagonist (VKA). However, the features and outcomes of NOAC-associated ICH are still unclear, especially for Asian populations. METHODS: We retrospectively analyzed 49 consecutive patients who had spontaneous ICH while using NOAC or VKA. We compared the clinical characteristics, ICH volume, 7-day and 3-month mortality, and functional outcomes at discharge and 3 months post-stroke using the modified Rankin Scale (mRS) between NOAC- and VKA-associated ICH. The clinical features, ICH volume, ICH location, and/or treatment methods were statistically adjusted. RESULTS: Among the 49 ICH patients, 15 (30.6%) were using NOAC and 34 (69.4%) were taking VKA. There were no significant differences in the initial ICH volume between groups (mean volume 34.2 ± 43.8 vs. 59.4 ± 46.5 mL, p = 0.061). The percentage of early mortality (within 7 days post-ICH) was significantly lower in the NOAC group (13.3% vs. 44.1%; p = 0.047), but the 3-month mortality was similar (33.3% vs. 47.1%; p = 0.294). The functional outcome was equally poor in both groups at discharge (p = 0.670) and 3 months post-ICH (mean mRS score 4.7 ± 1.3 vs. 4.6 ± 1.7, p = 0.766). CONCLUSION: There were no significant differences in initial ICH volume, 90-day mortality, or functional outcomes between NOAC and VKA-associated ICH in Asians.