Abstract
Stenosis, characterized by partial vessel narrowing, alters blood hemodynamics and can lead to unpredictable thrombosis. Existing models struggle to accurately represent the complex vascular ...geometries and hemodynamics involved in such conditions. To address this challenge, a microvasculature‐on‐a‐post chip is developed to mimic partially stenotic vascular geometries and thrombogenicity, featuring isolated 3D micropost structures with variable sizes that recreate disturbed flow profiles. To emulate the diseased vessel wall, the post microfluidics are vascularized with a confluent layer of endothelial cells. Subsequently, human blood is perfused through the endothelialized post microfluidics, observing the temporal and spatial thrombotic response governed by Virchow's triad, including vessel wall injury, hemodynamic disturbance, and hypercoagulability. The innovative model offers valuable insights into stenosis‐induced thrombosis and endothelial behavior, paving the way for improved assessment of thrombotic risks associated with stenotic vessels. This advanced microfluidic platform also offers new approaches for evaluation of prothrombotic phenotypes and cardiovascular risk assessment in the future.
Background Patients with acute ischemic stroke and large vessel occlusion (LVO) may benefit from prehospital identification and transfer to a center offering endovascular therapy. Aims We aimed to ...assess the accuracy of an existing 8-item stroke scale (National Institutes of Health Stroke Scale-8 NIHSS-8) for identification of patients with acute stroke with LVO. Methods We retrospectively calculated NIHSS-8 scores in a population of consecutive patients with presumed acute stroke assessed by emergency medical services (EMS). LVO was identified on admission computed tomography angiography. Accuracy to identify LVO was calculated using receiver operating characteristics analysis. We used weighted Cohen's kappa statistics to assess inter-rater reliability for the NIHSS-8 score between the EMS and the hospital stroke team on a prospectively evaluated subgroup. Results Of the 551 included patients, 381 had a confirmed ischemic stroke and 136 patients had an LVO. NIHSS scores were significantly higher in patients with LVO (median 18; interquartile range 14-22). The NIHSS-8 score reliably predicted the presence of LVO (area under the receiver operating characteristic curve .82). The optimum NIHSS-8 cutoff of 8 or more had a sensitivity of .81, specificity of .75, and Youden index of .56 for prediction of LVO. The EMS and the stroke team reached substantial agreement (κ = .69). Conclusions Accuracy of the NIHSS-8 to identify LVO in a population of patients with suspected acute stroke is comparable to existing prehospital stroke scales. The scale can be performed by EMS with reasonable reliability. Further validation in the field is needed to assess accuracy of the scale to identify patients with LVO eligible for endovascular treatment in a prehospital setting.
Abstract
Cerebral venous sinus thrombosis (CVST) is a type of stroke associated with COVID‐19 vaccine‐induced immune thrombotic thrombocytopenia. The precise etiology of CVST often remains elusive ...due to the highly heterogeneous nature of its governing mechanisms, specifically, Virchow's triad that involves altered blood flow, endothelial dysfunction, and hypercoagulability, which varies substantially amongst individuals. Existing diagnostic and monitoring approaches lack the capability to reflect the combination of these patient‐specific thrombotic determinants. In response to this challenge, we introduce a Vein‐Chip platform that recapitulates the CVST vascular anatomy from magnetic resonance venography and the associated hemodynamic flow profile using the “Chinese Movable Type‐like” soft stereolithography technique. The resultant full‐lumen personalized Vein‐Chips, functionalized with endothelial cells, enable in‐vitro thrombosis assays that can elucidate distinct thrombogenic scenarios between normal vascular conditions and those of endothelial dysfunction. The former displayed minimal platelet aggregation and negligible fibrin deposition, while the latter presented significant fibrin extrusion from platelet aggregations. The low‐cost movable typing technique further enhances the potential for commercialization and broader utilization of personalized Vein‐Chips in surgical labs and at‐home monitoring. Future research and development in this direction will pave the way for improved management and prevention of CVST, ultimately benefiting both patients and healthcare systems.
Background
Multi-modal CT (MMCT) to guide decision making for reperfusion treatment is increasingly used, but there remains a perceived risk of contrast-induced nephropathy (CIN). At our center, MMCT ...is used empirically without waiting for serum-creatinine (sCR) or renal profiling.
Aims
To determine the incidence of CIN, examine the risk factors predisposing to its development, and investigate its effects on clinical outcome in the acute stroke population.
Methods
An institution-wide protocol was implemented for acute stroke presentations to have MMCT (100–150 ml nonionic tri-iodinated contrast, perfusion CT and CT angiography) without waiting for serum-creatinine to minimize delays. Intravenous saline is routinely infused (80–125 ml/h) for at least 24-h after MMCT. Serial creatinine levels were measured at baseline, risk period, and follow-up. Renal profiles and clinical progress were reviewed up to 90 days.
Results
We analyzed 735 consecutive patients who had MMCT for the evaluation of acute ischemic or hemorrhagic stroke during the last five-years. A total of 623 patients met the inclusion criteria for analysis: 16 cases (2·6%) biochemically qualified as CIN; however, the risk period serum-creatinine for 15 of these cases was confounded by dehydration, urinary tract infection, or medications. None of the group had progression to chronic kidney disease or required dialysis.
Conclusions
The incidence of CIN is low when MMCT is used routinely to assess acute stroke patients. In this population, CIN was a biochemical phenomenon that did not have clinical manifestations, cause chronic kidney disease, require dialysis, or negatively impact on 90-day mRS outcomes. Renal profiling and waiting for a baseline serum-creatinine are an unnecessary delay to emergency reperfusion treatment.
Background Telestroke networks aim to address variability in both quality and access to stroke care in rural areas, by providing remote access to expert stroke neurologists. Implementation of ...telestroke requires adaptation of workflow processes and education. We previously developed virtual reality (VR) workflow training and documented acceptability, utility and feasibility. The effects on acute stroke treatment metrics have not been previously described. Aims The overall aim was to improve hyperacute stroke metrics and shorten the time-to-reperfusion therapy administration in rural settings. Methods This study applies a natural experiment approach, collecting stroke metric data during transition from a pre-existing pilot to a statewide telestroke service at five rural hospitals. Pre- and post-intervention data included baseline patient demographics and assessment, diagnosis, and treatment delivery metrics. The primary study outcome was door-to-decision time (thrombolysis and endovascular thrombectomy). Secondary outcomes included door-to-computerized tomography time, door-to-thrombolysis time and proportion of patients receiving thrombolysis or thrombectomy treatment. Usage data relating to the VR stroke workflow training of interprofessional healthcare professionals was automatically captured via Wi-Fi. Statistical comparisons of clinical metrics between the pre- and post-intervention time periods, defined as the timeframes before and after VR deployment, were performed. Results A total of 2,683 patients were included (April 2013–December 2022); 1910 pre- and 773 post-intervention. All acute stroke time metrics significantly improved post-intervention. The primary outcome, door-to-decision time, decreased from 80 min 56–118 to 54 min 40–76; P < 0.001. Secondary outcomes also improved, including door-to-thrombolysis time (90 min 68–114 vs. 68.5 min 54–90; P < 0.001) and proportion of patients thrombolysed (11 vs. 16%; P < 0.001). The proportion of patients transferred for thrombectomy was unchanged (6 vs. 7%; P = 0.69). Seventy VR sessions totaling 15 h 39 min of training time were logged. VR training usage varied across sites (3–31 sessions per site). Conclusions Delivery of a multi-factorial intervention including infrastructure, funding, education and training (with VR workflow training) as part of a state-wide telestroke rollout was associated with improved acute stroke treatment metrics. Additional work is required to identify the contribution of each intervention component on clinical outcomes and to increase training uptake and sustainment.
Trials of endovascular therapy for ischemic stroke have produced variable results. We conducted this study to test whether more advanced imaging selection, recently developed devices, and earlier ...intervention improve outcomes.
We randomly assigned patients with ischemic stroke who were receiving 0.9 mg of alteplase per kilogram of body weight less than 4.5 hours after the onset of ischemic stroke either to undergo endovascular thrombectomy with the Solitaire FR (Flow Restoration) stent retriever or to continue receiving alteplase alone. All the patients had occlusion of the internal carotid or middle cerebral artery and evidence of salvageable brain tissue and ischemic core of less than 70 ml on computed tomographic (CT) perfusion imaging. The coprimary outcomes were reperfusion at 24 hours and early neurologic improvement (≥8-point reduction on the National Institutes of Health Stroke Scale or a score of 0 or 1 at day 3). Secondary outcomes included the functional score on the modified Rankin scale at 90 days.
The trial was stopped early because of efficacy after 70 patients had undergone randomization (35 patients in each group). The percentage of ischemic territory that had undergone reperfusion at 24 hours was greater in the endovascular-therapy group than in the alteplase-only group (median, 100% vs. 37%; P<0.001). Endovascular therapy, initiated at a median of 210 minutes after the onset of stroke, increased early neurologic improvement at 3 days (80% vs. 37%, P=0.002) and improved the functional outcome at 90 days, with more patients achieving functional independence (score of 0 to 2 on the modified Rankin scale, 71% vs. 40%; P=0.01). There were no significant differences in rates of death or symptomatic intracerebral hemorrhage.
In patients with ischemic stroke with a proximal cerebral arterial occlusion and salvageable tissue on CT perfusion imaging, early thrombectomy with the Solitaire FR stent retriever, as compared with alteplase alone, improved reperfusion, early neurologic recovery, and functional outcome. (Funded by the Australian National Health and Medical Research Council and others; EXTEND-IA ClinicalTrials.gov number, NCT01492725, and Australian New Zealand Clinical Trials Registry number, ACTRN12611000969965.).
Intravenous infusion of alteplase is used for thrombolysis before endovascular thrombectomy for ischemic stroke. Tenecteplase, which is more fibrin-specific and has longer activity than alteplase, is ...given as a bolus and may increase the incidence of vascular reperfusion.
We randomly assigned patients with ischemic stroke who had occlusion of the internal carotid, basilar, or middle cerebral artery and who were eligible to undergo thrombectomy to receive tenecteplase (at a dose of 0.25 mg per kilogram of body weight; maximum dose, 25 mg) or alteplase (at a dose of 0.9 mg per kilogram; maximum dose, 90 mg) within 4.5 hours after symptom onset. The primary outcome was reperfusion of greater than 50% of the involved ischemic territory or an absence of retrievable thrombus at the time of the initial angiographic assessment. Noninferiority of tenecteplase was tested, followed by superiority. Secondary outcomes included the modified Rankin scale score (on a scale from 0 no neurologic deficit to 6 death) at 90 days. Safety outcomes were death and symptomatic intracerebral hemorrhage.
Of 202 patients enrolled, 101 were assigned to receive tenecteplase and 101 to receive alteplase. The primary outcome occurred in 22% of the patients treated with tenecteplase versus 10% of those treated with alteplase (incidence difference, 12 percentage points; 95% confidence interval CI, 2 to 21; incidence ratio, 2.2; 95% CI, 1.1 to 4.4; P=0.002 for noninferiority; P=0.03 for superiority). Tenecteplase resulted in a better 90-day functional outcome than alteplase (median modified Rankin scale score, 2 vs. 3; common odds ratio, 1.7; 95% CI, 1.0 to 2.8; P=0.04). Symptomatic intracerebral hemorrhage occurred in 1% of the patients in each group.
Tenecteplase before thrombectomy was associated with a higher incidence of reperfusion and better functional outcome than alteplase among patients with ischemic stroke treated within 4.5 hours after symptom onset. (Funded by the National Health and Medical Research Council of Australia and others; EXTEND-IA TNK ClinicalTrials.gov number, NCT02388061 .).
The incidence and natural history of large vessel occlusion (LVO) stroke in children is largely unknown. These knowledge gaps limit the uptake of reperfusion therapies and reduce the efficiency of ...pediatric acute stroke pathways.
To determine the incidence and natural history of pediatric LVO stroke.
This retrospective population-based cohort study was conducted between January 2010 and December 2019, with a mean (SD) follow-up of 37.0 (28.8) months. Admissions from all pediatric hospitals in the state of New South Wales, Australia, with a final diagnosis of arterial ischemic stroke (AIS) in patients 1 month to younger than 17 years were included. A total of 85 of 251 identified cases were excluded based on selection criteria. Data were analyzed from July 2020 to June 2021.
One-third of patients with LVO received mechanical thrombectomy with or without intravenous thrombolysis while the remainder were treated conservatively.
The primary outcome was the pediatric modified Rankin Scale (ped-mRS) score 3 months after stroke. Ordinal logistic regression was used to compare non-LVO, LVO without thrombectomy, and LVO with thrombectomy groups.
Of 161 included patients, 56 (34.8%) were female, and the mean (SD) age was 6.1 (5.4) years. A total of 166 AIS admissions were studied, and clinical follow-up was available for 164 of 166 admissions. LVO was present in 39 admissions (23.5%). The incidence of LVO stroke was 0.24 per 100 000 patients per year (95% CI, 0.13-0.35). Patients with LVO who did not receive thrombectomy (n = 26) had poor neurological outcomes, with 19 (73.1%) experiencing moderate to severe disability or death (ped-mRS score of 3 to 6) at 3 months (6 of 12 patients receiving thrombectomy 50.0%; 25 of 38 patients with LVO 65.8%). Patients with LVO without thrombectomy had significantly worse clinical outcomes than patients with non-LVO at 3 months (odds ratio, 3.64; 95% CI, 1.68-7.87; P = .001). Most patients with LVO presented within time windows suitable for thrombectomy (27 of 39 69.2% within 6 hours; 35 of 39 89.7% within 24 hours).
In this population-based cohort study, the natural history of pediatric patients with LVO stroke treated conservatively was poor, with most experiencing lifelong disability or death. Nearly 90% of pediatric patients with LVO presented within time windows suitable for thrombectomy.
Pediatric large-vessel occlusion has a poor natural history. Recent retrospective studies have demonstrated the potential benefits, feasibility, and safety profile of mechanical thrombectomy in ...children. However, the role of thrombectomy in pediatric M2 occlusions remains uncertain. In this clinical report, we present a multicenter series of 6 pediatric patients with acute M2 occlusion (female = 1, male = 5; age range, 0.9-16.0 years, mean = 9.2). All 6 patients having undergone thrombectomy had excellent clinical outcomes (pediatric mRS = 0-1) at 3 months and final available follow-up (median, 12 months; range, 3-72 months). Factors relevant to treatment decision-making in pediatric M2 occlusions are discussed, including the important role of multidisciplinary team discussions during acute management.
Organ on Chips
In article number 2214179, Lining Arnold Ju and co‐workers, devised a novel, cost‐effective, and high‐throughput fabrication method for the creation of personalized vein‐chips, ...employing movable typing stereolithography and organ‐on‐chip technologies. This innovative chip accurately replicates an individual patient's unique anatomy and hemodynamics, thereby facilitating the investigation of clot formation in cerebral venous sinus thrombosis. The vein‐chip demonstrates significant potential for future personalized thrombotic assessment and monitoring.
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