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Gottlieb M, Carlson JN, Westrick J, Peksa GD. Endovascular thrombectomy with versus without intravenous thrombolysis for acute ischaemic stroke. Cochrane Database Syst Rev 2025; 4:CD015721. [PMID: 40271574 PMCID: PMC12019923 DOI: 10.1002/14651858.cd015721.pub2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/25/2025]
Abstract
RATIONALE Acute ischaemic stroke is a major cause of death and disability worldwide. Once diagnosed, treatment is generally limited to intravenous thrombolysis (IVT), endovascular thrombectomy, or both. Intravenous thrombolysis has theoretical benefits (enhancing reperfusion, dissolving smaller thrombi) and harms (delaying time to endovascular intervention, allergic reaction, increased bleeding risk). OBJECTIVES To assess the effects of endovascular thrombectomy with IVT versus without IVT on functional independence (defined as a modified Rankin Scale score (mRS) < 3) within 90 days in people with acute ischaemic stroke. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, Scopus, LILACS, Google Scholar, the International HTA database, and two trial registries to November 2023. ELIGIBILITY CRITERIA We included randomised controlled trials of adults with acute ischaemic stroke who received endovascular therapy and were randomised to either intravenous thrombolysis within 4.5 hours or a control. OUTCOMES Outcomes were: functional independence (mRS score < 3), excellent functional outcome (mRS score < 2), mortality, asymptomatic intracranial haemorrhage, symptomatic intracranial haemorrhage, successful revascularisation (thrombolysis in cerebral infarction (TICI) grades 2b to 3), and complete revascularisation (TICI grade 3 only), within 90 days. RISK OF BIAS We used the Cochrane RoB 2 tool to assess the following potential sources of bias for each outcome: bias arising from the randomisation process; bias due to deviations from intended interventions; bias due to missing outcome data; bias in measurement of the outcome; and bias in selection of the reported result. SYNTHESIS METHODS We pooled outcome data using the random-effects model and performed meta-analyses using the Mantel-Haenszel method. We assessed the statistical heterogeneity of pooled data by visually inspecting forest plots to consider the direction and magnitude of effects, and used the Chi2 test and I2 statistic to quantify the heterogeneity. We used GRADE to assess the certainty of evidence. INCLUDED STUDIES We included six studies, with a total of 2336 participants (1166 control and 1170 intervention). The mean age was 71 years. There were 1034 women and 1302 men. Four studies used alteplase 0.9 mg/kg, one study used alteplase 0.6 mg/kg, and one study used either alteplase 0.9 mg/kg or tenecteplase 0.25 mg/kg. There were no important variations in the outcomes reported across studies. SYNTHESIS OF RESULTS All six studies were at overall low risk of bias for each outcome. There was probably little to no difference in functional independence between the IVT and control groups (risk ratio (RR) 1.03, 95% confidence interval (CI) 0.92 to 1.14; P = 0.62; 6 studies, 2336 participants; moderate-certainty evidence). There was no evidence of a difference in excellent functional outcome between the IVT and control groups (RR 0.99, 95% CI 0.92 to 1.05; P = 0.67; 6 studies, 2336 participants; high-certainty evidence). There was no evidence of a difference in mortality between the IVT and control groups (RR 0.94, 95% CI 0.78 to 1.14; P = 0.54; 6 studies, 2336 participants; high-certainty evidence). There was no evidence of a difference in asymptomatic intracranial haemorrhage between the IVT and control groups (RR 1.13, 95% CI 1.00 to 1.29; P = 0.06; 6 studies, 2334 participants; high-certainty evidence). There was probably little to no difference in symptomatic intracranial haemorrhage between the IVT and control groups (RR 1.20, 95% CI 0.84 to 1.70; P = 0.31; 6 studies, 2336 participants; moderate-certainty evidence). There was a higher rate of successful revascularisation with IVT over control (RR 1.04, 95% CI 1.01 to 1.08; P = 0.008; 6 studies, 2326 participants; high-certainty evidence). There was a higher rate of complete revascularisation with IVT over control (RR 1.14, 95% CI 1.02 to 1.28; P = 0.02; 5 studies, 2037 participants; high-certainty evidence). Limitations included: differences in inclusion and exclusion criteria between studies (e.g. age thresholds, pre-existing comorbidities or baseline functional status, time periods, diagnostic imaging, specific vessels); specific endovascular device used; thrombolysis medication and dose; and potential conflict of interest, as multiple study authors reported receiving funding or fees from pharmaceutical companies. For functional independence, assessed as an mRS score < 3 within 90 days, we downgraded the certainty of evidence by one level due to a high I2 value, indicating that heterogeneity may be substantial for this outcome. For symptomatic intracranial haemorrhage within 90 days, we downgraded the certainty of evidence by one level because the 95% CI included both important benefits and important harms. AUTHORS' CONCLUSIONS The evidence does not currently support a clear benefit or harm for routine intravenous thrombolysis amongst people receiving endovascular thrombectomy. Amongst participants receiving endovascular thrombectomy, IVT did not demonstrate evidence of a difference in functional independence, excellent functional outcome, mortality, and asymptomatic intracranial haemorrhage, or symptomatic intracranial haemorrhage, when compared with no IVT. However, IVT did result in a higher rate of successful and complete revascularisation when compared with no IVT. Future research should include more high-quality trials to further evaluate the role of intravenous thrombolysis in people receiving endovascular thrombectomy to provide more robust data and further narrow the confidence intervals. Future research should also identify whether time- and person-specific factors influence the effect of IVT amongst those receiving endovascular thrombectomy. FUNDING None REGISTRATION: Gottlieb M, Carlson JN, Westrick J, Peksa GD. Endovascular thrombectomy with versus without intravascular thrombolysis for acute ischaemic stroke. Cochrane Database of Systematic Reviews. 2024;2:1465-1858.
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Affiliation(s)
- Michael Gottlieb
- Department of Emergency Medicine, Rush University Medical Center, Chicago, IL, USA
| | - Jestin N Carlson
- Department of Emergency Medicine, Allegheny Health Network, Erie, PA, USA
| | - Jennifer Westrick
- Library of Rush University Medical Center, Rush University Medical Center, Chicago, IL, USA
| | - Gary D Peksa
- Department of Emergency Medicine, Rush University Medical Center, Chicago, IL, USA
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Musialek P, Bonati LH, Bulbulia R, Halliday A, Bock B, Capoccia L, Eckstein HH, Grunwald IQ, Lip PL, Monteiro A, Paraskevas KI, Podlasek A, Rantner B, Rosenfield K, Siddiqui AH, Sillesen H, Van Herzeele I, Guzik TJ, Mazzolai L, Aboyans V, Lip GYH. Stroke risk management in carotid atherosclerotic disease: a clinical consensus statement of the ESC Council on Stroke and the ESC Working Group on Aorta and Peripheral Vascular Diseases. Cardiovasc Res 2025; 121:13-43. [PMID: 37632337 DOI: 10.1093/cvr/cvad135] [Citation(s) in RCA: 14] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Revised: 08/20/2023] [Accepted: 08/21/2023] [Indexed: 08/28/2023] Open
Abstract
Carotid atherosclerotic disease continues to be an important cause of stroke, often disabling or fatal. Such strokes could be largely prevented through optimal medical therapy and carotid revascularization. Advancements in discovery research and imaging along with evidence from recent pharmacology and interventional clinical trials and registries and the progress in acute stroke management have markedly expanded the knowledge base for clinical decisions in carotid stenosis. Nevertheless, there is variability in carotid-related stroke prevention and management strategies across medical specialities. Optimal patient care can be achieved by (i) establishing a unified knowledge foundation and (ii) fostering multi-specialty collaborative guidelines. The emergent Neuro-Vascular Team concept, mirroring the multi-disciplinary Heart Team, embraces diverse specializations, tailors personalized, stratified medicine approaches to individual patient needs, and integrates innovative imaging and risk-assessment biomarkers. Proposed approach integrates collaboration of multiple specialists central to carotid artery stenosis management such as neurology, stroke medicine, cardiology, angiology, ophthalmology, vascular surgery, endovascular interventions, neuroradiology, and neurosurgery. Moreover, patient education regarding current treatment options, their risks and advantages, is pivotal, promoting patient's active role in clinical care decisions. This enables optimization of interventions ranging from lifestyle modification, carotid revascularization by stenting or endarterectomy, as well as pharmacological management including statins, novel lipid-lowering and antithrombotic strategies, and targeting inflammation and vascular dysfunction. This consensus document provides a harmonized multi-specialty approach to multi-morbidity prevention in carotid stenosis patients, based on comprehensive knowledge review, pinpointing research gaps in an evidence-based medicine approach. It aims to be a foundational tool for inter-disciplinary collaboration and prioritized patient-centric decision-making.
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Affiliation(s)
- Piotr Musialek
- Jagiellonian University Department of Cardiac and Vascular Diseases, St. John Paul II Hospital, ul. Pradnicka 80, 31-202 Krakow, Poland
| | | | - Richard Bulbulia
- Medical Research Council Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford OX3 7LF, UK
- Medical Research Council Population Health Research Unit, Nuffield Department of Population Health, University of Oxford, Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford OX3 7LF, UK
| | - Alison Halliday
- Medical Research Council Population Health Research Unit, Nuffield Department of Population Health, University of Oxford, Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford OX3 7LF, UK
| | | | - Laura Capoccia
- Department of Surgery 'Paride Stefanini', Policlinico Umberto I, 'Sapienza' University of Rome, Rome, Italy
| | - Hans-Henning Eckstein
- Department for Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - Iris Q Grunwald
- Department of Radiology, Ninewells Hospital, University of Dundee, Dundee, UK
- Tayside Innovation MedTech Ecosystem (TIME), Division of Imaging Science and Technology, University of Dundee, Dundee, UK
| | | | - Andre Monteiro
- Department of Neurosurgery, Gates Vascular Institute at Kaleida Health, Buffalo, NY, USA
| | | | - Anna Podlasek
- Tayside Innovation MedTech Ecosystem (TIME), Division of Imaging Science and Technology, University of Dundee, Dundee, UK
- Division of Radiological and Imaging Sciences, University of Nottingham, Nottingham, UK
| | - Barbara Rantner
- Vascular Surgery Department, Ludwig Maximilian University Hospital, Campus Grosshadern, Munich, Germany
| | | | - Adnan H Siddiqui
- Department of Radiology, Jacobs School of Medicine and Biomedical Sciences, and Canon Stroke and Vascular Research Center, University at Buffalo, Buffalo, NY, USA
- Jacobs Institute, Buffalo, NY, USA
| | - Henrik Sillesen
- Department of Vascular Surgery, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Isabelle Van Herzeele
- Department of Thoracic and Vascular Surgery, Ghent University Hospital, Ghent, Belgium
| | - Tomasz J Guzik
- Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK
- Department of Internal Medicine, Jagiellonian University Collegium Medicum, Krakow, Poland
| | - Lucia Mazzolai
- Department of Angiology, University Hospital Lausanne, Lausanne, Switzerland
| | - Victor Aboyans
- Department of Cardiology, CHRU Dupuytren Limoges, Limoges, France
| | - Gregory Y H Lip
- Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool, UK
- Danish Center for Health Services Research, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
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3
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Aleid A, Aldanyowi S, Aljabr A, Almalki S, Alessa A, Alhodibi M, Alsuwaylih M, Alanazi Y, Almutair A. Comparing the efficacy and safety of bridging therapy vs. monotherapy in patients with minor stroke: a meta-analysis. J Med Life 2025; 18:1-9. [PMID: 40071157 PMCID: PMC11891610 DOI: 10.25122/jml-2024-0318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Accepted: 11/04/2024] [Indexed: 03/14/2025] Open
Abstract
The two main therapeutic approaches for stroke treatment are endovascular thrombectomy, which involves mechanically removing the thrombus, and bridging therapy, which uses intravenous thrombolytics (IVT) prior to endovascular thrombectomy (EVT). This study aimed to compare monotherapy (EVT or IVT alone) with bridging therapy (IVT+EVT) in terms of efficacy and safety outcomes in patients with minor ischemic stroke. After a thorough screening, eight studies were included for qualitative synthesis and meta-analysis, comprising a total of 3,117 patients across the treatment arms. The main outcomes of interest were the efficacy of treatment modality, the rate of intracerebral hemorrhage (ICH), and mortality. In terms of functional outcomes measured by the Modified Rankin Score (mRs) 0-1, no significant difference was observed when comparing IVT monotherapy with bridging therapy (IVT+EVT), with an odds ratio of 0.79 (P = 0.41). However, IVT was associated with a decreased risk of symptomatic intracranial hemorrhage (sICH) compared to bridging therapy (OR = 0.51; P = 0.02), while EVT was associated with an increased risk of sICH compared to bridging therapy (OR = 8.33; P = 0.01). Mortality rates were comparable between IVT alone compared to bridging therapy and EVT alone compared to bridging therapy (P = 0.14). Although both treatment modalities share similar efficacy, there was a trend in favoring bridging therapy for mortality rates, but it was not statistically significant. Future randomized controlled trials and updated systematic reviews are needed within five to ten years to increase sample sizes and potentially identify statistically significant differences in mortality and other outcomes.
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Key Words
- CI, Confidence Interval
- EVT, Endovascular Thrombectomy
- GSR-ET, German Stroke Registry–Endovascular Treatment
- I2, Statistical Measure of Study Heterogeneity Used in Meta-Analysis
- IVT, Intravenous Thrombolysis
- LVO, Large Vessel Occlusion
- NIHSS, National Institutes of Health Stroke Scale
- NOS, Newcastle-Ottawa Scale
- OR, Odds Ratio
- PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses
- RCT, Randomized Controlled Trials
- SITS-ISTR, Safe Implementation of Treatments in Stroke–International Stroke Thrombolysis Registry
- bridging therapy
- endovascular thrombectomy
- intravenous thrombolysis
- mRs, Modified Rankin Score
- meta-analysis
- minor stroke
- monotherapy
- sICH, Symptomatic Intracranial Hemorrhage
- systematic review
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Affiliation(s)
- Abdulsalam Aleid
- Department of Surgery, Medical College, King Faisal University, Ahsa, Saudi Arabia
| | - Saud Aldanyowi
- Department of Surgery, Medical College, King Faisal University, Ahsa, Saudi Arabia
| | - Abdulmajeed Aljabr
- King Saud bin Abdulaziz for Health Science, College of Medicine, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi Arabia
| | - Sami Almalki
- Department of Surgery, Medical College, King Faisal University, Ahsa, Saudi Arabia
| | - Awn Alessa
- Department of Neurosurgery, King Fahad Hospital, Hofuf, Ahsa, Saudi Arabia
| | | | - Mohammed Alsuwaylih
- Department of Internal Medicine, Bahrain Defense Hospital, Riffa, Saudi Arabia
| | - Yousef Alanazi
- Department of Internal Medicine, Northern Border University, Arar, Saudi Arabia
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Ma Y, Xiang H, Busse JW, Yao M, Guo J, Ge L, Li B, Luo X, Mei F, Liu J, Wang Y, Liu Y, Li W, Zou K, Li L, Sun X. Tenecteplase versus alteplase for acute ischemic stroke: a systematic review and meta-analysis of randomized and non-randomized studies. J Neurol 2024; 271:2309-2323. [PMID: 38436679 DOI: 10.1007/s00415-024-12243-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2024] [Revised: 02/07/2024] [Accepted: 02/07/2024] [Indexed: 03/05/2024]
Abstract
OBJECTIVE Alteplase is the current standard of care for acute ischemic stroke. Tenecteplase is a newer fibrinolytic agent with preferable administration and lower costs; however, its comparative effectiveness to alteplase remains uncertain. We set out to perform a systematic review and meta-analysis to establish the benefits and harms of tenecteplase versus alteplase for acute ischemic stroke. METHODS We searched PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov from inception to April 2023 for randomized and non-randomized studies that compared tenecteplase versus alteplase for acute ischemic stroke. Paired reviewers independently assessed risk of bias and extracted data. We performed both conventional meta-analyses and Bayesian network meta-analyses (NMA) with random-effects models and used the GRADE approach to evaluate the certainty of evidence. Our primary efficacy outcome was excellent functional outcome at 3 months, defined as a score of 0-1 on the modified Rankin Scale. Our primary safety outcomes were symptomatic intracranial hemorrhage and all-cause mortality. RESULTS Thirty-six studies were eligible for review, including 12 randomized (n = 5533) and 24 non-randomized studies (n = 44,956). Moderate certainty evidence showed that there was no difference between tenecteplase and alteplase in increasing the proportion of patients achieving excellent functional outcome at 3 months (odds ratio [OR], 1.10; 95% CI 0.98-1.23; risk difference [RD] 2.4%, 95% CI - 0.5 to 5.2), while moderate certainty evidence from NMA suggested that 0.25 mg/kg tenecteplase significantly improved excellent functional outcome at 3 months (OR, 1.16; 95% credible interval 1.02-1.32). Moderate certainty evidence showed that, compared to alteplase, tenecteplase may make little to no difference in the prevalence of symptomatic intracranial hemorrhage (OR, 1.12; 95% CI 0.79-1.59; RD 0.3%, 95% CI - 0.5 to 1.4), and probably reduces all-cause mortality (adjusted odds ratio [aOR], 0.44; 95% CI 0.30-0.64; RD - 4.6%; 95% CI - 5.8 to - 2.9). CONCLUSIONS Moderate certainty evidence suggested that there was little to no difference between tenecteplase and alteplase in increasing the proportion of patients achieving excellent functional outcome at 3 months and the risk of symptomatic intracranial hemorrhage, while compared to alteplase, tenecteplase probably reduce all-cause mortality. Administration of 0.25 mg/kg tenecteplase after acute ischemic stroke is suggestive of increasing the proportion of patients that achieve excellent functional outcome at 3 months.
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Affiliation(s)
- Yu Ma
- Department of Neurology and Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, China
- NMPA Key Laboratory for Real World Data Research and Evaluation in Hainan, Chengdu, 610041, China
- Sichuan Center of Technology Innovation for Real World Data, Chengdu, 610041, China
| | - Hunong Xiang
- Department of Neurology and Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, China
- NMPA Key Laboratory for Real World Data Research and Evaluation in Hainan, Chengdu, 610041, China
- Sichuan Center of Technology Innovation for Real World Data, Chengdu, 610041, China
| | - Jason W Busse
- Michael G. DeGroote National Pain Centre, McMaster University, Hamilton, ON, L8S 4K1, Canada
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, L8S 4K1, Canada
- Department of Anaesthesia, McMaster University, Hamilton, ON, L8S 4K1, Canada
| | - Minghong Yao
- Department of Neurology and Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, China
- NMPA Key Laboratory for Real World Data Research and Evaluation in Hainan, Chengdu, 610041, China
- Sichuan Center of Technology Innovation for Real World Data, Chengdu, 610041, China
| | - Jian Guo
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Long Ge
- Evidence Based Social Science Research Centre, School of Public Health, Lanzhou University, Lanzhou, 730000, China
- Department of Social Medicine and Health Management, School of Public Health, Lanzhou University, Lanzhou, 730000, China
| | - Bo Li
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300381, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300381, China
| | - Xiaochao Luo
- Department of Neurology and Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, China
- NMPA Key Laboratory for Real World Data Research and Evaluation in Hainan, Chengdu, 610041, China
- Sichuan Center of Technology Innovation for Real World Data, Chengdu, 610041, China
| | - Fan Mei
- Department of Neurology and Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, China
- NMPA Key Laboratory for Real World Data Research and Evaluation in Hainan, Chengdu, 610041, China
- Sichuan Center of Technology Innovation for Real World Data, Chengdu, 610041, China
| | - Jiali Liu
- Department of Neurology and Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, China
- NMPA Key Laboratory for Real World Data Research and Evaluation in Hainan, Chengdu, 610041, China
- Sichuan Center of Technology Innovation for Real World Data, Chengdu, 610041, China
| | - Yuning Wang
- Department of Neurology and Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, China
- NMPA Key Laboratory for Real World Data Research and Evaluation in Hainan, Chengdu, 610041, China
- Sichuan Center of Technology Innovation for Real World Data, Chengdu, 610041, China
| | - Yanmei Liu
- Department of Neurology and Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, China
- NMPA Key Laboratory for Real World Data Research and Evaluation in Hainan, Chengdu, 610041, China
- Sichuan Center of Technology Innovation for Real World Data, Chengdu, 610041, China
| | - Wentao Li
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300381, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300381, China
| | - Kang Zou
- Department of Neurology and Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, China
- NMPA Key Laboratory for Real World Data Research and Evaluation in Hainan, Chengdu, 610041, China
- Sichuan Center of Technology Innovation for Real World Data, Chengdu, 610041, China
| | - Ling Li
- Department of Neurology and Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, China.
- NMPA Key Laboratory for Real World Data Research and Evaluation in Hainan, Chengdu, 610041, China.
- Sichuan Center of Technology Innovation for Real World Data, Chengdu, 610041, China.
| | - Xin Sun
- Department of Neurology and Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, China.
- NMPA Key Laboratory for Real World Data Research and Evaluation in Hainan, Chengdu, 610041, China.
- Sichuan Center of Technology Innovation for Real World Data, Chengdu, 610041, China.
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Arrarte Terreros N, Stolp J, Bruggeman AAE, Swijnenburg ISJ, Lopes RR, van Meenen LCC, Groot AED, Kappelhof M, Coutinho JM, Roos YBWEM, Emmer BJ, Beenen LFM, Dippel DWJ, van Zwam WH, van Bavel E, Marquering HA, Majoie CBLM. Thrombus Imaging Characteristics to Predict Early Recanalization in Anterior Circulation Large Vessel Occlusion Stroke. J Cardiovasc Dev Dis 2024; 11:107. [PMID: 38667725 PMCID: PMC11050543 DOI: 10.3390/jcdd11040107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Revised: 03/23/2024] [Accepted: 03/25/2024] [Indexed: 04/28/2024] Open
Abstract
The early management of transferred patients with a large vessel occlusion (LVO) stroke could be improved by identifying patients who are likely to recanalize early. We aim to predict early recanalization based on patient clinical and thrombus imaging characteristics. We included 81 transferred anterior-circulation LVO patients with an early recanalization, defined as the resolution of the LVO or the migration to a distal location not reachable with endovascular treatment upon repeated radiological imaging. We compared their clinical and imaging characteristics with all (322) transferred patients with a persistent LVO in the MR CLEAN Registry. We measured distance from carotid terminus to thrombus (DT), thrombus length, density, and perviousness on baseline CT images. We built logistic regression models to predict early recanalization. We validated the predictive ability by computing the median area-under-the-curve (AUC) of the receiver operating characteristics curve for 100 5-fold cross-validations. The administration of intravenous thrombolysis (IVT), longer transfer times, more distal occlusions, and shorter, pervious, less dense thrombi were characteristic of early recanalization. After backward elimination, IVT administration, DT and thrombus density remained in the multivariable model, with an AUC of 0.77 (IQR 0.72-0.83). Baseline thrombus imaging characteristics are valuable in predicting early recanalization and can potentially be used to optimize repeated imaging workflow.
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Affiliation(s)
- Nerea Arrarte Terreros
- Department of Biomedical Engineering and Physics, Amsterdam University Medical Centers, Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands (E.v.B.)
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
| | - Jeffrey Stolp
- Department of Neurology, Amsterdam University Medical Centers, Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; (J.S.)
| | - Agnetha A. E. Bruggeman
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
| | - Isabella S. J. Swijnenburg
- Department of Biomedical Engineering and Physics, Amsterdam University Medical Centers, Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands (E.v.B.)
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
| | - Ricardo R. Lopes
- Department of Biomedical Engineering and Physics, Amsterdam University Medical Centers, Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands (E.v.B.)
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
| | - Laura C. C. van Meenen
- Department of Neurology, Amsterdam University Medical Centers, Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; (J.S.)
| | - Adrien E. D. Groot
- Department of Neurology, Amsterdam University Medical Centers, Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; (J.S.)
| | - Manon Kappelhof
- Department of Biomedical Engineering and Physics, Amsterdam University Medical Centers, Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands (E.v.B.)
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
| | - Jonathan M. Coutinho
- Department of Neurology, Amsterdam University Medical Centers, Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; (J.S.)
| | - Yvo B. W. E. M. Roos
- Department of Neurology, Amsterdam University Medical Centers, Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; (J.S.)
| | - Bart J. Emmer
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
| | - Ludo F. M. Beenen
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
| | | | - Wim H. van Zwam
- Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands;
| | - Ed van Bavel
- Department of Biomedical Engineering and Physics, Amsterdam University Medical Centers, Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands (E.v.B.)
| | - Henk A. Marquering
- Department of Biomedical Engineering and Physics, Amsterdam University Medical Centers, Location University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands (E.v.B.)
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
| | - Charles B. L. M. Majoie
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
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6
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Endovascular thrombectomy with versus without intravascular thrombolysis for acute ischaemic stroke. Cochrane Database Syst Rev 2024; 2024:CD015721. [PMCID: PMC10862547 DOI: 10.1002/14651858.cd015721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effects of receiving endovascular thrombectomy with intravascular thrombolysis versus without intravascular thrombolysis on functional independence (defined as a modified Rankin Scale score (mRS) of < 3) at up to 90 days in people with acute ischaemic stroke.
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Wu X, Chen T, Han Y, Wang K, Zhou J. Left atrial myxoma as a rare cause of stroke. Heliyon 2024; 10:e23897. [PMID: 38223711 PMCID: PMC10784162 DOI: 10.1016/j.heliyon.2023.e23897] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Revised: 12/13/2023] [Accepted: 12/15/2023] [Indexed: 01/16/2024] Open
Abstract
Cerebrovascular events may attribute to the fragmentation of a cardiac tumor. Due to the small number of reported cases of large vascular occlusion-acute ischemic stroke (LVO-AIS) associated with atrial myxoma, current guidelines still follow the principle of intravenous thrombolysis priority, even if LVO-AIS patients are eligible for mechanical thrombectomy, and have not recommended the timing of cardiac surgery or preoperative anticoagulation and antithrombotic therapy. Surgical removal is the definitive therapy for cardiac myxomas, especially for left-sided myxomas. With this case, we aim to demonstrate the main challenges that clinicians may encounter when dealing with patients with AIS secondary to cardiac myxoma: the difficulties with clinical diagnosis, strategies for reperfusion therapy, and therapeutic management of cardiac myxoma.
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Affiliation(s)
- Xindi Wu
- Department of Intensive Care Unit, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine affiliated to Shanghai Traditional Chinese Medicine, Shanghai, China
| | - Tongyu Chen
- Department of Cardiothoracic Surgery, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine affiliated to Shanghai Traditional Chinese Medicine, Shanghai, China
| | - Yan Han
- Department of Neurology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine affiliated to Shanghai Traditional Chinese Medicine, Shanghai, China
| | - Ke Wang
- Department of Clinical Research Institute of Acupuncture and Anaesthetic, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine affiliated to Shanghai Traditional Chinese Medicine, Shanghai, China
| | - Jia Zhou
- Department of Cardiothoracic Surgery, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine affiliated to Shanghai Traditional Chinese Medicine, Shanghai, China
- Department of Clinical Research Institute of Acupuncture and Anaesthetic, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine affiliated to Shanghai Traditional Chinese Medicine, Shanghai, China
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Liu W, Zhao J, Liu H, Li T, Zhou T, He Y, Zhu L, Ding Y, Hui FK, He Y. Safety and Efficacy of Direct Thrombectomy Versus Bridging Therapy in Patients with Acute Ischemic Stroke Eligible for Intravenous Thrombolysis: A Meta-Analysis of Randomized Controlled Trials. World Neurosurg 2023; 175:113-121.e3. [PMID: 37040841 DOI: 10.1016/j.wneu.2023.04.018] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Accepted: 04/05/2023] [Indexed: 04/13/2023]
Abstract
OBJECTIVE In the present study, we conducted a meta-analysis of reported randomized controlled trials (RCTs) comparing the safety and efficacy of direct thrombectomy (DT) and bridging therapy (BT) for patients eligible for intravenous thrombolysis (IVT). METHODS A comprehensive search of PubMed, Cochrane Library, EMBASE, and Web of Science up to July 11, 2022 was performed. RCTs comparing DT and BT were included. The relative risk or rate difference and their 95% confidence intervals in a Mantel-Haenszel fixed effects model were used as the effect index of each outcome. The noninferior margin was specified as 80% for the relative risk or -10% for the rate difference. The primary outcome was the proportion of patients with a favorable functional outcome, defined as a modified Rankin scale (mRS) score of 0-2 or a return to baseline at 90 days. Additional efficacy and safety outcomes included successful recanalization at the end of thrombectomy, excellent clinical outcomes (defined as an mRS score of 0-1), death within 90 ± 14 days, symptomatic intracerebral hemorrhage, any type of intracerebral hemorrhage, and clot migration. RESULTS Six RCTs with 2334 patients were pooled for the meta-analysis. The results showed the noninferiority of DT for favorable functional outcomes, higher successful recanalization rates, and any intracerebral hemorrhage in the BT group, with no statistically significant differences for other outcomes. The risk of bias for all RCTs in our analysis was low. CONCLUSIONS DT achieved noninferiority to BT for favorable functional outcomes. Patient-level pooled analysis and subgroup analysis are needed to provide more information to distinguish which patients will benefit more from which therapy.
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Affiliation(s)
- Wenbo Liu
- Department of Cerebrovascular Disease, Zhengzhou University People's Hospital, Henan University People's Hospital, Henan Provincial People's Hospital, Henan Provincial Neurointerventional Engineering Research Center, Henan International Joint Laboratory of Cerebrovascular Disease and Henan Engineering Research Center of Cerebrovascular Intervention, Zhengzhou, China
| | - Jingge Zhao
- Clinical Research Center, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, China
| | - Huan Liu
- Department of Cerebrovascular Disease, Zhengzhou University People's Hospital, Henan University People's Hospital, Henan Provincial People's Hospital, Henan Provincial Neurointerventional Engineering Research Center, Henan International Joint Laboratory of Cerebrovascular Disease and Henan Engineering Research Center of Cerebrovascular Intervention, Zhengzhou, China
| | - Tianxiao Li
- Department of Cerebrovascular Disease, Zhengzhou University People's Hospital, Henan University People's Hospital, Henan Provincial People's Hospital, Henan Provincial Neurointerventional Engineering Research Center, Henan International Joint Laboratory of Cerebrovascular Disease and Henan Engineering Research Center of Cerebrovascular Intervention, Zhengzhou, China
| | - Tengfei Zhou
- Department of Cerebrovascular Disease, Zhengzhou University People's Hospital, Henan University People's Hospital, Henan Provincial People's Hospital, Henan Provincial Neurointerventional Engineering Research Center, Henan International Joint Laboratory of Cerebrovascular Disease and Henan Engineering Research Center of Cerebrovascular Intervention, Zhengzhou, China
| | - Yanyan He
- Department of Cerebrovascular Disease, Zhengzhou University People's Hospital, Henan University People's Hospital, Henan Provincial People's Hospital, Henan Provincial Neurointerventional Engineering Research Center, Henan International Joint Laboratory of Cerebrovascular Disease and Henan Engineering Research Center of Cerebrovascular Intervention, Zhengzhou, China
| | - Liangfu Zhu
- Department of Cerebrovascular Disease, Zhengzhou University People's Hospital, Henan University People's Hospital, Henan Provincial People's Hospital, Henan Provincial Neurointerventional Engineering Research Center, Henan International Joint Laboratory of Cerebrovascular Disease and Henan Engineering Research Center of Cerebrovascular Intervention, Zhengzhou, China
| | - Yonghong Ding
- Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA
| | - Ferdinand K Hui
- University of Hawaii, Queen's Medical Center, Honolulu, Hawaii, USA
| | - Yingkun He
- Department of Cerebrovascular Disease, Zhengzhou University People's Hospital, Henan University People's Hospital, Henan Provincial People's Hospital, Henan Provincial Neurointerventional Engineering Research Center, Henan International Joint Laboratory of Cerebrovascular Disease and Henan Engineering Research Center of Cerebrovascular Intervention, Zhengzhou, China.
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Horvath LC, Bergmann F, Hosmann A, Greisenegger S, Kammerer K, Jilma B, Siller-Matula JM, Zeitlinger M, Gelbenegger G, Jorda A. Endovascular thrombectomy with or without intravenous thrombolysis in large-vessel ischemic stroke: A non-inferiority meta-analysis of 6 randomised controlled trials. Vascul Pharmacol 2023; 150:107177. [PMID: 37116733 DOI: 10.1016/j.vph.2023.107177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Revised: 04/23/2023] [Accepted: 04/25/2023] [Indexed: 04/30/2023]
Abstract
BACKGROUND It is unclear whether thrombectomy alone is non-inferior to thrombectomy with intravenous thrombolysis in patients with acute ischemic stroke due to large-vessel occlusion. PURPOSE To perform a comprehensive, trial-level data, non-inferiority meta-analysis of randomised controlled trials comparing endovascular thrombectomy with and without intravenous thrombolysis in patients with ischemic stroke due to large-vessel occlusion of anterior circulation. METHODS The prespecified primary efficacy outcome was functional independence, defined as a modified Rankin scale (mRS)score of 0 to 2 at 90 days. The two prespecified non-inferiority margins were risk differences of -10% and - 5%. The study was registered in PROSPERO (CRD42022361110) and conducted according to PRISMA guidelines. RESULTS Six trials were included in this analysis (DIRECT-MT, DEVT, SKIP, MR CLEAN-NO IV, DIRECT-SAFE and SWIFT DIRECT) comprising a total of 2334 patients. Functional independence at 90 days was achieved by 570 (49·0%) of 1164 patients in the thrombectomy alone group and 595 (50·9%) of 1170 patients in the thrombectomy with thrombolysis group (pooled risk difference - 0·02, [95% CI -0·06-0·02]). Combined thrombectomy and thrombolysis were associated with significantly higher rates of successful reperfusion (pooled risk ratio 0·96 [95% CI, 0·93-0·99], p = 0·006) but at the expense of a significantly increased risk of overall - but not symptomatic - intracranial haemorrhage (pooled risk ratio 0·87 [95% CI, 0·77-0·98], p = 0·02). CONCLUSIONS Compared with a combined treatment approach, thrombectomy alone was non-inferior at -10% non-inferiority margin, but not at a - 5% inferiority margin for functional independence. Current evidence cannot exclude clinically important differences between the two treatment approaches.
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Affiliation(s)
| | - Felix Bergmann
- Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria; Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Vienna, Vienna, Austria
| | - Arthur Hosmann
- Department of Neurosurgery, Medical University of Vienna, Vienna, Austria
| | | | - Kerstin Kammerer
- Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
| | - Bernd Jilma
- Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
| | - Jolanta M Siller-Matula
- Department of Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria; Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology (CEPT), Medical University of Warsaw, Warsaw, Poland
| | - Markus Zeitlinger
- Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
| | - Georg Gelbenegger
- Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
| | - Anselm Jorda
- Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
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Abstract
PURPOSE OF REVIEW This review aims to summarize the therapeutic advances and evidence in the medical management of acute ischemic stroke (AIS). Recent evidence comparing the efficacy and safety of tenecteplase (TNK) with alteplase for intravenous thrombolysis (IVT) in AIS will be highlighted. Recent advances and evidence on improving micro-circulation following endovascular procedures and neuroprotection will be reviewed. RECENT FINDINGS A significant number of randomized control studies now support the use of tenecteplase for IVT in AIS. TNK 0.25 mg/kg single bolus is as effective and well tolerated as alteplase 0.9 mg/kg infusion for IVT in AIS. Evidence from randomized control trials (RCTs) has shown effective and well tolerated expansion of the therapeutic window of IVT in the wake-up stroke and up to 9 h after last seen well, using advanced neuroimaging with computed tomography perfusion/MRI. Early evidence suggests that intra-arterial alteplase may help improve microcirculation in patients with large vessel occlusion following successful thrombectomy. However, more trials are required to confirm the results. Similarly, early evidence from a recent RCT showed that remote ischemic conditioning confers potential neuroprotection and improves outcomes in AIS. SUMMARY Converging evidence has demonstrated that for patients with ischemic stroke presenting at under 4.5 h from the onset, TNK is comparable to alteplase. These data along with the practical advantages of TNK have resulted in a shift to replace intravenous TNK as the standard for thrombolysis. Ongoing studies of IVT with TNK are focussed on defining the optimal dose, expanding the time window with multimodal imaging and defining the role of thrombolysis for bridging patients with stroke due to large vessel occlusion.
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Affiliation(s)
- Radhika Nair
- Division of Neurology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
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11
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Robbins BT, Howington GT, Swafford K, Zummer J, Woolum JA. Advancements in the management of acute ischemic stroke: A narrative review. J Am Coll Emerg Physicians Open 2023; 4:e12896. [PMID: 36817082 PMCID: PMC9930740 DOI: 10.1002/emp2.12896] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2022] [Revised: 12/25/2022] [Accepted: 01/06/2023] [Indexed: 02/17/2023] Open
Abstract
Primary literature detailing updated management principles of acute ischemic stroke outpaces current guidelines, resulting in heterogenous practices. Recent advancements in neuroimaging have shifted treatment from a time-based approach to an individualized, image-guided appraisal directed by the presence or absence of salvageable brain tissue. In addition, tenecteplase appears to be a safe and effective for the treatment of acute ischemic stroke and is becoming an attractive agent due to its practical administration. Several factors must be accounted for when implementing tenecteplase into the health-system including cost, education, and changes in clinician workflows. Larger studies with broad patient populations are needed to more definitively evaluate whether intravenous thrombolytics should be used in combination with endovascular thrombectomy in patients with anterior large-vessel occlusions. Although debate regarding the safety and efficacy of various endovascular therapies, delays encountered in the identification, triage, and care of acute ischemic stroke patients increase the likelihood of necrotic core lesion development and loss of salvageable penumbra.
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Affiliation(s)
- Blake T. Robbins
- Department of PharmacyUniversity of Kentucky HealthCareLexingtonKentuckyUSA
| | - Gavin T. Howington
- Department of PharmacyUniversity of Kentucky HealthCareLexingtonKentuckyUSA
- Department of Pharmacy Practice and ScienceUniversity of Kentucky College of PharmacyLexingtonKentuckyUnited States
| | - Kara Swafford
- Department of NeurologyUniversity of Kentucky HealthCareLexingtonKentuckyUSA
| | - Jaryd Zummer
- Department of Emergency MedicineUniversity of Kentucky HealthCareLexingtonKentuckyUSA
| | - Jordan A. Woolum
- Department of PharmacyUniversity of Kentucky HealthCareLexingtonKentuckyUSA
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12
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Gou LK, Li C. Qixue Shuangbu decoction and acupuncture combined with Western medicine in acute severe stroke patients. World J Clin Cases 2023; 11:556-565. [PMID: 36793635 PMCID: PMC9923850 DOI: 10.12998/wjcc.v11.i3.556] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Revised: 06/18/2022] [Accepted: 12/21/2022] [Indexed: 01/23/2023] Open
Abstract
BACKGROUND Stroke is a common and frequently occurring disease of the nervous system and one of the three major diseases leading to human death. The incidence and mortality of stroke in China increase with age. Overall, 70 % of patients with stroke have serious disability, which results in heavy burden to their families and the society.
AIM To analyze the effects of Qixue Shuangbu decoction and acupuncture combined with Western medicine on immune indexes and digestive tract function in patients with acute severe stroke.
METHODS A total of 68 patients with acute severe stroke admitted to Lanzhou Second People’s Hospital between March 2018 and September 2021 were selected and divided into the control and observation groups according to a random number table method. The control group was administered routine Western medicine treatment, such as dehydration, lowering intracranial pressure, anticoagulation, improving cerebral blood circulation and cerebral nerve protection according to the “Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke in China.” The observation group was administered Qixue Shuangbu decoction via nasal feeding tube on the basis of the routine Western medicine treatment with simultaneous acupuncture. The two groups were compared.
RESULTS The acute physiology and chronic health evaluation II, organ dysfunction syndrome score, National Institutes of Health Stroke Scale, and traditional Chinese medicine syndrome scores of the two groups were significantly decreased compared with those measured before treatment, and the complements C3 and C4, and immunoglobulins (Ig) M and G were significantly increased compared with those observed before treatment (P < 0.05). After treatment, the scores of the observation group were lower than those of the control group, and the complement and Ig levels were higher than those of the control group (P < 0.05). The levels of diamine oxidase (DAO), D-lactic acid (D-LA), and calcitonin gene-related peptide (CGRP) in the two groups were significantly higher than those before treatment, while the levels of lipopolysaccharide, ubiquitin carboxyl-terminal hydrolase 1 (UCH-L1), tumor necrosis factor-α (TNF-α), interleukin (IL) -2, and IL-8 were significantly lower than those before treatment (P < 0.05). After treatment, DAO, D-LA, and CGRP were higher in the observation group than in the control group, while lipopolysaccharide, UCH-L1, TNF-α, IL-2, and IL-8 were lower than in the control group (P < 0.05). The hospitalization time of individuals in the observation group was shorter than that of the control group (P < 0.05).
CONCLUSION Qixue Shuangbu decoction and acupuncture combined with Western medicine for the treatment of acute severe stroke can regulate intestinal flora, reduce inflammation, improve intestinal mucosal barrier function and immune function related indicators, and promote recovery.
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Affiliation(s)
- Li-Kun Gou
- Department of Critical Care Medicine, Lanzhou Second People’s Hospital, Lanzhou 730046, Gansu Province, China
| | - Chun Li
- Department of Critical Care Medicine, Lanzhou Second People’s Hospital, Lanzhou 730046, Gansu Province, China
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13
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Wang J, Liu X, Li Q. Interventional strategies for ischemic stroke based on the modulation of the gut microbiota. Front Neurosci 2023; 17:1158057. [PMID: 36937662 PMCID: PMC10017736 DOI: 10.3389/fnins.2023.1158057] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Accepted: 02/20/2023] [Indexed: 03/06/2023] Open
Abstract
The microbiota-gut-brain axis connects the brain and the gut in a bidirectional manner. The organism's homeostasis is disrupted during an ischemic stroke (IS). Cerebral ischemia affects the intestinal flora and microbiota metabolites. Microbiome dysbiosis, on the other hand, exacerbates the severity of IS outcomes by inducing systemic inflammation. Some studies have recently provided novel insights into the pathogenesis, efficacy, prognosis, and treatment-related adverse events of the gut microbiome in IS. In this review, we discussed the view that the gut microbiome is of clinical value in personalized therapeutic regimens for IS. Based on recent non-clinical and clinical studies on stroke, we discussed new therapeutic strategies that might be developed by modulating gut bacterial flora. These strategies include dietary intervention, fecal microbiota transplantation, probiotics, antibiotics, traditional Chinese medication, and gut-derived stem cell transplantation. Although the gut microbiota-targeted intervention is optimistic, some issues need to be addressed before clinical translation. These issues include a deeper understanding of the potential underlying mechanisms, conducting larger longitudinal cohort studies on the gut microbiome and host responses with multiple layers of data, developing standardized protocols for conducting and reporting clinical analyses, and performing a clinical assessment of multiple large-scale IS cohorts. In this review, we presented certain opportunities and challenges that might be considered for developing effective strategies by manipulating the gut microbiome to improve the treatment and prevention of ischemic stroke.
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Tu WJ, Xu Y, Liu Y, Du J, Zhao J. Endovascular thrombectomy or bridging therapy in minor ischemic stroke with large vessel occlusion. Thromb Res 2022; 219:150-154. [PMID: 36183595 DOI: 10.1016/j.thromres.2022.09.020] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 09/19/2022] [Accepted: 09/22/2022] [Indexed: 11/25/2022]
Abstract
BACKGROUND Whether direct endovascular thrombectomy (EVT) is non-inferior to bridging therapy (intravenous thrombolysis [IVT] followed by EVT) in minor acute ischemic stroke due to large vessel occlusions (AIS-LVO) is not clear. Therefore, this study aimed to assess whether direct EVT is non-inferior to bridging therapy in minor AIS-LVO. METHODS 903 patients with acute ischemic stroke due to large vessel occlusion and National Institutes of Health Stroke Scale (NIHSS) score <6 receiving EVT treatment were enrolled at Bigdata Observatory Platform for Stroke of China in China from January 1, 2019, to December 31, 2020, with final follow-up on March 31, 2021. The primary efficacy endpoint was a favorable outcome defined as a modified Rankin Scale score of 0 to 2 at three months. In addition, there were three prespecified secondary efficacy endpoints, including symptomatic intracerebral hemorrhage (ICH), in-hospital mortality, and mortality by month 3. RESULTS A total of 662 patients treated with direct EVT (age 65.9 ± 10.5 years, 71.5 % male, NIHSS score 2.4 [standard deviation {SD}. 1.8]) were compared to 241 bridging-treated patients (age 65.7 ± 10.8, 75.9 % female, NIHSS score 2.5 [1.8]). The rate of symptomatic ICH in the EVT group was lower than in the bridging group (4.2 % vs. 8.3 %; P = 0.02). The in-hospital mortality was not different between the two groups (EVT vs. bridging group: adjusted hazard ratio {HR}, 0.9 [95 % confidence interval {CI}, 0.5 to 1.9]; P = 0.93). There was no significant difference in 3-month poor functional outcome rate (EVT vs. bridging group: 17.1 % vs. 16.2 % [absolute difference, 0.9 % {95 % CI, -0.8 % to 2.4 %}, P = 0.75; adjusted hazard ratio {HR}, 1.0 {95 % CI, 0.6 to 1.7}, P = 0.83]) and mortality rate (13.0 % vs. 11.2 % [absolute difference, 1.5 % {95 % CI, -3.9 % to 6.8 %}, P = 0.47; adjusted HR, 1.1 {95 % CI, 0.8 to 1.9}, P = 0.55]) between those two groups. CONCLUSION Among patients with minor AIS-LVO, direct EVT, compared with bridging therapy, met the prespecified statistical threshold for noninferiority for the 3-month prognosis.
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Affiliation(s)
- Wen-Jun Tu
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
| | - Yicheng Xu
- Department of Neurology, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine, Beijing, China
| | - Yakun Liu
- Department of General Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
| | - Jichen Du
- Department of Neurology, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine, Beijing, China.
| | - Jizong Zhao
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
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Wang Y, Wu H, Sheng H, Wang Y, Li X, Wang Y, Zhao L. Discovery of anti-stroke active substances in Guhong injection based on multi-phenotypic screening of zebrafish. Biomed Pharmacother 2022; 155:113744. [PMID: 36156365 DOI: 10.1016/j.biopha.2022.113744] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 09/20/2022] [Accepted: 09/21/2022] [Indexed: 11/02/2022] Open
Abstract
Ischemic stroke is a leading cause of death worldwide, and it remains an urgent task to develop novel and alternative therapeutic strategies for the disease. We previously reported the positive effects of Guhong injection (GHI), composed of safflower extract and aceglutamide, in promoting functional recovery in ischemic stroke mice. However, the active substances and pharmacological mechanism of GHI is still elusive. Aiming to identify the active anti-stroke components in GHI, here we conducted a multi-phenotypic screening in zebrafish models of phenylhydrazine-induced thrombosis and ponatinib-induced cerebral ischemia. Peripheral and cerebral blood flow was quantified endogenously in erythrocytes fluorescence-labeled thrombosis fish, and baicalein and rutin were identified as major anti-thrombotic substances in GHI. Moreover, using a high-throughput video-tracking system, the effects of locomotion promotion of GHI and its main compounds were analyzed in cerebral ischemia model. Chlorogenic acid and gallic acid showed significant effects in preventing locomotor dyfunctions. Finally, GHI treatment greatly decreased the expression levels of coagulation factors F7 and F2, NF-κB and its mediated proinflammatory cytokines in the fish models. Molecular docking suggested strong affinities between baicalein and F7, and between active substances (baicalein, chlorogenic acid, gallic acid, and rutin) and NF-κB p65. In summary, our findings established a novel drug discovery method based on multi-phenotypic screening of zebrafish, provided endogenous evidences of GHI in preventing thrombus formation and promoting behavioral recovery after cerebral ischemia, and identified baicalein, rutin, chlorogenic acid, and gallic acid as active compounds in the management of ischemic stroke.
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Affiliation(s)
- Yule Wang
- Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Xihu District, Hangzhou 310012, China
| | - Huimin Wu
- Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Xihu District, Hangzhou 310012, China
| | - Hongda Sheng
- Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Xihu District, Hangzhou 310012, China
| | - Yingchao Wang
- Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University, 291 Fucheng Road, Qiantang District, Hangzhou 310020, China
| | - Xuecai Li
- Tonghua Guhong Pharmaceutical Co., Ltd., 5099 Jianguo Road, Meihekou 135099, China
| | - Yi Wang
- Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Xihu District, Hangzhou 310012, China; Jinan Microecological Biomedicine Shandong Laboratory, 3716 Qingdao Road, Huaiyin District, Jinan 250117, China; State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Beihua South Road, Jinghai District, Tianjin 301617, China.
| | - Lu Zhao
- Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Xihu District, Hangzhou 310012, China.
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Li D, Li L, Quan F, Wang T, Xu S, Li S, Tian K, Feng M, He N, Tian L, Chen B, Zhang H, Wang L, Wang J. Identification of circulating immune landscape in ischemic stroke based on bioinformatics methods. Front Genet 2022; 13:921582. [PMID: 35957686 PMCID: PMC9358692 DOI: 10.3389/fgene.2022.921582] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2022] [Accepted: 07/06/2022] [Indexed: 11/19/2022] Open
Abstract
Ischemic stroke (IS) is a high-incidence disease that seriously threatens human life and health. Neuroinflammation and immune responses are key players in the pathophysiological processes of IS. However, the underlying immune mechanisms are not fully understood. In this study, we attempted to identify several immune biomarkers associated with IS. We first retrospectively collected validated human IS immune-related genes (IS-IRGs) as seed genes. Afterward, potential IS-IRGs were discovered by applying random walk with restart on the PPI network and the permutation test as a screening strategy. Doing so, the validated and potential sets of IS-IRGs were merged together as an IS-IRG catalog. Two microarray profiles were subsequently used to explore the expression patterns of the IS-IRG catalog, and only IS-IRGs that were differentially expressed between IS patients and controls in both profiles were retained for biomarker selection by the Random Forest rankings. CLEC4D and CD163 were finally identified as immune biomarkers of IS, and a classification model was constructed and verified based on the weights of two biomarkers obtained from the Neural Network algorithm. Furthermore, the CIBERSORT algorithm helped us determine the proportions of circulating immune cells. Correlation analyses between IS immune biomarkers and immune cell proportions demonstrated that CLEC4D was strongly correlated with the proportion of neutrophils (r = 0.72). These results may provide potential targets for further studies on immuno-neuroprotection therapies against reperfusion injury.
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Affiliation(s)
- Danyang Li
- Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Lifang Li
- Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Fei Quan
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China
| | - Tianfeng Wang
- Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Si Xu
- Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Shuang Li
- Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Kuo Tian
- Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Meng Feng
- Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Ni He
- Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Liting Tian
- Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Biying Chen
- Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Huixue Zhang
- Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
- *Correspondence: Huixue Zhang, ; Lihua Wang, ; Jianjian Wang,
| | - Lihua Wang
- Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
- *Correspondence: Huixue Zhang, ; Lihua Wang, ; Jianjian Wang,
| | - Jianjian Wang
- Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
- *Correspondence: Huixue Zhang, ; Lihua Wang, ; Jianjian Wang,
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17
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Risk Score for Symptomatic Intracranial Haemorrhage in Patients with Acute Ischaemic Stroke Receiving Endovascular Treatment. Clin Neurol Neurosurg 2022; 215:107184. [DOI: 10.1016/j.clineuro.2022.107184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 02/19/2022] [Accepted: 02/22/2022] [Indexed: 11/18/2022]
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18
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Quantitative analysis of thrombus migration before mechanical thrombectomy: Determinants and relationship with procedural and clinical outcomes. J Neuroradiol 2021; 49:385-391. [PMID: 34808221 DOI: 10.1016/j.neurad.2021.11.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 11/11/2021] [Accepted: 11/13/2021] [Indexed: 10/19/2022]
Abstract
BACKGROUND AND PURPOSE In patients with acute ischemic stroke (AIS) and a large vessel occlusion (LVO), thrombus migration (T-Mig) is a common phenomenon before mechanical thrombectomy (MT), revealed by pre-treatment imaging. Previous works have used qualitative scales to define T-Mig. The aim of this study was to evaluate the determinants and impact of quantitatively assessed T-Mig on procedural characteristics and clinical outcome. METHODS Consecutive patients with AIS due to LVO treated by MT at a reference academic hospital were analysed. Distance between vessel origin and beginning of the thrombus on MRI (3D-time-of-flight and/or contrast-enhanced magnetic-resonance-angiography) and digital-substracted-angiography (DSA) were measured in millimeters using a curve tool. Thrombus migration was defined quantitatively as ∆TD calculated as the difference between pre-MT-DSA and MRI thrombus location. ∆TD was rated as significant if above 5mm. RESULTS A total of 267 patients were included (mean age 70±12 years; 46% females) were analyzed. Amongst them, 65 (24.3%) experienced any degree of T-Mig. T-Mig was found to be associated with iv-tPA administration prior to thrombectomy (β-estimate 2.52; 95% CI [1.25-3.79]; p<0.001), fewer device passes during thrombectomy (1.22±1.31 vs 1.66±0.99; p<0.05), and shorter pre-treatment thrombi (β-estimate -0.1millimeter; 95% CI [-0.27-0.07]; p<0.05). There was no association between T-Mig and a favourable outcome (defined by a 0-to-2 modified-Rankin-Scale at 3months, adjusted OR: 2.16 [0.93 - 5.02]; p=0.06) CONCLUSION: Thrombus migration happens in almost a fourth of our study sample, and its quantitative extent was associated with iv-tPA administration prior to MT, but not with clinical outcome.
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McDonough R, Ospel J, Kashani N, Kappelhof M, Liu J, Yang P, Majoie C, Roos Y, Goyal M. Influence of recent direct-to-EVT trials on practical decision-making for the treatment of acute ischemic stroke patients. Interv Neuroradiol 2021; 28:668-674. [PMID: 34787489 DOI: 10.1177/15910199211057984] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Current guidelines recommend that eligible acute ischemic stroke (AIS) patients receive intravenous alteplase (IVT) prior to endovascular treatment (EVT). Six randomized controlled trials recently sought to determine the risks of administering IVT prior to EVT, five of which have been published/presented. It is unclear whether and how the results of these trials will change guidelines. With the DEBATE survey, we assessed the influence of the recent trials on physicians' IVT treatment strategies in the setting of EVT for large vessel occlusion (LVO) stroke. METHODS Participants were provided with 15 direct-to-mothership case-scenarios of LVO stroke patients and asked whether they would treat with IVT + EVT or EVT alone, a) before publication/presentation of the direct-to-EVT trials, and b) now (knowing the trial results). Logistic regression clustered by respondent was performed to assess factors influencing the decision to adopt an EVT-alone paradigm after publication/presentation of the trial results. RESULTS 289 participants from 37 countries provided 4335 responses, of which 13.5% (584/4335) changed from an IVT + EVT strategy to EVT alone after knowing the trial results. Very few switched from EVT alone to IVT + EVT (8/4335, 0.18%). Scenarios involving a long thrombus (RR 1.88, 95%CI:1.56-2.26), cerebral micro-hemorrhages (RR 1.78, 95%CI:1.43-2.23), and an expected short time to recanalization (RR 1.46 95%CI:1.19-1.78) had the highest chance of participants switching to an EVT-only strategy. CONCLUSION In light of the recent direct-to-EVT trials, a sizeable proportion of stroke physicians appears to be rethinking IVT treatment strategies of EVT-eligible mothership patients with AIS due to LVO in specific situations.
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Affiliation(s)
- Rosalie McDonough
- Department of Diagnostic and Interventional Neuroradiology, 37734University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,Department of Diagnostic Imaging, Foothills Medical Center, 2129University of Calgary, Calgary, AB, Canada
| | - Johanna Ospel
- Division of Neuroradiology, Clinic of Radiology and Nuclear Medicine, 30262University Hospital Basel, University of Basel, Basel, Switzerland
| | - Nima Kashani
- Department of Diagnostic Imaging, Foothills Medical Center, 2129University of Calgary, Calgary, AB, Canada
| | - Manon Kappelhof
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Jianmin Liu
- Department of Neurosurgery, Changhai Hospital, 12521Naval Medical University, Shanghai, China
| | - Pengfei Yang
- Department of Neurosurgery, Changhai Hospital, 12521Naval Medical University, Shanghai, China
| | - Charles Majoie
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Yvo Roos
- Department of Neurology, University of Amsterdam, Amsterdam, The Netherlands
| | - Mayank Goyal
- Department of Diagnostic Imaging, Foothills Medical Center, 2129University of Calgary, Calgary, AB, Canada
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20
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Zhu B, Yan L, Ren H, Li Q, Chen X. Predictive Value of Apelin and Vaspin on Hemorrhagic Transformation in Patients with Acute Ischemic Stroke after Intravenous Thrombolysis and Analysis of Related Factors. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2021; 2021:5020622. [PMID: 34707670 PMCID: PMC8545532 DOI: 10.1155/2021/5020622] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Accepted: 09/29/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND Acute ischemic stroke (CIS) is a high-risk condition among the elderly, and intravenous thrombolytic therapy (ITT) is the most effective means for it. However, ITT is prone to induce hemorrhagic transformation (HT) that further threatens the life and health of patients. As paramount substances in cardiovascular and cerebrovascular diseases, adipocyte factor (Apelin) and serine protease inhibitor (Vaspin) are strongly bound up with CIS. OBJECTIVE To analyze the predictive significance of Apelin and Vaspin on HT in CIS patients after ITT and offer effective reference to HT prevention in the future. METHODS A total of 109 CIS patients treated with intravenous thrombolysis (IT) in two hospitals between June 2017 and February 2018 were enrolled. Among them, 48 patients who suffered HT after therapy were assigned to the research group (Res group) and the other 61 patients who did not suffer it after therapy were assigned to the control group (Con group). Serum Apelin, Vaspin, inflammatory factors, and oxidative stress levels were quantified, and receiver operating characteristic (ROC) curves were drawn for analyzing the predictive value of Apelin and Vaspin on HT after ITT and their associations with inflammatory factors and oxidative stress. CIS patients who suffered HT were followed up for 3 years for prognostic significance analysis of Apelin and Vaspin. RESULTS After ITT, the Res group showed lower Apelin and Vaspin levels than the Con group (all P < 0.05), and patients with a higher HT grade had lower Apelin and Vaspin levels (all P < 0.05). The joint detection of Apelin and Vaspin showed a sensitivity of 77.08% and a specificity of 73.77% for forecasting HT in CIS patients after thrombolytic therapy (all P < 0.001). In addition, after thrombolytic therapy, the Res group presented higher levels of interleukin-1β (IL-1β) and IL-6 as well as malondialdehyde (MDA) than the Con group, and the levels had negative associations with Apelin and Vaspin (all P < 0.05). The Res group showed a lower superoxide dismutase (SOD) level than the Con group, and the level presented a positive association with Apelin and Vaspin (all P < 0.05). According to Logistic analysis, IL-1β, IL-6, and MDA were independent risk factors for HT in CIS patients after IT, while Apelin, Vaspin, and SOD were independent protective factors (all P < 0.05). According to the follow-up results, Apelin and Vaspin demonstrated excellent value in forecasting the death of patients with both CIS and HT (P < 0.05), and their lower levels indicate a higher risk of death (all P < 0.05). CONCLUSION Apelin and Vaspin can help effectively forecast the occurrence of HT in CIS patients after ITT as independent protective factors of HT, so they are of a high clinical application value.
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Affiliation(s)
- Benju Zhu
- Department of Neurology, Shanghai Eighth People's Hospital, Shanghai 200235, China
| | - Lili Yan
- Department of Neurology, Kailuan General Hospital, Tangshan 067000, Hebei, China
| | - Haiyan Ren
- Department of Neurology, Shanghai Eighth People's Hospital, Shanghai 200235, China
| | - Qiang Li
- Department of Neurology, Shanghai Eighth People's Hospital, Shanghai 200235, China
| | - Xu Chen
- Department of Neurology, Shanghai Eighth People's Hospital, Shanghai 200235, China
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21
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Mokin M, Waqas M, Fifi JT, De Leacy R, Fiorella D, Levy EI, Snyder K, Hanel RA, Woodward K, Chaudry I, Rai AT, Frei D, Delgado Almandoz JE, Kelly M, Arthur AS, Baxter BW, English J, Linfante I, Fargen KM, Turk A, Mocco J, Siddiqui AH. Intravenous alteplase has different effects on the efficacy of aspiration and stent retriever thrombectomy: analysis of the COMPASS trial. J Neurointerv Surg 2021; 14:992-996. [PMID: 34649935 DOI: 10.1136/neurintsurg-2021-017943] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 09/30/2021] [Indexed: 01/01/2023]
Abstract
BACKGROUND There is conflicting evidence on the utility of intravenous (IV) alteplase in patients with emergent large vessel occlusion (ELVO) treated with mechanical thrombectomy (MT). METHODS This was a post hoc analysis of the COMPASS: a trial of aspiration thrombectomy versus stent retriever thrombectomy as first-line approach for large vessel occlusion. We compared clinical, procedural and angiographic outcomes of patients with and without prior IV alteplase administration. RESULTS In the COMPASS trial, 235 patients had presented to the hospital within the first 4 hours of stroke symptom onset and were eligible for analysis. On univariate analysis, administration of IV alteplase prior to MT was found to be significantly associated with favorable outcomes (modified Rankin scale (mRS) 0-2 at 3 months; 55.6% vs 40.0% in the MT-only group, P=0.037). However, on multivariate analysis, only baseline (pre-stroke) mRS, admission National Institutes of Health Stroke Scale (NIHSS) score and age were identified as independent predictors of favorable outcomes at 3 months. We found higher final thrombolysis in cerebral infarction (TICI) 2b/3 rates in patients without the use of alteplase prior to the aspiration first approach (100.0% vs 87.9% in IV altepase +aspiration first MT, P=0.03). In the stent retriever first group, final TICI 2b/3 rates were identical in patients with and without IV alteplase administration (87.5% and 87.5%, P=1.0). CONCLUSIONS Prior administration of IV alteplase may adversely affect the efficacy of aspiration, but does not seem to influence the stent retriever first approach to MT in patients with anterior circulation ELVO.
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Affiliation(s)
- Maxim Mokin
- Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, Tampa, Florida, USA
| | - Muhammad Waqas
- Department of Neurosurgery, University at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York, USA
| | - Johanna T Fifi
- Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Reade De Leacy
- Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - David Fiorella
- Department of Neurosurgery, Stony Brook University, Stony Brook, New York, USA
| | - Elad I Levy
- Department of Neurosurgery, University at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York, USA
| | - Kenneth Snyder
- Department of Neurosurgery, University at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York, USA
| | - Ricardo A Hanel
- Lyerly Neurosurgery, Baptist Medical Center Downtown, Jacksonville, Florida, USA
| | - Keith Woodward
- Fort Sanders Regional Medical Center, Knoxville, Tennessee, USA
| | - Imran Chaudry
- Neurosurgery, Prisma Health Upstate, Greenville, South Carolina, USA
| | - Ansaar T Rai
- Interventional Neuroradiology, West Virginia University Rockefeller Neuroscience Institute, Morgantown, West Virginia, USA
| | - Donald Frei
- Interventional Neuroradiology, Radiology Imaging Associates, Englewood, Colorado, USA
| | | | - Michael Kelly
- Neurosurgery, Royal University Hospital, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - Adam S Arthur
- Semmes-Murphey Neurologic and Spine Institute, Memphis, Tennessee, USA
| | | | - Joey English
- Neurology and Radiology, University of California San Francisco (UCSF), San Francisco, California, USA
| | - Italo Linfante
- Baptist Cardiac and Vascular Institute, Miami, Florida, USA
| | - Kyle M Fargen
- Neurological Surgery and Radiology, Wake Forest University, Winston-Salem, North Carolina, USA
| | - Aquilla Turk
- Neurosurgery, Prisma Health Upstate, Greenville, South Carolina, USA
| | - J Mocco
- Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Adnan H Siddiqui
- Department of Neurosurgery, University at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York, USA
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22
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Zhang J, Chen S, Shi S, Zhang Y, Kong D, Xie Y, Deng X, Tang J, Luo J, Liang Z. Direct endovascular treatment versus bridging therapy in patients with acute ischemic stroke eligible for intravenous thrombolysis: systematic review and meta-analysis. J Neurointerv Surg 2021; 14:321-325. [PMID: 34349014 DOI: 10.1136/neurintsurg-2021-017928] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Accepted: 07/26/2021] [Indexed: 01/17/2023]
Abstract
OBJECTIVE In this review and meta-analysis we sought to compare the efficacy and safety of direct endovascular thrombectomy (EVT) and bridging therapy for intravenous thrombolysis (IVT)-eligible patients with acute ischemic stroke caused by large vessel occlusions (AIS-LVO). METHODS We searched Medline, Embase, and the Cochrane Library for published randomized clinical trials (RCTs) and observational studies providing outcomes of patients with IVT-eligible AIS-LVO who have undergone EVT with or without IVT. The primary outcome was the proportion of patients achieving a modified Rankin Scale (mRS) score of 0-2 at 90 days. The secondary outcomes included the rates of (1) an excellent outcome defined as an mRS score of 0 or 1 at 90 days, (2) mortality at 90 days, (3) symptomatic intracranial hemorrhage (sICH), (4) any type of intracranial hemorrhage (ICH), (5) successful recanalization, and (6) clot migration. RESULTS We included three RCTs and six observational studies (4 of which were propensity score-adjusted studies) with a total of 3133 patients. In unadjusted and adjusted analyses, no differences in the rates of mRS scores 0-2, mRS scores 0-1, mortality at 90 days, sICH or successful recanalization were detected between patients with AIS-LVO who underwent direct EVT or bridging therapy. The patients treated with direct EVT had a lower risk ratio for any type of ICH and clot migration than did the patients treated with bridging therapy. CONCLUSION Compared with bridging therapy, direct EVT may be equally effective and yield a lower rate of ICH and clot migration in patients with AIS. TRAIL REGISTRATION NUMBER PROSPERO: CRD42021236691.
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Affiliation(s)
- Jian Zhang
- Department of Neurology, Guangxi Medical University First Affiliated Hospital, Nanning, China
| | - Shijian Chen
- Department of Neurology, Guangxi Medical University First Affiliated Hospital, Nanning, China
| | - Shengliang Shi
- Department of Neurology, Guangxi Medical University Second Affiliated Hospital, Nanning, China
| | - Yueling Zhang
- Department of Neurology, Guangxi Medical University Second Affiliated Hospital, Nanning, China
| | - Deyan Kong
- Department of Neurology, Guangxi Medical University Second Affiliated Hospital, Nanning, China
| | - Yiju Xie
- Department of Neurology, Guangxi Medical University First Affiliated Hospital, Nanning, China
| | - Xuhui Deng
- Department of Neurology, Guangxi Medical University First Affiliated Hospital, Nanning, China
| | - Jian Tang
- Department of Neurology, Guangxi Medical University Second Affiliated Hospital, Nanning, China
| | - Jinglian Luo
- Department of Neurology, Guangxi Medical University Second Affiliated Hospital, Nanning, China
| | - Zhijian Liang
- Department of Neurology, Guangxi Medical University First Affiliated Hospital, Nanning, China
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23
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Lin CH, Saver JL, Ovbiagele B, Huang WY, Lee M. Endovascular thrombectomy without versus with intravenous thrombolysis in acute ischemic stroke: a non-inferiority meta-analysis of randomized clinical trials. J Neurointerv Surg 2021; 14:227-232. [PMID: 34266909 PMCID: PMC8862103 DOI: 10.1136/neurintsurg-2021-017667] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 06/25/2021] [Indexed: 11/03/2022]
Abstract
OBJECTIVE To conduct a meta-analysis of randomized trials to comprehensively compare the effect of endovascular thrombectomy (EVT) versus intravenous thrombolysis (IVT) plus EVT on functional independence (modified Rankin Scale (mRS) 0-2) after acute ischemic stroke due to large vessel occlusions (AIS-LVO). METHODS We searched Pubmed, EMBASE, CENTRAL, and clinicaltrials.gov from January 2000 to February 2021 and abstracts presented at the International Stroke Conference in March 2021 to identify trials comparing EVT alone versus IVT plus EVT in AIS-LVO. Five non-inferiority margins established in the literature were assessed: -15%, -10%, -6.5%, -5%, and -1.3% for the risk difference for functional independence at 90 days. RESULTS Four trials met the selection criteria, enrolling 1633 individuals, with 817 participants randomly assigned to EVT alone and 816 to IVT plus EVT. Crude cumulative rates of 90-day functional independence were 46.0% with EVT alone versus 45.5% with IVT plus EVT. Pooled results showed the risk difference of functional independence was 1% (95% CI -4% to 5%) between EVT alone versus IVT plus EVT. The lower 95% CI bound of -4% fell within the non-inferiority margins of -15%, -10%, -6.5%, and -5%, but not -1.3%. Pooled results also showed the risk difference between EVT alone versus IVT plus EVT was 1% (95% CI -3% to 5%) for mRS 0-1, and 1% (95% CI -1% to 3%) for symptomatic intracranial hemorrhage. CONCLUSIONS This meta-analysis suggests that EVT alone is non-inferior to IVT plus EVT for several, but not the most stringent, non-inferiority margins.
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Affiliation(s)
- Chun-Hsien Lin
- Department of Neurology, Chang Gung University College of Medicine, Chang Gung Memorial Hospital, Chiayi Branch, Puzi, Taiwan
| | - Jeffrey L Saver
- Department of Neurology and Stroke Center, University of California, Los Angeles (UCLA), Los Angeles, California, USA
| | - Bruce Ovbiagele
- Department of Neurology, University of California, San Francisco, California, USA
| | - Wen-Yi Huang
- Department of Neurology, Chang Gung University College of Medicine, Chang Gung Memorial Hospital, Keelung Branch, Keelung, Taiwan
| | - Meng Lee
- Department of Neurology, Chang Gung University College of Medicine, Chang Gung Memorial Hospital, Chiayi Branch, Puzi, Taiwan
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24
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Brenna CTA, Ku JC, Pasarikovski CR, Priola SM, Dyer EE, Howard P, Kumar A, da Costa L, Yang VXD. Access-site complications in ultrasound-guided endovascular thrombectomy: a single-institution retrospective cohort study. Neurosurg Focus 2021; 51:E3. [PMID: 34198250 DOI: 10.3171/2021.4.focus2198] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Accepted: 04/06/2021] [Indexed: 11/06/2022]
Abstract
OBJECTIVE Mechanical endovascular thrombectomy (EVT) is an increasingly relied-on treatment for clot retrieval in the context of ischemic strokes, which otherwise are associated with significant morbidity and mortality. Despite several known risks associated with this procedure, there is a high degree of technical heterogeneity across both centers and operators. The most common procedural complications occur at the point of transfemoral access (the common femoral artery), and include access-site hematomas, dissections, and pseudoaneurysms. Other interventional fields have previously popularized the use of ultrasound to enhance the anatomical localization of structures relevant to vascular access and thereby reducing access-site complications. In this study, the authors aimed to describe the ultrasound-guided EVT technique performed at a large, quaternary neurovascular referral center, and to characterize the effects of ultrasound guidance on access-site complications. METHODS A retrospective chart review of all patients treated with EVT at a single center between January 2013 and August 2020 was performed. Patients in this cohort were treated using a universal, unique, ultrasound-guided, single-wall puncture technique, which bears several theoretical advantages over the standard technique of arterial puncture via palpation. RESULTS There were 479 patients treated with EVT within the study period. Twenty patients in the cohort were identified as having experienced some form of access-site complication. Eight (1.67%) of these patients experienced minor access-site complications, all of which were groin hematomas and none of which were clinically significant, as defined by requiring surgical or interventional management or transfusion. The remaining 12 patients experienced arterial dissection (n = 5), arterial pseudoaneurysm (n = 4), retroperitoneal hematoma (n = 2), or arterial occlusion (n = 1), with only 1.04% (5/479) requiring surgical or interventional management or transfusion. CONCLUSIONS The authors found an overall reduction in total access-site complications as well as minor access-site complications in the study cohort compared with previously published randomized controlled trials and observational studies in the recent literature. The findings suggested that there may be a role for routine use of ultrasound-guided puncture techniques in EVT to decrease rates of complications.
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Affiliation(s)
| | - Jerry C Ku
- 2Division of Neurosurgery, Department of Surgery, University of Toronto.,3Division of Neurosurgery, Sunnybrook Health Sciences Centre, Toronto
| | - Christopher R Pasarikovski
- 2Division of Neurosurgery, Department of Surgery, University of Toronto.,3Division of Neurosurgery, Sunnybrook Health Sciences Centre, Toronto
| | - Stefano M Priola
- 4Department of Neurosurgery, Health Sciences North, Northern Ontario School of Medicine, Sudbury
| | - Erin E Dyer
- 5Division of Neurosurgery, Windsor Regional Hospital, Windsor; and
| | - Peter Howard
- 6Division of Neuroradiology, Department of Medical Imaging, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
| | - Ashish Kumar
- 2Division of Neurosurgery, Department of Surgery, University of Toronto.,3Division of Neurosurgery, Sunnybrook Health Sciences Centre, Toronto
| | - Leodante da Costa
- 2Division of Neurosurgery, Department of Surgery, University of Toronto.,3Division of Neurosurgery, Sunnybrook Health Sciences Centre, Toronto.,6Division of Neuroradiology, Department of Medical Imaging, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
| | - Victor X D Yang
- 2Division of Neurosurgery, Department of Surgery, University of Toronto.,3Division of Neurosurgery, Sunnybrook Health Sciences Centre, Toronto
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25
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Magoufis G, Safouris A, Raphaeli G, Kargiotis O, Psychogios K, Krogias C, Palaiodimou L, Spiliopoulos S, Polizogopoulou E, Mantatzis M, Finitsis S, Karapanayiotides T, Ellul J, Bakola E, Brountzos E, Mitsias P, Giannopoulos S, Tsivgoulis G. Acute reperfusion therapies for acute ischemic stroke patients with unknown time of symptom onset or in extended time windows: an individualized approach. Ther Adv Neurol Disord 2021; 14:17562864211021182. [PMID: 34122624 PMCID: PMC8175833 DOI: 10.1177/17562864211021182] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Accepted: 05/10/2021] [Indexed: 02/05/2023] Open
Abstract
Recent randomized controlled clinical trials (RCTs) have revolutionized acute ischemic stroke care by extending the use of intravenous thrombolysis and endovascular reperfusion therapies in time windows that have been originally considered futile or even unsafe. Both systemic and endovascular reperfusion therapies have been shown to improve outcome in patients with wake-up strokes or symptom onset beyond 4.5 h for intravenous thrombolysis and beyond 6 h for endovascular treatment; however, they require advanced neuroimaging to select stroke patients safely. Experts have proposed simpler imaging algorithms but high-quality data on safety and efficacy are currently missing. RCTs used diverse imaging and clinical inclusion criteria for patient selection during the dawn of this novel stroke treatment paradigm. After taking into consideration the dismal prognosis of nonrecanalized ischemic stroke patients and the substantial clinical benefit of reperfusion therapies in selected late presenters, we propose rescue reperfusion therapies for acute ischemic stroke patients not fulfilling all clinical and imaging inclusion criteria as an option in a subgroup of patients with clinical and radiological profiles suggesting low risk for complications, notably hemorrhagic transformation as well as local or remote parenchymal hemorrhage. Incorporating new data to treatment algorithms may seem perplexing to stroke physicians, since treatment and imaging capabilities of each stroke center may dictate diverse treatment pathways. This narrative review will summarize current data that will assist clinicians in the selection of those late presenters that will most likely benefit from acute reperfusion therapies. Different treatment algorithms are provided according to available neuroimaging and endovascular treatment capabilities.
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Affiliation(s)
- Georgios Magoufis
- Interventional Neuroradiology Unit, Metropolitan Hospital, Piraeus, Greece
| | - Apostolos Safouris
- Stroke Unit, Metropolitan Hospital, Piraeus, Greece
- Interventional Neuroradiology Unit, Rabin Medical Center, Beilinson Hospital, Petach-Tikva, Israel
- Second Department of Neurology, National & Kapodistrian University of Athens, School of Medicine, “Attikon” University Hospital, Athens, Greece
| | - Guy Raphaeli
- Interventional Neuroradiology Unit, Rabin Medical Center, Beilinson Hospital, Petach-Tikva, Israel
| | | | - Klearchos Psychogios
- Stroke Unit, Metropolitan Hospital, Piraeus, Greece
- Second Department of Neurology, National & Kapodistrian University of Athens, School of Medicine, “Attikon” University Hospital, Athens, Greece
| | - Christos Krogias
- Department of Neurology, St. Josef-Hospital, Ruhr University Bochum, Bochum, Germany
| | - Lina Palaiodimou
- Second Department of Neurology, National & Kapodistrian University of Athens, School of Medicine, “Attikon” University Hospital, Athens, Greece
| | - Stavros Spiliopoulos
- Second Department of Radiology, Interventional Radiology Unit, “ATTIKON” University General Hospital, Athens, Greece
| | - Eftihia Polizogopoulou
- Emergency Medicine Clinic, National & Kapodistrian University of Athens, School of Medicine, “Attikon” University Hospital, Athens, Greece
| | - Michael Mantatzis
- Department of Radiology, University Hospital of Alexandroupolis, Democritus University of Thrace, School of Medicine, Alexandroupolis, Greece
| | - Stephanos Finitsis
- Department of Interventional Radiology, AHEPA University General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Theodore Karapanayiotides
- Second Department of Neurology, Aristotle University of Thessaloniki, School of Medicine, Faculty of Health Sciences, AHEPA University Hospital, Thessaloniki, Greece
| | - John Ellul
- Department of Neurology, University Hospital of Patras, School of Medicine, University of Patras, Patras, Greece
| | - Eleni Bakola
- Second Department of Neurology, National & Kapodistrian University of Athens, School of Medicine, “Attikon” University Hospital, Athens, Greece
| | - Elias Brountzos
- Second Department of Radiology, Interventional Radiology Unit, “ATTIKON” University General Hospital, Athens, Greece
| | - Panayiotis Mitsias
- Department of Neurology Medical School, University of Crete, Heraklion, Crete, Greece
| | - Sotirios Giannopoulos
- Second Department of Neurology, National & Kapodistrian University of Athens, School of Medicine, “Attikon” University Hospital, Athens, Greece
| | - Georgios Tsivgoulis
- Second Department of Neurology, National & Kapodistrian, University of Athens, School of Medicine, “Attikon” University Hospital, Iras 39, Gerakas Attikis, Athens, 15344, Greece
- Department of Neurology, The University of Tennessee Health Science Center, Memphis, TN, USA
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Georgakopoulou T, van der Wijk AE, Bakker ENTP, vanBavel E. Recovery of Hypoxic Regions in a Rat Model of Microembolism. J Stroke Cerebrovasc Dis 2021; 30:105739. [PMID: 33765634 DOI: 10.1016/j.jstrokecerebrovasdis.2021.105739] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 03/01/2021] [Accepted: 03/02/2021] [Indexed: 12/27/2022] Open
Abstract
OBJECTIVES Endovascular treatment (EVT) has become the standard of care for acute ischemic stroke. Despite successful recanalization, a limited subset of patients benefits from the new treatment. Human MRI studies have shown that during removal of the thrombus, a shower of microclots is released from the initial thrombus, possibly causing new ischemic lesions. The aim of the current study is to quantify tissue damage following microembolism. MATERIALS AND METHODS In a rat model, microembolism was generated by injection of a mixture of polystyrene fluorescent microspheres (15, 25 and 50 µm in diameter). The animals were killed at three time-points: day 1, 3 or 7. AMIRA and IMARIS software was used for 3D reconstruction of brain structure and damage, respectively. CONCLUSIONS Microembolism induces ischemia, hypoxia and infarction. Infarcted areas persist, but hypoxic regions recover over time suggesting that repair processes in the brain rescue the regions at risk.
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Affiliation(s)
- Theodosia Georgakopoulou
- Amsterdam UMC, University of Amsterdam, Biomedical Engineering and Physics, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands.
| | - Anne-Eva van der Wijk
- Amsterdam UMC, University of Amsterdam, Biomedical Engineering and Physics, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands.
| | - Erik N T P Bakker
- Amsterdam UMC, University of Amsterdam, Biomedical Engineering and Physics, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands.
| | - Ed vanBavel
- Amsterdam UMC, University of Amsterdam, Biomedical Engineering and Physics, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands.
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