-
International Journal of Stroke :... Jun 2023There are multiple stroke guidelines globally. To synthesize these and summarize what existing stroke guidelines recommend about the management of people with stroke,...
BACKGROUND
There are multiple stroke guidelines globally. To synthesize these and summarize what existing stroke guidelines recommend about the management of people with stroke, the World Stroke Organization (WSO) Guideline committee, under the auspices of the WSO, reviewed available guidelines.
AIMS
To systematically review the literature to identify stroke guidelines (excluding primary stroke prevention and subarachnoid hemorrhage) since 1 January 2011, evaluate quality (The international Appraisal of Guidelines, Research and Evaluation (AGREE II)), tabulate strong recommendations, and judge applicability according to stroke care available (minimal, essential, advanced).
SUMMARY OF REVIEW
Searches identified 15,400 titles; 911 texts were retrieved, 200 publications scrutinized by the three subgroups (acute, secondary prevention, rehabilitation), and recommendations extracted from most recent version of relevant guidelines. For acute treatment, there were more guidelines about ischemic stroke than intracerebral hemorrhage; recommendations addressed pre-hospital, emergency, and acute hospital care. Strong recommendations were made for reperfusion therapies for acute ischemic stroke. For secondary prevention, strong recommendations included establishing etiological diagnosis; management of hypertension, weight, diabetes, lipids, and lifestyle modification; and for ischemic stroke, management of atrial fibrillation, valvular heart disease, left ventricular and atrial thrombi, patent foramen ovale, atherosclerotic extracranial large vessel disease, intracranial atherosclerotic disease, and antithrombotics in non-cardioembolic stroke. For rehabilitation, there were strong recommendations for organized stroke unit care, multidisciplinary rehabilitation, task-specific training, fitness training, and specific interventions for post-stroke impairments. Most recommendations were from high-income countries, and most did not consider comorbidity, resource implications, and implementation. Patient and public involvement was limited.
CONCLUSION
The review identified a number of areas of stroke care where there was strong consensus. However, there was extensive repetition and redundancy in guideline recommendations. Future guideline groups should consider closer collaboration to improve efficiency, include more people with lived experience in the development process, consider comorbidity, and advise on implementation.
Topics: Humans; Stroke; Ischemic Stroke; Hypertension; Exercise; Atrial Fibrillation
PubMed: 36725717
DOI: 10.1177/17474930231156753 -
Frontiers in Immunology 2022Cerebral infarction/ischemia-reperfusion injury is currently the disease with the highest mortality and disability rate of cardiovascular disease. Current studies have... (Review)
Review
Cerebral infarction/ischemia-reperfusion injury is currently the disease with the highest mortality and disability rate of cardiovascular disease. Current studies have shown that nerve cells die of ischemia several hours after ischemic stroke, which activates the innate immune response in the brain, promotes the production of neurotoxic substances such as inflammatory cytokines, chemokines, reactive oxygen species and - nitrogen oxide, and mediates the destruction of blood-brain barrier and the occurrence of a series of inflammatory cascade reactions. Meanwhile, the expression of adhesion molecules in cerebral vascular endothelial cells increased, and immune inflammatory cells such as polymorphonuclear neutrophils, lymphocytes and mononuclear macrophages passed through vascular endothelial cells and entered the brain tissue. These cells recognize antigens exposed by the central nervous system in the brain, activate adaptive immune responses, and further mediate secondary neuronal damage, aggravating neurological deficits. In order to reduce the above-mentioned damage, the body induces peripheral immunosuppressive responses through negative feedback, which increases the incidence of post-stroke infection. This process is accompanied by changes in the immune status of the ischemic brain tissue in local and systemic systems. A growing number of studies implicate noncoding RNAs (ncRNAs) as novel epigenetic regulatory elements in the dysfunction of various cell subsets in the neurovascular unit after cerebral infarction/ischemia-reperfusion injury. In particular, recent studies have revealed advances in ncRNA biology that greatly expand the understanding of epigenetic regulation of immune responses and inflammation after cerebral infarction/ischemia-reperfusion injury. Identification of aberrant expression patterns and associated biological effects of ncRNAs in patients revealed their potential as novel biomarkers and therapeutic targets for cerebral infarction/ischemia-reperfusion injury. Therefore, this review systematically presents recent studies on the involvement of ncRNAs in cerebral infarction/ischemia-reperfusion injury and neuroimmune inflammatory cascades, and elucidates the functions and mechanisms of cerebral infarction/ischemia-reperfusion-related ncRNAs, providing new opportunities for the discovery of disease biomarkers and targeted therapy. Furthermore, this review introduces clustered regularly interspaced short palindromic repeats (CRISPR)-Display as a possible transformative tool for studying lncRNAs. In the future, ncRNA is expected to be used as a target for diagnosing cerebral infarction/ischemia-reperfusion injury, judging its prognosis and treatment, thereby significantly improving the prognosis of patients.
Topics: Mice; Animals; Humans; RNA, Long Noncoding; Endothelial Cells; Reactive Oxygen Species; Neuroinflammatory Diseases; Epigenesis, Genetic; Mice, Inbred C57BL; Reperfusion Injury; Brain Ischemia; RNA, Untranslated; Cerebral Infarction; Inflammation; Cytokines
PubMed: 36275741
DOI: 10.3389/fimmu.2022.930171 -
International Journal of Emergency... Jan 2022Thrombolysis for acute ischemic stroke (AIS) with alteplase is the currently approved therapy for patients who present within 4.5 h of symptom onset and meet criteria.... (Review)
Review
INTRODUCTION
Thrombolysis for acute ischemic stroke (AIS) with alteplase is the currently approved therapy for patients who present within 4.5 h of symptom onset and meet criteria. Recently, there has been interest in the thrombolytic tenecteplase, a modified version of alteplase, due to its lower cost, ease of administration, and studies reporting better outcomes when compared to alteplase. This systematic review compares the efficacy of tenecteplase vs. alteplase with regard to three outcomes: (1) rate of symptomatic hemorrhage, (2) functional outcome at 90 days, and (3) reperfusion grade after thrombectomy to compare the efficacy of both thrombolytics in AIS METHODS: The search was conducted in August 2021 in PubMed, filtered for randomized controlled trials, and studies in English. The main search term was "tenecteplase for acute stroke."
RESULTS
A total of 6 randomized clinical trials including 1675 patients with AIS was included. No one's study compared alteplase to tenecteplase with all three outcomes after acute ischemic stroke; however, by using a combination of the results, this systematic review summarizes whether tenecteplase outperforms alteplase.
CONCLUSIONS
The available evidence suggests that tenecteplase appears to be a better thrombolytic agent for acute ischemic stroke when compared to alteplase.
PubMed: 34983359
DOI: 10.1186/s12245-021-00399-w -
International Journal of Surgery... Sep 2016Hepatic ischemia reperfusion injury (IRI) is not only a pathophysiological process involving the liver, but also a complex systemic process affecting multiple tissues... (Review)
Review
Hepatic ischemia reperfusion injury (IRI) is not only a pathophysiological process involving the liver, but also a complex systemic process affecting multiple tissues and organs. Hepatic IRI can seriously impair liver function, even producing irreversible damage, which causes a cascade of multiple organ dysfunction. Many factors, including anaerobic metabolism, mitochondrial damage, oxidative stress and secretion of ROS, intracellular Ca(2+) overload, cytokines and chemokines produced by KCs and neutrophils, and NO, are involved in the regulation of hepatic IRI processes. Matrix Metalloproteinases (MMPs) can be an important mediator of early leukocyte recruitment and target in acute and chronic liver injury associated to ischemia. MMPs and neutrophil gelatinase-associated lipocalin (NGAL) could be used as markers of I-R injury severity stages. This review explores the relationship between factors and inflammatory pathways that characterize hepatic IRI, MMPs and current pharmacological approaches to this disease.
Topics: Animals; Antioxidants; Biomarkers; Cytokines; Genetic Therapy; Hepatectomy; Kupffer Cells; Leukocytes; Liver; Liver Diseases; Liver Transplantation; Male; Matrix Metalloproteinases; Mitochondria, Liver; Oxidative Stress; Prognosis; Reperfusion Injury; Risk Assessment
PubMed: 27255130
DOI: 10.1016/j.ijsu.2016.05.050 -
JAMA Apr 2015Acute ischemic stroke is a major cause of mortality and morbidity in the United States. We review the latest data and evidence supporting catheter-directed treatment for... (Review)
Review
IMPORTANCE
Acute ischemic stroke is a major cause of mortality and morbidity in the United States. We review the latest data and evidence supporting catheter-directed treatment for proximal artery occlusion as an adjunct to intravenous thrombolysis in patients with acute stroke.
OBJECTIVE
To review the pathophysiology of acute brain ischemia and infarction and the evidence supporting various stroke reperfusion treatments.
EVIDENCE REVIEW
Systematic literature search of MEDLINE databases published between January 1, 1990, and February 11, 2015, was performed to identify studies addressing the role of thrombolysis and mechanical thrombectomy in acute stroke management. Studies included randomized clinical trials, observational studies, guideline statements, and review articles. Sixty-eight articles (N = 108,082 patients) were selected for review.
FINDINGS
Intravenous thrombolysis is the mainstay of acute ischemic stroke management for any patient with disabling deficits presenting within 4.5 hours from symptom onset. Randomized trials have demonstrated that more patients return to having good function (defined by being independent and having slight disability or less) when treated within 4.5 hours after symptom onset with intravenous recombinant tissue plasminogen activator (IV rtPA) therapy. Mechanical thrombectomy in select patients with acute ischemic stroke and proximal artery occlusions has demonstrated substantial rates of partial or complete arterial recanalization and improved outcomes compared with IV rtPA or best medical treatment alone in multiple randomized clinical trials. Regardless of mode of reperfusion, earlier reperfusion is associated with better clinical outcomes.
CONCLUSIONS AND RELEVANCE
Intravenous rtPA remains the standard of care for patients with moderate to severe neurological deficits who present within 4.5 hours of symptom onset. Outcomes for some patients with acute ischemic stroke and moderate to severe neurological deficits due to proximal artery occlusion are improved with endovascular reperfusion therapy. Efforts to hasten reperfusion therapy, regardless of the mode, should be undertaken within organized stroke systems of care.
Topics: Brain; Brain Infarction; Brain Ischemia; Endovascular Procedures; Fibrinolytic Agents; Humans; Infusions, Intravenous; Reperfusion; Stroke; Thrombectomy; Thrombolytic Therapy; Tissue Plasminogen Activator
PubMed: 25871671
DOI: 10.1001/jama.2015.3058 -
Brain and Behavior Oct 2019Approximately, half of the acute stroke patients with minor symptoms were excluded from thrombolysis in some randomized controlled trials (RCTs). There is little... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Approximately, half of the acute stroke patients with minor symptoms were excluded from thrombolysis in some randomized controlled trials (RCTs). There is little evidence on treating minor strokes with rt-PA. Here, we performed a systematic review and meta-analysis to assess the safety and efficacy of thrombolysis in these patients.
METHODS
PubMed, Embase, Web of Science, and Cochrane Library were searched in July 2018. All available RCTs and retrospective comparative studies that compared thrombolysis with nonthrombolysis' for acute minor stroke (NIHSS ≤ 5) with quantitative outcomes were included.
RESULTS
Ten studies, including a total of 4,333 patients, were identified. The risk of intracranial hemorrhage (ICH) was higher in the rt-PA group as compared with that in the non-rt-PA group (3.8% vs. 0.6%; p = .0001). However, there is no significant difference in the rate of mortality between the two groups (p = .96). The pooled rate of a good outcome in 90 days was 67.8% in those with rt-PA and 63.3% in those without rt-PA (p = .07). Heterogeneity was 43% between the studies (p = .08). After adjusting for the heterogeneity, thrombolysis was associated with good outcome (68.3% vs. 63.0%, OR 1.47; 95% CI 1.14-1.89; p = .003). In post hoc analyses, including only RCTs, the pooled rate of good outcome had no significant differences between the two groups (86.6% vs. 85.7%, 95% CI 0.44-3.17, p = .74; 87.4% vs. 91.9%, 95% CI 0.35-1.41, p = .32; before and after adjusting separately).
CONCLUSIONS
Although thrombolysis might increase the risk of ICH based on existing studies, patients with acute minor ischemic stroke could still benefit from thrombolysis at 3 months from the onset.
Topics: Fibrinolytic Agents; Humans; Male; Reperfusion; Retrospective Studies; Stroke; Thrombolytic Therapy; Tissue Plasminogen Activator; Treatment Outcome
PubMed: 31532082
DOI: 10.1002/brb3.1398 -
Journal of Integrative Neuroscience Mar 2023Early neurological deterioration (END), generally defined as the increment of National Institutes of Health Stroke Scale (NIHSS) score ≥4 within 24 hours, lead to poor... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Early neurological deterioration (END), generally defined as the increment of National Institutes of Health Stroke Scale (NIHSS) score ≥4 within 24 hours, lead to poor clinical outcome in acute ischemic stroke (AIS) patients receiving reperfusion therapies including intravenous thrombolysis (IVT) and/or endovascular treatment (EVT). This systematic review and meta-analysis aimed to explore multiple predictors of END following reperfusion therapies.
METHODS
We searched PubMed, Web of Science and EBSCO for all studies on END in AIS patients receiving IVT and/or EVT published between January 2000 and December 2022. A random-effects meta-analysis was conducted and presented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The quality of each included studies was assessed by calculating a total score according to the STROBE or CONSORT criteria. Publication bias and heterogeneity were also evaluated using the Eggers/Peters test, funnel plots and sensitivity analysis.
RESULTS
A total of 29 studies involving 65,960 AIS patients were included. The quality of evidence is moderate to high, and all studies have no publication bias. The overall incidence of END occurring after reperfusion therapy in AIS patients was 14% ((95% confidence intervals (CI), 12%-15%)). Age, systolic blood pressure (SBP), glucose levels at admission, the onset to treatment time (OTT), hypertension, diabetes mellitus, arterial fibrillation, and internal cerebral artery occlusion were significantly associated with END following reperfusion therapy.
CONCLUSIONS
Numerous factors are associated with END occurrence in AIS patients receiving reperfusion therapy. Management of the risk factors of END may improve the functional outcome after reperfusion treatment.
Topics: Humans; Stroke; Brain Ischemia; Ischemic Stroke; Fibrinolytic Agents; Treatment Outcome; Reperfusion
PubMed: 36992598
DOI: 10.31083/j.jin2202052 -
Journal of Translational Medicine May 2021Mitochondria are essential organelles that provide energy for cellular functions, participate in cellular signaling and growth, and facilitate cell death. Based on their... (Review)
Review
BACKGROUND
Mitochondria are essential organelles that provide energy for cellular functions, participate in cellular signaling and growth, and facilitate cell death. Based on their multifactorial roles, mitochondria are also critical in the progression of critical illnesses. Transplantation of mitochondria has been reported as a potential promising approach to treat critical illnesses, particularly ischemia reperfusion injury (IRI). However, a systematic review of the relevant literature has not been conducted to date. Here, we systematically reviewed the animal and human studies relevant to IRI to summarize the evidence for mitochondrial transplantation.
METHODS
We searched MEDLINE, the Cochrane library, and Embase and performed a systematic review of mitochondrial transplantation for IRI in both preclinical and clinical studies. We developed a search strategy using a combination of keywords and Medical Subject Heading/Emtree terms. Studies including cell-mediated transfer of mitochondria as a transfer method were excluded. Data were extracted to a tailored template, and data synthesis was descriptive because the data were not suitable for meta-analysis.
RESULTS
Overall, we identified 20 animal studies and two human studies. Among animal studies, 14 (70%) studies focused on either brain or heart IRI. Both autograft and allograft mitochondrial transplantation were used in 17 (85%) animal studies. The designs of the animal studies were heterogeneous in terms of the route of administration, timing of transplantation, and dosage used. Twelve (60%) studies were performed in a blinded manner. All animal studies reported that mitochondrial transplantation markedly mitigated IRI in the target tissues, but there was variation in biological biomarkers and pathological changes. The human studies were conducted with a single-arm, unblinded design, in which autologous mitochondrial transplantation was applied to pediatric patients who required extracorporeal membrane oxygenation (ECMO) for IRI-associated myocardial dysfunction after cardiac surgery.
CONCLUSION
The evidence gathered from our systematic review supports the potential beneficial effects of mitochondrial transplantation after IRI, but its clinical translation remains limited. Further investigations are thus required to explore the mechanisms of action and patient outcomes in critical settings after mitochondrial transplantation. Systematic review registration The study was registered at UMIN under the registration number UMIN000043347.
Topics: Animals; Cell Death; Child; Humans; Mitochondria; Reperfusion Injury
PubMed: 34001191
DOI: 10.1186/s12967-021-02878-3 -
Neurology Apr 2024Remote ischemic conditioning (RIC) is a low-cost, accessible, and noninvasive neuroprotective treatment strategy, but its efficacy and safety in acute ischemic stroke... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
Remote ischemic conditioning (RIC) is a low-cost, accessible, and noninvasive neuroprotective treatment strategy, but its efficacy and safety in acute ischemic stroke are controversial. With the publication of several randomized controlled trials (RCTs) and the recent results of the RESIST trial, it may be possible to identify the patient population that may (or may not) benefit from RIC. This systematic review and meta-analysis aims to evaluate the effectiveness and safety of RIC in patients with ischemic stroke receiving different treatments by pooling data of all randomized controlled studies to date.
METHODS
We searched the PubMed, Embase, Cochrane, Elsevier, and Web of Science databases to obtain articles in all languages from inception until May 25, 2023. The primary outcome was the modified Rankin Scale (mRS) score at the specified endpoint time in the trial. The secondary outcomes were change in NIH Stroke Scale (NIHSS) and recurrence of stroke events. The safety outcomes were cardiovascular events, cerebral hemorrhage, and mortality. The quality of articles was evaluated through the Cochrane risk assessment tool. This study was registered in PROSPERO (CRD42023430073).
RESULTS
There were 7,657 patients from 22 RCTs included. Compared with the control group, patients who received RIC did not have improved mRS functional outcomes, regardless of whether they received medical management, reperfusion therapy with intravenous thrombolysis (IVT), or mechanical thrombectomy (MT). In the medical management group, patients who received RIC had decreased incidence of stroke recurrence (risk ratio 0.63, 95% CI 0.43-0.92, = 0.02) and lower follow-up NIHSS score by 1.72 points compared with the control group ( < 0.00001). There was no increased risk of adverse events including death or cerebral hemorrhage in the IVT or medical management group.
DISCUSSION
In patients with ischemic stroke who are not eligible for reperfusion therapy, RIC did not affect mRS functional outcomes but significantly improved the NIHSS score at the follow-up endpoint and reduced stroke recurrence, without increasing the risk of cerebral hemorrhage or death. In patients who received IVT or MT, the benefit of RIC was not observed.
Topics: Humans; Fibrinolytic Agents; Brain Ischemia; Thrombolytic Therapy; Stroke; Cerebral Hemorrhage; Ischemic Stroke; Reperfusion; Treatment Outcome; Thrombectomy
PubMed: 38457772
DOI: 10.1212/WNL.0000000000207983 -
Interventional Neuroradiology : Journal... Jun 2023Limited randomized controlled trials (RCTs) have been performed comparing endovascular thrombectomy (EVT) to medical therapy (MEDT) for acute ischemic stroke with... (Review)
Review
BACKGROUND
Limited randomized controlled trials (RCTs) have been performed comparing endovascular thrombectomy (EVT) to medical therapy (MEDT) for acute ischemic stroke with extensive baseline ischemic injury (AIS-EBI). We conducted a systematic review and meta-analysis of RCTs reporting EVT for AIS-EBI.
METHODS
Using the Nested Knowledge AutoLit software, we conducted a systematic literature review from inception to 12 February 2023 within Web of Science, Embase, Scopus, and PubMed databases. Results of the TESLA trial were included on 10 June 2023. We included RCTs that compared EVT to MEDT for AIS with large ischemic core volume. The primary outcome of interest was a modified Rankin Score (mRS) 0-2. Secondary outcomes of interest included early neurological improvement (ENI), mRS 0-3, thrombolysis in cerebral infarction (TICI) 2b-3, symptomatic intracranial hemorrhage (sICH), and mortality. A random-effects model was used to calculate risk ratios (RRs) and their corresponding 95% confidence intervals (CIs).
RESULTS
We included four RCTs with 1310 patients, 661 of whom underwent EVT and 649 of whom were treated with MEDT. EVT was associated with greater rates of mRS 0-2 (RR = 2.33, 95% CI = 1.75-3.09; -value < 0.001), mRS 0-3 (RR = 1.68, 95% CI = 1.33-2.12; -value < 0.001), and ENI (RR = 2.24, 95% CI = 1.55-3.24; -value < 0.001). Rates of sICH (RR = 1.99, 95% CI = 1.07-3.69; -value = 0.03) were greater in the EVT group. Mortality (RR = 0.98, 95% CI = 0.83-1.15; -value = 0.79) was comparable between the EVT and MEDT groups. The rate of successful reperfusion in the EVT group was 79.9% (95% CI = 75.6-83.6).
CONCLUSIONS
Although the rate of sICH was greater in the EVT group, EVT conferred a greater clinical benefit to MEDT for AIS-EBI based on available RCTs.
PubMed: 37376869
DOI: 10.1177/15910199231185738