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Over the past 20 years, clinical research has focused on the development of reperfusion therapies for acute ischemic stroke (AIS), which include the use of systemic intravenous thrombolytics (alteplase, desmoteplase, or tenecteplase), the augmentation of systemic intravenous recanalization with ultrasound, the bridging of intravenous with intra-art...
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Background and Purpose
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Citations
... Reperfusion is a therapeutic technique used to treat ischemic stroke and involves the infusion of tissue plasminogen activator (t-PA) or mechanical thrombectomy (MT). 33 To overcome this problem, numerous neuroprotectants have been developed to reduce reperfusion-induced damage. However, all of them lack clinical approval because drugs cannot be effectively delivered to the brain through the BBB, drugs that circulate quickly, are unstable or poisonous, and it is difficult to select the proper drug regimen and dosages because of heterogenicity. ...
New nanotechnology strategies for enhancing drug delivery in brain disorders have recently received increasing attention from drug designers. The treatment of neurological conditions, including brain tumors, stroke, Parkinson’s Disease (PD), and Alzheimer’s disease (AD), may be greatly influenced by nanotechnology. Numerous studies on neurodegeneration have demonstrated the effective application of nanomaterials in the treatment of brain illnesses. Nanocarriers (NCs) have made it easier to deliver drugs precisely to where they are needed. Thus, the most effective use of nanomaterials is in the treatment of various brain diseases, as this amplifies the overall impact of medication and emphasizes the significance of nanotherapeutics through gene therapy, enzyme replacement therapy, and blood-barrier mechanisms. Recent advances in nanotechnology have led to the development of multifunctional nanotherapeutic agents, a promising treatment for brain disorders. This novel method reduces the side effects and improves treatment outcomes. This review critically assesses efficient nano-based systems in light of obstacles and outstanding achievements. Nanocarriers that transfer medications across the blood-brain barrier and nano-assisted therapies, including nano-immunotherapy, nano-gene therapy, nano enzyme replacement therapy, scaffolds, and 3D to 6D printing, have been widely explored for the treatment of brain disorders. This study aimed to evaluate existing literature regarding the use of nanotechnology in the development of drug delivery systems that can penetrate the blood-brain barrier (BBB) and deliver therapeutic agents to treat various brain disorders.
... Stroke is the main leading cause of mortality and disability in adults [1]. Nowadays, intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) is the primary reperfusion therapy with proven efficacy for managing acute ischaemic stroke, saving cerebral ischaemic tissue and reducing neurologic sequelae [2]. Unfortunately, the functional outcome after rt-PA thrombolysis is not always optimal, as some patients may still have some neurological deficits. ...
Background
The potential impact of insulin resistance on stroke prognosis after IV thrombolysis is poorly understood. This study aimed to assess the effect of insulin resistance and metabolic syndrome on the outcome of IV thrombolysis in non-diabetic patients with acute ischaemic stroke.
Methods
This prospective observational study was conducted on 70 non-diabetic acute ischaemic stroke patients who received rt-PA within 3 h of stroke onset. Patients were subjected to baseline and follow-up NIHSS measurements at 24 h and 3 months post-treatment. Stroke outcome was assessed after 3 months using the Modified Rankin Scale (mRS). The homeostasis model assessment–insulin resistance (HOMA-IR) was calculated for the included patients at stroke onset.
Results
The mean age of included patients was 57.04 ± 14.39 years. Patients with unfavourable outcome had a significantly higher frequency of insulin resistance and metabolic syndrome, higher values of baseline NIHSS, insulin, HOMA-IR, uric acid and lower levels of HDL than those with favourable outcome ( P value = 0.035, 0.007, ≤ 0.001, 0.001, ≤ 0.001, 0.002, 0.033, respectively). Each point increase in NIHSS before rt-PA increased the odds of an unfavourable outcome by 2.06 times (95% CI 1.22 − 3.478). Also, insulin resistance increased the odds of the unfavourable outcome by 11.046 times (95% CI 1.394–87.518). There was a statistically significant improvement in NIHSS 3 months after receiving rt-PA in all patients, significantly higher in patients who did not have insulin resistance or metabolic syndrome.
Conclusion
Insulin resistance and metabolic syndrome were associated with worse functional outcomes in non-diabetic stroke patients after receiving rt-PA.
... 2,3 Although tenecteplase has been the thrombolytic agent of choice for the treatment of acute myocardial infarction for decades, the use of tenecteplase in the treatment of patients with acute ischemic stroke (AIS) has not been officially approved to date. 4,5 Accumulating evidence from clinical trials suggests that tenecteplase might be an equally effective thrombolytic agent compared to alteplase for the treatment of patients with AIS who are eligible for intravenous thrombolysis (IVT). 6,7 In clinical trials enrolling AIS patients with confirmed large vessel occlusions (LVOs) eligible for IVT, tenecteplase was associated with higher odds of successful recanalization and more favorable clinical outcomes at 3 months compared to alteplase. ...
Objective:
Intravenous thrombolysis (IVT) with tenecteplase has been associated with better clinical outcomes in acute ischemic stroke (AIS) patients with confirmed large vessel occlusions compared to IVT with alteplase. However, the utility of tenecteplase for the treatment of all AIS patients eligible for IVT has not been established.
Methods:
We compared the safety and efficacy of tenecteplase versus alteplase in AIS patients by analyzing propensity score matched data from 20 centers participating in the Safe Implementation of Treatments in Stroke-International Stroke Thrombolysis Register. Patients receiving IVT with tenecteplase were matched with up to 3 patients receiving alteplase from the same center. The primary outcome of interest was the distribution of 3-month functional outcomes. Secondary outcomes included the rates of patients with symptomatic intracranial hemorrhage (SICH) in the first 24 hours, excellent (modified Rankin Scale [mRS] score = 0-1) or good (mRS score = 0-2) functional outcome, and all-cause mortality at 3 months.
Results:
A total of 331 tenecteplase-treated AIS patients were matched to 797 patients treated with alteplase (median age = 70 years, 43.9% women, median National Institutes of Health Stroke Scale score = 11, interquartile range = 6-17). Patients treated with tenecteplase had better 3-month functional outcomes (common odds ratio [OR] = 1.54, 95% confidence interval [CI] = 1.18-2.00) with higher odds of good functional outcome (OR = 2.00, 95% CI = 1.45-2.77) and a lower likelihood of all-cause mortality (OR = 0.43, 95% CI = 0.27-0.67) at 3 months, compared to alteplase-treated patients. No difference was found in the likelihood of the 3-month excellent functional outcomes (OR = 1.31, 95% CI = 0.96-1.78) and 24-hour SICH (1.0% vs 1.3%, OR = 0.72, 95% CI = 0.20-2.64).
Interpretation:
IVT with tenecteplase was associated with better 3-month clinical outcomes compared to IVT with alteplase in AIS patients, with no increased risk of symptomatic intracranial bleeding. ANN NEUROL 2022.
... Stroke represents as a common cause of death and disability worldwide [1]. Reperfusion therapies for acute ischemic stroke mainly include the use of systemic intravenous thrombolytics and mechanical thrombectomy using different stent retrievers or thromboaspiration devices [2]. The treatment with intravenous tissue plasminogen activator (tPA) remains the fastest and easiest way to initiate acute stroke reperfusion treatment, and should continue to be the first-line treatment for patients with acute ischemic stroke within 4.5 h from onset [2]. ...
... Reperfusion therapies for acute ischemic stroke mainly include the use of systemic intravenous thrombolytics and mechanical thrombectomy using different stent retrievers or thromboaspiration devices [2]. The treatment with intravenous tissue plasminogen activator (tPA) remains the fastest and easiest way to initiate acute stroke reperfusion treatment, and should continue to be the first-line treatment for patients with acute ischemic stroke within 4.5 h from onset [2]. However, due to the narrow treatment time window, approximately 30% of patients do not undergo intravenous thrombolysis, since the stroke onset time is indeterminate, although the stroke may actually have occurred within the time window [3][4][5]. ...
Background
Radiomics analysis is a newly emerging quantitative image analysis technique. The aim of this study was to extract a radiomics signature from the computed tomography (CT) imaging to determine the infarction onset time in patients with acute middle cerebral artery occlusion (MCAO).
Methods
A total of 123 patients with acute MCAO in the M1 segment (85 patients in the development cohort and 38 patients in the validation cohort) were enrolled in the present study. Clinicoradiological profiles, including head CT without contrast enhancement and computed tomographic angiography (CTA), were collected. The time from stroke onset (TFS) was classified into two subcategories: ≤ 4.5 h, and > 4.5 h. The middle cerebral artery (MCA) territory on CT images was segmented to extract and score the radiomics features associated with the TFS. In addition, the clinicoradiological factors related to the TFS were identified. Subsequently, a combined model of the radiomics signature and clinicoradiological factors was constructed to distinguish the TFS ≤ 4.5 h. Finally, we evaluated the overall performance of our constructed model in an external validation sample of ischemic stroke patients with acute MCAO in the M1 segment.
Results
The area under the curve (AUC) of the radiomics signature for discriminating the TFS in the development and validation cohorts was 0.770 (95% confidence interval (CI): 0.665–0.875) and 0.792 (95% CI: 0.633–0.950), respectively. The AUC of the combined model comprised of the radiomics signature, age and ASPECTS on CT in the development and validation cohorts was 0.808 (95% CI: 0.701–0.916) and 0.833 (95% CI: 0.702–0.965), respectively. In the external validation cohort, the AUC of the radiomics signature was 0.755 (95% CI: 0.614–0.897), and the AUC of the combined model was 0.820 (95% CI: 0.712–0.928).
Conclusions
The CT-based radiomics signature is a valuable tool for discriminating the TFS in patients with acute MCAO in the M1 segment, which may guide the use of thrombolysis therapy in patients with indeterminate stroke onset time.
... In most cases, intravenous alteplase intervention induces partial recanalization, since stroke patients often have a large thrombus burden. Thus, the presence of a proximal arterial occlusion does not necessarily lead to alteplase intervention failure, since some degree of recanalization can occur even with large thrombi [13]. The American Heart Association/ American Stroke Association [14] and the Chinese Stroke Association guidelines [15] are recommending intravenous alteplase intervention before endovascular thrombectomy if patients are eligible to do so but the beneficial effects of endovascular thrombectomy are different in Chinese patients with stroke than those of white patients because more numbers of cases with intracranial atherosclerosis among Chinese patients with stroke [16]. ...
Background
The American Heart Association/ American Stroke Association and the Chinese Stroke Association guidelines are recommending intravenous alteplase intervention before endovascular thrombectomy if patients are eligible to do so but the benefits of endovascular thrombectomy are different in Chinese patients with stroke than those of the white patients. The objective of the study was to compare outcomes of patients with acute ischemic stroke treated with endovascular thrombectomy with intravenous alteplase against those treated with endovascular thrombectomy alone.
Methods
A report is a retrospective analysis of comparing demographics, imaging, clinical and adverse outcomes in the Han Chinese patient who underwent mechanical thrombectomy for acute ischemic stroke with large vessel occlusion, with or without preceding intravenous alteplase administration. Patients with terminus and non-terminus intracranial occlusions and ≤ 2 points neurologic deficit underwent endovascular thrombectomy preceded by 0.9 mg/ kg intravenous alteplase (ET cohort, n = 184) and those who had contra-indication for intravenous alteplase were treated with endovascular thrombectomy alone (EA cohort, n = 141).
Results
The most common procedural complications were embolization into new territory ( p = 0.866) and uneventful artery vasospasm ( p = 0.712). Insignificant differences were reported for any procedural complications ( p = 0.991), imaging outcomes, the modified Rankin scale score ( p = 0.663), and death (28 vs. 24, p = 0.761) within 90 days between patients of both cohorts. At the discharge of the hospital, the National Institutes of Health Stroke Scale scores of patients of the ET cohort were lower than those of the EA cohort (8.58 ± 3.79 vs. 10.23 ± 4.97, p = 0.003). The Barthel Index of survivors at 90 days after endovascular thrombectomy was higher for patients of the ET cohort than those of the EA cohort (87.47 ± 12.58 vs. 84.01 ± 13.47, p = 0.032). The most common adverse effect was asymptomatic intracranial hemorrhage ( p = 0.297). Insignificant differences were reported for adverse effects after thrombectomy between survivors of both cohorts.
Conclusions
Outcome measures in Han Chinese patients with acute ischemic stroke treated with endovascular thrombectomy alone were statistically the same as those treated with endovascular thrombectomy plus intravenous alteplase.
Level of evidence
Iii
Technical efficacy stage
4.
... Stroke is the second leading cause of severe disability in adults [1]. Ischemic stroke accounts for approximately 87% of all stroke cases and has been reported in depth [2]. ...
Long non-coding RNAs (lncRNAs) play a key role in a variety of disease processes. Plasmacytoma variant translocation 1 (PVT1), a lncRNA, is known to regulate cell functions and play a key role in the pathogenesis of many malignant tumors. The function and molecular mechanisms of lncRNA-PVT1 in cerebral ischemia remain unknown. Real-time PCR (qRT-PCR) was used to detect lncRNA-PVT1 and microRNA-30c-5p (miR-30c-5p) expression in the brain tissues of mice underwent middle cerebral artery occlusion/reperfusion (MCAO/R) and oxygen–glucose deprivation/reperfusion (OGD/R)-treated mouse primary brain neurons. Gain- or loss-of-function approaches were used to manipulate PVT1, miR-30c-5p, and Rho-associated protein kinase 2 (Rock2). The mechanism of PVT1 in ischemic stroke was evaluated both in vivo and in vitro via bioinformatics analysis, CCK-8, flow cytometry, TUNEL staining, luciferase activity assay, RNA FISH, and Western blot. PVT1 was upregulated in the brain tissues of mice treated with MCAO/R and primary cerebral cortex neurons of mice treated with OGD/R. Mechanistically, PVT1 knockdown resulted in a lower infarct volume and ameliorated neurobehavior in MCAO mice. Consistent with in vivo results, PVT1 upregulation significantly decreased the viability and induced apoptosis of neurons cultured in OGD/R. Moreover, we demonstrated that PVT1 acts as a competitive endogenous RNA (ceRNA) that competes with miR-30c-5p, thereby negatively regulating its endogenous target Rock2. Overexpression of miR-30c-5p significantly promoted cell proliferation and inhibited apoptosis. Meanwhile, PVT1 was confirmed to target miR-30c-5p, thus activating Rock2 expression, which finally led to the activation of MAPK signaling. We demonstrated that PVT1, as a ceRNA of miR-30c-5p, could target and regulate the level of Rock2, which aggravates cerebral I/R injury via activation of the MAPK pathway. These findings reveal a new function of PVT1, which helps to broadly understand cerebral ischemic stroke and provide a new treatment strategy for this disease.
... Breast cancer cells expressing HER2 receptors can be attached by means of the HER2 antibody (herceptin) trastuzumab, conjugated with iron oxide NPs. When attached to the tumor magnetically, it can exhibit increased antitumor activity with cytotoxic molecules such as doxorubicin [171]. ...
Healthcare, as a basic human right, has often become the focus of the development of innovative technologies. Technological progress has significantly contributed to the provision of high-quality, on-time, acceptable, and affordable healthcare. Advancements in nanoscience have led to the emergence of a new generation of nanostructures. Each of them has a unique set of properties that account for their astonishing applications. Since its inception, nanotechnology has continuously affected healthcare and has exerted a tremendous influence on its transformation, contributing to better outcomes. In the last two decades, the world has seen nanotechnology taking steps towards its omnipresence and the process has been accelerated by extensive research in various healthcare sectors. The inclusion of nanotechnology and its allied nanocarriers/nanosystems in medicine is known as nanomedicine, a field that has brought about numerous benefits in disease prevention, diagnosis, and treatment. Various nanosystems have been found to be better candidates for theranostic purposes, in contrast to conventional ones. This review paper will shed light on medically significant nanosystems, as well as their applications and limitations in areas such as gene therapy, targeted drug delivery, and in the treatment of cancer and various genetic diseases. Although nanotechnology holds immense potential, it is yet to be exploited. More efforts need to be directed to overcome these limitations and make full use of its potential in order to revolutionize the healthcare sector in near future.
... Cerebral ischemia initiates a cascade of pathological processes, eventually causing neuron death. Reperfusion is a clinical method to restore the blood flow in the brain by administration of tissue plasminogen activator (t-PA) or mechanical thrombectomy (MT) for treatment of ischemic stroke [4]. However, reperfusion often leads to tissue damage because oxygen influx of reperfusion generates reactive oxygen species (ROS), initiating inflammatory responses including cytokine production and leukocyte infiltration [5]. ...
Stroke is a severe brain disease leading to disability and death. Ischemic stroke dominates in stroke cases, and there are no effective therapies in clinic, partly due to the challenges in delivering therapeutics to ischemic sites in the brain. This review is focused on the current knowledge of pathogenesis in ischemic stroke, and its potential therapies and diagnosis. Furthermore, we present recent advances in developments of nanoparticle-based therapeutics for improved treatment of ischemic stroke using polymeric NPs, liposomes and cell-derived nanovesicles. We also address several critical questions in ischemic stroke, such as understanding how nanoparticles cross the blood brain barrier and developing in vivo imaging technologies to address this critical question. Finally, we discuss new opportunities in developing novel therapeutics by targeting activated brain endothelium and inflammatory neutrophils to improve the current therapies for ischemic stroke.
... However, real world evidence is needed in order to unveil the real effectiveness of acute reperfusion stroke treatments in different countries and healthcare systems. Selection Criteria in Endovascular Thrombectomy and Thrombolytic Therapy (SECRET) is a prospective nationwide population multicenter registry that aims to explore the selection criteria and outcomes of patients who receive acute stroke reperfusion therapies in Korea [10]. SECRET investigators found significant increases in both the proportions of patients achieving successful recanalization (78.6% to 85.1%) and those discharged home (78.6% to 85.1%) from 2012 to 2017 [10]. ...
... Selection Criteria in Endovascular Thrombectomy and Thrombolytic Therapy (SECRET) is a prospective nationwide population multicenter registry that aims to explore the selection criteria and outcomes of patients who receive acute stroke reperfusion therapies in Korea [10]. SECRET investigators found significant increases in both the proportions of patients achieving successful recanalization (78.6% to 85.1%) and those discharged home (78.6% to 85.1%) from 2012 to 2017 [10]. A significant decrease in the time from hospital presentation to initiation of reperfusion therapy was also observed over the years 2012 to 2017 [10]. ...
... SECRET investigators found significant increases in both the proportions of patients achieving successful recanalization (78.6% to 85.1%) and those discharged home (78.6% to 85.1%) from 2012 to 2017 [10]. A significant decrease in the time from hospital presentation to initiation of reperfusion therapy was also observed over the years 2012 to 2017 [10]. These data from Korea provide reassurance on the beneficial effect of reperfusion therapies in the real-world setting and the temporal improvements in treatment delivery. ...
In recent years, there have been outstanding achievements in stroke diagnosis and care [...]
... [6] It occurs when blood flow is blocked by a clot, which limits the blood supply to the brain. [7][8][9] Several risk factors contribute to such disorder, including hyperextension, diabetes, heart diseases, smoking, age and gender, family history of stroke, and brain aneurysms or arteriovenous malformations. [10][11][12][13][14][15] If such disorder cannot be treated fairly well, it may cause a variety of sequelae in stroke survivors, which significantly affect their quality of life. ...
Background:
The target of this study is to summarize the association between the serum lipoprotein levels and neurological function in patients with acute ischemic stroke.
Methods:
A comprehensive search of Cochrane Library, PUBMED, EMBASE, Web of Science, and Chinese Biomedical Literature Database, China National Knowledge Infrastructure from inception to the February 29, 2020 without language and publication date restrictions. All searched studies will be selected by 2 authors independently against the eligibility criteria. Included studies will be critically appraised, and essential data will be extracted by 2 independent authors. If necessary, meta-analysis will be utilized to synthesize the outcome data from included articles. If it is not possible, a narrative synthesis will be undertaken.
Results:
This study will summarize the up-to-date evidence to investigate the association between serum lipoprotein levels and neurological function in patients with acute ischemic stroke.
Conclusion:
Its results may present beneficial evidence and guidance for the clinical practice and further studies.
Study registration number:
INPLASY202040043.
