https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(16)30468-8.pdf

Effects of aspirin on risk and severity of early recurrent stroke after transient ischaemic attack and ischaemic stroke: time-course analysis of randomised trials

Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Extracellular vesicles (EVs) are membrane-surrounded structures released by most cell types. They are characterized by a specific set of proteins, lipids and nucleic acids. EVs have been recognized as potent vehicles of intercellular communication to transmit biological signals between cells. In addition, pathophysiological roles of EVs in conditions like cancer, infectious diseases and neurodegenerative disorders are well established. In recent years focus has been shifted on therapeutic use of stem cell derived-EVs. Use of stem cell derived-EVs present distinct advantage over the whole stem cells as EVs do not replicate and after intravenous administration, they are less likely to trap inside the lungs. From the therapeutic perspective, the most promising cellular sources of EVs are mesenchymal stem cells (MSCs), which are easy to obtain and maintain. Therapeutic activity of MSCs has been shown in numerous animal models and the beneficial paracrine effect of MSCs may be mediated by EVs. The various components of MSC derived-EVs such as proteins, lipids and RNA might play a specific therapeutic role. In this review, we characterize the role of EVs in immune and central nervous system (CNS); present evidences for defective signalling of these vesicles in neurodegeneration and therapeutic role of EVs in CNS.

/pdf/extracellular-vesicles-in-physiology-pathology-and-therapy-3bx85vmuuo.pdf

Extracellular Vesicles in Physiology, Pathology, and Therapy of the Immune and Central Nervous System, with Focus on Extracellular Vesicles Derived from Mesenchymal Stem Cells as Therapeutic Tools.

Background
Aspirin is the prophylactic antiplatelet drug of choice for people with cardiovascular disease. Adding a second antiplatelet drug to aspirin may produce additional benefit for those at high risk and those with established cardiovascular disease.

Objectives
To quantify the benefit and harm of adding clopidogrel to standard long-term aspirin therapy for preventing cardiovascular events in people at high risk of cardiovascular disease and those with established cardiovascular disease.

Search methods
The searches have been updated: CENTRAL (Issue 3 2009), MEDLINE (2002 to September 2009) and EMBASE (2002 to September 2009).

Selection criteria
All randomized controlled trials comparing long term use of aspirin plus clopidogrel with aspirin plus placebo or aspirin alone in patients with coronary disease, ischemic cerebrovascular disease, peripheral arterial disease, or at high risk of atherothrombotic disease were included.

Data collection and analysis
Data on mortality, non-fatal myocardial infarction, non-fatal stroke, unstable angina, heart failure, revascularizations, major and minor bleeding, and all adverse events were collected. The overall treatment effect was estimated by the pooled odds ratio (OR) with 95% confidence interval (CI) using a fixed-effect model (Mantel-Haenszel).

Main results
No new studies were identified from the updated searches. A total of two RCTs were found: the CHARISMA and the CURE study. The CURE study enrolled only patients with a recent non-ST segment elevation acute coronary syndrome. The use of clopidogrel plus aspirin, compared with placebo plus aspirin, was associated with a lower risk of cardiovascular events (OR: 0.87, 95% CI 0.81 to 0.94; P<0.01) and a higher risk of major bleeding (OR 1.34, 95% CI 1.14 to 1.57; P<0.01). Overall, we would expect 13 cardiovascular events to be prevented for every 1000 patients treated with the combination, but 6 major bleeds would be caused. In the CURE trial, for every 1000 people treated, 23 events would be avoided and 10 major bleeds would be caused. In the CHARISMA trial, for every 1000 people treated, 5 cardiovascular events would be avoided and 3 major bleeds would be caused.

Authors' conclusions
The available evidence demonstrates that the use of clopidogrel plus aspirin is associated with a reduction in the risk of cardiovascular events and an increased risk of bleeding compared with aspirin alone. Only in patients with acute non-ST coronary syndrome benefits outweigh harms.

Clopidogrel plus aspirin versus aspirin alone for preventing cardiovascular events

Designing and scaling up integrated youth mental health care

Background: Antiplatelet agents are the mainstay for secondary prevention of non-cardioembolic stroke. This systematic review examined the safety and efficacy of

/pdf/aspirin-plus-clopidogrel-as-secondary-prevention-after-1lwk28c5lr.pdf

Aspirin plus Clopidogrel as Secondary Prevention after Stroke or Transient Ischemic Attack: A Systematic Review and Meta-Analysis

This study is to investigate the effects of human umbilical cord-mesenchymal stem cells (HUC-MSCs) transplantation combined with minimally invasive hematoma aspiration on neural functional recovery and p53 gene expression in rats with intracerebral hemorrhage (ICH). Collagenase type-IV was injected to the caudate nucleus of the rats to make ICH models. One hundred and twenty Sprague-Dawley rats with successful modeling were randomly divided into 4 groups, including the ICH group, hematoma aspiration group, HUC-MSCs transplantation group and HUC-MSCs transplantation combined with hematoma aspiration group (combination group). Neural functional status of the rats was assessed by modified neurological severity score (mNSS). Expression of p53 in the cerebral tissues surrounding ICH was detected by immunohistochemical assays. The scores of mNSS and the expression of p53 gene in the hematoma aspiration group, the HUC-MSCs transplantation group and the combination group were significantly lower than those in the ICH group at each indicated time point (p < 0.05). Intriguingly, mNSS scores and p53 expression in the combination group were significantly lower than those in the hematoma aspiration group on day 7, 14 and 30 (p < 0.05), and significantly lower than those in the HUC-MSCs transplantation group on day 14 and 30 (p < 0.05). HUC-MSCs transplantation combined with minimally invasive hematoma aspiration is more effective than either therapy alone in rats with ICH and could distinctly reduce the damage of nerve cells.

Effects of human umbilical cord mesenchymal stem cell transplantation combined with minimally invasive hematoma aspiration on intracerebral hemorrhage in rats.

Yanxia Li

Papers

Aspirin plus Clopidogrel as Secondary Prevention after Stroke or Transient Ischemic Attack: A Systematic Review and Meta-Analysis

Effects of human umbilical cord mesenchymal stem cell transplantation combined with minimally invasive hematoma aspiration on intracerebral hemorrhage in rats.