Reperfusion therapies are the mainstay of acute ischemic stroke (AIS) treatments and overall improve functional outcome. Among the established complications of intravenous (IV) tissue-type plasminogen activator (tPA), intracranial hemorrhage (ICH) is by far the most feared and has been extensively described by seminal works over the last two decades. Indeed, IV tPA is associated with increased odds of any ICH and symptomatic ICH responsible for increased mortality rate during the first week after an AIS. Despite these results, IV tPA has been found beneficial in several pioneering randomized trials and improves functional outcome at 3 months. Endovascular therapy (EVT) combined with IV tPA for AIS patients consecutive to an anterior circulation large-vessel occlusion does not increase ICH occurrence. Of note, EVT following IV tPA leads to significantly higher rates of early reperfusion than with IV tPA alone, with no difference in ICH, which challenges the paradigm of reperfusion as a major prognostic factor for ICH complications. However, several blood biomarkers (glycemia, platelet and neutrophil count), clinical factors (age, AIS severity, blood pressure management, diabetes mellitus), and neuroradiological factors (cerebral microbleeds, infarct size) have been identified as risk factors for ICH after reperfusion therapy. In the years to come, the ultimate goal will be to further improve either reperfusion rates and functional outcome, while reducing hemorrhagic complications. To this end, various approaches being investigated are discussed in this review, such as blood-pressure control after reperfusion or the use of new antiplatelet agents as an adjunct to IV tPA and exhibit reduced hemorrhagic potential during the early phase of AIS.

/pdf/intracranial-hemorrhage-after-reperfusion-therapies-in-acute-414sgtgdqd.pdf

Intracranial Hemorrhage After Reperfusion Therapies in Acute Ischemic Stroke Patients

Stroke is a complex disease and one of the main causes of morbidity and mortality among the adult population. A huge variety of factors is known to influence patient outcome, including demographic variables, comorbidities or genetics. In this review, we expound what is known about the influence of clinical variables and related genetic risk factors on ischemic stroke outcome, focusing on acute and subacute outcome (within 24 to 48 hours after stroke and until day 10, respectively), as they are the first indicators of stroke damage. We searched the PubMed data base for articles that investigated the interaction between clinical variables or genetic factors and acute or subacute stroke outcome. A total of 61 studies were finally included in this review. Regarding the data collected, the variables consistently associated with acute stroke outcome are: glucose levels, blood pressure, presence of atrial fibrillation, prior statin treatment, stroke severity, type of acute treatment performed, severe neurological complications, leukocyte levels, and genetic risk factors. Further research and international efforts are required in this field, which should include genome-wide association studies.

/pdf/clinical-variables-and-genetic-risk-factors-associated-with-1gh44w726r.pdf

Clinical Variables and Genetic Risk Factors Associated with the Acute Outcome of Ischemic Stroke: A Systematic Review

Combined prognostic significance of D-dimer level and platelet count in acute ischemic stroke

BACKGROUND AND PURPOSE Blood pressure (BP) variability has been associated with worse neurological outcomes in acute ischaemic stroke (AIS) patients receiving treatment with intravenous thrombolysis (IVT). However, no study to date has investigated whether pulse pressure (PP) variability may be a superior indicator of the total cardiovascular risk, as measured by clinical outcomes. METHODS Pulse pressure variability was calculated from 24-h PP measurements following tissue plasminogen activator bolus in AIS patients enrolled in the Combined Lysis of Thrombus using Ultrasound and Systemic Tissue Plasminogen Activator for Emergent Revascularization (CLOTBUST-ER) trial. The outcomes of interest were the pre-specified efficacy and safety end-points of CLOTBUST-ER. All associations were adjusted for potential confounders in multivariable regression models. RESULTS Data from 674 participants was analyzed. PP variability was identified as the BP parameter with the most parsimonious fit in multivariable models of all outcomes, and was independently associated (P < 0.001) with lower likelihood of both 24-h neurological improvement and 90-day independent functional outcome. PP variability was also independently related to increased odds of any intracranial bleeding (P = 0.011) and 90-day mortality (P < 0.001). Every 5-mmHg increase in the 24-h PP variability was independently associated with a 36% decrease in the likelihood of 90-day independent functional outcome (adjusted odds ratio 0.64, 95% confidence interval 0.52-0.80) and a 60% increase in the odds of 90-day mortality (adjusted odds ratio 1.60, 95% confidence interval 1.23-2.07). PP variability was not associated with symptomatic intracranial bleeding at either 24 or 36 h after IVT administration. CONCLUSIONS Increased PP variability appears to be independently associated with adverse short-term and long-term functional outcomes of AIS patients treated with IVT.

Pulse pressure variability is associated with unfavorable outcomes in acute ischaemic stroke patients treated with intravenous thrombolysis.

IntroductionTo assess the association between 24 h blood pressure variability (BPV) on functional outcome and treatment effect of intravenous alteplase in acute ischaemic stroke.Patients and method...

https://journals.sagepub.com/doi/pdf/10.1177/23969873211014758

24-hour blood pressure variability and treatment effect of intravenous alteplase in acute ischaemic stroke.

In this prospective study, we examined postoperative follow-up and preoperative IFN-γ T cell responses against 14 non-small cell lung cancer (NSCLC)-associated antigens in the blood of 51 patients with NSCLC, 7 patients with benign pulmonary tumors, and 10 tumor-free patients by enzyme-linked immunospot assay. The phenotype and function of T cells specific for tumor-associated antigens (TAAs) in the blood or tumor tissue of 9 NSCLC patients were characterized in detail using TNF-α, IL-2, and IFN-γ cytokine capture assays. We found that circulating TAA-specific T cells were significantly enriched in NSCLC compared with tumor-free patients. The most frequently recognized TAAs were Aurora kinase A, HER2/neu, NY-ESO-1, and p53. TNF-α was the most abundant cytokine secreted by TAA-specific T cells in the blood as well as by in situ-activated tumor-infiltrating lymphocytes, most of which were effector memory cells. The absence of TAA-reactive T cells identified patients at higher risk of tumor recurrence, irrespective of tumor stage (OR = 8.76, 95% CI: 1.57-34.79, p = 0.008). We conclude that pre-existing TAA-reactive circulating T cells are a strong independent prognostic factor for recurrence-free survival. These data may help discriminating high-risk from low-risk patients, improving prognostication, and redirecting adjuvant therapy. Our findings suggest the therapeutic relevance of Aurora kinase A, HER2/neu, NY-ESO-1, and p53 as targets for immunotherapy. This study is registered on Clinicaltrials.gov with trial identification number: NCT02515760.

Functional T cells targeting tumor-associated antigens are predictive for recurrence-free survival of patients with radically operated non-small cell lung cancer.

Background and Purpose—Significance and management of blood pressure (BP) changes in acute stroke care are unclear Here, we aimed to investigate the impact of 24-hour BP variability (BPV) on outco

Reciprocal Interaction of 24-Hour Blood Pressure Variability and Systolic Blood Pressure on Outcome in Stroke Thrombolysis.

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Functional T cells targeting tumor-associated antigens are predictive for recurrence-free survival of patients with radically operated non-small cell lung cancer.

Reciprocal Interaction of 24-Hour Blood Pressure Variability and Systolic Blood Pressure on Outcome in Stroke Thrombolysis.