Intravenous Recombinant Tissue Plasminogen Activator Research Articles

Association of admission neutrophil serine proteinases levels with the outcomes of acute ischemic stroke: a prospective cohort study

BackgroundNeutrophil serine proteinases (NSPs), released by activated neutrophils, are key proteins involved in the pathophysiologic processes of stroke. NSPs are also implicated in the process and response of thrombolysis. This study aimed to analyze three NSPs (neutrophil elastase, cathepsin G, and proteinase 3) in relation to acute ischemic stroke (AIS) outcomes and in relation to the outcomes of patients treated with intravenous recombinant tissue plasminogen activator (IV-rtPA).MethodsAmong 736 patients prospectively recruited at the stroke center from 2018 to 2019, 342 patients diagnosed with confirmed AIS were included. Plasma neutrophil elastase (NE), cathepsin G (CTSG), and proteinase 3 (PR3) concentrations were measured on admission. The primary endpoint was unfavorable outcome defined as modified Rankin Scale score 3–6 at 3 months, and the secondary endpoints were symptomatic intracerebral hemorrhage (sICH) within 48 h, and mortality within 3 months. In the subgroup of patients who received IV-rtPA, post-thrombolysis early neurological improvement (ENI) (defined as National Institutes of Health Stroke Scale score = 0 or decrease of ≥ 4 within 24 h after thrombolysis) was also included as the secondary endpoint. Univariate and multivariate logistic regression analyses were performed to evaluate the association between NSPs levels and AIS outcomes.ResultsHigher NE and PR3 plasma levels were associated with the 3-month mortality and 3-month unfavorable outcome. Higher NE plasma levels were also associated with the risk of sICH after AIS. After adjusting for potential confounders, plasma NE level > 229.56 ng/mL (odds ratio [OR] = 4.478 [2.344–8.554]) and PR3 > 388.77 ng/mL (OR = 2.805 [1.504–5.231]) independently predicted the 3-month unfavorable outcome. Regarding rtPA treatment, patients with NE plasma concentration > 177.22 ng/mL (OR = 8.931 [2.330–34.238]) or PR3 > 388.77 ng/mL (OR = 4.275 [1.045–17.491]) were over 4 times more likely to suffer unfavorable outcomes after rtPA treatment. The addition of NE and PR3 to clinical predictors of unfavorable functional outcome after AIS and the outcome after rtPA treatment improved discrimination as well as reclassification (integrated discrimination improvement = 8.2% and 18.1%, continuous net reclassification improvement = 100.0% and 91.8%, respectively).ConclusionsPlasma NE and PR3 are novel and independent predictors of 3-month functional outcomes after AIS. Plasma NE and PR3 also possess predictive value to identify patients with unfavorable outcomes after rtPA treatment. NE is probably an important mediator of the effects of neutrophils on stroke outcomes, which worth further investigation.

Abstract Number ‐ 242: Safety and Effectiveness of Intravenous Thrombolytic in Patients with Concurrent Migraine‐Headaches and Focal Neurological Deficits.

Introduction It is relatively well recognized that migraine headaches can present with focal neurological deficits. Current guidelines do not exclude such patients from receiving intravenous recombinant tissue plasminogen activator (rt‐PA). Methods We reviewed the records of migraine patients with ischemic stroke using a combination of retrospective chart review and prospective identification. The migraine was classified based on the criteria proposed by the third International Classification of Headache Disorders (ICHD‐3) into migraine with aura, and hemiplegic migraine. We ascertained rates of early neurological improvement (defined by reduction in National Institutes of Health Stroke Scale (NIHSS) score of 4 points or greater or NIHSS score of 0 at24 hours), any intracerebral hemorrhage within 24 hours, and excellent functional outcome based on modified Rankin Scale (mRS 0–1) at one month. Results A total of 25 patients (mean age ± SD; 45.3 ± 10.6 years; 15 were women) who met the criteria of migraine headaches concurrently presented with focal neurological deficits and received intravenous rt‐PA. The migraine was classified as hemiplegic migraine and migraine with aura in 22 and 3 patients, respectively. Intravenous rt‐PA was administered at a mean period of 142 minutes(range 60–255 minutes). Computed tomographic angiography was performed in 24 patients and did not reveal any large vessel arterial occlusion. Early neurological improvement was seen in 13 of 25 patients. None of the patients developed post thrombolytic intracerebral hemorrhage. Excellent functional outcome was seen in all patients. Diffusion‐weighted magnetic resonance imaging (MRI) was performed in 25 patients within 72 hours of symptom onset and demonstrated a new infarction in 1 patient. Conclusions In our analysis, intravenous rt‐PA was associated with high rates of early neurological improvement and excellent functional outcome at 1 month in patients with concurrent migraine headaches and focal neurological deficits.

Specificity and sensitivity of the SeLECT score in predicting late seizures in patients undergoing intravenous thrombolytic treatment and the effect of diabetes mellitus and leukoaraiosis

Seizures after stroke can negatively affect the prognosis of ischemic stroke and cause a decrease in quality of life. The efficacy of intravenous (IV) recombinant tissue plasminogen activator (rt-PA) treatment in acute ischemic stroke has been demonstrated in many studies, and IV rt-PA treatment has been increasingly used around the world. The SeLECT score is a useful score for the prediction of late seizures after stroke and includes the severity of stroke (Se), large artery atherosclerosis (L), early seizure (E), cortical involvement (C), and the territory of the middle cerebral artery (T). However, the specificity and sensitivity of the SeLECT score have not been studied in acute ischemic stroke patients that received IV rt-PA treatment. In the present study, we aimed to validate and develop the SeLECT score in acute ischemic stroke patients receiving IV rt-PA treatment. The present study included 157 patients who received IV thrombolytic treatment in our third-stage hospital. The 1-year seizure rates of the patients were detected. SeLECT scores were calculated. In our study, we found that the SeLECT score had low sensitivity but high specificity for predicting the likelihood of late seizure after stroke in patients administered IV rt-PA therapy. In addition to the SeLECT score, we found that the specificity and sensitivity were higher when we evaluated diabetes mellitus (DM) and leukoaraiosis. We found that DM was an independent risk factor for late seizures after stroke in a patient group receiving thrombolytic therapy, and late seizures after stroke were less frequent in patients with leukoaraiosis.

Comparison of Effectiveness and Safety of Low-Dose Versus Standard-Dose Intravenous Recombinant Tissue Plasminogen Activator in Patients With Acute Ischemic Stroke: A Meta-Analysis.

The aim of the present meta-analysis is to compare the efficacy and safety of low-dose and standard-doserecombinant tissue plasminogen activators (r-tPA) in patients with acute ischemic stroke. The present meta-analysis was conducted according to the Meta-Analysis of Observational Studies in Epidemiology (MOOSE)guidelines. We conducted a systematic search in PubMed, Embase, and the Cochrane Library to identify studies published between January 1, 2010, and January 31, 2023, using the following terms: "stroke," "alteplase," "doses," "efficacy," "tissue plasminogen activator," "r-tPA," and "safety."Primary efficacyoutcomes included favorable outcomes (Modified Rankin Scale scores of 0-2), while secondary efficacy outcome was all-cause mortality at 90 days. Safety outcomes included asymptomatic intracerebral hemorrhage (ICH)and symptomatic ICH assessed using the National Institute of Neurological Disorders and Stroke (NINDS) study and the Safe Implementation of Thrombolysis in Stroke-Monitoring (SITS-MOST) study. We also compared parenchymal hematomas as safety outcome between the two groups defined by the authors themselves in their research.A totalof 16 studies were included in the present meta-analysis. The meta-analysis did not report any significant difference between low-dose and standard-dose r-tPA in terms of mortality, symptomatic intracranial hemorrhage (SICH), asymptomatic ICH, and parenchymal hematomas. However, the favorable outcome was significantly greater in patients receiving a standard dose of r-tPA.

Recanalization Rate and Clinical Outcomes of Intravenous Tissue Plasminogen Activator Administration for Large Vessel Occlusion Stroke Patients.

Stroke caused from large vessel occlusion (LVO) has emerged as the most common stroke subtype worldwide. Intravenous tissue plasminogen activator administration (IV-tPA) and additional intraarterial thrombectomy (IA-Tx) is regarded as standard treatment. In this study, the authors try to find the early recanalization rate of IV-tPA in LVO stroke patients. Total 300 patients undertook IA-Tx with confirmed anterior circulation LVO, were analyzed retrospectively. Brain computed tomography angiography (CTA) was the initial imaging study and acute stroke magnetic resonance angiography (MRA) followed after finished IV-tPA. Early recanalization rate was evaluated by acute stroke MRA within 2 hours after the IV-tPA. In 167 patients undertook IV-tPA only and 133 non-recanalized patients by IV-tPA, additional IA-Tx tried (IV-tPA + IA-Tx group). And 131 patients, non-recanalized by IV-tPA (IV-tPA group) additional IA-Tx recommend and tried according to the patient condition and compliance. Early recanalization rate of LVO after IV-tPA was 12.0% (36/300). In recanalized patients, favorable outcome (modified Rankin Scale, 0-2) was 69.4% (25/36) while it was 32.1% (42/131, p<0.001) in non-recanalized patients. Among 133 patients, nonrecanalized after intravenous recombinant tissue plasminogen activator and undertook additional IA-Tx, the clinical outcome was better than not undertaken additional IA-Tx (favorable outcome was 42.9% vs. 32.1%, p=0.046). Analysis according to the perfusion/diffusion (P/D)-mismatching or not, in patient with IV-tPA with IA-Tx (133 patients), favorable outcome was higher in P/ D-mismatching patient (52/104; 50.0%) than P/D-matching patients (5/29; 17.2%; p=0.001). Which treatment tired, P/D-mismatching was favored in clinical outcome (iv-tPA only, p=0.008 and IV-tPA with IA-Tx, p=0.001). The P/D-mismatching influences on the recanalization and clinical outcomes of IV-tPA and IA-Tx. The authors would like to propose that we had better prepare IA-Tx when LVO is diagnosed on initial diagnostic imaging. Furthermore, if the patient shows P/D-mismatching on MRA after IV-tPA, additional IA-Tx improves treatment results and lessen the futile recanalization.

The Impact of Gender on Mortality and Symptomatic Intracerebral Hemorrhage in Acute Ischemic Stroke Patients After Intravenous Recombinant Tissue Plasminogen Activator (rt-PA)

Objective: The characteristics and risk factors of stroke differ between men and women. Women have a lower mortality but a higher disability rate after a stroke, as well as a higher rate of response to intravenous recombinant tissue plasminogen activator (rt-PA). However, the data regarding gender and outcomes after rt-PA in Asian populations is limited. Hence, this study aimed to make a comparison between men and women regarding mortality and symptomatic intracerebral hemorrhage (S-ICH) after rt-PA. Material and Methods: This was a retrospective cohort study conducted in a specialized stroke unit at a 1000-bed university hospital in Thailand. Adult patients, who were eligible for rt-PA, were recruited from the Stroke Fast Track Registry between 2015-2019. The clinical data and radiological results were collected and analyzed. Results: There was a total of 278 patients,138 of whom were men (49.6%). The men had a lower average age (63 vs. 68 years, p-value&lt;0.001), had higher creatinine levels and higher diastolic blood pressure than the women (1.22±0.93 vs. 0.97±0.84 mg/dl, and 90±15 vs. 86±18 mmHg, all p-values&lt;0.001). The mortality and S-ICH rates were comparable (2.3% vs. 5%, and 8.0% vs. 11.4%, respectively, all p-values&gt;0.05). Having had a history of anti-platelet therapy was a strong risk factor for S-ICH in men (OR 6.43, 95% CI 1.39–29.69); whereas, age was significantly associated with mortality in women (OR 1.13, 95% CI 1.03–1.24). Conclusion: Men and women had similar rates of mortality and S-ICH after rt-PA.

Multimodal CT imaging characteristics may predict post-reperfusion infarct volume in wake-up stroke patients.

Accurate prediction of subsequent infarct volume in acute ischemic stroke (AIS) patients helps determine appropriate interventions and prognosis. The objectives are to assess whether early multimodal CT imaging characteristics of wake-up stroke (WUS) patients could predict post-reperfusion infarct volume and evaluate the accuracy of baseline infarct and penumbra volumes for predicting follow-up infarct volume. This retrospective study included WUS patients, last seen well (LSW) >6 h, with multimodal CT imaging at baseline. Baseline non-contrast CT (NCCT) and CT perfusion were analyzed using RAPID software, and CT angiography using maximum intensity projection. Post-reperfusion infarct volume was assessed at 24-h following reperfusion on magnetic resonance diffusion-weighted imaging (DWI). Patients were stratified by treatment module for analyses. Of 34 eligible patients, 9 (26.5%) received intravenous recombinant tissue plasminogen activator (r-tPA) alone and 25 (73.5%) received both endovascular thrombectomy (EVT) and r-tPA. All patients had a strong correlation between baseline NCCT alberta stroke program early CT score, clot burden score (CBS), Tan score, infarct volume, penumbra volume with 24-h post-reperfusion infarct volume (respectively, r=0.172, P=0.015; r=0.118, P=0.047; r=0.149, P=0.024; r=0.311, P=0.001 and r=0.120; P=0.045). Among reperfusion therapies, WUS patients who received EVT had a significantly lower 24-h post-reperfusion infarct volume and had a significant difference between baseline infarct volume and 24-h post-reperfusion infarct volume (respectively, 82 vs. 14, P=0.032 and 47 vs. 14, P=0.04). Primarily obtained multimodal CT imaging characteristics may predict post-reperfusion infarct volume in WUS patients, and those who underwent EVT had a significantly lower post-reperfusion infarct volume.

Abstract 90: Butylphthalide Improves Functional Outcome In Patients With Acute Ischemic Stroke Receiving Intravenous Thrombolysis And/or Endovascular Treatment In Comparison To Placebo

Introduction: Butylphthalide is a cerebro-protection drug that was originally extracted from seeds of Apium graveolens. Pre-clinical experiments have shown the cerebro-protective effect of Butylphthalide in animal models of ischemia-reperfusion. This study evaluated whether Butylphthalide can improve the functional outcome in acute ischemic stroke patients who receive intravenous recombinant tissue plasminogen activator (rt-PA) and/or endovascular treatment (EVT) compared to placebo. Methods: In the randomized, double-blinded, placebo-controlled trial, we enrolled patients with acute ischemic stroke who received intravenous rt-PA and/or EVT in 59 centers. Patients were randomized in a 1:1 ratio to receive either Butylphthalide or placebo daily for 90 days, including 14 days of intravenous injections and 76 days of oral capsules. All trial personnel and patients were masked to treatment allocation. The primary outcome was an adjusted favorable outcome at 90 days after randomization, defined as a score of 0 on the modified Rankin Scale (mRS) in patients with a baseline score of 4-7 on the National Institutes of Health Stroke Scale (NIHSS); an mRS score of 0-1 in patients with a baseline NIHSS score of 8-14; and an mRS score of 0-2 in patients with a baseline NIHSS score of 15-25. Secondary outcomes included symptomatic intracranial hemorrhage, recurrent stroke and mortality. The analysis was done in the intention-to-treat population and in subgroups of age, sex, baseline NIHSS score, hypertension, and reperfusion treatment methods. This trial is registered with ClinicalTrials.gov, NCT03539445. Results: Between July 1, 2018 and 19 February, 2022, 1216 patients were enrolled, with 607 assigned to the butylphthalide group and 609 to the placebo group. The primary outcome of a favorable outcome on day 90 occurred in 344 patients (56.7%) in the butylphthalide group and 268 patients (44.0%) in the placebo group (OR, 1.70; 95% CI, 1.35 to 2.14; P &lt;0.001). Secondary outcomes were similar between groups. There was no evidence of treatment modification effect in the subgroups. Conclusions: In conclusion, Butylphthalide improved favorable clinical outcome compared with placebo in patients with acute ischemic stroke receiving intravenous rt-PA and/or EVT.

Prognostic factors for acute large vessel occlusion with NIHSS 5 or lower.

Intravenous recombinant tissue plasminogen activator (IV rt-PA) and endovascular treatment have been performed for severe large vessel occlusion (LVO) and the results have been reported at high levels of evidence. However, acute treatment for LVO with mild symptom remains controversial. We retrospectively examined prognostic factors for LVO with mild symptoms. We studied retrospectively the patients within 24 h of onset with large vessel occlusion with NIHSS score ??5. Outcomes were evaluated by modified Rankin Scale (mRS) at 90 days, with 0?2 defined as a good outcome and 3?6 as a poor outcome. Clinical characteristics of each case were examined. Participants comprised 76 patients. Of the 76 patients. ICA occlusion showed good outcome in 17?/?19 cases (90%), whereas MCA occlusion showed good outcome in 36?/?54 cases (67%). Among the 14 cases showing positive results for distal intraarterial signal (d-IAS), outcomes were good in 6 cases (43%). On the other hand, the 32 d-IAS-negative cases showed good outcome in 28 cases (88%). Outcomes were thus significantly poorer for d-IAS-positive cases. MCA occlusion is associated with poor prognosis, even with NIHSS score ??5, and d-IAS may provide a predictor. J. Med. Invest. 70 : 22-27, February, 2023.

Cost-effectiveness analysis of endovascular treatment with or without intravenous thrombolysis in acute ischemic stroke.

Intravenous (IV) recombinant tissue plasminogen activator (r-tPA) may not provide additional benefit in terms of functional outcomes in patients with acute ischemic stroke (AIS) who undergo endovascular treatment (EVT). In this context, the cost-effectiveness of EVT alone compared with its application following IV r-tPA has not been evaluated. The authors determined the average rates of death or disability in each of the two treatment groups from four randomized clinical trials that enrolled patients with AIS within 4.5 hours of symptom onset and randomly assigned patients to EVT alone and IV r-tPA and EVT. By using three sources derived from previous studies, the authors determined the cost of IV r-tPA, cost of staff time for administration, cost of the EVT, cost of hospital stay, costs of supported discharge and community care, and cost of posthospitalization care and disability. They then assessed the cost-effectiveness of EVT alone using a decision tree for the 1st year after AIS and a Markov model with a 10-year horizon, including probabilistic assessment by Monte Carlo simulations. The 1-year cost was higher with IV r-tPA and EVT compared with EVT alone (incremental cost ranging between $3554 and $13,788 per patient). The mean incremental cost-effectiveness ratios (ICERs) were -$1589, -$78,327, and -$15,471 per quality-adjusted life-year gained for cost sources 1, 2, and 3, respectively, for EVT alone compared with IV r-tPA and EVT at 10 years. The ceiling ICER (willingness to pay) for a probability of 100% that EVT alone was more cost-effective ranged between $25,000 and $100,000 in the three models. EVT alone appears to be more cost-effective compared with EVT and IV r-tPA for the treatment of AIS patients presenting within 4.5 hours of symptom onset.

Usefulness of carotid duplex ultrasonography in predicting residual large-vessel occlusions after intravenous recombinant tissue plasminogen activator therapy in patients with acute ischemic stroke.

Endovascular therapy (EVT) preceded by intravenous thrombolysis with recombinant tissue plasminogen activator (iv-rtPA) has been established as a standard treatment in patients with stroke caused by large-vessel occlusion (LVO). Primary stroke centers without EVT competence need to identify patients with residual LVO after iv-rtPA therapy and transport them to an EVT-capable facility. Carotid ultrasonography (CUS) is easily applicable at bed side and useful for detecting extra- and intracranial LVO. This study aimed to determine whether CUS findings at admission are useful to predict patients with residual LVO after iv-rtPA. Patients scheduled to undergo iv-rtPA for acute cerebral infarction were registered. Before iv-rtPA, they underwent CUS, followed by CTA or MRA evaluation within 6h after iv-rtPA. A model that can achieve 100% sensitivity for detecting residual LVO after iv-rtPA was studied. This study included 68 of 116 patients treated with iv-rtPA during the study period. National Institutes of Health Stroke Scale (NIHSS) score (cutoff value = 10) on arrival, hyperdense MCA sign on non-contrast CT, end-diastolic (ED) ratio on CUS, and eye deviation were significantly different between patients with residual LVO after iv-rtPA and those without. If any of these clinical features are positive in the screening test, residual LVO could be predicted with 100% sensitivity, 50% specificity, 64% positive predictive value, and 100% negative predictive value. Prediction of residual LVO with 100% sensitivity may be feasible by adding CUS to NIHSS score > 10, the presence of eye deviation, and hyperdense MCA sign.

Rescue stenting after the failure of intravenous thrombolysis and bridging thrombolysis: an initial Vietnamese report.

Intravenous (IV) recombinant tissue plasminogen activator is the standard of care for patients with acute ischemic stroke (AIS) who present to the hospital within 4.5 hours of symptom onset. However, IV thrombolysis, even bridging thrombolysis (combining intravenous thrombolysis and mechanical thrombectomy) has limited efficacy among patients who had occlusive lesions associated with high-grade arterial stenosis requiring revascularization to improve neurological deficits. We evaluated whether rescue stenting results in good outcomes among patients after the failure of intravenous thrombolysis and bridging thrombolysis. We retrospectively analyzed patients with AIS who underwent rescue stenting for large vessel occlusion with severe atherosclerotic stenosis between May 2020 and August 2022 at Can Tho S.I.S General Hospital. Primary outcomes included the incidence of hemorrhagic transformation and the rate of good outcomes (modified Rankin Scale < 3) at 3-month follow-up. We identified 13 patients who received rescue stenting after the failure of IV alteplase and bridging thrombolysis, but only 11 patients met the inclusion criteria. All patients experienced successful recanalization, and 1 (9.1%) patient experienced new infarcts. Of these 11 patients, 10 (90.9%) had good outcomes 3 months after rescue stenting. Additionally, a loading dose of dual antiplatelet therapy (DAPT) applied concurrently with IV alteplase improved the recanalization rate for large target arteries but had no significant effect on the incidence of symptomatic intracranial hemorrhage. Rescue stenting appears to represent an additional therapeutic option in cases that fail to resolve with IV alteplase, which may improve clinical outcomes.

The Utility of Automated ASPECTS in Acute Ischemic Stroke for Intravenous Recombinant Tissue Plasminogen Activator (IV-rtPA) Therapy.

This study aimed to investigate the accuracy and clinical significance of an artificial intelligence (AI)-based automated Alberta Stroke Program Early Computed Tomography (ASPECT) scoring software of head CT for the indication of intravenous recombinant tissue plasminogen activator (rt-PA) therapy. This study included two populations of acute ischemic stroke: one comprised patients who had undergone head CT within 48 h of presentation (Population #1, n = 448), while the other included patients within 4.5 h from onset (Population #2, n = 132). The primary endpoint was the concordance rate of ASPECTS of the neurologists and AI software against the benchmark score. The secondary endpoints were to validate the accuracy of the neurologist and AI software in assessing the ability to rule out extensive infarction (ASPECTS of 0-5) in population #2. The reading accuracy of AI software was comparable to that of the board-certified vascular neurologists. The detection rate of cardiogenic cerebral embolism was better than that of atherothrombotic cerebral infarction. By excluding extensive infarction, AI-software showed a higher specificity and equivalent sensitivity compared to those of experts. The AI software for ASPECTS showed convincing agreement with expert evaluation and would be supportive in determining the indications of intravenous rt-PA therapy.

High Neutrophil-Lymphocyte Ratio and Low Lymphocyte-Monocyte Ratio Combination after Thrombolysis Is a Potential Predictor of Poor Functional Outcome of Acute Ischemic Stroke.

(1) Background: Ischemic stroke is one of the leading causes of death and disability. An inflammatory response is observed in multiple stages of cerebral ischemia, particularly in the acute phase. Recent publications revealed that the neutrophil–lymphocyte ratio (NLR) and lymphocyte–monocyte ratio (LMR) may be used to predict long-term prognosis in acute ischemic stroke (AIS) after thrombolysis. To test whether there is a relationship between the combination of these parameters and long-term prognosis, we analyzed the NLR–LMR combination in AIS patients treated with intravenous recombinant tissue plasminogen activator (rtPA); (2) Methods: The study included 285 adults with a diagnosis of AIS and rtPA treatment within a 4.5 h time window. Blood samples were obtained at admission and 24 h after thrombolysis to calculate pre- and post-thrombolysis NLR and LMR. Clinical data, including NIHSS was registered on admission and day 1. The long-term outcome was defined 90 days post-event by the modified Rankin Scale (mRS). Therapy-associated intracranial hemorrhage (ICH) was classified according to ECASS II. Receiver operating characteristic curve (ROC) analysis was performed to determine optimal cutoffs of NLR and LMR as predictors of therapy outcomes; (3) Results: Patients were stratified by cutoffs of 5.73 for NLR and 2.08 for LMR. The multivariate logistic regression model, including all possible confounders, displayed no significant association between NLR or LMR with 3-months functional prognosis. The combination of high NLR–low LMR vs. low NRL–high LMR as obtained 24 h after thrombolysis was found to be an independent predictor of poor 3-months functional outcome (mRS ≥ 2; OR 3.407, 95% CI 1.449 to 8.011, p = 0.005). The proportion of patients between low NLR–high LMR and high NLR–low LMR groups from admission to day 1 showed no significant change in the good outcome group. On the other hand, in the poor outcome group (mRS ≥ 2), low NLR–high LMR and high NLR–low LMR groups displayed a significant shift in patient proportions from 67% and 21% at admission (p = 0.001) to 36% and 49% at 24 h after thrombolysis (p < 0.001), respectively; (4) Conclusions: Our study demonstrated for the first time that a high NLR–low LMR combination as observed at 24 h after thrombolysis can serve as an independent predictor of 3-months poor outcome in AIS patients. This simple and readily available data may help clinicians to improve the prognostic estimation of patients and may provide guidance in selecting patients for personalized and intensified care post-thrombolysis.

Factors associated with favorable outcomes in acute severe stroke patients: A real-world, national database study.

Thrombolytic therapy is useful in severe stroke, but it increases the risk of intracerebral hemorrhage. In addition, it may have limited use in resource-limited due to a lack of trained neurologists and equipment to perform CT scans. There are limited data available from studies of national databases on stroke outcomes and predictors of severe stroke. This study, therefore, aimed to evaluate acute severe ischemic stroke outcomes in a real-world setting. Additionally, predictors of favorable stroke outcomes were explored using a retrospective cohort. Data were extracted from the National Health Security Office (NHSO) in Thailand. The inclusion criteria were: Aged ≥18 years or older, diagnosis of acute severe ischemic stroke (defined by an admission National Institutes of Health Stroke Scale score of 15-24), and available data on stroke outcomes. Outcomes were evaluated at discharge using a modified Rankin score at discharge. Factors associated with good outcomes were determined using multivariate logistic regression analysis. During the study period, 268 severe stroke patients met the inclusion criteria. Of those, 38 (14.18%) had good outcomes at discharge. A total of 223 patients received intravenous recombinant tissue plasminogen activator (83.21%). Of those, 38 (17.04%) had favorable outcomes. A predictive model for good outcomes revealed two independent factors: Male sex and atrial fibrillation with adjusted odds ratios (95% confidence interval) of 2.30 (1.10-4.82) and 0.38 (0.16-0.91), respectively. Predictors for good stroke outcomes in severe stroke patients included rtPA treatment, atrial fibrillation, and male sex.

Effect of the interaction between atrial fibrillation and rt-PA dose on the prognosis of acute ischaemic stroke with intravenous thrombolysis

BackgroundThe association between atrial fibrillation (AF) and the prognosis of acute ischaemic stroke (AIS) remains controversial; whether the recombinant tissue plasminogen activator dose influences this association remains poorly understood.MethodsPatients who...

Effect of the interaction between atrial fibrillation and rt-PA dose on the prognosis of acute ischaemic stroke with intravenous thrombolysis.

The association between atrial fibrillation (AF) and the prognosis of acute ischaemic stroke (AIS) remains controversial; whether the recombinant tissue plasminogen activator dose influences this association remains poorly understood. Patients who had an AIS were enrolled from eight stroke centres in China. According to the recombinant tissue plasminogen activator dose, patients treated with intravenous recombinant tissue plasminogen activator within 4.5 hours after symptom onset were divided into a low-dose group (recombinant tissue plasminogen activator <0.85 mg/kg) and a standard-dose group (recombinant tissue plasminogen activator ≥0.85 mg/kg). Patients who had an AIS in the low-dose group and the standard dose group were divided into whether or not they had AF. The main outcomes were major disability (modified Rankin scale (mRS) score 3-5), mortality and vascular events occurring within 3 months. The study included 630 patients who received recombinant tissue plasminogen activator after AIS, including 391 males and 239 females, with a mean age of 65.8 years. Of these patients, 305 (48.4%) received low-dose recombinant tissue plasminogen activator and 325 (51.6%) received standard dose recombinant tissue plasminogen activator. The recombinant tissue plasminogen activator dose significantly influenced the association between AF and death or major disability (p-interaction=0.036). After multivariate adjustment, AF was associated with an increased risk of death or major disability (OR 2.90, 95% CI 1.47 to 5.72, p=0.002), major disability (OR 1.93, 95% CI 1.04 to 3.59, p=0.038) and vascular events (HR 5.01, 95% CI 2.25 to 11.14, p<0.001) within 3 months in patients with standard-dose recombinant tissue plasminogen activator. No significant association was found between AF and any clinical outcome in patients with low-dose recombinant tissue plasminogen activator (all p>0.05). With AF, the mRS score distribution showed a significantly worse shift in patients with standard-dose recombinant tissue plasminogen activator (p=0.016) than in those with low-dose recombinant tissue plasminogen activator (p=0.874). AF may be a strong predictor of poor prognosis in patients who had an AIS receiving standard-dose recombinant tissue plasminogen activator, suggesting that low-dose recombinant tissue plasminogen activator should be administered to patients who had a stroke with AF to improve their prognosis.

Pregnancy-Related Stroke: A Review.

The maternal risk of strokes in the United States is approximately 30/100,000 pregnancies, and strokes are the eighth leading cause of maternal death. Because of the relationship between stroke and significant neurological disability/maternal death, obstetrical health care providers must be able to identify, evaluate, diagnosis, and treat these women. PubMed was searched using the search terms "stroke" OR "cerebrovascular accident" OR "intracranial hemorrhage" AND "pregnancy complications" OR "risk factors" OR "management" OR "outcome." The search was limited to the English language and was restricted to articles from 2000 to 2020. There were 319 abstracts identified, and 90 of the articles were ultimately used as the basis of this review. Presenting stroke signs and symptoms include headache, composite neurologic defects, seizures, and/or visual changes. Diagnosis is typically made with computed tomography scan using abdominal shielding or magnetic resonance imaging without contrast. Management options for an ischemic stroke include reperfusion therapy with intravenous recombinant tissue plasminogen activator catheter-based thrombolysis and/or mechanical thrombectomy. Hemorrhagic strokes are treated similarly to strokes outside of pregnancy, and that treatment is based on the severity and location of the hemorrhage. Early recognition and management are integral in decreasing the morbidity and mortality associated with a stroke in pregnancy. This study was an evidence-based review of stroke in pregnancy and how to diagnose and mange a pregnancy complicated by a stroke.

Efficacy and Safety of Alteplase on Treatment of Acute Single Small Subcortical Infarction.

Single Small Subcortical Infarction (SSSI) is an isolated small infarction in the territory of perforating artery with a maximum diameter of 20 mm in axial Diffusion-Weighted Imaging (DWI). About 20 to 30% of SSSI patients were reported to have Early Neurological Deterioration (END) in the acute phase, which brought adverse effects on long-term outcomes. The effect of the alteplase on the outcome of SSSI, especially END and long-term outcomes, was ambiguous. The study aims to find out the efficacy and safety of intravenous recombinant tissue Plasminogen Activator (rt-PA) on long-term and short- outcomes of patients with SSSI as compared to patients who received standard medical care. The patients were retrospectively screened from a stroke registry of the neurology department of 1st Affiliated Hospital of Zhengzhou University from January 2013 to December 2020. Based on treatment modality, patients were dichotomized into alteplase and standard medical care groups. To minimize confounding factors in subgroups, a propensity score matching analysis was done. The primary outcome was the favorable functional outcome 3 months after stroke onset, defined by attaining a score of ≤2 points on the modified Rankin scale (mRS), secondary outcome was the prevention of occurrence of END, defined as an increase of ≥2 points in the total score or ≥1point on motor subunit in the National Institutes of Health Stroke Scale (NIHSS) score within 72 hours after admission, safety features were symptomatic intracranial hemorrhage (sICH) or death. Multivariate analysis was employed to find the efficacy and safety of alteplase in the treatment of SSSI. A total of 717 patients with anterior circulation SSSI were selected, and 132 were included in the final analysis. Forty-five patients were treated with alteplase within 4.5 hours and 87 with standard medical care, and 44 pairs were successfully matched by propensity score. Pre-match data showed that the alteplase thrombolysis group showed a higher proportion of favorable outcomes at 3-month follow-up [OR=0.315, 95%CI:0.106, 0.931, P = 0.037] but did not reduce the incidence of END compared with the non-thrombolytic group [OR = 1.033, 95%CI:0.417,2.554, P = 0.943]. Post-match data showed that the alteplase group also showed a higher proportion of favorable outcomes at 3-month follow-up [OR = 0.247, 95%CI: 0.074, 0.830, P = 0.024]; however, it did not reduce the incidence of END compared with the non-thrombolytic group [OR = 1.241, 95%CI: 0.433,3.554, P = 0.688]. There was one case of asymptomatic ICH in alteplase treated patients. Patients with SSSI in the anterior circulation are more likely to achieve 3 months favorable outcomes than those who were treated with standard medical care; however, treatment with alteplase may not prevent the occurrence of END.

Safety and efficacy of a new modified intravenous recombinant tissue plasminogen activator (rt-PA) regimen in Chinese patients with acute ischemic stroke: A descriptive retrospective cohort study with subgroup-analysis of different rt-PA dose

Evidence for effects of the dose of recombinant tissue plasminogen activator(rt-PA) in Asian populations is inconclusive. The standard dose may cause drug waste and increase economic burden in developing country. Therefore, we preliminarily describe the safety and efficacy of a new modified dose of rt-PA regimen(0.6 or 0.9 mg/kg, with a maximum dose of 50 mg) in real world settings. 265 consecutive patients with ischemic stroke were treated with intravenous(IV) rt-PA alone from all the 323 consecutive patients treated with reperfusion therapy between January 1, 2017 and March 31, 2020. Safety and Efficacy was assessed by early neurological improvement(ENI), early neurological deterioration(END), symptomatic intracranial hemorrhage(sICH) and 90-day outcome defined by modified Rankin scale(mRS). Subgroup analysis was conducted to draw comparisons between different dose groups ([0.5,0.6)mg/kg, [0.6,0.7)mg/kg, [0.7,0.8)mg/kg, [0.8,0.9]mg/kg). Among the 265 patients, 150(56.60%) had a favorable outcome at 3 months(3 M); Mortality occurred in 17(6.40%) in 3 M; sICH in 12(4.50%); ENI in 70(26.40%); END2 in 29(10.90%) and END4 in 18(6.80%). In subgroup analysis, there was a significant difference in sICH that more patients developed sICH in [0.8–0.9]mg/kg group(P = 0.044) in univariate analysis of different dose. After adjusting, there was no significant difference between 4 dosage groups. Significant differences were seen in gender, atrial fibrillation and baseline NIHSS in the multivariable model of favorable outcome at 3 M. Our study preliminarily shows a good safety and efficacy of our modified rt-PA regimen, indicating that this regimen should be worthy of further study especially in developing country to reduce the financial burden of patients and avoid drug waste.