Search Results (37)

In line with AHA/ASA guidance, intravenous alteplase has served as the standard first-line reperfusion treatment in acute ischemic stroke (AIS). Hemorrhagic transformation (HT) is a common spontaneous complication after thrombolytic therapy for AIS with increased mortality. Restoration of flow in an occluded artery can precipitate blood–brain barrier breakdown and heighten the risk of HT. However, the pathogenesis of HT is multifactorial, and identifying patients at high risk after recanalization therapy (RT) has a defining role in ensuring optimal treatment. At the same time, it is still under debate how these patients can best be identified based on clinical and biological characteristics. Preventing HT will become increasingly essential. In this review, our primary objective was to identify research focused on the cardiovascular risk factors predicting HT after AIS treated with thrombolytics, as this may help develop targeted treatment strategies and diminish the risk of HT. Full article

Tenecteplase (TNK), a genetically modified tissue plasminogen activator, has emerged as a promising alternative to alteplase (ALT) for intravenous thrombolysis (IVT) in acute ischemic stroke (AIS). Our aim was to synthesize the current clinical evidence on TNK use in AIS patients, comparing efficacy, safety, and workflow benefits to ALT. A narrative review was conducted by searching PubMed and Scopus (January 2024–March 2025) for studies comparing TNK and ALT in AIS. A total of 35 eligible papers were included. Data were grouped by treatment scenario: IVT-only, bridging before endovascular therapy (EVT), and intra-arterial thrombolysis (IAT). The results showed that TNK is non-inferior—and in some analyses, superior—to ALT regarding functional outcomes, especially in large vessel occlusion. TNK facilitates shorter treatment delays due to its single-bolus administration. While some trials report higher rates of intracranial hemorrhage, overall safety and mortality are comparable. In conclusion, TNK appears to exert equivalent or superior efficacy and safety compared to ALT in multiple AIS scenarios. Its pharmacological and logistical advantages support its broader clinical adoption. Further trials are needed, especially for IAT, central retinal artery occlusion, and patients on dabigatran. Full article

Background/Objectives: We report on the association of clinical, demographic, and peri- and intraoperative factors with patient outcomes in large- and, separately, medium-vessel acute ischemic stroke (AIS) occlusions treated with mechanical thrombectomy or medical thrombolysis. Increasingly, neuroimaging, particularly novel markers of collateral status, has become useful in predicting response to endovascular treatment (EVT) among AIS patients. However, the relationship between these neuroimaging markers, documented predictors of stroke outcomes, and post-EVT functional status in anterior circulation large-vessel occlusions (LVOs) as compared to medium-vessel occlusions (MeVOs) remains unclear. We evaluated whether shared predictors of 90-day post-EVT functional outcomes in LVO compared to MeVO AIS patients within our institution exist. Methods: We retrospectively evaluated AIS patients treated at our institution between 9 January 2017 and 10 January 2023. The following were the inclusion criteria were applied: (i) CTA confirmed anterior circulation large or medium vessel occlusion; (ii) diagnostic CT perfusion was performed; (iii) mechanical thrombectomy was performed. A low modified Rankin score (mRS) indicating good functional outcomes (i.e., functional independence) was defined as less than or equal to 2, in accordance with prior studies. Univariate and multivariate logistic regression analyses were conducted to determine associations between demographic, clinical, and radiologic factors and mRS ≤ 2. Results: A total of 249 LVO (mean age 65.3 ± 16.2, 53.8% female) and 91 MeVO (mean age 68.9 ± 13.3, 46.2% female) patients met the inclusion criteria. Upon multivariate regression adjusted for race, age, hypertension, diabetes mellitus, radiologic features, IV alteplase, admission NIHSS, and reperfusion status, young age (p = 0.004), low admission NIHSS (p = 0.0001), and good reperfusion status (p = 0.007) were associated with good functional outcomes in LVO stroke. By contrast, no factors were significantly associated with good functional outcomes in MeVO stroke. Conclusions: Known factors, including young age, low admission stroke severity, and successful reperfusion predict EVT outcomes in LVO stroke but not necessarily in MeVO stroke. Further studies regarding predictors of MeVO outcomes in nonsurgical cases, including collateral status, may guide optimal medical management for this population. Full article

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are among the most widespread drugs for the prevention of cardiovascular mortality and morbidity. Nevertheless, they are known to cause bradykinin (BK)-mediated angioedema (AE), a paroxysmal, localized, self-limiting, and potentially fatal swelling of the subcutaneous and/or submucosal tissue, due to a temporary increase in vascular permeability. Unlike hereditary angioedema (HAE), which can be mediated similarly by BK, no diagnostic tools, guidelines, or drugs have yet been approved for the diagnosis and treatment of acute non-allergic drug-induced AE. Besides ACEIs and ARBs, inhibitors of dipeptidyl peptidase-IV, neprilysin inhibitors, and tissue plasminogen activators are known to cause AE as an adverse effect. Currently, there are insufficient data on the prevention of AE caused by pharmacological therapies. In addition, the molecular mechanisms underlying BK-mediated AE caused by drugs, which are discussed here, are not fully explained. Specific approved drugs and a structured diagnostic workflow are unmet needs and are required for the management of this kind of AE. The aim of this review is to provide physicians with accurate knowledge of potentially life-threatening drug reactions so that they can be better understood and managed. Full article

Background/Objectives: This study aims to compare the safety of tenecteplase versus alteplase for acute ischemic stroke. Methods: This was a multicenter, retrospective cohort study including 11 Memorial Hermann Health System hospitals in Houston from 7 December 2022 to 7 June 2023. Adults presenting with an acute ischemic stroke who received alteplase or tenecteplase were included in this study. The primary outcome was the incidence of hemorrhagic conversion after 24 h of thrombolytic administration. Secondary outcomes included door-to-needle time, incidence of a major or minor bleed, length of hospital stay, incidence of any adverse effect, modified Rankin score at discharge, patient discharge disposition, medication cost, and mortality. Results: A total of 173 patients were reviewed, with 87 patients in the tenecteplase group and 86 patients in the alteplase group. Gender, actual body weight, and use of aspirin or dual antiplatelet therapy within 24 h of thrombolytic administration were statistically disproportionate between both groups. Hemorrhagic conversion occurred in seven patients in the tenecteplase group and eight patients in the alteplase group (p = 0.79). Medication cost was statistically significant between both groups. All other secondary outcomes were similar between tenecteplase and alteplase. Conclusions: In this underpowered study, we did not observe a statistically significant difference in the rate of 24 h hemorrhagic conversion between the tenecteplase and alteplase groups. Further studies with a large sample size are warranted to assess safety outcomes. Full article

Background: Intravenous thrombolysis (IVT) is the standard treatment for ischemic stroke within 4.5 h of symptom onset. However, a significant proportion of patients present beyond this window. This study aims to evaluate the efficacy and safety of IVT beyond the 4.5 h window in selected patients. Methods: A systematic literature search was conducted across PubMed, Cochrane Library, and Google Scholar from inception to April 2025. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Results: A total of 12 RCTs were included, with 3236 patients. Compared to controls, IVT significantly improved excellent functional outcomes [OR: 1.40; 95% CI: 1.21–1.62] and good functional outcomes [OR: 1.26; 95% CI: 1.06–1.50] at 90 days. IVT also improved recanalization [OR: 2.47; 95% CI: 1.96–3.12], reperfusion [OR: 2.20; 95% CI: 1.26–3.84], and early neurological improvement [OR: 1.91; 95% CI: 1.12–3.26]. However, it was associated with a significantly higher risk of symptomatic intracranial hemorrhage (sICH) [OR: 2.17; 95% CI: 1.25–3.79], any ICH [OR: 1.49; 95% CI: 1.09–2.04], and type-II parenchymal hemorrhage (PH) [OR: 2.14; 95% CI: 1.19–3.83]. No significant difference was observed in systemic hemorrhage, 90-day all-cause mortality, 7-day mortality, or 90-day intervention-related mortality (p > 0.05). Conclusions: IVT beyond 4.5 h improves neurological outcomes in patients with ischemic stroke without increasing overall mortality or systemic bleeding, though it raises the risk of sICH, any ICH, and type-II PH. Further large RCTs are needed to confirm these findings and guide clinical practice. Full article

Objective: To evaluate the safety and efficacy of recombinant human prourokinase (rhPro-UK) administered via intravenous (IV) and intra-arterial (IA) routes in acute ischemic stroke (AIS) patients compared with standard treatments. Methods: A comprehensive search was conducted in accordance with PRISMA guidelines across Scopus, Web of Science, and PubMed until 11 December 2024. Randomized controlled trials (RCTs) assessing rhPro-UK’s efficacy and safety were included. Outcomes included the modified Rankin Scale (mRS), the National Institutes of Health Stroke Scale (NIHSS), mortality, and adverse events (AEs). Data analysis used risk difference (RD) with 95% confidence intervals (CIs). Results: Six RCTs (n = 3993) met the inclusion criteria. IV rhPro-UK showed comparable efficacy to the comparator for the mRS 0–1 at 90 days (RD: 0.00, 95% CI: [−0.04, 0.04]) and the mRS 0–2 (RD: −0.01, 95% CI: [−0.03, 0.01], P = 0.23). IA rhPro-UK significantly improved the mRS 0–1 (RD: 0.13, 95% CI: [0.01, 0.26], P = 0.04). The NIHSS reduction was significant for IV rhPro-UK (MD: −0.83, 95% [CI: −1.36, −0.29]). IV rhPro-UK did not significantly reduce the risk of systemic bleeding (RD: −0.10, 95% CI: [−0.24, 0.03], P = 0.12), serious AEs (RD: −0.01, 95% CI: [−0.04, 0.02], P = 0.53), or mortality (RD: 0.01, 95% CI: −0.01, 0.02). IA rhPro-UK significantly increased hemorrhage with neurological deterioration (RD: 0.08, 95% CI: [0.01, 0.14], P = 0.02). Conclusions: IV rhPro-UK provides non-inferior efficacy to both alteplase and standard care with a better safety profile at 35 mg, while IA rhPro-UK enhances functional outcomes in middle cerebral artery occlusions, albeit with safety concerns. Further trials are needed to confirm long-term outcomes, optimal dosing, and broader applicability. Full article

Background: Prosthetic valve thrombosis is a rare but serious complication of mechanical valve replacement. Traditionally, prosthetic valve thrombosis has been managed by surgical intervention; however, there is increasing data to support the use of thrombolytics. Methods: We present a case of a 74-year-old female with a history of rheumatic fever and subsequent mechanical aortic valve replacement on warfarin who presented to the emergency department with disequilibrium and chest pain. Results: She was found to have a subtherapeutic international normalized ratio and thrombosed mechanical aortic valve seen on transthoracic echocardiography, transesophageal echocardiography, and fluoroscopy. Conclusions: She was treated with a low-dose ultraslow alteplase infusion of 25 mg of alteplase administered over 25 h. Post-infusion transthoracic echocardiography immediately following infusion and four months later confirmed resolution of thrombosis. Full article

Intravenous thrombolysis remains the most accessible and effective reperfusion therapy available to patients with acute ischaemic stroke. Treatment with intravenous thrombolysis improves the odds of favourable functional outcome with the unacceptably low risk of haemorrhagic complications. Even in the current era of endovascular thrombectomy, intravenous thrombolysis remains the backbone of acute stroke treatment due to its accessibility and relative ease of administration. Since intravenous alteplase was first approved for acute ischaemic stroke in the mid 1990s, there have been significant advances in expanding the indication and time window for treatment, in addition to transitioning towards tenecteplase use for stroke thrombolysis. In this review, we will provide a narrative on the use of thrombolysis in acute ischaemic stroke including an up-to-date discussion on recent advances in thrombolytic therapy. Full article

Background: Intravenous thrombolysis is one of the most effective therapies for the treatment of acute ischemic stroke (AIS), with urokinase offering a cost-effective alternative to newer agents like alteplase and tenecteplase, especially in resource-limited settings. Methods: This review provides a comprehensive overview of the application of intravenous thrombolysis with urokinase for AIS in the clinical practice of stroke management, including the efficacy, safety, and cost-effectiveness of urokinase compared to other thrombolytic agents. Results: Urokinase, a first-generation thrombolytic drug, is a non-specific plasminogen activator that offers a cost-effective alternative. It has been used in clinical practice for over two decades to improve neurological outcomes in patients with AIS if administered within 6 h of ictus. Numerous studies have indicated that urokinase remains a viable option for patients who cannot access alteplase or tenecteplase because of economic constraints, time window limitations, availability, or other reasons. Conclusions: In low- and middle-income countries, urokinase is a cost-effective alternative thrombolytic drug. High-level evidence-based medical research is therefore urgently needed to confirm that urokinase is not inferior to new-generation thrombolytic drugs, and to assess whether it may even be superior in some patient populations. Full article

In contrast to other common anticoagulants such as citrate and low-molecular-weight heparin (LMWH), high-molecular-weight heparin (HMWH) induces the expression of matrix metalloproteinase (MMP)-9, which is also measured as a biomarker for stroke in blood samples. Mechanistically, HMWH-stimulated T cells produce cytokines that induce monocytic MMP-9 expression. Here, the influence of further anticoagulants (Fondaparinux, Hirudin, and Alteplase) and the heparin-contaminating glycosaminoglycans (GAG) hyaluronic acid (HA), dermatan sulfate (DS), chondroitin sulfate (CS), and over-sulfated CS (OSCS) on MMP-9 was analyzed to assess its suitability as a biomarker under various conditions. Therefore, starved Jurkat T cells were stimulated with anticoagulants/contaminants. Subsequently, starved monocytic THP-1 cells were incubated with the conditioned Jurkat supernatant, and MMP-9 mRNA levels were monitored (quantitative (q)PCR). Jurkat-derived mediators secreted in response to anticoagulants/contaminants were also assessed (proteome profiler array). The supernatants of HMWH-, Hirudin-, CS-, and OSCS-treated Jurkat cells comprised combinations of activating mediators and led to a significant (in the case of OSCS, dramatic) MMP-9 induction in THP-1. HA induced MMP-9 only in high concentrations, while LMWH, Fondaparinux, Alteplase, and DS had no effect. This indicates that depending on molecular weight and charge (but independent of anticoagulant activity), anticoagulants/contaminants provoke the expression of T-cell-derived cytokines/chemokines that induce monocytic MMP-9 expression, thus potentially impairing the diagnostic validity of MMP-9. Full article

Pleural effusion is the most common manifestation of pleural disease, and chest ultrasound is crucial for diagnostic workup and post-treatment monitoring. Ultrasound helps distinguish the various types of pleural effusion and enables the detection of typical manifestations of empyema, which presents as a complicated, septated effusion. This may benefit from drainage and the use of intrapleural enzyme therapy or may require more invasive approaches, such as medical or surgical thoracoscopy. The mechanism of action of intrapleural enzymatic therapy (IPET) is the activation of plasminogen to plasmin, which breaks down fibrin clots that form septa or the loculation of effusions and promotes their removal. In addition, IPET has anti-inflammatory properties and can modulate the immune response in the pleural space, resulting in reduced pleural inflammation and improved fluid reabsorption. In this article, we briefly review the literature on the efficacy of IPET and describe a case series in which most practical applications of IPET are demonstrated, i.e., as a curative treatment but also as an alternative, propaedeutic, or subsequent treatment to surgery. Full article

Thrombosis is a major health concern that contributes to the development of several cardiovascular diseases and a significant number of fatalities worldwide. While stent surgery is the current recommended treatment according to the guidelines, percutaneous coronary intervention (PCI) is the optimal approach for acute myocardial infarction (AMI). However, in remote areas with limited resources, PCI procedures may not be feasible, leading to a delay in treatment and irreversible outcomes. In such cases, preoperative thrombolysis becomes the primary choice for managing AMI in remote settings. The market for thrombolytic drugs is continuously evolving, and identifying a safe and effective thrombolytic agent for treating AMI is crucial. This study evaluated Urokinase, Alteplase, and Recombinant Human TNK Tissue-type Plasminogen Activator for Injection (rhTNK) as representatives of first-, second-, and third-generation thrombolytic drugs, respectively. The research included in vitro thrombolysis experiments, exposure of human cardiomyocytes, zebrafish tail vein injections, and vascular endothelial transgenic zebrafish models. The findings revealed that rhTNK is the most effective thrombolytic drug with the least adverse effects and lowest bleeding rate, highlighting its potential as the preferred treatment option for AMI. The order of thrombolytic effectiveness was Urokinase < Alteplase < rhTNK, with adverse effects on cardiomyocytes post-thrombolytic therapy ranking similarly as Urokinase < Alteplase < rhTNK, while the bleeding rate after thrombolysis followed the order of Urokinase > Alteplase > rhTNK. Full article

Background and Objectives: Current guidelines and the alteplase product insert recommend that antithrombotic therapy be avoided within 24 h of intravenous thrombolytic therapy with rt-PA in acute ischemic stroke. Therefore, the rate of stroke recurrence is unclear in terms of early neurological deterioration, which we could prevent with the early administration of antithrombotic therapy. We do not know the effect of early antithrombotic therapy after intravenous thrombolysis with rt-PA in acute stroke on the outcome in patients after 90 days either. Design: Prospective monocentric observational cohort study. Methods: Data were collected from consecutive patients treated with alteplase for acute ischemic stroke between January 2015 and January 2023. We examined functional outcome at 90 days, including the risk of symptomatic intracranial hemorrhage and mortality rate as safety indicators and stroke recurrence events in both early and standard antithrombotic therapy at 24 h after intravenous thrombolysis. Results: A total of 489 patients were included, of which 278 (56.9%) were men. Of these, 407 (83.2%) patients received early antithrombotic therapy. No symptomatic intracranial hemorrhage occurred in any participants. There was a significantly higher number of patients with an excellent outcome (mRS 0-1) in early antithrombotic treatment (211 (53.1%) versus 28 (34.6%) in standard antithrombotic treatment (p = 0.002, OR 0.47, 95% CI: 0.28–0.76). Conclusions: Early antithrombotic treatment after intravenous therapy in patients with acute ischemic stroke revealed no safety concerns compared with standard antithrombotic therapy and resulted in a significantly higher proportion of patients with an excellent functional outcome. Full article

While tumor emboli are a rare cause of stroke in cancer patients, they highlight the importance of gross observations and pathological assessments in the evaluation of clots. In this case report, a 70-year-old male with type 2 diabetes mellitus and coronary artery disease presented with acute left-sided weakness. He was clinically diagnosed with stroke and given alteplase at 1.5 h from last known normal. He then underwent CT angiography that showed right internal carotid artery occlusion and immediate thrombectomy. The recovered clot was white and lipid-like; due to its atypical appearance, it was sent for pathological assessment, where it was shown to bear features of malignancy. Subsequent imaging identified masses indicating malignancy in the left gluteus, right pleural hilum, and spine. Tumor embolic stroke is a rare pathology. Embolic diseases such as strokes and pulmonary embolisms are common in patients with cancer. Embolic stroke of undetermined source (ESUS) represents a significant portion of cancer strokes. Tumor emboli, though rare, may be an underappreciated source of ESUS in cancer patients. We intend for this case to demonstrate the value of pathological assessment for atypical thrombi as well as highlight the etiology of tumor embolic strokes. Full article