[Catheter-assisted local lysis therapy for submassive pulmonary embolism]. / Kathetergestützte lokale Lysetherapie bei submassiven Lungenembolien.

BACKGROUND: Pulmonary embolism is the third most common cardiovascular disease. Interventional treatment options as an alternative to systemic lysis therapy of hemodynamically stable, submassive pulmonary embolisms have received an unprecedented boost in innovation in recent years. The treatment options are heterogeneous and can be roughly divided into local thrombolysis and local thrombectomy. For years in our center we have been carrying out catheter-assisted, locoregional lysis therapy with side-hole lysis catheters and a cumulative dose per pulmonary branch of 10 mg alteplase over 15 h for hemodynamically stable, submassive pulmonary emboli. AIM: The aim of this retrospective study was to review this therapeutic concept and to collect data on clinical endpoints and possible complications. METHODS: The study included data from 01/2018-03/2023. For this purpose, the patients were selected based on the OPS codes (8.838.60 and 1­276.0), and the data was collected using the medical records. Biometric data, data on previous illnesses and vital parameters, laboratory chemistry data, CT diagnostic data, echocardiographic data, data on drug treatment and data on complications were collected anonymously. RESULTS: There was a significant reduction in the strain on the right heart. Peripheral oxygen saturation also improved significantly and heart rate decreased significantly. The complication rate remained low and was almost exclusively limited to access-related problems. CONCLUSION: Catheter-assisted, locoregional lysis therapy is a safe and effective treatment method for submassive pulmonary embolism.

Platelet glycoprotein IIb/IIIa antagonists in ischemic stroke patients without endovascular therapy: A meta-analysis.

Platelet glycoprotein (GP) IIb/IIIa antagonists have been employed in selective patients after endovascular therapy (EVT) for acute ischemic stroke (AIS), yet application in patients without EVT is debated. This meta-analysis of randomized controlled studies on AIS patients without EVT assessed the effectiveness and safety of platelet GP IIb/IIIa antagonists compared with traditional antiplatelet or thrombolysis therapy. Articles were retrieved from databases, including PubMed, Web of Science, EMBASE, and Cochrane. The risk of bias and certainty level of evidence were assessed. Fifteen studies were included. GP IIb/IIIa antagonists increased the proportion of patients with modified Rankin Scale (mRS) 0-1 (odd ratio [OR] 1.37, 95% confidence interval [CI] 1.04-1.81, p = 0.03), mRS 0-2 (OR 1.27, 95% CI 1.12-1.46, p = 0.0004), and Barthel Index (BI) 95-100 (OR 1.25, p = 0.005); decreased the proportion of stroke progression within 5 days (OR 0.66, p = 0.006); and lowered the mean mRS score at 90 days (mean difference [MD] -0.43, p = 0.002) and the National Institute of Health stroke scale score at 7 days (MD -1.64, p < 0.00001) compared with conventional treatment. Proportions of stroke recurrence within 90 days (OR 1.20, p = 0.60), any intracranial hemorrhage (aICH) (OR 1.20, p = 0.12), symptomatic intracranial hemorrhage (sICH) (OR 0.91, p = 0.88), and death (OR 0.87, p = 0.25) had no statistical difference between both groups. This meta-analysis finds that compared with traditional antiplatelet or thrombolysis therapy, GP IIb/IIIa antagonists administered within 24-96 h of ischemic stroke onset significantly improve functional prognosis of patients with AIS not receiving EVT, as indicated by mRS and BI at 90 days, and do not increase the incidence of aICH, sICH, and death.

Competências do enfermeiro no cuidado a pacientes com acidente vascular cerebral elegíveis à terapia trombolítica / Competencias de enfermería en el cuidado de personas con accidente cerebrovascular elegibles para terapia trombolítica / Nursing competencies in the care of patients with stroke who are eligible for thrombolytic therapy

Resumo Introdução: O acidente vascular cerebral isquêmico tem como tratamento a terapia trombolítica, aplicada ainda na fase aguda, promovendo melhora importante nas sequelas acarretadas por este agravo. Considerando a complexidade da terapia trombolítica, torna-se necessário que os enfermeiros compreendam suas competências para auxiliar no cuidado. Objetivo: Identificar evidências científicas acerca das competências do enfermeiro no cuidado a pacientes com acidente vascular cerebral elegíveis à terapia trombolítica. Metodologia: Revisão integrativa composta por seis etapas em seis etapas (elaboração da questão, busca na literatura, coleta de dados, análise, discussão e apresentação da revisão), realizada nas bases de dados MEDLINE, LILACS, BDENF, IBECS, PubMed, Scopus, Web of Science, Embase e CINAHL. A busca foi realizada entre agosto e setembro de 2022 adotando como critérios de inclusão estudos primários; gratuitos, disponíveis eletronicamente na íntegra; nos idiomas inglês, português e espanhol. Foram obtidos inicialmente 2.830 estudos, os quais passaram por uma seleção, onde foram incluídos aqueles que atendiam os critérios previamente estabelecidos. Resultados: Com base nos doze estudos incluídos nesta revisão identificaram-se competências voltadas à três atividades do cuidado: gestão do cuidado como trabalho em equipe, códigos, fluxos e protocolos, assistência ao paciente antes, durante e após a utilização da terapia trombolítica e educação em saúde para equipe, pacientes e familiares. Conclusão: Os achados desta revisão puderam evidenciar as competências do enfermeiro no cuidado aos pacientes elegíveis a terapia trombolítica, as quais perpassam diferentes áreas de atuação do enfermeiro. Para este estudo prevaleceram as competências assistências, seguida por competências gerenciais.

Resumen Introducción: El accidente cerebrovascular isquémico se trata con terapia trombolítica, aplicada incluso en la fase aguda, que promueve una mejoría significativa de las secuelas provocadas por este padecimiento. Considerando la complejidad de la terapia trombolítica, es necesario que las personas profesionales de enfermería comprendan sus competencias para ayudar en el cuidado. Objetivo: Identificar evidencias científicas sobre las competencias del personal de enfermería en el cuidado de pacientes con accidente cerebrovascular elegibles para terapia trombolítica. Metodología: Revisión integradora que consta de seis etapas (elaboración de la pregunta, búsqueda bibliográfica, recolección de datos, análisis, discusión y presentación de la revisión), realizada en las bases de dados MEDLINE, LILACS, BDENF, IBECS, PubMed, Scopus, Web of Science, Embase y CINAHL. La búsqueda se realizó entre agosto y septiembre de 2022. Los criterio de inclusión fueron: estudios primarios, gratuito, disponible electrónicamente en su totalidad, en inglés, portugués y español. Inicialmente se obtuvieron 2830 estudios, los cuales fueron sometidos a un proceso de selección, que incluyó aquellos que cumplían con los criterios previamente establecidos. Resultados: A partir de los doce estudios incluidos en esta revisión, se identificaron competencias centradas en tres actividades asistenciales: gestión del cuidado como trabajo en equipo, códigos, flujos y protocolos, atención a pacientes antes, durante y después del uso de la terapia trombolítica y educación en salud para personal, pacientes y familias. Conclusión: Los hallazgos de esta revisión pudieron resaltar las competencias de las personas profesionales en enfermería en el cuidado de personas elegibles para terapia trombolítica, que abarcan diferentes áreas de actuación del personal de enfermería. Para este estudio, prevalecieron las habilidades asistenciales, seguidas de las competencias gerenciales.

ABSTRACT Introduction: Ischemic stroke is treated with thrombolytic therapy, applied even in the acute phase, promoting a significant improvement in the after-effects caused by this condition. Considering the complexity of thrombolytic therapy, it is necessary for nurses to understand the skills required to assist in care. Objective: To identify scientific evidence about the competencies of nurses in the care of patients with stroke who are eligible for thrombolytic therapy. Methodology: An integrative review consisting of six stages (elaboration of the question, literature review, data collection, analysis, discussion, and presentation), conducted in MEDLINE, LILACS, BDENF, IBECS, PubMed, Scopus, Web of Science, Embase, and CINAHL databases. The search was carried out between August and September 2022 using primary studies as the inclusion criteria: free of charge, fully available electronically, published in English, Portuguese, or Spanish. Initially, 2.830 studies were obtained, which underwent a selection process that included only those studies that met the previously established criteria. Results: Based on the twelve studies included in this review, competencies focused on three care activities were identified: care management such as teamwork; codes; flows and protocols; patient care before, during, and after the use of thrombolytic therapy; and education health education for staff, patients, and families. Conclusion: The findings of this review highlighted the nurses' competencies in the care of patients eligible for thrombolytic therapy, which encompass different areas of the nurse's work. For this study, assistance competencies prevailed, followed by management competencies.

The Clinical Impact of Access Site Selection for Successful Thrombolysis and Intervention in Acute Critical Lower Limb Ischaemia (RAD-ALI Registry).

Background: Acute limb ischaemia (ALI) is of great clinical importance due to its consequent serious complications and high comorbidity and mortality rates. The purpose of this study was to compare the acute success and complication rates of CDT performed via transradial, transbrachial, and transfemoral access sites in patients with acute lower limb vascular occlusion and to investigate the 1-year outcomes of CDT and MT for ALI. Methods: Between 2008 and 2019, 84 consecutive patients with ALI were treated with CDT in a large community hospital. Data were collected and retrospectively analysed. The primary ("safety") endpoints encompassed major adverse events (MAEs), major adverse limb events (MALEs), and the occurrence of complications related to the access site. Secondary ("efficacy") endpoints included both technical and clinical achievements, treatment success, fluoroscopy time, radiation dose, procedure time, and the crossover rate to an alternative puncture site. Results: CDT was started with radial (n = 17), brachial (n = 9), or femoral (n = 58) access. CDT was technically successful in 74/84 patients (88%), but additional MT and angioplasty and/or stent implantation was necessary in 17 (20.2%) and 45 cases (53.6%), respectively. Clinical success was achieved in 74/84 cases (88%). The mortality rate at 1 year was 14.3%. The cumulative incidence of MAEs and MALEs at 12 months was 50% and 40.5%, respectively. After conducting multivariate analysis, history of Rutherford stage IIB (hazard ratio [HR], 3.64; 95% confidence interval [CI], 1.58-8.41; p = 0.0025), occlusion of the external iliac artery (HR, 27.52; 95% CI, 2.83-267.33; p = 0.0043), being a case of clinically unsuccessful thrombolysis (HR, 7.72; 95% CI, 2.48-23.10; p = 0.0004), and the presence of diabetes mellitus (HR, 2.18; 95% CI, 1.01-4.71; p = 0.047) were independent predictors of a high MAE mortality rate at 12 months. For MALEs, statistically significant differences were detected with the variables history of Rutherford stage IIB (HR, 4.30; 95% CI, 1.99-9.31; p = 0.0002) and external iliac artery occlusion (HR, 31.27; 95% CI, 3.47-282.23; p = 0.0022). Conclusions: Based on the short-term results of CDT, acute limb ischaemia can be successfully, safely, and effectively treated with catheter-directed thrombolytic therapy with radial, brachial, or femoral access. However, radial access is associated with fewer access site complications. A history of Rutherford stage IIB, occlusion of external iliac artery, unsuccessful thrombolysis, and the presence of diabetes mellitus were independently associated with an increased risk of MAEs. A history of Rutherford stage IIB and external iliac artery occlusion are independent predictors of MALEs.

Caught in the Clot: A Case Report of Arrested Pulmonary Embolism.

Pulmonary embolism (PE) is a life-threatening condition resulting from the obstruction of pulmonary arteries by blood clots, usually originating from deep veins. Symptoms of PE might vary from nothing to sudden death. Clinically, individuals may present very differently. When a diagnosis of PE is suspected, any possible life-saving intervention must be implemented because survival from cardiac arrest following PE is often quite low. Although there are not many randomized controlled trials that provide guidelines for treating suspected PE in cardiac arrest victims, the few published case reports and other minor studies suggest that thrombolysis and other therapies are associated with good outcomes. We report a patient with PE who presented in cardiac arrest with its clinical, electrographic, and radiologic findings, along with the appropriate therapy chosen based on hemodynamic stability. It is important to intervene early to prevent severe complications and improve the patient's outcomes.

Fibrinogen binding to activated platelets and its biomimetic thrombus-targeted thrombolytic strategies.

Thrombosis is associated with various fatal arteriovenous syndromes including ischemic stroke, myocardial infarction, and pulmonary embolism. However, current clinical thrombolytic treatment strategies still have many problems in targeting and safety to meet the thrombolytic therapy needs. Understanding the molecular mechanism that underlies thrombosis is critical in developing effective thrombolytic strategies. It is well known that platelets play a central role in thrombosis and the binding of fibrinogen to activated platelets is a common pathway in the process of clot formation. Based on this, a concept of biomimetic thrombus-targeted thrombolytic strategy inspired from fibrinogen binding to activated platelets in thrombosis was proposed, which could selectively bind to activated platelets at a thrombus site, thus enabling targeted delivery and local release of thrombolytic agents for effective thrombolysis. In this review, we first summarized the main characteristics of platelets and fibrinogen, and then introduced the classical molecular mechanisms of thrombosis, including platelet adhesion, platelet activation and platelet aggregation through the interactions of activated platelets with fibrinogen. In addition, we highlighted the recent advances in biomimetic thrombus-targeted thrombolytic strategies which inspired from fibrinogen binding to activated platelets in thrombosis. The possible future directions and perspectives in this emerging area are briefly discussed.

Impact of capacity building and tele ECG based decision support on change in thrombolysis rate and inhospital and one year mortality in patients with STEMI, using hub and spoke model; multi-phasic intervention trial.

BACKGROUND: We report the impact of capacity building and teleconsultation on change in the thrombolysis rates and one-year mortality in patients with STEMI using a hub and the spoke model of STEMI care. METHODS: Twenty secondary care public hospitals were linked with a teaching hospital as a hub centre and the impact of the intervention on change in ischemic time, thrombolysis rates and all-cause in-hospital and one-year mortality was compared. RESULTS: 29 patients with STEMI were treated during pre-intervention from April 2020 to June 2020 and 255 patients during the post-intervention period from July 2020 to Oct 2021 in spoke centres. 245 patients were reported to a hub centre during the study period. The thrombolysis rate was significantly higher in the spoke centres after intervention (65.5%vs. 27.5 % p < 0.001) and was also significantly higher than in patients treated in a hub centre (65.5 % vs. 45.7 % p < 0.01). The in-hospital mortality was significantly lower in patients treated at spoke centres compared to those treated at the hub centre (7.8 % vs. 15.5 % < 0.003). The significant difference in mortality rate continued at one year (11.0 % vs.18.4 % p < 0.01). The median time from symptoms to thrombolytic therapy was significantly lower in STEMI patients treated in spoke centres compared to a hub centre (230 min vs. 356 min p < 0.001). CONCLUSION: The hub and spoke model of STEMI care is effective in increasing thrombolysis rate, and decreasing in-hospital and one-year mortality rate.

RhPro-UK in acute ischemic stroke within 4.5 hours of stroke onset trial-2(The PROST-2 study): Rationale and design of a multicenter, prospective, randomized, open-label, blinded-endpoint, controlled phase 3 non-inferiority trial.

BACKGROUND: Recombinant human prourokinase (rhPro-UK) is a specific plasminogen activator, which has been approved to treat acute myocardial infarction in China. AIM: This phase III trial aimed to further demonstrate the efficacy and safety of rhPro-UK in patients with acute ischemic stroke (AIS) within 4.5 hours of symptom onset. METHODS AND DESIGN: RhPro-UK in AIS within 4.5 hours of stroke onset trial-2 (PROST-2) is a multicenter, prospective randomized, open-label, blinded end-point, non-inferiority, recombinant tissue plasminogen activator (rt-PA)-controlled, phase 3 trial. A total of 1,552 patients who are eligible for intravenous thrombolytic therapy from 72 clinical sites will be randomly assigned to receive either rhPro-UK 35 mg (15 mg bolus+ 20 mg infusion/30 minutes) or rt-PA 0.9 mg/kg (10% bolus +90% infusion/1 hour). STUDY OUTCOMES: The primary outcome is the proportion of patients with a modified Rankin Scale (mRS) score of 0-1 at 90 days. Secondary efficacy outcomes include the proportion of patients with mRS score of 0-2, the distribution of mRS, self-care ability in daily life on the Barthel Index at 90 days, the proportion of subjects with ≥ 4 points decrease in National Institutes of Health Stroke Scale (NIHSS) score or NIHSS score ≤ 1 from baseline at 24 hours and 7 days after treatment. Safety outcomes are symptomatic intracranial hemorrhage (sICH) and major systematic bleeding within 7 days as well as death from all causes within 90 days. DISCUSSION: The results from the PROST-2 trial will comprehensively elucidate the efficacy and safety profile of rhPro-UK as a potential alternative agent for stroke thrombolysis. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT05700591.

Clinical Outcomes of Percutaneous Transcatheter Release of Stuck Mechanical Mitral Valve With Cerebral Embolic Protection.

BACKGROUND: Surgery or fibrinolysis is the currently available evidence-based treatment for obstructive mechanical valve thrombus. We reported the feasibility and short-term outcomes of percutaneous transcatheter therapy with cerebral embolic protection. Mid- and long-term outcomes remain unknown. METHODS: From 2020 to 2023, 24 patients underwent percutaneous transcatheter release of stuck leaflets with cerebral embolic protection for obstructive mitral mechanical valve thrombus. The indications for the transcatheter therapy were failed fibrinolysis, contraindications for fibrinolysis, not willing for fibrinolysis, or high risk for surgery. The study participants were followed up for a median period of 344.50 (65.00-953.75) days. RESULTS: Technical success was achieved in 91.67% (n=22) of procedures. During the follow-up, 12.50% (n=3) all-cause death, 4.17% (n=1) stroke, and 16.67% (n=4) recurrence were seen. The mean survival time free from death was 1101.48 (95% CI, 929.49-1273.47) days, stroke was 1211.38 (95% CI, 1110.40-1312.35) days, and recurrence was 907.71 (95% CI, 760.20-1055.21) days. CONCLUSIONS: Transcatheter release of the stuck mitral mechanical valve with cerebral embolic protection is an alternative therapy with promising mid-term outcomes where surgery or fibrinolysis is not possible or in failed fibrinolysis subsets.

Ischemic Stroke Outcome Predicted by Serum Albumin Levels.

OBJECTIVE AND AIM:  This research aims to assess the predictive importance of serum albumin levels in individuals who have recently experienced an acute ischemic stroke and to establish a correlation between these two variables. MATERIALS AND METHODS: A prospective hospital-based investigation with 50 participants was conducted after receiving ethical approval from Sunshine Hospital, Hyderabad, India. Patients older than 18 years old who had radiological or clinical evidence of having suffered an acute ischemic stroke were considered for participation in the research. RESULTS:  Albumin levels in the blood are typically about 3.6 g/dL. One patient between the ages of 46 and 55 had low serum albumin levels. Many people in both groups had albumin levels of about 4.4. Serum albumin concentration was measured using the modified Rankin Scale (mRS). After one week and three months, 32 patients had mRS values of less than three, whereas 16 had mRS values of greater than three-one; the individual presented with an mRS value over 3, as well as a blood albumin level below 3.5. The p-value ended up being 0.428. No link could be supported by the statistical evidence identified. P = 0.249 indicated no association between serum albumin and National Institutes of Health Stroke Scale (NIHSS) scores. According to the findings of this inquiry, there is no correlation between the amounts of albumin in the blood and the NIHSS scores. CONCLUSION: This study did not find a correlation between higher blood albumin levels and a worse outcome after an ischemic stroke. It contradicts the corpus of current knowledge.

Efficacy of Low-Dose Streptokinase Infusion in Late-Onset Permanent Tunnel Catheter Dysfunction: A Single-Center Interventional Study.

Introduction Hemodialysis is a vital modality for patients with renal dysfunction, with venous access being a significant factor in its success. While arteriovenous fistulas are preferred, tunneled catheters serve as important alternatives, especially in challenging cases. Late-onset tunneled catheter dysfunction, often due to fibrin sheath formation, impedes hemodialysis efficiency. Streptokinase, a low-cost thrombolytic agent, has shown promise in resolving such complications, yet its efficacy in the Indian context remains unexplored. Methods We conducted a single-center interventional study at Mahatma Gandhi Mission (MGM) Hospital, Aurangabad, India, from May 2023 to October 2023. Ethical approval was obtained, and 10 eligible patients experiencing late-onset permanent tunnel catheter dysfunction were enrolled. Patients were treated with low-dose streptokinase, and outcomes were monitored for 60 days. Results Ten patients, evenly distributed by gender, participated, with a mean age of 48.2 ± 11.96 years. Diabetes was the predominant cause of chronic kidney disease (CKD) at 33% (3/10). All patients achieved the primary endpoint of blood flow rate (BFR) >300 ml/min post-streptokinase treatment, with an overall success rate of 100%. Group A had the highest average gain in catheter days (80.6 ± 7.59), followed by Group B (64 ± 1), while Group C showed variations in catheter days between the first (26.2 ± 6.8) and second insertion (32.5 ± 1.76). Eight patients maintained catheter patency during the 60-day follow-up. Adverse effects, primarily minor, were observed. The dosage rationale involved an eight-hour infusion at 4,000 units per hour. Conclusion Streptokinase emerges as cost-effective and efficacious for maintaining the patency of late-onset tunnel catheter dysfunction in resource-limited settings, particularly in younger patients. Caution is advised for older individuals with prolonged CKD.

Effectiveness and safety of bridging therapy and endovascular therapy in patients with large cerebral infarctions: from ANGEL-ASPECT.

BACKGROUND AND PURPOSE: The benefits of thrombolytic therapy before endovascular thrombectomy in cases of acute ischaemic stroke, with a large infarction volume, remain unclear. This analysis aims to evaluate the effectiveness and safety of bridging therapy and endovascular therapy among patients with large cerebral infarctions. METHODS: In this post-hoc analysis of the multicentre prospective study of ANGEL-ASPECT (Acute Anterior Circulation Large Vessel Occlusive Patients with a Large Infarct Core), participants were divided into two groups: an endovascular therapy group and a bridging therapy group. The primary outcome was the modified Rankin Scale (mRS) score at 90 days. The primary safety outcome was symptomatic intracranial haemorrhage. Ordinal logistic regression was performed to compare the primary endpoint between the two groups. Subgroup analyses were conducted to further explore potential risk factors associated with the outcomes. RESULTS: 122 patients were included, of whom 77 (63%) underwent endovascular therapy and 45 (37%) underwent bridging therapy. The median scores on mRS at 90 days of the bridging therapy group and the endovascular therapy group were 3 (2-5) and 4 (2-6), with no significant differences (common OR 1.36; 95% CI 0.71 to 2.61). Symptomatic intracranial haemorrhage was reported in three patients who were in the endovascular and bridging therapy groups (relative risk (RR) 1.71; 95% CI 0.36 to 8.12). The mortality between two groups did not differ (RR 0.75; 95% CI 0.37 to 1.54). CONCLUSIONS: Our study indicated that endovascular therapy alone might be a viable option for patients with large cerebral infarctions, displaying no noticeable disparity in outcomes compared with bridging therapy.

Successful Treatment of Massive Pulmonary Embolism in Pregnancy with Catheter-Directed Embolectomy.

Introduction Pulmonary embolism (PE) is associated with approximately 10.5% of maternal deaths in the United States. Despite heightened awareness of its mortality potential, there islittle data available to guide its management in pregnancy. We present the case of a massive PE during gestation successfully treated with catheter-directed embolectomy. Case Presentation A 37-year-old G2P1001 presented with a syncopal episode preceded by dyspnea and chest pain. Upon presentation, she was hypotensive, tachycardiac, and hypoxic. Imaging showed an occlusive bilateral PE, right heart strain, and a possible intrauterine pregnancy. Beta-human chorionic gonadotropin was positive. She was taken emergently for catheter-directed embolectomy. Her condition immediately improved afterward. Postprocedure pelvic ultrasound confirmed a viable intrauterine pregnancy at 10 weeks gestation. She was discharged with therapeutic enoxaparin and gave birth to a healthy infant at 38 weeks gestation. Conclusion Despite being the gold standard for PE treatment in nonpregnant adults, systemic thrombolysis is relatively contraindicated in pregnancy due to concern for maternal or fetal hemorrhage. Surgical or catheter-based thrombectomies are rarely recommended. Limited alternative options force their consideration, particularly in a hemodynamically unstable patient. Catheter-directed embolectomy can possibly bypass such complications. Our case exemplifies the consideration of catheter-directed embolectomy as the initial treatment modality of a hemodynamically unstable gestational PE.

Factors affecting improvement after intravenous administration of recombinant tissue plasminogen activator (rtPA) among patients with acute ischemic stroke: A historical cohort study.

Background: One of the most effective treatments for patients with acute ischemic stroke (AIS) is intravenous recombinant tissue plasminogen activator (rtPA) which can minimize mortality and morbidities. In this historical cohort study, we investigate the factors affecting clinical outcomes after IV thrombolysis for AIS. Methods: We included 87 patients with acute ischemic stroke who were treated with rtPA between 2015 and 2019. Demographic and clinical data were recorded. The National Institutes of Health Stroke Scale (NIHSS) was used to assess the clinical outcomes. Results: 36 patients showed lack of improvement at discharge. In unadjusted model, hypercholesterolemia was the only predictor of lack of improvement (P= 0.043; OR=0.304; CI= 0.096-0.963). After adjusting, hypertension (P= 0.018; OR= 0.18; CI= 0.043-0.749) and hypercholesterolemia (P= 0.008; OR= 8.68; CI= 1.773-42.54) were independent determinants of lack of clinical response. To evaluate risk factors in association with the duration of hospitalization, we found variables which lengthened hospitalization span including; age over 60 years (HR= 0.42 P= 0.002), hypercholesterolemia (HR= 2.19 P= 0.031), Angiotensin-converting enzyme (ACE) Inhibitors consumption (HR= 1.87 P= 0.022), and type of infarction (non-lacunar) (HR= 0.51 P= 0.026). Results indicated no considerable relationship between dose of rtPA and the appropriate response to treatment (OR=8.686 P= 0.324). Conclusion: The closer dose of rtPA goes up to standard range, the more chance of improvement will gain without increasing the risk of symptomatic intra-cerebral hemorrhage (SICH). Determining factors involved in intravenous reperfusion outcomes help physicians to identify the patients who benefit the most from rtPA.

Arterial Recanalization During Interhospital Transfer for Thrombectomy.

BACKGROUND: Patients with acute ischemic stroke harboring a large vessel occlusion admitted to nonendovascular-capable centers often require interhospital transfer for thrombectomy. We evaluated the incidence and predictors of arterial recanalization during transfer, as well as the relationship between interhospital recanalization and clinical outcomes. METHODS: We analyzed data from 2 cohorts of patients with an anterior circulation large vessel occlusion transferred for consideration of thrombectomy to a comprehensive center, with arterial imaging at the referring hospital and on comprehensive stroke center arrival. Interhospital recanalization was determined by comparison of the baseline and posttransfer arterial imaging and was defined as revised arterial occlusive lesion (rAOL) score 2b to 3. Pretransfer variables independently associated with interhospital recanalization were studied using multivariable logistic regression analysis. RESULTS: Of the 520 included patients (Montpellier, France, n=237; Stanford, United States, n=283), 111 (21%) experienced interhospital recanalization (partial [rAOL=2b] in 77% and complete [rAOL=3] in 23%). Pretransfer variables independently associated with recanalization were intravenous thrombolysis (adjusted odds ratio, 6.8 [95% CI, 4.0-11.6]), more distal occlusions (intracranial carotid occlusion as reference: adjusted odds ratio, 2.0 [95% CI, 0.9-4.5] for proximal first segment of the middle cerebral artery, 5.1 [95% CI, 2.3-11.5] for distal first segment of the middle cerebral artery, and 5.0 [95% CI, 2.1-11.8] for second segment of the middle cerebral artery), and smaller clot burden (clot burden score 0-4 as reference: adjusted odds ratio, 3.4 [95% CI, 1.5-7.6] for 5-7 and 5.6 [95% CI, 2.4-12.7] for 8-9). Recanalization on arrival at the comprehensive center was associated with less interhospital infarct growth (rAOL, 0-2a: 11.6 mL; rAOL, 2b: 2.2 mL; rAOL, 3: 0.6 mL; Ptrend<0.001) and greater interhospital National Institutes of Health Stroke Scale score improvement (0 versus -5 versus -6; Ptrend<0.001). Interhospital recanalization was associated with reduced 3-month disability (adjusted common odds ratio, 2.51 [95% CI, 1.68-3.77]) with greater benefit from complete than partial recanalization. CONCLUSIONS: Recanalization is frequently observed during interhospital transfer for thrombectomy and is strongly associated with favorable outcomes, even when partial. Broadening thrombolysis indications in primary centers, and developing therapies that increase recanalization during transfer, will likely improve clinical outcomes.

Outcomes of Bridging Intravenous Thrombolysis Versus Endovascular Therapy Alone in Late-Window Acute Ischemic Stroke.

BACKGROUND: Studies comparing bridging intravenous thrombolysis (IVT) with direct endovascular therapy (EVT) in patients with acute ischemic stroke who present late are limited. We aimed to compare the clinical outcomes and safety of bridging IVT in patients with acute ischemic stroke due to anterior circulation large vessel occlusion who underwent EVT 6 to 24 hours after time last known well. METHODS: We enrolled patients with anterior circulation large vessel occlusion stroke and a National Institutes of Health Stroke Scale score of ≥6 from 20 centers across 10 countries in the multicenter retrospective CLEAR study (CT for Late Endovascular Reperfusion) between January 2014 and May 2022. We used inverse probability of treatment weighting modeling adjusted for clinical and imaging confounders to compare functional outcomes, reperfusion success, symptomatic intracranial hemorrhage, and mortality between EVT patients with and without prior IVT. RESULTS: Of 5098 patients screened for eligibility, we included 2749 patients, of whom 549 received bridging IVT before EVT. The timing of IVT was not recorded. Witnessed stroke onset and transfer rates were higher in the bridging IVT group (25% versus 12% and 77% versus 55%, respectively, P value for both <0.0001), and time intervals between stroke onset and treatment were shorter (time last known well-start of EVT median 560 minutes [interquartile range, 432-791] versus 724 minutes [interquartile range, 544-912]; P<0.0001). After adjustment for confounders, there was no difference in functional outcome at 3 months (adjusted common odds ratio for modified Rankin Scale shift, 1.03 [95% CI, 0.89-1.19]; P=0.72) or successful reperfusion (adjusted odds ratio, 1.19 [95% CI, 0.81-1.75]; P=0.39). There were no safety concerns associated with bridging IVT versus direct EVT (symptomatic intracranial hemorrhage: adjusted odds ratio, 0.75 [95% CI, 0.38-1.48]; P=0.40; mortality: adjusted odds ratio, 1.14 [95% CI, 0.89-1.46]; P=0.31). Results were unchanged when the analysis was limited to patients who received IVT >6 hours after last known well. CONCLUSIONS: In patients with an anterior circulation large vessel occlusion stroke who underwent EVT 6 to 24 hours from last known well, bridging IVT was not associated with a difference in outcomes compared with direct EVT. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04096248.

How Clot Composition Influences Fibrinolysis in the Acute Phase of Stroke: A Proteomic Study of Cerebral Thrombi.

BACKGROUND: The dramatic clinical improvement offered by mechanical thrombectomy raised questions about the relevance of prior intravenous thrombolysis in large-vessel occlusion strokes. Hence, studying intravenous thrombolysis susceptibility and its dependence on thrombus composition is crucial. We used an observational proteomic study of whole thrombi retrieved by mechanical thrombectomy to identify factors associated with fibrin content and fibrinolytic activity (FA). METHODS: In 104 stroke patients, the thrombi proteome was established by mass spectrometry coupled to liquid chromatography. FA was estimated in clots both outside (FAout) by measuring D-dimer levels at the blood-thrombus interface and inside (FAin) by evaluating the ratio of fibrinogen α to its plasmin-cleaved forms using proteomics coupled with protein electrophoresis. The factors associated with fibrin content, FAin, and FAout were determined by intravenous thrombolysis-adjusted linear regression. RESULTS: FAout (P<0.0001) and FAin (P=0.0147) were driven by recombinant tissue-type plasminogen activator (r-tPA) administration (47/104) and thrombus composition. Indeed, FAout was greater with fibrin-rich than erythrocyte-rich thrombi, presumably because of more (r)tPA substrates. Thus, FAout was increased with cardioembolic thrombi (72/104), which are rich in fibrin (P=0.0300). Opposite results were found inside the thrombus, suggesting that (r)tPA penetrability was hampered by the density of the fibrinous cap. Moreover, blood cells had a strong impact on thrombus structure and susceptibility to (r)tPA. Indeed, fibrin content was negatively associated with erythrocyte-specific proteins in the thrombus, admission hematocrit (P=0.0139), and hemoglobin level (P=0.0080), which underlines the key role of erythrocytes in thrombus composition. Also, an increased number of neutrophils impaired FAout (P=0.0225), which suggests that their aggregation around the thrombus prevented the (r)tPA attack. Only FAout was significantly associated with reduced thrombus weight (P=0.0310), increased recanalization rate (P=0.0150), good clinical outcome (P=0.0480), and reduced mortality (P=0.0080). CONCLUSIONS: Proteomics can offer new insights into the close relationship between thrombus composition and susceptibility to fibrinolysis, paving the way for new adjuvant therapies.

Lack of Interactions Between Alteplase/Tenecteplase and the Adenosine A1R/A3R Agonist AST-004.

BACKGROUND: AST-004, a small molecule agonist of the adenosine A1 and A3 receptors, is a potential cerebroprotectant for patients with acute stroke and is currently in clinical trials. Drug-drug interactions are critically important to assess in the context of acute stroke care. Lytic therapy with tPA (tissue-type plasminogen activator)-induced plasmin formation (alteplase) is the only available pharmacotherapy for acute stroke. Consequently, it is imperative to evaluate potential interactions between AST-004 and tPAs such as alteplase and tenecteplase. METHODS: The interactions between AST-004 and tPAs were evaluated in 3 ways in preparation for AST-004 phase II trials. First, the metabolic stability of AST-004 was determined in the presence of alteplase and plasmin. Second, the potential for AST-004 to influence the thrombolytic efficacy of alteplase and tenecteplase was evaluated with an in vitro assay system utilizing a fluorogenic substrate of plasmin. Finally, the potential for AST-004 to influence the thrombolytic efficacy of alteplase was also determined with an in vitro thrombolysis assay of human blood thrombi. RESULTS: Neither alteplase nor plasmin affected the stability of AST-004 in vitro. In 2 different in vitro systems, AST-004 had no effect on the ability of alteplase or tenecteplase to generate plasmin, and AST-004 had no effect on the thrombolytic efficacy of alteplase to lyse blood clots in human blood. CONCLUSIONS: These studies indicate that there will be no interactions between AST-004 and tPAs such as alteplase or tenecteplase in patients with stroke undergoing thrombolytic therapy.