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Background: Stroke in young needs an individualized approach before considering thrombolysis. Here we present a case of undiagnosed mitral valve prolapse presenting with stroke due to associated infective endocarditis. Young stroke patients presenting with fever need a panoramic approach. Case summary: This 39-year-old female with a background history of fever and loss of weight for two months presented to the emergency department with a history of altered sensorium and aphasia. The Magnetic Resonance Imaging (MRI) showed a hyperacute infarct. Hence, thrombolysis with alteplase was considered. Post thrombolysis, the patient had a parenchymal bleed. The diagnostic evaluation yielded stroke secondary to infective endocarditis because of undiagnosed mitral valve prolapse. Conclusion: Mitral valve prolapse is not associated with stroke in young patients. However, the undiagnosed infective endocarditis and subsequent septic emboli led to an increased risk. Emergency physicians and intensivists should anticipate infective causes before considering thrombolysis, as the results could be counterproductive. [ABSTRACT FROM AUTHOR]

Key Points: Question: Is tenecteplase noninferior to alteplase for patients with acute ischemic stroke (AIS) eligible for intravenous thrombolysis within 4.5 hours after stroke onset? Findings: In this noninferiority randomized clinical trial including 1489 participants, a total of 72.7% of patients receiving tenecteplase and 70.3% receiving alteplase achieved modified Rankin Scale scores of 0 or 1 (excellent functional outcome), resulting in a risk ratio of 1.03 (95% CI, 0.97-1.09), which met the predefined noninferiority margin of 0.937. Meaning: Findings from this study support tenecteplase as a suitable alternative to alteplase for patients with AIS eligible for thrombolysis. Importance: Tenecteplase is a bioengineered variant of alteplase with greater fibrin specificity and a longer half-life, allowing single-bolus administration. Evidence on the treatment effect of tenecteplase 0.25 mg/kg in Chinese patients with acute ischemic stroke (AIS) is limited. Objective: To establish the noninferiority of tenecteplase to alteplase in patients with AIS within 4.5 hours of symptom onset. Design, Setting, and Participants: The ORIGINAL study was a multicenter, active-controlled, parallel-group, randomized, open-label, blinded end point, noninferiority trial conducted between July 14, 2021, and July 14, 2023. Participants were recruited from 55 neurology clinics and stroke centers in China and were eligible if they had AIS with a National Institutes of Health Stroke Scale score of 1 to 25 with measurable neurologic deficit and were symptomatic for at least 30 minutes without significant improvement. Interventions: Patients were randomized (1:1) within 4.5 hours of symptom onset to receive intravenous tenecteplase (0.25 mg/kg) or intravenous alteplase (0.9 mg/kg). Main Outcomes and Measures: The primary outcome was the proportion of patients with a modified Rankin Scale (mRS) score of 0 or 1 (no symptoms or no significant disability) at day 90, tested for noninferiority (risk ratio [RR] margin, 0.937). Safety end points included symptomatic intracerebral hemorrhage (per European Cooperative Acute Stroke Study III definition) and 90-day all-cause mortality. Results: Among the 1489 patients randomized, 1465 patients were included in the full analysis set (732 in the tenecteplase group; 733 in the alteplase group) and 446 (30.4%) were female. The primary outcome occurred in 72.7% (532/732) of patients receiving tenecteplase and 70.3% (515/733) receiving alteplase (RR, 1.03 [95% CI, 0.97-1.09]; noninferiority threshold met). Symptomatic intracerebral hemorrhage occurred in 9 patients (1.2%) in each group (RR, 1.01 [95% CI, 0.37-2.70]). The 90-day mortality rate was 4.6% (34/732) in the tenecteplase group and 5.8% (43/736) in the alteplase group (RR, 0.80 [95% CI, 0.51-1.23]). Conclusions and Relevance: In patients with AIS eligible for intravenous thrombolysis within 4.5 hours after stroke onset, tenecteplase was noninferior to alteplase with respect to excellent functional outcome (mRS score of 0 or 1) at 90 days and had a similar safety profile. Findings from this study support tenecteplase as a suitable alternative to alteplase in this setting. Trial Registration: ClinicalTrials.gov Identifier: NCT04915729 This noninferiority randomized clinical trial investigates whether tenecteplase is noninferior to alteplase for the treatment of Chinese patients with acute ischemic stroke eligible for intravenous thrombolysis within 4.5 hours after symptom onset. [ABSTRACT FROM AUTHOR]

Background: Extracorporeal membrane oxygenation (ECMO) might be required as a treatment option in patients with critical pulmonary embolism (PE). However, the clinical features and outcomes of the use of ECMO for critical acute PE are still limited. The present study aimed to clarify the clinical characteristics, management strategies and outcomes of patients with acute PE requiring ECMO in the current era using data from a large-scale observational database. Methods: We analyzed the data of the COMMAND VTE Registry-2: a physician-initiated, multicenter, retrospective cohort study enrolling consecutive patients with acute symptomatic venous thromboembolism (VTE). Among 2035 patients with acute symptomatic PE, there were 76 patients (3.7%) requiring ECMO. Results: Overall, the mean age was 58.4 years, and 34 patients (44.7%) were men. Cardiac arrest or circulatory collapse at diagnosis was reported in 67 patients (88.2%). The 30-day incidence of all-cause death was 30.3%, which were all PE-related deaths. The 30-day incidence of major bleeding was 54.0%, and the vast majority of bleedings were procedure site-related bleeding events and surgery-related bleeding (22.4%). The 30-day incidence of all-cause death was 6.3% in 16 patients with surgical intervention, 43.8% in 16 patients with catheter intervention, 25.0% in 16 patients with thrombolytic therapy, and 39.3% in 28 patients with anticoagulation only. Conclusions: The current large real-world VTE registry in Japan revealed clinical features and outcomes of critical acute PE requiring ECMO in the current era, which suggested several unmet needs for future clinical trials. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVDs) cause 30% of deaths each year, and in 2030, around 23.6 million people will die due to CVDs. The major challenge is to obtain molecules with minimal adverse reactions that can prevent and dissolve blood clots. In this context, fibrinolytic enzymes from diverse microorganism sources have been extensively investigated due to their potential to act directly and specifically on the fibrin clot, preventing side effects and performing potential thrombolytic effects. However, most researches focus on the purification and characterization of proteases, with little emphasis on the mechanism of action and pharmacological characteristics, including toxicity assays which are essential to assess safety and side effects. Therefore, this work aims to emphasize the importance of evaluations indicating the toxicological profile of fibrinolytic proteases through in vitro and in vivo tests. Both types of assays contribute as preclinical stage in drug development and are crucial for clinical applications. This scarcity creates arbitrary barriers to further studies. This work should further encourage the development of studies to ensure the safety and effectivity of fibrinolytic proteases. HIGHLIGHTS: Suggested pre-clinical trials aim to validate more specific methods for fibrinolytic enzymes; Current toxicity standards can be adapted to better assess the profile of fibrinolytic enzymes; The class of fibrinolytic enzymes must be carefully evaluated according to the method of application. [ABSTRACT FROM AUTHOR]

Introduction: In recent years, tenecteplase has been competing with alteplase as a treatment for acute ischemic stroke given its ease of administration, lower dosage, cost-effectiveness, and better safety data. This paper seeks to analyze academic literature regarding the burgeoning usage of tenecteplase as a treatment for acute ischemic stroke across the world. Method: The Web of Science database was used to collect the data from articles containing the keywords "Tenecteplase" and "Stroke" published from 1999 to 2023. The search resulted in 576 journal articles. This study analyzed metadata related to the country, institution, keywords, and date published for each article in the database pertaining to tenecteplase use for stroke. Results: The United States led in publications (260, 39.93%), followed by Australia (101, 15.51%), and a tie for third place between Canada and China (77, 11.83% each). The three most prevalent keywords were tenecteplase (N = 324), alteplase (N = 284), and thrombolysis (N = 244). The University of Melbourne and the University of Calgary were the leading institutions publishing on the use of tenecteplase as a treatment for stroke. In 2023, the number of publications on the usage of tenecteplase for stroke was the greatest, making up 24.3% of all papers on the topic. Conclusion: The surge in academic papers regarding tenecteplase in stroke in 2023 could be a good indicator of the drug's increasing prevalence as a treatment for stroke. Despite this finding, tenecteplase is currently not an FDA-approved therapy in the US as Genentech, the drug's manufacturer, has yet to file for federal approval for acute ischemic stroke treatment. [ABSTRACT FROM AUTHOR]

Prosthetic valve thrombosis, although rare, is a life-threatening complication of valve replacement surgery. The authors present an atypical case of a modified Bentall procedure with the CarboSeal Valsalva™ conduit complicated by an early mechanical prosthetic aortic valve thrombosis and coronary embolism. The patient was successfully treated with an emergency percutaneous coronary angioplasty and intracoronary thrombus aspiration of the left anterior descending artery, followed by a systemic 10 mg bolus of tissue plasminogen activator followed by ultraslow (25 h) infusion of low-dose (25 mg), while supported with venoarterial extracorporeal membrane oxygenation. Article highlights Prosthetic valve thrombosis, although rare, is a life-threatening complication of a modified Bentall procedure. Although surgical treatment is usually preferred in cases of obstructive prosthetic valve thrombosis, therapeutic options include: optimizing anticoagulation with unfractionated heparin ± antiplatelet therapy; thrombolysis; surgery. Ultraslow infusion of low-dose of tissue plasminogen activator (25 mg/25 h), after an initial bolus (10 mg), could be considered as a viable treatment in critically ill patients with hemodynamic instability due to obstructive prosthetic heart valve thrombosis, supported with venoarterial extracorporeal membrane oxygenation and with a non-negligible risk of bleeding. [ABSTRACT FROM AUTHOR]

Objective: To investigate the inhibitory effect of Celastrus orbiculatus extracts (COE) on the proliferation of lymphoma cells and the immune regulation ability on inflammation and thrombophilia in vivo. Methods: The 38B9 lymphoma cells were treated with COE (160 µ g/mL) and CTX (25 µ mol/L). The apoptosis rate and cell cycle of each group were detected by flow cytometry. The secretion of inflammatory factors, including interleukin (IL)-6, IL-10, and tumor necrosis factor α (TNF-α), in cell supernatant was detected by enzyme-linked immunosorbent assay (ELISA). In vivo, BALB/c mice were subcutaneously injected with 38B9 lymphoma cells to establish lymphoma model. COE (3 mg·kg−1·d−1) and CTX (40 mg·kg−1·d−1) were administered to the model mice, respectively. The expression of plasma inflammatory factors (IL-6, IL-10 and TNF-α) and thrombus indexes, including D-dimer (D-D), von Willebrand factor (vWF) and tissue factor (TF), were detected by ELISA before tumor bearing (1 d), after tumor formation (14 d) and after intervention (21 d). PicoGreen dsDNA was used to detect the level of serum neutrophil extracellular traps (NETs). Flow cytometry was used to detect the expression of platelet activation marker calcium-dependent lectin-like receptor 2 (CLEC-2). The tumor growth and survival of mice were recorded. Results: The 38B9 lymphoma cells were apoptotic after the intervention of COE and CTX. The ratio of G2-M phase cells decreased in COE intervented cells compared with the control cells (P<0.05), and S phase cells decreased in CTX intervented cells (P<0.05). Also, the secretion level of IL-6 was significantly reduced after COE or CTX intervention (P<0.05), and IL-10 was significantly increased (P<0.05). Furthermore, the tumor mass was reduced, and the median survival time was longer in COE and CTX intervented tumor-bearing mice than in non-intervented mice. The significantly lower levels of TNF-α, IL-6, NETs, TF, DD and CLEC-2, as well as higher IL-10 were observed in COE and CTX treatment mice in comparision with the control mice (P<0.05). Conclusion: COE has a mild and stable anti-tumor effect, which can reduce the secretion of inflammatory factors by lymphoma cells and regulate thrombophilic state caused by tumor inflammatory microenvironment. [ABSTRACT FROM AUTHOR]

Objective Methods Results Interpretation About 25% of patients with acute ischemic stroke (AIS) present within the intravenous thrombolytic (IVT) therapeutic window of <4.5 h. This study is to elucidate the safety and efficacy of IVT in the extended therapeutic window (ETW) in patients with AIS.Using PRISMA guidelines, a systematic review was conducted using PubMed, Embase, and Scopus. A rigorous risk of bias assessment was conducted using the RoB2 tool. Rates of excellent and good functional outcome (mRS 0–1 and mRS 0–2) at 90 days, symptomatic intracranial hemorrhage (sICH), and mortality at 90 days were pooled using generalized linear mixed model and compared with controls. Meta‐analyses were conducted employing random‐effect models with risk ratio (RR) and 95% confidence intervals (CIs). Subgroup analysis was performed to assess the effect of imaging modalities used for patient selection.Eight randomized controlled trials (n = 2221, 59% male) were included. At 90 days IVT showed higher rates of functional recovery: mRS 0–1: RR 1.21 95% CI 1.1–1.34, p < 0.001, and mRS 0–2: RR 1.11 95% CI 1.03–1.18, p = 0.004. Rate of mortality at 90 day was not different between groups: RR 1.17 95% CI 0.93–1.48, p = 0.17. However, the rate of sICH was higher among IVT group: RR 2.93 95% CI 1.53–5.6, p = 0.001. Subgroup analysis showed higher mRS 0–1 among patients who were selected based on perfusion imaging (p < 0.05).The use of IVT in AIS in ETW is beneficial especially with the use of perfusion imaging for patients' selection. [ABSTRACT FROM AUTHOR]

Venous thromboembolism (VTE) is a serious health condition and represents an important cause of morbidity and, in some cases, mortality due to the lack of effective treatment options. According to the Centers for Disease Control and Prevention, 3 out of 10 people with VTE will have recurrence of a clotting event within ten years, presenting a significant unmet medical need. For some VTE patients, symptoms can last longer and have a higher than average risk of serious complications; in contrast, others may experience complications arising from insufficient therapies. People with VTE are initially treated with anticoagulants to prevent conditions such as stroke and to reduce the recurrence of VTE. However, thrombolytic therapy is used for people with pulmonary embolism (PE) experiencing low blood pressure or in severe cases of DVT. New drugs are under development, with the aim to ensure they are safe and effective, and may provide an additional option for the treatment of VTE. In this review, we summarize all ongoing trials evaluating anticoagulant interventions in VTE listed in clinicaltrials.gov, clarifying their underlying mechanisms and evaluating whether they prevent the progression of DVT to PE and recurrence of thrombosis. Moreover, this review summarizes the available evidence that supports the use of antiplatelet therapy for VTE. Since thrombolytic agents would cause off-target effects, targeted drug delivery platforms are used to develop various therapeutics for thrombotic diseases. We discuss the recent advances achieved with thrombus-targeting nanocarriers as well as the major challenges associated with the use of nanoparticle-based therapeutics. [ABSTRACT FROM AUTHOR]

The Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is a valuable and easy-to-use method for assessing acute ischemic stroke. It aids in identifying suitable candidates for thrombolytic therapies and evaluating treatment effectiveness. However, ASPECTS evaluation primarily relies on visual observation in current clinical practice, lacking a common standardized space. Additionally, different doctors may have varying clinical experiences, leading to a poor inter-reader agreement and potential errors in the final ASPECTS scoring. To address these issues and fill in the absence of a publicly available ASPECTS atlas, this work constructs age-specific Chinese ASPECTS atlases based on non-contrast computed tomography images of 281 healthy subjects across different age groups. Images of different age groups are warped into respective common averaged spaces, where the average intensity atlases are computed. More importantly, 10 ASPECTS regions can be obtained during this process. We develop an automated ASPECTS region mapping pipeline and collect an independent dataset to validate our atlas. The results prove that the age-specific ASPECTS atlas is of great promise in clinical availability. [ABSTRACT FROM AUTHOR]

Recent years have seen ticagrelor, a potent P2Y12 inhibitor, emerge as a significant advancement in the peri-thrombolytic management of patients with ST-segment elevation myocardial infarction (STEMI), offering a promising alternative to traditional antiplatelet drugs like clopidogrel. This review critically examines the efficacy and safety of ticagrelor during the peri-thrombolytic phase in STEMI patients, drawing on evidence from key clinical trials such as TREAT and MIRTOS, as well as other relevant studies. These investigations underscore ticagrelor's superior platelet inhibition capabilities, which are crucial for minimizing thrombotic complications post-thrombolysis without increasing bleeding risks. Despite its potential, clopidogrel remains the guideline-recommended choice for such patients, leaving the appropriateness of ticagrelor in this context open to debate. By summarizing the current evidence and identifying gaps in our understanding, this study advocates for targeted research to clarify the long-term benefits and optimal deployment of ticagrelor, highlighting its evolving significance in cardiovascular care. [ABSTRACT FROM AUTHOR]

Recent advances in therapy and the promulgation of multidisciplinary pulmonary embolism teams show great promise to improve management and outcomes of acute pulmonary embolism (PE). However, the absence of randomized evidence and lack of consensus leads to tremendous variations in treatment and compromises the wide implementation of new innovations. Moreover, the changing landscape of health care, where quality, cost, and accountability are increasingly relevant, dictates that a broad spectrum of outcomes of care must be routinely monitored to fully capture the impact of modern PE treatment. We set out to standardize data collection in patients with PE undergoing evaluation and treatment, and thus establish the foundation for an expanding evidence base that will address gaps in evidence and inform future care for acute PE. To do so, >100 international PE thought leaders convened in Washington, DC, in April 2022 to form the Pulmonary Embolism Research Collaborative. Participants included physician experts, key members of the US Food and Drug Administration, patient representatives, and industry leaders. Recognizing the multidisciplinary nature of PE care, the Pulmonary Embolism Research Collaborative was created with representative experts from stakeholder medical subspecialties, including cardiology, pulmonology, vascular medicine, critical care, hematology, cardiac surgery, emergency medicine, hospital medicine, and pharmacology. A list of critical evidence gaps was composed with a matching comprehensive set of standardized data elements; these data points will provide a foundation for productive research, knowledge enhancement, and advancement of clinical care within the field of acute PE, and contribute to answering urgent unmet needs in PE management. Evidence produced through the Pulmonary Embolism Research Collaborative, as it is applied to data collection, promises to provide crucial knowledge that will ultimately produce a robust evidence base that will lead to standardization and harmonization of PE management and improved outcomes. [ABSTRACT FROM AUTHOR]

Background: Stroke remains a significant global health challenge, contributing to mortality and disability burdens. Optimizing stroke care involves understanding the complexities of in-hospital management, especially in regions like East Azerbaijan Province, where stroke incidence is high. Objectives: This study evaluates the effectiveness of Emergency Stroke Code (ESC) activation and thrombolytic therapy in acute ischemic stroke care at Imam Reza Hospital, Tabriz, a referral center. Methods: A cross-sectional study was carried out between April 2021 and March 2022, including patients with activated ESC or receiving thrombolysis at Imam Reza Hospital, Tabriz. Data on patient demographics, risk factors, time intervals, thrombolysis administration, adverse events, and outcomes were collected and analyzed using SPSS software. Results: Among 748 acute stroke patients, 165 received thrombolysis, with 117 having ESC activation. The main reasons for not administering tissue plasminogen activator (tPA) in patients with ESC code activation included mild symptoms (23.6%), exceeding thrombolysis time (14.8%), and hemorrhagic stroke (10.4%). Pre-hospital ESC activation significantly reduced time intervals from hospital arrival to CT-scan and tPA injection (P < 0.001). The incidence of intracranial hemorrhage was 6.7% overall, with rare systemic bleeding (0.6%). Pre-hospital notification did not show significant changes in the National Institutes of Health Stroke Scale (NIHSS) or Modified Rankin Scale (MRS) scores. Conclusions: While ESC activation streamlines in-hospital processes, it alone may not improve clinical outcomes without efficient out-of-hospital systems. Pre-hospital communication systems like ESC can aid in reducing in-hospital processing time for thrombolysis but must be coupled with efforts to enhance early diagnosis and efficient dispatch systems to optimize stroke care. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: Wake-up Stroke (WUS) accounts for about 25% of all ischemic strokes. Differences according to sex in the WUS subgroup has been poorly investigated so far, so we aimed to assess these differences by differentiating the enrolled population based on treatment administered. Materials & methods: We retrospectively analysed clinical and imaging data of WUS patients admitted to our hospital between November 2013 and December 2018 dividing them in two groups: rTPA-treated and non-rTPA treated group. To point out outcome differences we evaluated: NIHSS at 7 days or at discharge, mRS at discharge and ΔNIHSS. Results: We enrolled 149 WUS patients, 74 rTPA treated and 75 non-rTPA treated. Among rTPA treated patients, time from last known well (LKW) to Emergency Department (ED) admission was longer in females than males (610 vs 454 min), while females had a higher ΔNIHSS than males (5 vs 3). Finally, among non-rTPA treated patients, females were older than males (85 vs 79 years), had a higher pre-admission mRS (although very low in both cases), had a longer length of stay (17 vs 13 days) and shown a higher NIHSS at discharge (4 vs 2) compared to males. Conclusions: Females not receiving thrombolytic treatment had worse functional outcome than males, showing a higher NIHSS at discharge but, in contrast, when treated with rTPA they showed better neurological recovery as measured by a greater ΔNIHSS. We emphasize the importance of a prompt recognition of WUS in females since they seem to benefit more from rTPA treatment. [ABSTRACT FROM AUTHOR]

Dyslipidemia is an important risk factor for cardiovascular morbidity and mortality. Although low-density lipoprotein (LDL) is primarily responsible, the importance of triglyceride (TG) and high-density lipoprotein (HDL) has also been recognized. The present study investigated the effect of the atherogenic index of plasma (AIP), in which atherogenic and protective lipoproteins were evaluated together, on the initial flow in patients with ST elevation myocardial infarction. AIP was calculated as log(TG/HDL-cholesterol). Patients included in the study (n = 1535) were divided into Thrombolysis in Myocardial Infarction (TIMI) flow grade 0 and >0. AIP was found to be significantly different between 2 groups (.55 ±.23 vs.67 ±.21; P <.001). AIP was an independent predictor for pre-intervention TIMI flow (Odds Ratio: 2.778). A moderate correlation was found between TIMI frame count measurements, calculated in patients with TIMI 2–3, and AIP (Pearson correlation coefficient:.63, P <.001). In the receiver operating characteristic analysis, AIP showed the highest area under curve (AUC) compared with other lipid parameters for predicting vascular patency. The AUC of AIP was.634, the cut-off value was.59, and the sensitivity and specificity were 67.6% and 68.4%, respectively (P <.001). In conclusion, AIP was found to be an important marker affecting pre-percutaneous coronary intervention TIMI flow. [ABSTRACT FROM AUTHOR]

Background: Standard treatment for eligible patients presenting with acute ischemic stroke (AIS) is thrombolysis with tissue plasminogen activators alteplase or tenecteplase. Current guidelines recommend monitoring patients in an intensive care unit (ICU) for 24 h after thrombolytic therapy. However, recent studies have questioned the need for prolonged ICU monitoring. This retrospective cohort study aims to identify potential candidates for early transition to a lower level of care by assessing risk factors for neurological deterioration, symptomatic intracranial hemorrhage (sICH), or need for ICU intervention within 24 h post-thrombolysis. Methods: This retrospective cohort study included adult patients 18 years and older with AIS who received thrombolysis. Patients were excluded if they were transferred to another facility, if they were transitioned to comfort care or hospice care within 24 h, or if they lacked imaging and National Institutes of Health Stroke Scale (NIHSS) score data. The primary end point was incidence of sICH between 0–12 and 12–24 h. Secondary end points included the need for ICU intervention and rates of neurological deterioration. Results: The analysis included 204 patients who received the full dose of alteplase. Among them, ten patients (4.9%) developed sICH, with the majority (n = 7) occurring within 12 h post-thrombolysis. Sixty-two patients required ICU interventions within 12 h compared with four patients after 12 h. Twenty-four patients had neurological deterioration within 12 h, and seven patients had neurological deterioration after 12 h. Multivariable analysis identified mechanical thrombectomy and increased blood pressure at presentation as predictors of ICU need beyond 12 h post-thrombolysis. Conclusions: Our study demonstrates that sICH, neurological deterioration, and need for ICU intervention rarely occur beyond 12 h after thrombolytic administration. Patients presenting with blood pressures < 140/90 mm Hg, NIHSS scores < 10, and not undergoing mechanical thrombectomy may be best candidates for early de-escalation. Larger prospective studies are needed to more fully evaluate the safety, feasibility, and financial impact of early transition out of the ICU. [ABSTRACT FROM AUTHOR]

Background: Stroke is a major cause of death and disability worldwide and presents a significant burden on healthcare systems. This retrospective study aims to analyze the characteristics and outcomes of stroke patients admitted to Hamad General Hospital (HGH) stroke service in Qatar from January 2014 to July 2022. Methods: The medical records of 15,859 patients admitted during the study period were analyzed. The data collected included patient demographics, stroke types, admission location, procedures performed, mortality rates, and other clinical characteristics. Results: Of the total cohort, 70.9% were diagnosed with a stroke, and 29.1% were diagnosed with stroke mimics. Of the stroke patients, 85.3% had an ischemic stroke, and 14.7% had a hemorrhagic stroke. Male patients below 65 years old (80.2%) and of South Asian ethnicity (44.6%) were the most affected. The mortality rate was 4.6%, significantly higher for hemorrhagic stroke than ischemic stroke (12.6% vs. 3.2%). Female patients had a higher stroke-related mortality rate than male patients (6.8% vs. 4%). The thrombolysis rate was 9.5%, and the thrombectomy rate was 3.4% of the ischemic stroke cohort. The mean door-to-needle time for thrombolysis was 61.2 minutes, and the mean door-to-groin time for thrombectomy was 170 minutes. Stroke outcomes were good, with 59.3% of patients having favorable outcomes upon discharge (mRS ≤2), which improved to 68.2% 90 days after discharge. Conclusion: This study provides valuable insights into stroke characteristics and outcomes in Qatar. The findings suggest that stroke mortality rates are low, and favorable long-term disability outcomes are achievable. However, the study identified a higher stroke-related mortality rate among female patients and areas for improvement in thrombolysis and thrombectomy time. [ABSTRACT FROM AUTHOR]

Background and Aims: We aimed to evaluate the association between electrocardiography (ECG) and echocardiographic findings in patients with pulmonary embolism (PE) before and after systemic thrombolysis. Methods: We included 38 PE patients admitted to the hospital with approved right ventricular (RV) dysfunction who were indicated for systemic thrombolysis. Indications for systemic thrombolysis were considered as patients who were either hemodynamically unstable on admission or became unstable in the course of hospital admission. Systemic thrombolysis was performed by either Reteplase or Alteplase. ECG and echocardiographic findings were documented at baseline and 12–24 h following systemic thrombolysis. Results: Our results showed that TAPSE significantly increased while RV size and pulmonary artery systolic pressure (PAP) notably decreased after systemic thrombolysis (p < 0.001). The ECG abnormalities markedly diminished after systemic thrombolysis in PE patients (p < 0.001). Additionally, 100% of our patients had more than one ECG abnormality at baseline, while 55.3% had no ECG abnormalities after systemic thrombolysis. Further, the median number of ECG abnormalities remarkably attenuated after systemic thrombolysis (from 2.0 (1.0) to 0.0 (1.0), p < 0.001). Our results also revealed that delta RV size (r = 0.51, p = 0.001) and delta TAPSE (r = 0.4, p = 0.012) were positively correlated while mortality (r = −0.55, p = 0.001) was negatively associated with changes in the number of ECG abnormalities before and after systemic thrombolysis. Conclusion: We showed that systemic thrombolysis improved echocardiographic and electrocardiographic findings in PE patients. Additionally, a greater decreased number of ECG abnormalities after systemic thrombolysis was accompanied by more improvement in RV size and TAPSE and a lower mortality rate. [ABSTRACT FROM AUTHOR]

Interventional procedures for the recanalization of blood vessels to treat deep vein thrombosis carry a high risk of vessel wall injuries or hemorrhaging. Focused ultrasound (FUS) has been used to non-invasively break down blood clots that occlude the vessels in both in vitro and in vivo studies. Previous studies have either used thrombolytic drugs or ultrasound contrast agents (e.g., microbubbles) in combination with FUS. Several studies have applied very high peak-negativepressures (PNP) during FUS treatment to achieve successful thrombolysis without the use of contrast agents. In the current study, we demonstrated that cavitation activity could be significantly enhanced by placing a nitinol wire, whose surface was roughed by laser etching, in the focal region of a FUS field. We demonstrated in vitro in a mock thrombosis that the thrombolysis efficacy of a 500 kHz FUS transducer was significantly enhanced using a surface-etched nitinol wire as compared to an unetched nitinol wire, whereas FUS-alone at the same pressure level did not result in any thrombolysis. These results suggest that a surface modified nitinol catheter exposed to FUS can result in intense cavitation activities leading to enhanced thrombolysis without the use of additional pharmacological or contrast agents. [ABSTRACT FROM AUTHOR]

This article explores the effectiveness and safety of intravenous thrombolysis (IVT) in patients with acute ischemic stroke (AIS) who are taking direct oral anticoagulants (DOACs). While there is ongoing debate about the use of IVT in DOAC-treated patients, some studies suggest that it may be more effective due to the altered structure of blood clots formed in the presence of DOACs. However, further research is needed to fully understand this relationship. The article also provides a list of references that cover various aspects of thrombolysis and anticoagulant use in AIS patients, offering valuable information for researchers and healthcare professionals. Additionally, a systematic review and meta-analysis included in the article conclude that recanalization therapy appears to be safe in AIS patients receiving anticoagulation treatment, with no significant increase in adverse events. This information is useful for healthcare professionals working with stroke patients on anticoagulation therapy. [Extracted from the article]

Objective: Plasminogen activator inhibitor-1 (PAI-1) is the most important inhibitor of plasminogen activator. The functional 4G/5G polymorphism of the gene coding for PAI-1 may affect PAI-1 plasmatic activity, influencing the imbalance between coagulation and fibrinolysis cascades. In this study, we investigated the association between the PAI-1 4G/5G genotype and the development and residual thrombus of acute primary mesenteric venous thrombosis (MVT). Methods: The clinical data of 34 patients who underwent acute primary MVT were retrospectively reviewed. Fluorescence in situ hybridization was used to determine if patients had the 4G/5G polymorphism in the promoter of the PAI-1 gene. Patients were stratified according to the genotype of PAI-1. Results: 11 patients (32.3%) were homozygous for the 4G genotype, 23 patients (67.6%) were non-homozygous for the 4G genotype (5G/5G). The extent of thrombosis was not correlated with the PAI-4G/5G polymorphism. After a mean follow-up of 16.6 ± 10.4 months, the 4G/4G genotype had a significantly larger thrombus burden (p < 0.05). 54% of patients in the 4G/4G genotype group had no lessening in the degree of mesenteric venous thrombosis, significantly higher than other patients (4G/5G + 5G/5G genotypes) (p < 0.05). Conclusion: The PAI-1 4G/4G predicts residual thrombus of mesenteric veins after the acute phase. [ABSTRACT FROM AUTHOR]

Acute pulmonary embolism (PE) is a leading cause of mortality. Not only is PE associated with short-term mortality, but up to ~20% of patients might suffer from long-term consequences such as post-PE syndrome and chronic thromboembolic pulmonary hypertension. Current risk stratification tools poorly predict those who are at risk for short-term deterioration and those who develop long-term consequences. Traditionally, systemic thrombolysis has been considered the first-line therapy for patients with high-risk PE without contraindications; however, it comes with the risk of major bleeding (notably intracranial hemorrhage). The use of catheter-directed interventions (embolectomy or thrombolysis) has been increasing owing to their low bleeding risk; however, randomized trial data supporting their efficacy in improving clinical outcomes are limited. In this review, we highlight the evidence supporting the available advanced therapies for high- and intermediate-risk PE and summarize the ongoing trials which are evaluating these therapies. [ABSTRACT FROM AUTHOR]

Background: Acute pulmonary embolism is recorded as one of the most common and critical medical conditions, resulting in a notable mortality rate requiring a multidisciplinary management. In this series, we address the management of massive and sub-massive pulmonary embolism utilizing catheter-based intervention, in particular the conjunction of mechanical thrombus disruption and aspiration with pharmacological thrombolysis (pharmacomechanical thrombectomy). Results: 37 patients were diagnosed with massive and sub-massive pulmonary embolism based on the clinical and radiological findings. Pre-procedural vital parameters were obtained, including oxygen saturation, pulse rate, and blood pressure. Under continuous monitoring and conscious sedation, a pulmonary angiography via right common femoral vein access was performed for pre-procedural assessment. Pharmacomechanical thrombectomy was performed using the AngioJet Ultra System (Boston Scientific). Using the power pulse option, a fibrinolytic agent was infused into the thrombus. After 5–10 min, mechanical thrombectomy is performed with a maximum 3 passes through the thrombus. This technique is performed in the main pulmonary artery and lower branch. The procedure is repeated on the other side. The maximum duration of thrombectomy is 2–3 min on each side. Procedure success was based on improvement of vital signs and not related to post-procedure angiographic findings. All patients showed immediate improvement of vital signs (blood pressure, 02 saturation, and pulse rate) with progressive improvement over the following days. There were no procedure-related complications. Conclusion: Pharmacomechanical thrombectomy is a safe and effective technique in the treatment of massive and submassive pulmonary embolism. It can be a first-line treatment even in patients without absolute contraindication to systemic thrombolysis. [ABSTRACT FROM AUTHOR]

The article discusses the treatment options for acute ischemic stroke, which is a condition where blood supply to the brain is interrupted, leading to cell death. The two main strategies for treatment are thrombolysis, which involves the administration of a thrombolytic agent to dissolve the blood clot, and mechanical thrombectomy, which physically removes the clot from the occluded artery. Mechanical thrombectomy has shown higher recanalization rates and improved functional outcomes compared to thrombolysis, particularly in patients with large vessel occlusions. However, the availability and feasibility of time, as well as the unequal distribution of healthcare facilities, should also be considered when selecting a treatment modality. The article also highlights the need for further research to improve triage processes and explore adjuvant therapies for stroke rehabilitation. [Extracted from the article]

Venous thrombosis and pulmonary embolism (venous thromboembolism) are important causes of morbidity and mortality worldwide. In patients with venous thromboembolism, thrombi obstruct blood vessels and resist physiological dissolution (fibrinolysis), which can be life threatening and cause chronic complications. Plasminogen activator therapy, which was developed >50 years ago, is effective in dissolving thrombi but has unacceptable bleeding risks. Safe dissolution of thrombi in patients with venous thromboembolism has been elusive despite multiple innovations in plasminogen activator design and catheter-based therapy. Evidence now suggests that fibrinolysis is rigidly controlled by endogenous fibrinolysis inhibitors, including α2-antiplasmin, plasminogen activator inhibitor-1, and thrombin-activable fibrinolysis inhibitor. Elevated levels of these fibrinolysis inhibitors are associated with an increased risk of venous thromboembolism in humans. New therapeutic paradigms suggest that accelerated and effective fibrinolysis may be achieved safely by therapeutically targeting these fibrinolytic inhibitors in venous thromboembolism. In this article, we discuss the role of fibrinolytic components in venous thromboembolism and the current status of research and development targeting fibrinolysis inhibitors. [ABSTRACT FROM AUTHOR]

Background: Hemorrhagic transformation (HT) is a serious complication of thrombolytic therapy for acute ischemic stroke, limiting its indications and affecting treatment plans and clinical prognosis. Identifying risk factors for HT could help improve the risk–benefit ratio of thrombolytic therapy. We aimed to analyze the predictors of HT after reperfusion therapy with recombinant tissue plasminogen activator (rTPA) in patients with acute ischemic stroke. This study included 115 patients who received rTPA. All patients underwent history taking, clinical examination, neurological examination including Glasgow Coma Scale and National Institutes of Health Stroke Scale scores (NIHSS), radiological investigation, and cardiac investigation. Patients were followed up strictly every 2 h for 1st 24 h then for two weeks clinically using the NIHSS and radiologically using CT or MRI to detect HT. Results: Patients with HT represented 21.7% of all patients receiving rTPA, while symptomatic intracranial hemorrhage (sICH) represented 6.9%. Patients with HT had significantly higher blood pressure, respiratory rate, atrial fibrillation rate, NIHSS score, INR, prothrombin time, neutrophil-to-lymphocyte ratio (NLR), and lower platelet count, LDL level, higher Fazekas score, lower ASPECT score, and prolonged onset-to-needle time. Conclusion: Predicting HT in acute ischemic stroke patients is crucial for optimizing management and potentially improving outcomes. In our study, six predictors were associated with HT: higher respiratory rate, higher atrial fibrillation rate, higher NLR, lower LDL level, higher Fazekas score, lower ASPECT score, and onset-to-needle time greater than 180 min. [ABSTRACT FROM AUTHOR]

Aim: It remains controversial whether intravenous tissue plasminogen activator (IV tPA) increases complications in patients undergoing mechanical thrombolysis. In this study, we aimed to show the effect of IV tPA administration on complications. Methods: In this cross-sectional study, the records of patients who were followed up at the stroke center and underwent mechanical thrombectomy (MT) between 2022 and 2023 were retrospectively reviewed. Demographic data, cerebral angiography data, neuroimaging time, medical history, and medication use; neurologic examination findings at baseline, 24th hour, and 3rd month were obtained from the patient files. Patients were divided into two groups according to whether intracranial tPA was administered before MT and two groups according to the presence of intracranial hemorrhage at 24 hours. Results: A total of 172 patients [94 women (54.7%) and 78 men (45.3%)] were included in the study. Mean age was 67.6±14.7 years. At 24 h, the rate of symptomatic intracranial hemorrhage (sICH) was significantly (p=0.004) higher in the thrombectomy group than in the tPA plus thrombectomy group. The admission (p=0.033) and 24-hour National Institutes of Health Stroke Scale (p=0.001) scores were significantly higher in the sICH group than in the non-sICH group. Third-month modified Rankin scale score (p=0.003), diastolic embolism rate (p=0.009), and Tan score (p=0.007) were significantly higher in the sICH group than in the non-sICH group. Conclusion: Intravenous tissue plasminogen activator did not increase sICH or distal embolism in patients undergoing MT, and there was no difference in terms of favorable clinical outcomes. Symptomatic intracranial hemorrhage was associated with increased mortality and poor clinical outcome. [ABSTRACT FROM AUTHOR]

Introduction. Prompt resolution of arteriovenous fistula (AVF) thrombosis is essential to minimize the need for temporary dialysis catheters. Identifying the ideal timing for the management of thrombosed arteriovenous fistula (AVF) is an area that has not been thoroughly explored. Herein, we examined a local infusion of urokinase for thrombolysis followed by ultrasound-guided percutaneous transluminal balloon angioplasty (PTA) in acute and subacute AVF thromboses. Methods. This retrospective cohort research assessed thrombosed AVF in patients referred to the Second Xiangya Hospital. We included patients who underwent local thrombolysis followed by ultrasound-guided PTA treatment between January 1, 2018, and January 1, 2020. Results. We enrolled the records of 86 patients into the present study, including 44 patients with acute AVF thrombosis (group 1: thrombus age, < 72 hours) and 42 patients with subacute AVF thrombosis (group2: thrombus age, 72 hours to seven days). The thrombolytic success rate was 79.5% in group 1 and 42.9% in group 2 (P < .001). All patients underwent ultrasound-guided PTA to dissolve any residual thrombi regardless of thrombolytic success. Technical success after PTA procedures was achieved in 93.2% of patients in group 1 and 88.1% in group 2 (P = .417). Primary patency at six months was comparable between the two groups (67.5% vs. 64.8%, P = .564). We observed that thrombolytic effect does not affect PTA success rate, and six-month patency rate. Conclusion. Direct local infusion of urokinase to the affected area followed by ultrasound-guided PTA constitutes a minimally invasive and effective method for salvaging thrombosed AVF in contrast to abandoning the occluded fistula. [ABSTRACT FROM AUTHOR]

The article titled "Prospective multicentre observational study evaluating acute lower limb ischaemia (PROMOTE-ALI)" presents the findings of a large-scale study on acute lower limb ischaemia (ALI). The study aimed to evaluate current treatment strategies and outcomes for ALI patients, with a focus on risk factors for loss of amputation-free survival (AFS). The study included 705 patients from 12 European countries and found that chronic kidney disease, smoking, and pre-existing direct oral anticoagulation were significantly associated with loss of 90-day AFS. The study also highlighted the importance of individualized revascularization strategies and post-procedural surveillance to improve outcomes for ALI patients. The document is a list of authors and their affiliations for the study, along with information about funding, author contributions, conflicts of interest, and data availability. The study aims to evaluate risk factors and outcomes of acute limb ischemia and compare different treatment approaches, emphasizing the importance of data collection and adherence to reporting standards. [Extracted from the article]

Purpose: To investigate and compare the efficacy of two different types of thrombolysis combined with percutaneous transluminal angioplasty (PTA) for acute thrombosis in arteriovenous fistula (AVF) and graft (AVG). Methods: A total of 128 patients on hemodialysis with acute AVF/AVG occlusion, from May 2021 to May 2023 at Jiangmen Central Hospital, Guangdong, were randomly assigned to study group (catheterdirected thrombolysis) (CDT) comprising of 62 patients and control group (scalp needle thrombolysis) comprising of 66 patients. Patients whose thrombolysis was unsuccessful on the first day, received PTA therapy the next day. Thrombolytic success rates, urokinase dosage, PTA therapy rates, mural thrombus occurrence, and post-thrombolytic complications were evaluated and compared. Result: There was no significant difference in overall thrombolytic success rate, PTA combination rate and incidence of hemorrhage (p > 0.05) between study and control groups. Recanalization rate after urokinase thrombolytic therapy on first day was significantly higher in the study group than in the control group (p < 0.05). Urokinase dosage (first day) of patients whose thrombolytic therapy was successful was significantly lower in the study group than in the control group (p < 0.001). Conclusion: Mechanical fragmentation by angiography catheter combined with urokinase thrombolysis improves efficacy, but shows no advantage when combined with PTA. Additional studies using a larger patient population on anticoagulant therapy and longer investigation time are recommended to enhance the generalizability of this treatment approach. [ABSTRACT FROM AUTHOR]

Significant advancements have shaped the landscape of anticoagulant therapy in the past two decades, including the introduction of direct oral anticoagulants (DOACs), characterized by favorable safety and efficacy profiles and reduced drug-to-drug or food interaction resulting in excellent patient compliance. However, residual concerns still exist with standard-of-care anticoagulant therapy, including the inability to use DOACs in several clinical settings and the need to further reduce the risk of bleeding. Recent improvements in the understanding of the mechanisms behind thrombus formation have led to the awareness that the intrinsic pathway of the coagulation cascade may play an important role in pathological thrombosis, but not in hemostasis. This has represented the rationale for targeting this pathway with factor XI (FXI) inhibitors, with the aim of uncoupling hemostasis and thrombosis. Clinical evidence from patients with FXI deficiency further supports this concept. A number of compounds with different mechanisms of action have been developed to target FXI (i.e., asundexian, abelacimab, Ionis-FXIRx, milvexian, osocimab, and Xisomab 3G). To date, the majority of available trials have not gone beyond completion of phase 2 and results are conflictive making it difficult to appraise the clinical benefit of these compounds in the different clinical settings where they have been tested (i.e., atrial fibrillation, acute ischemic stroke, acute myocardial infarction, end-stage renal disease, total knee arthroplasty). Moreover, the largest phase 3 randomized trial designed to test the efficacy of asundexian over apixaban in patients with atrial fibrillation, the OCEANIC-AF, has been prematurely stopped as a result of the inferior efficacy of asundexian. In this review we discuss the pharmacological properties and available evidence generated thus far for factor XI inhibitors, providing a perspective on the current state of these drugs. [ABSTRACT FROM AUTHOR]

Studies aiming to understand the effects of storage on whole blood (WB) clotting often rely on characterizing coagulation under static conditions. Minimal work has explored the effects of physiologic shear on clot formation and thrombolysis utilizing fractionated and reconstituted whole blood (rWB) products. WB was fractionated into platelet‐free plasma, packed red blood cells, and platelets storing each component under its ideal conditions—including platelet cryopreservation. Recombination at their native ratios was accomplished over 91 days of storage and clotting/thrombolysis was analyzed utilizing thromboelastography and Chandler loop. rWB preserved clot strength through 91 days with minimal deviation from baseline, in contrast to WB stored at 4°C which experienced a significant decline by storage Day‐42. Clot formation under shear for both rWB and WB led to increased clot mass through storage. No significant deviation from baseline was appreciated until Day 70 of storage in rWB. Increasing degrees of thrombolysis were seen in both groups, with rWB significantly deviating from baseline at Day 70. No significant changes in overall clot architecture occurred throughout storage and recombination. This fractionation and recombination protocol serves as a method to further develop reproducible in vitro clot analogs for preclinical thrombolytic therapy screening. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia, defined as the loss of skeletal muscle mass, has been associated with a worse functional outcome after stroke. Measurement of temporal muscle thickness (TMT) has been introduced as an easily obtainable surrogate marker to identify patients with sarcopenia. Our study aims to investigate the correlation between pre-stroke sarcopenia, measured by TMT assessment, and functional outcome in patients treated with revascularization procedures for acute ischemic stroke. Methods: We included consecutive adult patients who underwent thrombolysis, endovascular thrombectomy or both for acute ischemic stroke at our Centre from January 2020 to June 2022. Besides collecting baseline clinical and neuroradiological features, TMT was measured on brain computed tomography scans according to a standardized protocol. Modified Rankin Scale (mRS) scores at 3 months represented the main endpoint of functional outcome. Results: A total of 261 patients were available for the analysis. In univariate models, patients with excellent outcomes (mRS = 0–1) were younger, had higher TMT values and lower pre-event disability and stroke severity. In multivariate models higher TMT values resulted independently associated with reduced mortality (Odds Ratio 0.708, 95% Confidence Interval 0.538–0.930, p = 0.013). Age, diabetes, brain bleeding events and stroke severity were found to be predictors of mortality, too. Conclusions: Our retrospective analysis shows that in patients who underwent revascularization treatments for ischemic stroke TMT is as an independent predictor of survival easily obtainable from the baseline CT scan. Further investigation is required to confirm the role of sarcopenia assessment and TMT measurement in the prognostication toolkit of this disease. [ABSTRACT FROM AUTHOR]

Background: While mechanical thrombectomy is considered standard of care for large vessel occlusions, scientific evidence to support treatment for distal and medium vessel occlusions remains scarce. Purpose: To evaluate feasibility, safety, and outcomes in patients with low National Institute of Health Stroke Scale scores undergoing mechanical thrombectomy for treatment of distal medium vessel occlusions. Materials and methods: Retrospective data review and analysis of prospectively maintained databases at 41 academic centers in North America, Asia, and Europe between January 2017 and January 2022. Characteristics and outcomes were compared between groups with low stroke scale score (≤ 6) versus and higher stroke scale scores (> 6). Propensity score matching using the optimal pair matching method and 1:1 ratio was performed. Results: Data were collected on a total of 1068 patients. After propensity score matching, there were a total of 676 patients included in the final analysis, with 338 patients in each group. High successful reperfusion rates were seen in both groups, 90.2% in ≤ 6 and 88.7% in the > 6 stroke scale groups. The frequency of excellent and good functional outcome was seen more common in low versus higher stroke scale score patients (64.5% and 81.1% versus 39.3% and 58.6%, respectively). The 90-day mortality rate observed in the ≤ 6 stroke scale group was 5.3% versus 13.3% in the > 6 stroke scale group. Conclusion: Mechanical thrombectomy in distal and medium vessel occlusions, specifically in patients with low stroke scale scores is feasible, though it may not necessarily improve outcomes over IVT. [ABSTRACT FROM AUTHOR]

Background The COVID-19 pandemic has significantly affected acute ischemic stroke (AIS) care. In this study, we examined the effects of the pandemic on neurosurgical AIS care by means of decompressive surgery (DS). Methods In this retrospective observational study, we compared the characteristics, in-hospital processes, and in-hospital mortality rates among patients hospitalized for AIS during the first four waves of the pandemic (between January 1, 2020 and October 26, 2021) versus the corresponding periods in 2019 (prepandemic). We used administrative data from a nationwide hospital network in Germany. Results Of the 177 included AIS cases with DS, 60 were from 2019 and 117 from the first four pandemic waves. Compared with the prepandemic levels, there were no changes in weekly admissions for DS during the pandemic. The same was true for patient age (range: 51.7–60.4 years), the number of female patients (range: 33.3–57.1%), and the prevalence of comorbidity, as measured by the Elixhauser Comorbidity Index (range: 13.2–20.0 points). Also, no alterations were observed in transfer to the intensive care unit (range: 87.0–100%), duration of in-hospital stay (range: 14.6–22.7 days), and in-hospital mortality rates (range: 11.8–55.6%). Conclusion In Germany, compared with the prepandemic levels, AIS patients undergoing DS during the first four waves of the pandemic showed no changes in demographics, rates of comorbidity, and in-hospital mortality rates. This is in contrast to previous evidence on patients with less critical types of AIS not requiring DS and underlines the uniqueness of the subgroup of AIS patients requiring DS. Our findings suggests that these patients, in contrast to AIS patients in general, were unable to forgo hospitalization during the COVID-19 pandemic. Maintaining the delivery of DS is an essential aspect of AIS care during a pandemic. [ABSTRACT FROM AUTHOR]

The article focuses on the efficacy of intravenous thrombolysis (IVT) with tenecteplase for large vessel occlusion strokes when administered beyond the standard 4.5-hour window and the comparison of tenecteplase to placebo in a Chinese cohort, its potential benefits over traditional treatments.

Objectives: This study explores whether textural features from initial non-contrast CT scans of infarcted brain tissue are linked to hemorrhagic transformation susceptibility. Materials and methods: Stroke patients undergoing thrombolysis or thrombectomy from Jan 2012 to Jan 2022 were analyzed retrospectively. Hemorrhagic transformation was defined using follow-up magnetic resonance imaging. A total of 94 radiomic features were extracted from the infarcted tissue on initial NCCT scans. Patients were divided into training and test sets (7:3 ratio). Two models were developed with fivefold cross-validation: one incorporating first-order and textural radiomic features, and another using only textural radiomic features. A clinical model was also constructed using logistic regression with clinical variables, and test set validation was performed. Results: Among 362 patients, 218 had hemorrhagic transformations. The LightGBM model with all radiomics features had the best performance, with an area under the receiver operating characteristic curve (AUROC) of 0.986 (95% confidence interval [CI], 0.971–1.000) on the test dataset. The ExtraTrees model performed best when textural features were employed, with an AUROC of 0.845 (95% CI, 0.774–0.916). Minimum, maximum, and ten percentile values were significant predictors of hemorrhagic transformation. The clinical model showed an AUROC of 0.544 (95% CI, 0.431–0.658). The performance of the radiomics models was significantly better than that of the clinical model on the test dataset (p < 0.001). Conclusions: The radiomics model can predict hemorrhagic transformation using NCCT in stroke patients. Low Hounsfield unit was a strong predictor of hemorrhagic transformation, while textural features alone can predict hemorrhagic transformation. Clinical relevance statement: Using radiomic features extracted from initial non-contrast computed tomography, early prediction of hemorrhagic transformation has the potential to improve patient care and outcomes by aiding in personalized treatment decision-making and early identification of at-risk patients. Key Points: • Predicting hemorrhagic transformation following thrombolysis in stroke is challenging since multiple factors are associated. • Radiomics features of infarcted tissue on initial non-contrast CT are associated with hemorrhagic transformation. • Textural features on non-contrast CT are associated with the frailty of the infarcted tissue. [ABSTRACT FROM AUTHOR]

Stroke is a devastating clinical condition characterized by an acute neurological impairment secondary to cerebrovascular disease. Globally, stroke is the second leading cause of mortality and disability, with prominent risk factors including age, hypertension, hyperlipidemia, atrial fibrillation, diabetes, smoking, preexisting vascular anomalies and obesity. Acute neurological deficits are commonly encountered in the inpatient wards. Heightened clinical suspicion and prompt evaluation involving neurological examination and imaging are crucial for effective management. At many hospitals, hospitalists are tasked with managing stroke patients with consultation from neurologists. The management of stroke is constantly evolving as new and advanced therapies emerge. This review of the literature seeks to summarize current practice in stroke management in hopes it is helpful to those hospitalists who care for this patient population frequently. A search of the literature was performed to summarize current research as well as management and therapeutic strategies. [ABSTRACT FROM AUTHOR]

Pulmonary Embolism (PE) is a life-threatening condition initiated by the presence of blood clots in the pulmonary arteries, leading to severe morbidity and mortality. Underlying mechanisms involve endothelial dysfunction, including impaired blood flow regulation, a pro-thrombotic state, inflammation, heightened oxidative stress, and altered vascular remodeling. These mechanisms contribute to vascular diseases stemming from PE, such as recurrent thromboembolism, chronic thromboembolic pulmonary hypertension, post-thrombotic syndrome, right heart failure, and cardiogenic shock. Detailing key risk factors and utilizing hemodynamic stability-based categorization, the review aims for precise risk stratification by applying established diagnostic tools and scoring systems. This article explores both conventional and emerging biomarkers as potential diagnostic tools. Additionally, by synthesizing existing knowledge, it provides a comprehensive outlook of the current enhanced PE management and preventive strategies. The conclusion underscores the need for future research to improve diagnostic accuracy and therapeutic effectiveness in PE. [ABSTRACT FROM AUTHOR]

Background: Pulmonary embolism (PE) is a critical condition requiring effective management strategies. Several options are available, including thrombolytic therapy and anticoagulants. Objectives: To assess the impact of thrombolytic therapy either combined with anticoagulant (AC) or alone versus AC alone on mortality, recurrence, clinical deterioration, bleeding, and hospital stay. Method: This study included 25 previously published studies from 1990 to 2023, with a total of 12 836 participants. Dichotomous and continuous analysis models were used to evaluate outcomes, with heterogeneity and publication bias tests applied. A random model was used for data analysis. Several databases were searched for the identification and inclusion of studies, such as Ovid, PubMed, Cochrane Library, Google Scholar, and Embase. Results: For sub‐massive PE, CDT plus AC significantly reduced in‐hospital, 30‐day, and 12‐month mortality compared to AC alone, odds ratio (OR) of −0.99 (95% CI [−1.32 to −0.66]), with increased major bleeding risk but no difference in minor bleeding or hospital stay, OR = 0.46, 95% CI [−0.03 to 0.96]). For acute intermediate PE, systemic thrombolytic therapy did not affect all‐cause or in‐hospital mortality but increased minor bleeding, reduced recurrent PE, and prevented clinical deterioration. The heterogeneity of different models in the current study varied from 0% to 37.9%. Conclusion: The addition of CDT to AC improves mortality outcomes for sub‐massive PE but raises the risk of major bleeding. Systemic thrombolytic therapy reduces recurrence and clinical decline in acute intermediate PE despite increasing minor bleeding. Individualized patient assessment is essential for optimizing PE management strategies. [ABSTRACT FROM AUTHOR]

The aim of the present European Stroke Organisation (ESO) guideline is to provide evidence-based recommendations on the acute management of patients with basilar artery occlusion (BAO). These guidelines were prepared following the Standard Operational Procedure of the ESO and according to the GRADE methodology. Although BAO accounts for only 1-2% of all strokes, it has very poor natural outcome. We identified 10 relevant clinical situations and formulated the corresponding Population Intervention Comparator Outcomes (PICO) questions, based on which a systematic literature search and review was performed. The working group consisted of 10 voting members (five representing ESO and five representing the European Society of Minimally Invasive Neurological Therapy (ESMINT)) and three nonvoting junior members. The certainty of evidence was generally very low. In many PICOs, available data were scarce or lacking, hence, we provided expert consensus statements. First, we compared intravenous thrombolysis (IVT) to no IVT, but specific BAO-related data do not exist. Yet, historically, IVT was standard of care for BAO patients who were also included (although in small numbers) in IVT trials. Non-randomized studies of IVT-only cohorts showed a high proportion of favorable outcomes. Expert Consensus suggests using IVT up to 24 hours unless otherwise contraindicated. We further suggest IVT plus endovascular treatment (EVT) over direct EVT. EVT on top of best medical treatment (BMT) was compared with BMT alone within 6 and 6-24 hours from last seen well. In both time windows, we observed a different effect of treatment depending on a) the region where the patients were treated (Europe vs Asia), b) on the proportion of IVT in the BMT arm, and c) on the initial stroke severity. In case of high proportion of IVT in the BMT group and in patients with a National Institutes of Health Stroke Scale (NIHSS) score below 10, EVT plus BMT was not found better than BMT alone. Based on very low certainty of evidence, we suggest EVT+BMT over BMT alone (this is based on results of patients with at least 10 NIHSS points and a low proportion of IVT in BMT). For patients with an NIHSS score below 10, we found no evidence to recommend EVT over BMT. In fact, BMT was nonsignificantly better and safer than EVT. Furthermore, we found a stronger treatment effect of EVT+BMT over BMT alone in proximal and middle locations of BAO compared with distal location. While recommendations for patients without extensive early ischemic changes in the posterior fossa can, in general, follow those of other PICOs, we formulated an Expert Consensus Statement suggesting against reperfusion therapy in those with extensive bilateral and/or brainstem ischemic changes. Another Expert Consensus suggests reperfusion therapy regardless of collateral scores. Based on limited evidence, we suggest direct aspiration over stent retriever as the first-line strategy of mechanical thrombectomy. As an Expert Consensus, we suggest rescue percutaneous transluminal angioplasty and/or stenting after a failed EVT procedure. Finally, based on very low certainty of evidence, we suggest add-on antithrombotic treatment during EVT or within 24 hours after EVT in patients with no concomitant IVT and in whom EVT was complicated (defined as failed or imminent re-occlusion, or need for additional stenting or angioplasty). [ABSTRACT FROM AUTHOR]

Background: Thrombosis is the abnormal formation of blood clots within blood vessels; it results from an imbalance between fibrinolytic, pro-coagulant, and anticoagulant systems. Pediatric arterial thrombosis, especially related to catheter usage, is an emerging issue with limited evidence. This study evaluates the efficacy of enoxaparin in treating arterial thrombosis in pediatric patients at a single center. Methods: A retrospective single-center study included children under 14 years old diagnosed with catheter-related arterial thrombosis (CAT) and treated with low-molecular-weight heparin (LMWH) at King Abdulaziz Medical City between 2016 and 2021. Patients without follow-up at our institution or those using other anticoagulants were excluded. Data collected included age, sex, weight, catheter type, location and degree of thrombosis, ultrasonographic results, treatment duration, hemoglobin and platelet levels, and missed refills. Radiologic confirmation of CAT was required for inclusion. Results: This study included 111 children treated with enoxaparin for non-cerebral arterial thrombosis. The median age at diagnosis was 3 months, with 58% being male patients. Most cases (87%) involved cardiac catheterization, and all were confirmed using ultrasonography. Complete thrombus resolution was achieved in 90% of patients, partial resolution in 8.1%, and 1.8% had no resolution. The median duration of enoxaparin therapy was 20 days. Multivariate analysis indicated that higher age and lower body weight were associated with a higher risk of non-resolution. Indwelling catheters also posed a greater risk of non-resolution compared to cardiac catheters. Conclusions: Enoxaparin proved effective in treating catheter-related arterial thrombosis in children, with high resolution rates and few side effects. This study helps inform treatment strategies in pediatric thrombosis management and highlights the need for further research to refine treatment durations and address patient risk factors. [ABSTRACT FROM AUTHOR]

Thromboembolism (TE) complicates the course of pediatric cancer in a considerable number of cases. Cancer-related TE is attributed to an interaction of the underlying malignancy, the effects of therapy, and a possible thrombophilia predisposition. More specifically, recognized risk factors include a very young age and adolescence, non-O blood group, type and site of cancer, inherited thrombophilia, presence of central venous catheter, and type of chemotherapy. TE in children with cancer most commonly occurs in their extremities. In the absence of evidence-based guidelines for the management of thrombotic complications in pediatric oncology patients, TE management follows general recommendations for the management of pediatric TEs. Given the limitations of conventional anticoagulant therapy, direct oral anticoagulants could provide an alternative; however, their safety and efficacy in children with cancer remain to be seen. As for thromboprophylaxis, numerous studies have been conducted, albeit with conflicting results. Although the survival of pediatric oncology patients has significantly improved in recent years, morbidity due to cancer-related TE remains, underlying the need for large multicenter trials investigating both TE management with currently available agents and primary prevention. [ABSTRACT FROM AUTHOR]

Nan Chen, Jiadi Gao, Hanshu Zhao, Sihan Liu, Yubing Zhou, Yushuang Liu, Zhongling Zhang, Shanshan Yang Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People’s Republic of ChinaCorrespondence: Shanshan Yang; Zhongling Zhang, Department of Neurology, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Stree, Nangang District, Harbin, Heilongjiang Province, 150001, People’s Republic of China, Tel +86-451-85553681 ; + 86-451-85555918, Fax +86-451-85555918, Email yangshanshan81@163.com; zhangzhongling7@126.comObjective: Stroke is a leading cause of disability and mortality worldwide, posing a significant public health challenge. While treatment of acute ischemic stroke (AIS) with recombinant tissue plasminogen activator (rt-PA) is effective but increases the risk of hemorrhagic transformation (HT). This study aimed to explore the determinants of HT in AIS patients treated with rt-PA and investigate the association between blood glucose levels and HT risk.Methods: We conducted a prospective cohort study at the First Affiliated Hospital of Harbin Medical University from January 2018 to December 2021. Patients with AIS and who received rt-PA within 4.5 hours of symptom onset were included. Demographic, clinical, laboratory, and imaging data were collected.Results: Of the 426 patients, 15% experienced HT post-rt-PA, occurred more frequently in patients with a history of cardiac embolism, higher prethrombolysis NIHSS scores, and elevated fasting blood glucose (FBG) levels. The frequency of HT was higher in non-diabetic patients with FBG levels ≥ 7.0 mmol/L compared to diabetic patients. Elevated blood glucose levels were significantly associated with HT, regardless of diabetes history.Conclusion: The findings suggest importance of precise glycemic control during AIS management to improve patient outcomes, particularly in non-diabetic patients. Future protocols for AIS treatment should incorporate these findings to reduce HT risks. Further large-scale studies are needed to confirm these associations and guide clinical practices.Keywords: Acute ischemic stroke, thrombolytic therapy, rt-PA, hemorrhagic transformation, blood glucose, outcomes

Acute ischemic stroke (AIS) occupies one of the leading places in the structure of disability and mortality in adult population throughout the world, which causes a significant social and economic burden of this pathology. Recent advances in AIS diagnosis and treatment have significantly reduced mortality and improved functional outcomes in patients. However, categories of patients with unsatisfactory results and complications of reperfusion therapy still remain. In some of them, mortality may exceed the overall rate. To this day, there are controversial aspects in determining indications and choosing the preferred method of cerebral reperfusion. The presented cases describe the results of using thrombolytic therapy and thromboextraction in AIS patients of different age groups. The importance of various neuroimaging methods (multislice computed tomography, computed angiography, duplex ultrasound of extra- and intracranial arteries) for timely diagnosis and determination of optimal revascularization tactics was noted.

Abstract Recent years have seen ticagrelor, a potent P2Y12 inhibitor, emerge as a significant advancement in the peri-thrombolytic management of patients with ST-segment elevation myocardial infarction (STEMI), offering a promising alternative to traditional antiplatelet drugs like clopidogrel. This review critically examines the efficacy and safety of ticagrelor during the peri-thrombolytic phase in STEMI patients, drawing on evidence from key clinical trials such as TREAT and MIRTOS, as well as other relevant studies. These investigations underscore ticagrelor’s superior platelet inhibition capabilities, which are crucial for minimizing thrombotic complications post-thrombolysis without increasing bleeding risks. Despite its potential, clopidogrel remains the guideline-recommended choice for such patients, leaving the appropriateness of ticagrelor in this context open to debate. By summarizing the current evidence and identifying gaps in our understanding, this study advocates for targeted research to clarify the long-term benefits and optimal deployment of ticagrelor, highlighting its evolving significance in cardiovascular care.

Aim: It remains controversial whether intravenous tissue plasminogen activator (IV tPA) increases complications in patients undergoing mechanical thrombolysis. In this study, we aimed to show the effect of IV tPA administration on complications. Methods: In this cross-sectional study, the records of patients who were followed up at the stroke center and underwent mechanical thrombectomy (MT) between 2022 and 2023 were retrospectively reviewed. Demographic data, cerebral angiography data, neuroimaging time, medical history, and medication use; neurologic examination findings at baseline, 24th hour, and 3rd month were obtained from the patient files. Patients were divided into two groups according to whether intracranial tPA was administered before MT and two groups according to the presence of intracranial hemorrhage at 24 hours. Results: A total of 172 patients [94 women (54.7%) and 78 men (45.3%)] were included in the study. Mean age was 67.6±14.7 years. At 24 h, the rate of symptomatic intracranial hemorrhage (sICH) was significantly (p=0.004) higher in the thrombectomy group than in the tPA plus thrombectomy group. The admission (p=0.033) and 24-hour National Institutes of Health Stroke Scale (p=0.001) scores were significantly higher in the sICH group than in the non-sICH group. Third-month modified Rankin scale score (p=0.003), diastolic embolism rate (p=0.009), and Tan score (p=0.007) were significantly higher in the sICH group than in the non-sICH group. Conclusion: Intravenous tissue plasminogen activator did not increase sICH or distal embolism in patients undergoing MT, and there was no difference in terms of favorable clinical outcomes. Symptomatic intracranial hemorrhage was associated with increased mortality and poor clinical outcome.

Background: Recombinant prourokinase (rhPro-UK) is a specific plasmin activator, which has been approved to treat acute myocardial infarction in China. Aim: This phase 3 trial aimed to further demonstrate the efficacy and safety of rhPro-UK in patients with acute ischemic stroke (AIS) within 4.5 h of symptom onset. Methods and design: RhPro-UK in AIS within 4.5 h of stroke onset trial-2 (PROST-2) is a multicenter, prospective randomized, open-label, blinded end-point, non-inferiority, recombinant tissue plasmin activator (rt-PA)-controlled, phase 3 trial. A total of 1552 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 min) or rt-PA 0.9 mg/kg (10% bolus + 90% infusion/1 h). 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 h 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. [ABSTRACT FROM AUTHOR]