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BACKGROUND: Despite its approval for acute ischemic stroke >25 years ago, intravenous thrombolysis (IVT) remains underused, with inequities by age, sex, race, ethnicity, and geography. Little is known about IVT rates by insurance status. METHODS AND RESULTS: We assessed temporal trends from 2002 to 2015 in IVT for acute ischemic stroke in the Nationwide Inpatient Sample using adjusted, survey-weighted logistic regression. We calculated odds ratios for IVT for each category in 2002 to 2008 (period 1) and 2009 to 2015 (period 2). IVT use for acute ischemic stroke increased from 1.0% in 2002 to 6.8% in 2015 (adjusted annual relative ratio, 1.15). Individuals aged ≥85 years had the most pronounced increase during 2002 to 2015 (adjusted annual relative ratio, 1.18) but were less likely to receive IVT compared with 18- to 44-year-olds in period 1 (adjusted odds ratio [aOR], 0.23) and period 2 (aOR, 0.36). Women were less likely than men to receive IVT, but the disparity narrowed over time (period 1: aOR, 0.81; period 2: aOR, 0.94). Inequities in IVT resolved for Hispanic individuals in period 2 (aOR, 0.96) but not for Black individuals (period 2: aOR, 0.81). The disparity in IVT for Medicare patients, compared with privately insured patients, lessened over time (period 1: aOR, 0.59; period 2: aOR, 0.75). Patients treated in rural hospitals remained less likely to receive IVT than in urban hospitals; a more dramatic increase in urbanity widened the inequity (period 2, urban nonteaching versus rural: aOR, 2.58, period 2, urban teaching versus rural: aOR, 3.90). CONCLUSIONS: IVT for acute ischemic stroke increased among adults. Despite some encouraging trends, the remaining disparities highlight the need for intensified efforts at addressing inequities.

Background: Alteplase (tPA) is the initial treatment for acute ischemic stroke. Current tPA guidelines exclude patients who took direct oral anticoagulants (DOAC) within the prior 48 hours. In this propensity-matched retrospective study we compared acute ischemic stroke patients treated with tPA who had received DOACs within 48 hours of thrombolysis to those not previously treated with DOACs, regarding three outcomes: mortality; intracranial hemorrhage (ICH); and need for acute blood transfusions (as a marker of significant blood loss).Methods: Using the United States cohort of 54 healthcare organizations in the TriNetx database, we identified 8,582 stroke patients treated with tPA on DOACs within 48 hours of thrombolysis and 46,703 stroke patients treated with tPA not on DOACs since January 1, 2012. We performed propensity score matching on demographic information and seven prior clinical diagnostic groups, resulting in a total of 17,164 acute stroke patients evenly matched between groups. We recorded mortality rates, frequency of ICH, and need for blood transfusions for each group over the ensuing 7- and 30-day periods.Results: Patients treated with tPA on DOACs had reduced mortality (3.3% vs 7.3%; risk ratio [RR] 0.456; P < 0.001), fewer ICHs (6.8% vs 10.1%; RR 0.678; P < 0.001), and less risk of major bleeding as measured by frequency of blood transfusions (0.5% vs 1.5%; RR 0.317; p < 0.001) at 7 days post thrombolytic, than the tPA patients not on DOACS. Findings for 30 days post-thrombolytics were similar/statistically significant with lower mortality rate (7.2% vs 13.1%; RR 0.550; P < 0.001), fewer ICHs (7.6%vs 10.8%; RR 0.705; P < 0.001), and fewer blood transfusions (0.9% vs 2.0%; RR 0.448; P < 0.001).Conclusion: Acute ischemic stroke patients treated with tPA who received DOACs within 48 hours of thrombolysis had lower mortality rates, reduced incidence of ICH, and less blood loss than those not on DOACs. Our study suggests that prior use of DOACs should not be a contraindication to thrombolysis for ischemic stroke.

Background: Pulmonary intravascular thrombus formation has been widely observed in patients with respiratory failure, for example, in patients with SARS-CoV-2 infection (COVID-19). The aim of this study was to evaluate the efficacy/safety of alteplase thrombolysis in COVID-19 severe hypoxemic respiratory failure. In this multicenter, open-label study, patients were randomized to receive alteplase (low- or high-dose) over 5 days plus standard of care (SOC), or SOC alone. The primary endpoint was time to clinical improvement (≥ 2-point decrease on WHO Clinical Progression Scale, or hospital discharge) up to Day 28. Secondary endpoints included all-cause mortality at Day 28, treatment failure at Day 28 and change in arterial oxygen partial pressure/fractional inspired oxygen (PaO2/FiO2) ratio at Day 6 versus baseline. Results: Sixty-nine patients were randomized to alteplase (low- or high-dose) and 35 to SOC; 65% were on high-flow oxygen or non-invasive ventilation at baseline. Median time to clinical improvement was 25 days in the alteplase group and > 28 days (median not reached) in the SOC group. All-cause mortality was 8/69 (12%) versus 10/35 (29%) in the alteplase versus SOC groups, respectively (unadjusted risk difference [RD], − 17% [95% confidence interval (CI) − 34 to 0], p = 0.047; adjusted RD, − 16% [95% CI − 31 to 1], p = 0.058). The PaO2/FiO2 ratio (mean [standard deviation]) increased by + 30 (84) mmHg in the alteplase group and decreased by − 12 (59) mmHg in the SOC group (adjusted mean difference vs. SOC, p = 0.052). Differences were greater in patients receiving high-dose alteplase, and in those not receiving invasive ventilation. Eighteen patients (26.1%) in the alteplase group discontinued treatment due to adverse events. Major bleeding was more frequent with alteplase than with SOC (9 vs. 0 patients); no bleeding was fatal. The study closed early due to insufficient patient recruitment. Conclusion: Alteplase was not associated with faster clinical recovery from COVID-19 severe hypoxemic respiratory failure. A numerical difference in survival and PaO2/FiO2 ratio was observed, particularly in patients not receiving invasive ventilation. These exploratory findings merit further investigation in larger patient cohorts that are adequately powered to confirm the hypotheses generated in this study regarding the impact of alteplase on treatment outcomes. Trial registration ClinicalTrials.gov: NCT04640194 (November 23, 2020); https://clinicaltrials.gov/study/NCT04640194 (early discontinuation due to insufficient patient recruitment). [ABSTRACT FROM AUTHOR]

Introduction: Thrombolysis and endovascular thrombectomy (EVT) are standard treatments after stroke. We previously reported that these therapies benefit stroke patients over 80 years old. Now, we aimed to study reperfusion therapies specifically in nonagenarians, hypothesizing a poorer prognosis in this group. Methods: Nonagenarian stroke patients were identified from our prospective monocentric cohort, which included consecutive patients ≥80 years old treated with thrombolysis and/or EVT from 2015 to 2019. Baseline characteristics, treatments, and outcomes, as well as complications and mortality were analyzed. Results: Ninety-six nonagenarians were treated with thrombolysis (69.8%) and/or EVT (81.1%). A total of 51% had a pre-stroke modified Rankin score (mRS) ≤2. Cardioembolism was the most common etiology (67.7%). Age was associated with a higher mRS after stroke with a turning point at 90 years old: (90–99 years old: odds ratio [OR] = 0.33, 95% confidence interval [95% CI]: 0.13–0.83, p = 0.02) versus (85–89 years old: OR = 0.72, 95% CI: 0.34–1.50, p = 0.38), with 80- to 84-year-old patients as the reference. In nonagenarians, previous coronary artery disease (OR = 8.02, 95% CI: 1.66–38.68, p = 0.01), initial National Institute of Health Stroke Score (NIHSS) (OR = 1.11, 95% CI: 1.03–1.19, p = 0.01), pre stroke independence (OR = 0.25, 95% CI: 0.08–0.71, p = 0.01), and “drip-and-ship” status (OR = 3.35, 95% CI: 1.22–9.16, p = 0.02) were associated with 3-month mortality. Nonagenarians had more baseline comorbidities (p = 0.003) and lower levels of pre-stroke independence (p = 0.002) than octogenarians (n = 261). Despite no difference in the use of acute treatments, timelines, and rates of successful reperfusion, a good functional status at 3 months was less common in nonagenarians than octogenarians (14.3% vs. 34.0%, p < 0.001) with a higher mortality (60.2% vs. 16.4%, p < 0.001). A total of 9.5% of nonagenarians experienced a symptomatic intracranial hemorrhage. Conclusions: Age is a crucial factor affecting prognosis after stroke with a turning point at 90 years old. However, age alone should not be a limiting factor for treatment decision. Despite higher mortality and poorer functional prognosis overall, some nonagenarians may benefit from reperfusion therapies. [ABSTRACT FROM AUTHOR]

Background and purpose: Posterior circulation strokes, accounting for 20% of acute ischemic strokes, significantly contribute to morbidity and mortality. Fibrinolysis by rtPA improves outcomes in stroke but the risk of intracranial hemorrhage limits benefit. Arterial recanalization of basilar artery occlusion by thrombolysis or endovascular thrombectomy improves outcomes in posterior circulation strokes. This study investigates a VWF-targeting RNA aptamer as a safer and more effective alternative to rtPA in a canine model. Materials and methods: Autologous clots were placed into the basilar artery to induce stroke in 24 beagles. To compare reperfusion, 0.9 mg/kg rtPA, 0.5 mg/kg BB-031, or vehicle were administered 60 min after the initiation of occlusion. Digital subtraction angiography, laser speckle imaging and magnetic resonance imaging were used to assess recanalization, reperfusion and infarct volume, respectively. Results: Treatment with BB-031 resulted in recanalization of the posterior circulation on digital subtraction angiography with no evidence of microembolism assessed at sacrifice. 66.5% of animals treated with BB-031 resulted in reperfusion with a TICI score of =1 whereas vehicle remained at TICI score 0 as did all but one rtPA animal at sacrifice. Improved perfusion was seen in the basilar artery and surrounding blood vessels visualized through the cranial window with laser speckle imaging to ~47% of its original baseline in BB-031 group compared to rtPA at 37% and vehicle at 22%. Finally, BB-031-treatment resulted in an approximate 32% mean infarct volume, significantly smaller on magnetic resonance imaging compared to 56% in vehicle treated and 48% with rtPA treatment. Conclusion: Targeted inhibition of VWF by BB-031 increased recanalization and reperfusion, and reduced infarct volume in a canine model of BAO stroke. It represents a promising target based on preliminary results for treating acute ischemic stroke. [ABSTRACT FROM AUTHOR]

Background: Sex differences in stroke outcomes are notable, with women experiencing higher incidence rates, greater disability-adjusted life years, and poorer recovery compared to men, even after adjusting for age and comorbidities. Despite the disproportionate burden in women, studies have reported that women are less likely to receive appropriate stroke treatment than men. Aim: This study investigated temporal trends of sex differences in acute reperfusion therapy and early outcomes in patients with acute ischemic stroke over 10 years in South Korea. Methods: A retrospective analysis of Korean Stroke Registry included patients with acute ischemic stroke from 2012 to 2021. The study outcomes were the temporal trends of acute reperfusion therapy and early outcomes over 10 years in men and women, respectively. In addition, this study analyzed the temporal trends of sex differences in these parameters during the same period. Early outcomes include the proportions of favorable functional outcomes at discharge, discharge patterns, and in-hospital mortality. Results: A total of 93,692 patients (68.4 years, 40.1% women) with acute ischemic stroke were finally enrolled. Women had a higher age at stroke onset, a higher prevalence of atrial fibrillation, and more severe strokes than men. Women had lower proportion of favorable functional outcomes at discharge and higher proportion of in-hospital mortality compared to men each year. The proportion of patients who received intravenous thrombolysis was lower or similar in women compared to men in most years, and the proportion of patients who received endovascular thrombectomy did not significantly differ between sexes annually. Sex differences in acute reperfusion therapy remained unchanged over 10 years. Conclusion: Women have received acute reperfusion therapy at similar or lower rates than men and experienced poorer outcomes, despite having more stroke risk factors and often more severe strokes. [ABSTRACT FROM AUTHOR]

Background: The stroke center approach provides an effective solution for acute stroke management. Our study aims to systematically analyze our stroke center records to identify factors that affect acute stroke time-sensitive quality metrics. Methods: Data were prospectively collected from 524 acute stroke patients at the Comprehensive Stroke Center of Atatürk UniversityMedical Faculty Hospital between January 1, 2021, and September 30, 2021. Data collected included sociodemographic, clinical, admission type, initial National Institutes of Health Stroke Scale (NIHSS), treatment modality, and time-sensitive metrics and were statistically analyzed based on stroke quality metrics. Results: Patients with mild NIHSS scores (0-7) had longer onset-to-door (OTD) time, door-to-computed tomography (CT)/neurologist, and hospitalization times (P < .001). The OTD, door-to-CT/neurologist, and hospitalization times varied depending on the treatment methods used (P < .005). The OTD time was influenced by the patient's level of education (P = .004), admission type (P < .001), and geographical location (P = .002). A moderate negative correlation was found between patients' OTD time and baseline NIHSS (r = -0.270; P < 0.001). Conclusion: The results emphasize the significance of several factors, such as admission type, geographical location, and treatment methods, in shaping the time-sensitive quality metrics of stroke care. Additionally, the initial NIHSS score of patients plays a crucial role in both prehospital and in-hospital aspects of acute stroke management. [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: To investigate the contemporary use of extracorporeal membrane oxygenation (ECMO) in conjunction with reperfusion strategies in high-risk pulmonary embolism (PE). DESIGN: Observational epidemiological analysis. SETTING: The U.S. Nationwide Inpatient Sample (NIS) (years 2016-2020). PATIENTS: High-risk PE hospitalizations. MEASUREMENTS AND MAIN RESULTS: Use of ECMO in conjunction with thrombolysis-based reperfusion (systemic thrombolysis or catheter-directed thrombolysis) or mechanical reperfusion (surgical embolectomy or catheter-based thrombectomy) with regards to in-hospital mortality and major bleeding. We identified high-risk PE hospitalizations in the NIS (years 2016-2020) and investigated the use of ECMO in conjunction with thrombolysis-based (systemic thrombolysis or catheter-directed thrombolysis) and mechanical (surgical embolectomy or catheter-based thrombectomy) reperfusion strategies with regards to in-hospital mortality and major bleeding. Among 122,735 hospitalizations for high-risk PE, ECMO was used in 2,805 (2.3%); stand-alone in 1.4%, thrombolysis-based reperfusion in 0.4%, and mechanical reperfusion in 0.5%. Compared with neither reperfusion nor ECMO, ECMO plus thrombolysis-based reperfusion was associated with reduced in-hospital mortality (adjusted odds ratio [aOR] 0.61; 95% CI, 0.38-0.98), whereas no difference was found with ECMO plus mechanical reperfusion (aOR 1.03; 95% CI, 0.67-1.60), and ECMO stand-alone was associated with increased in-hospital mortality (aOR 1.60; 95% CI, 1.22-2.10). In the cardiac arrest subgroup, ECMO was associated with reduced in-hospital mortality (aOR 0.71; 95% CI, 0.53-0.93). Among all patients on ECMO, thrombolysis-based reperfusion was significantly associated (aOR 0.55; 95% CI, 0.33-0.91), and mechanical reperfusion showed a trend (aOR 0.75; 95% CI, 0.47-1.19) toward reduced in-hospital mortality compared with no reperfusion, without increases in major bleeding. CONCLUSIONS: In patients with high-risk PE and refractory hemodynamic instability, ECMO may be a valuable supportive treatment in conjunction with reperfusion treatment but not as a stand-alone treatment especially for patients suffering from cardiac arrest. [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]

Background: This study evaluated the correlation between corrected Thrombolysis in Myocardial Infarction (TIMI) frame count (CTFC) and major adverse cardiovascular events (MACE) within the first month following primary percutaneous coronary intervention (PPCI). Methods: Eighty patients who underwent PPCI at Ayatollah Rouhani teaching Hospital in Babol Eighty patients who underwent PPCI at Ayatollah Rouhani teaching Hospital in Babol were included. CTFC, a measure of coronary blood flow, was assessed. Demographic and clinical data, were collected. ST segment resolution, a criterion for successful PPCI, was evaluated. MACE, including cardiac deaths, need for repeat revascularization of culprit vessels, and recurrent non-fatal myocardial infarction, and CVA (cerebrovascular accident) were recorded. Statistical analyses were performed to assess the association between CTFC and demographic/clinical variables, as well as ST resolution and MACE. Results: The majority of patients were (78.8%) men and (81.2%) nonsmokers. No significant association was found between CTFC and demographic/clinical variables. The left anterior descending (LAD) artery was the most commonly involved vessel (48.8%). ST segment resolution of more than 50% was observed in 51.2% of patients. During the one-month follow-up, 13.7% of patients experienced MACE, including 7 cardiac deaths. However, there was no significant association between CTFC and MACE. (P=0.30) Conclusion: This study concludes that CTFC is not a reliable predictor of MACE within the first month after PPCI. Furthermore, ST segment resolution of more than 50% was associated with a lower prevalence of cardiovascular events. [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]

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Background: FNDs mimicking a stroke represent a growing challenge in the emergency department (ED). A comprehensive diagnostic approach involving clinical evaluation and neuroimaging is essential to differentiate stroke from mimics. The safety profile of thrombolysis justifies its use where FNDs cannot be ruled out. This approach highlights the need for more precise diagnostic tools and protocols to improve patient care and reduce unnecessary treatments. Distinguishing FNDs from actual cerebrovascular events is critical yet difficult, particularly under time constraints. Given the urgency and potential severity of strokes, intravenous thrombolysis is frequently administered even when FNDs cannot be definitively excluded. Methods: This retrospective study analyzed data of participants admitted to the Trieste University Hospital Stroke Unit between January 2018 and December 2022, focusing on those presenting with sudden-onset focal neurological deficits mimicking a stroke, with some presenting within the reperfusion treatment window (<4.5 h from symptoms onset). We obtained detailed clinical evaluations and neuroimaging, and administered thrombolytic therapy in selected cases. Results and discussion: We included 84 participants presenting with stroke mimics (average age of 45 yo) predominantly female (65.5%). Most common presentations: hemiparesis or hemisensory loss (75%), speech disorder (10.7%), vertigo/gait disorders (4.8%). History of psychiatric disorders was found in 32.1% of cases, and 48.8% had prior neurological disease or stroke risk factors. Advanced neuroimaging was performed in 43 cases yielding normal or nonspecific results. Thrombolysis was safely administered in 31%. Patients mostly recovered within the first 24 h from admission (44.7%). We compared this FND's sample with 291 patients with mild ischemic stroke (NIHSS ≤7). [ABSTRACT FROM AUTHOR]

This study presents systematic design guidelines for AI-powered clinical decision support systems (AI-CDSS) based on a comprehensive literature review and theme analysis. The proposed guidelines are divided into two parts, comprising 25 items: "How—design methods" and "What—design content and forms." The usability of these guidelines is demonstrated through an AI-CDSS design practice for stroke diagnosis and thrombolytic risk assessment in a Chinese clinical setting. The empirical case study provides practical suggestions for similar AI-CDSS designs that require fast decision-making. Challenges concerning system transparency or explainability and the impact of bias on system output are considered key issues in designing an effective and satisfying AI-CDSS. The potential usefulness of AI-CDSS in clinical decision-making scenarios has been indicated by numerous studies, with efficient design guidelines still needed to address these challenges. [ABSTRACT FROM AUTHOR]

Background: For patients experiencing ischemic stroke despite receiving therapy with direct oral anticoagulants (DOAC) and without endovascular treatment options, therapeutic prospects are currently dismal. Current guidelines recommend intravenous thrombolysis (IVT) only for patients who have received DOAC in very restricted settings, as an increased risk of bleeding is suspected. However, recent retrospective observational studies suggest that IVT is safe despite DOAC pretreatment. Objectives: To provide further evidence that IVT despite previous DOAC treatment is not associated with an increased risk of bleeding. Design: Observational retrospective study. Methods: Demographic, clinical, and radiological data of patients who received IVT (+/− endovascular thrombectomy) despite DOAC pretreatment between June 2021 and January 2024 were analyzed using descriptive statistics, including DOAC plasma concentration at admission. Secondary intracranial hemorrhages and functional outcomes at 3 months were assessed. Since 2023, patients have been treated according to a modified local standard operating procedure at our hospital, allowing for IVT despite DOAC pretreatment regardless of DOAC plasma levels or the use of reversal agents. Results: Of 1821 patients treated with acute recanalization procedures during the study period, N = 35 had received IVT with (18) or without (17) additional endovascular therapy. Among these patients with a wide age range (42–97 years) and DOAC plasma concentrations up to 369 ng/ml, only one developed symptomatic intracranial hemorrhage. A favorable outcome (modified Rankin scale score 0–2) after 3 months was observed in 57% (20) of the patients. Conclusion: IVT despite direct oral anticoagulation seems to be safe, even at advanced age and high DOAC plasma levels. Plain language summary: Bleeding problems after stroke treatment with clot-busting drugs, even when taking blood thinners After local treatment rules were changed to allow clot-busting treatment for stroke even if patients had recently used blood thinners, the number of patients receiving this treatment more than tripled. Despite not checking blood test results before treatment, serious brain bleeding was not common. The levels of blood thinners in the patients' blood did not affect the chances of having any kind of brain bleeding. This new information supports the growing evidence that clot-busting treatment may be safe for patients taking novel blood thinners. [ABSTRACT FROM AUTHOR]

Introduction: The administration of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) in the treatment of acute ischemic stroke (AIS) has been a subject of debate, and its potential benefits remain uncertain. This retrospective study aimed to investigate the effect of preoperative IVT on glycocalyx damage in patients with cerebral ischemia-reperfusion injury (IRI). Methods: A cohort of 106 patients with acute large vessel occlusion in the anterior circulation treated with mechanical thrombectomy was enrolled. The levels of the glycocalyx damage marker, syndecan-1, were measured in the peripheral blood of these patients to assess glycocalyx damage during IRI, and clinical outcomes were compared between patients receiving MT alone vs. combined IVT and MT. Results: The study results indicate that thrombolytic drugs have a significant impact on syndecan-1 levels in the blood. Compared to patients who underwent direct MT, those who received preoperative IVT had significantly lower levels of syndecan-1 in their blood. Although preoperative IVT did not alter the final clinical outcomes, the levels of syndecan-1 shedding reflect the extent of damage to the endothelial glycocalyx. Discussion: This suggests that using thrombolytic drugs before mechanical thrombectomy may reduce endothelial glycocalyx damage in patients with ischemia-reperfusion injury. These findings provide indirect clinical evidence supporting the preoperative use of intravenous thrombolysis in such patients. [ABSTRACT FROM AUTHOR]

Background: Managing acute ischemic stroke in patients with significant comorbidities, such as hypertension, heart failure, and substance abuse, presents unique challenges. Timely intervention is critical, but the risk of complications and poor prognosis is high. Case Presentation: A 46-year-old male with a history of smoking, drug abuse, poorly controlled hypertension, and dilated cardiomyopathy with an ejection fraction of 25%-30% presented with sudden left-sided weakness, facial droop, and dysarthria. The initial National Institutes of Health Stroke Scal score was 6. Computed tomography (CT) brain showed no acute infarctions but revealed chronic lacunar infarctions and atrophy. CT angiography identified significant vascular abnormalities, including right internal carotid artery attenuation and non-visualization of both intracranial vertebral and basilar arteries. Intravenous thrombolysis (tPA) led to initial improvement, but recurrent strokes or transient ischemic attacks (TIAs) followed, leading to intubation and mechanical ventilation. Magnetic resonance imaging revealed evolving infarctions in the pons and cerebellum. A basilar artery thrombectomy was successfully performed, but postoperative complications included spontaneous pneumothorax and femoral artery pseudoaneurysm, requiring further interventions. Due to extensive posterior circulation infarction, the patient had a poor neurological prognosis and was placed on do not resuscitate status. Conclusion: This case highlights the complexities of treating acute ischemic stroke in patients with substantial comorbidities. While interventions such as thrombolysis and thrombectomy are critical, they carry risks. A multidisciplinary approach is necessary to balance immediate treatment with considerations of long-term prognosis and quality of life. [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]

Introduction: Endovascular treatment (EVT) is a therapeutic option for cerebral venous thrombosis (CVT); however, its benefit over conservative medical management has not been proven. Whether the current patient selection practices are appropriate for EVT is unclear. Methods: This was a nationwide study of the 2016–2020 National Inpatient Sample database. Adult CVT patients and EVT treatments were identified. Patient demographics, medical comorbidities, CVT risk factors, and CVT manifestations were identified. Presence of radiographic signs of advanced and severe CVT (venous infarction, cerebral edema, and intracranial hemorrhage) was recorded. Primary and secondary outcomes were good discharge outcomes and in-hospital mortality, respectively. Results: A total of 17,130 CVT patients were identified, and 56.7% had good discharge outcomes, while 4.6% died during hospitalization. 945 (5.5%) received EVT, and EVT patients were more likely to have cerebral infarction (35.4 vs. 21.8%, p < 0.001), edema (35.4 vs. 20.1%, p < 0.001), and hemorrhage (37.6 vs. 19.7%, p < 0.001). After multivariable adjustments, EVT for patients without infarction, edema, or hemorrhage was moderately associated with higher odds of good outcomes (OR 1.86 [95% CI 0.98–3.53], p = 0.059) and resulted in zero deaths. However, with the increasing burden of radiographic signs of advanced CVT measured by the cumulative presence of infarction, edema, and hemorrhage, EVT was associated with decreasing odds of good outcomes and increasing odds of in-hospital mortality compared to medical management (interaction p = 0.046 and 0.029, respectively). Conclusions: EVT may lead to higher rates of favorable hospitalization outcomes in patients who have not yet developed overt parenchymal manifestations of backpressure changes; presence of infarction, edema, and hemorrhage may diminish the short-term effectiveness of EVT. [ABSTRACT FROM AUTHOR]

Introduction: Careful monitoring of patients who receive intravenous thrombolysis (IVT) for acute ischemic stroke (AIS) is resource-intensive, and potentially less relevant in those with mild degrees of neurological impairment who are at low risk of symptomatic intracerebral hemorrhage (sICH) and other complications. Methods: OPTIMISTmain is an international, multicenter, prospective, stepped wedge, cluster randomized, blinded outcome assessed trial aims to determine whether a less-intensity monitoring protocol is at least as effective, safe, and efficient as standard post-IVT monitoring in patients with mild deficits post-AIS. Clinically stable adult patients with mild AIS (defined by a NIHSS <10) who do not require intensive care within 2 h post-IVT are recruited at hospitals in Australia, Chile, China, Malaysia, Mexico, UK, USA, and Vietnam. An average of 15 patients recruited per period (overall 60 patient participants) at 120 sites for a total of 7,200 IVT-treated AIS patients will provide 90% power (one-sided α 0.025). The initiation of eligible hospitals is based on a rolling process whenever ready, stratified by country. Hospitals are randomly allocated using permuted blocks into 3 sequences of implementation, stratified by country and the projected number of patients to be recruited over 12 months. These sequences have four periods that dictate the order in which they are to switch from control (usual care) to intervention (implementation of low intensity monitoring protocol) to different clusters of patients in a stepped manner. Compared to standard monitoring, the low-intensity monitoring protocol includes assessments of neurological and vital signs every 15 min for 2 h, 2 hourly (vs. every 30 min) for 8 h, and 4 hourly (vs. every 1 h) until 24 h, post-IVT. The primary outcome measure is functional recovery, defined by the modified Rankin scale (mRS) at 90 days, a seven-point ordinal scale (0 [no residual symptom] to 6 [death]). Secondary outcomes include death or dependency, length of hospital stay, and health-related quality of life, sICH, and serious adverse events. Conclusion: OPTIMISTmain will provide level I evidence for the safety and effectiveness of a low-intensity post-IVT monitoring protocol in patients with mild severity of AIS. [ABSTRACT FROM AUTHOR]

Background and objectives: In the era of personalized medicine, standard protocols regarding the management of acute ischemic stroke (AIS) focus on time targets alone without tailoring the protocol to the specific patient and hospital characteristics to increase IV thrombolysis rates and improve outcomes for these patients by considering organizational differences and patient-related factors that influence adherence to target times at the emergency department level. With this in mind, we evaluate the effect of achieving ED time targets from standard protocol and patient-related risk factors on the intravenous (IV) thrombolysis rate in patients with AIS in the therapeutic window. Materials and Methods: For our research, we enrolled people who arrived at the ED with signs of recent AIS with an onset of less than 4.5 h. Initially, 355 patients were included in the study, but through careful screening, only 258 were considered eligible to participate. Of the final group of 258 patients, only 46 received intravenous thrombolysis treatment. Results: In our study, when we are analyzing ED times in patients admitted with stroke symptoms in the therapeutic window, we found statistically significantly decreased ED times for patients that performed IV thrombolysis compared to patients not performing as follows: a median of 100 min in onset-to-ED door time (p < 0.001), a door-to-physician time (ED doctor) of 4 min (p = 0.009), door-to-blood-samples of 5 min (p = 0.026), a door-to-CT time of 15.5 min (p = 0.009), and door-to-CT results of 37 min (p < 0.001). In addition, patients who received intravenous thrombolysis were found to be significantly older (p < 0.001), with lower height and weight (p < 0.001 for both) and lower Glasgow Coma Scale (GCS) scores (9 ± 4.94 vs. 13.85 ± 2.41, p < 0.001). The logistic regression analysis indicated that the onset-to-ED time (p < 0.001) and the door-to-physician time (p = 0.014) for emergency medicine physicians are significant predictors of the likelihood of administering thrombolysis. By analyzing the impact of comorbidities, we observed that dyslipidemia, chronic arterial hypertension, and diabetes mellitus are significant predictive factors for performing IV thrombolysis (the presence of dyslipidemia and diabetes mellitus are predictive factors for performing IV thrombolysis, while the presence of arterial hypertension is not). Conclusions: The ED time targets that significantly influenced IV thrombolysis in our study were the onset-to-ED door time and the time it takes for the ED doctor to assess the AIS patient (door-to-physician time). The IV thrombolysis rate for these patients was 17.83%, lower than expected despite achieving most ED time targets, with the presence of chronic arterial hypertension as a significant predictive patient-related factor for not performing it. Even though our reported hospital's thrombolysis rate is favorable compared to international reports, there is always room for improvement. Based on our study results, it is necessary that new protocols to customized standard protocols and ED time targets for increasing IV thrombolysis rate in patients with AIS in the therapeutic window, focusing more on patient-related factors and type of hospitals, granting personalized medicine its right. Based on our study results, it is necessary that new protocols customize standard protocols and ED time targets for increasing IV thrombolysis rate in patients with AIS in the therapeutic window, focusing more on patient-related factors and type of hospitals, granting personalized medicine its right. [ABSTRACT FROM AUTHOR]

Patients undergoing transurethral resection of the prostate (TURP) surgery can develop TURP syndrome and post-TURP bleeding. Post-TURP bleeding can be surgical, from arteries or venous sinuses, or non-surgical, due to coagulopathy preventing clot formation. Non-surgical post-TURP bleeding may be due to high concentrations of urokinase and tissue plasminogen activator (tPA) in the urine that cause fibrinolytic changes and increase bleeding risk. Urine urokinase and tPA may have both local and systemic fibrinolytic effects that may prevent blood clot formation locally at the site of surgery, and cause fibrinolytic changes systemically through leaking into the blood stream. Another post-TURP complication that may happen is TURP syndrome, due to absorption of hypotonic glycine fluid through the prostatic venous plexus. TURP syndrome may present with hyponatremia, bradycardia, and hypotension, which may be preceded by hypertension. In this case report, we had a patient with benign prostatic hyperplasia (BPH) who developed both TURP syndrome and non-surgical post-TURP bleeding. These complications were transient for one day after surgery. The local effect of urine urokinase and tPA explains the non-surgical bleeding after TURP by preventing clot formation and inducing bleeding. Coagulation studies showed fibrinolytic changes that may be explained by urokinase and tPA leakage into the blood stream. In conclusion, non-surgical bleeding after TURP can be explained by the presence of fibrinolytic agents in the urine, including urokinase and tPA. There is a deficiency in existing studies explaining the pathophysiology of the fibrinolytic changes and risk of bleeding after TURP. Herein, we discuss the possible pathophysiology of developing fibrinolytic changes after TURP. More research effort should be directed to explore this area to investigate the appropriate medications to treat and prevent post-TURP bleeding. We suggest monitoring patients' coagulation profiles and electrolytes after TURP because of the risk of developing severe acute hyponatremia, TURP syndrome, fibrinolytic changes, and non-surgical bleeding. In our review of the literature, we discuss current clinical trials testing the use of an antifibrinolytic agent, Tranexamic acid, locally in the irrigation fluid or systemically to prevent post-TURP bleeding by antagonizing the fibrinolytic activity of urine urokinase and tPA. [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]

The hemojuvelin–hepcidin regulatory axis may play a key role in the iron metabolism both systemically and locally. There is a pressing need to evaluate this tightly regulated network of iron parameters and their potential impact on the development of ischemic stroke (IS). We aimed to assess iron metabolism biomarkers in patients after IS, evaluating changes over time and considering their clinical features. We studied 45 patients diagnosed with IS. We assessed major iron metabolism parameters, such as hepcidin, soluble hemojuvelin (sHJV), soluble transferrin receptor (sTfR), and ferritin, using immunoenzymathic methods at two time points: on admission and on the 7th day post IS. We found increased ferritin levels on the 7th day post IS compared to admission, and this was observed in the entire study group (p = 0.03) and in the subgroup treated with thrombolysis (p = 0.02). The hepcidin levels, on the other hand, showed a significant decrease on the 7th day, though this difference was only evident in the entire study group (p = 0.04). We also discovered significantly elevated sHJV levels in patients with PACI stroke compared to other stroke locations, both on admission and on the 7th day post IS (p < 0.05). Significantly higher sHJV levels were observed in patients treated with thrombolysis compared to those receiving conventional treatment, regardless of the time point (p < 0.0001 and p = 0.0002, respectively). Our study revealed changes in the iron metabolism parameters during stroke. The patients with anterior cerebral infarction and those treated with thrombolysis presented significantly elevated sHJV levels. [ABSTRACT FROM AUTHOR]

Background: There are no established patient selection criteria for endovascular thrombectomy (EVT) for anterior cerebral artery (ACA) stroke. Methods: This was a retrospective cohort study of the 2016–2020 National Inpatient Sample in the United States. Isolated ACA-occlusion stroke patients with moderate-to-severe stroke symptoms (NIH stroke scale [NIHSS] ≥ 6) were included. Primary outcome was hospital discharge to home with self-care. Secondary outcomes include in-hospital mortality and intracranial hemorrhage (ICH). Confounders were accounted for by multivariable logistic regression. Results: 6685 patients were included; 335 received EVT. Compared to medical management (MM), EVT patients were younger (mean 67.2 versus 72.2 years; p = 0.014) and had higher NIHSS (mean 16.0 versus 12.5; p < 0.001). EVT was numerically but not statistically significantly associated with higher odds of home discharge compared to MM (aOR 2.26 [95%CI 0.99–5.17], p = 0.053). EVT was significantly associated with higher odds of home discharge among patients with NIHSS 10 or greater (aOR 3.35 [95%CI 1.06–10.58], p = 0.039), those who did not receive prior thrombolysis (aOR 3.96 [95%CI 1.53–10.23], p = 0.005), and those with embolic stroke etiology (aOR 4.03 [95%CI 1.21–13.47], p = 0.024). EVT was not significantly associated with higher rates of mortality (aOR 1.93 [95%CI 0.80–4.63], p = 0.14); however, it was significantly associated with higher rates of ICH (22.4% vs. 8.5%, p < 0.001). Conclusion: EVT was associated with higher odds of favorable short-term outcomes for moderate-to-severe ACA-occlusion stroke in select patients. Future studies are needed to confirm the efficacy of EVT in terms of longer term neurological outcomes. [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 and purpose: A mobile stroke unit (MSU) reduces delays in stroke treatment by allowing thrombolysis on board and avoiding secondary transports. Due to the beneficial effect in comparison to conventional emergency medical services, current guidelines recommend regional evaluation of MSU implementation. Methods: In a descriptive study, current pathways of patients requiring a secondary transport for mechanical thrombectomy were reconstructed from individual patient records within a Danish (n = 122) and an adjacent German region (n = 80). Relevant timestamps included arrival times (on site, primary hospital, thrombectomy centre) as well as the initiation of acute therapy. An optimal MSU location for each region was determined. The resulting time saving was translated into averted disability‐adjusted life years (DALYs). Results: For each region, the optimal MSU location required a median driving time of 35 min to a stroke patient. Time savings in the German region (median [Q1; Q3]) were 7 min (−15; 31) for thrombolysis and 35 min (15; 61) for thrombectomy. In the Danish region, the corresponding time savings were 20 min (8; 30) and 43 min (25; 66). Assuming 28 thrombectomy cases and 52 thrombolysis cases this would translate to 9.4 averted DALYs per year justifying an annual net MSU budget of $0.8M purchasing power parity dollars (PPP‐$) in the German region. In the Danish region, the MSU would avert 17.7 DALYs, justifying an annual net budget of PPP‐$1.7M. Conclusion: The effects of an MSU can be calculated from individual patient pathways and reflect differences in the hospital infrastructure between Denmark and Germany. [ABSTRACT FROM AUTHOR]

Prompt identification of large vessel occlusion (LVO) in acute ischemic stroke (AIS) is crucial for expedited endovascular therapy (EVT) and improved patient outcomes. Prehospital stroke scales, such as the 3-Item Stroke Scale (3I-SS), could be beneficial in detecting LVO in suspected patients. This meta-analysis evaluates the diagnostic accuracy of 3I-SS for LVO detection in AIS. A systematic search was conducted in Medline, Embase, Scopus, and Web of Science databases until February 2024 with no time and language restrictions. Prehospital and in-hospital studies reporting diagnostic accuracy were included. Review articles, studies without reported 3I-SS cut-offs, and studies lacking the required data were excluded. Pooled effect sizes, including area under the curve (AUC), sensitivity, specificity, diagnostic odds ratio (DOR), positive and negative likelihood ratios (PLR and NLR) with 95% confidence intervals (CI) were calculated. Twenty-two studies were included in the present meta-analysis. A 3I-SS score of 2 or higher demonstrated sensitivity of 76% (95% CI: 52%–90%) and specificity of 74% (95% CI: 57%–86%) as the optimal cut-off, with an AUC of 0.81 (95% CI: 0.78–0.84). DOR, PLR, and NLR, were 9 (95% CI: 5–15), 2.9 (95% CI: 2.0–4.3) and 0.32 (95% CI: 0.17–0.61), respectively. Sensitivity analysis confirmed the analyses' robustness in suspected to stroke patients, anterior circulation LVO, assessment by paramedics, and pre-hospital settings. Meta-regression analyses pinpointed LVO definition (anterior circulation, posterior circulation) and patient setting (suspected stroke, confirmed stroke) as potential sources of heterogeneity. 3I-SS demonstrates good diagnostic accuracy in identifying LVO stroke and may be valuable in the prompt identification of patients for direct transfer to comprehensive stroke centers. [ABSTRACT FROM AUTHOR]

Purpose: Glial fibrillary acidic protein (GFAP) and neuroglobin (NGB) are important biomarkers of cerebral hypoxia. For this reason, an attempt was made to assess their concentrations in various time intervals and their impact on the severity of neurological symptoms and functional prognosis of thrombolytic ischemic stroke patients. Patients and Methods: The study involved 94 patients reporting to the emergency department of the Collegium Medicum University Hospital in Bydgoszcz within < 4.5 hours of the onset of stroke symptoms. GFAP and neuroglobin levels were measured in plasma at indicated times using a commercial ELISA kit. Results: Based on the data gathered, statistically significant differences were found between the concentration of biomarkers in stroke patients and the control group. The concentrations of both biomarkers, GFAP and NGB, were elevated in patients after ischemic stroke and the changes in their concentrations in the subsequent stages of stroke may suggest their prognostic value strictly dependent on time. NGB was determined on the 7th day, and mRS - after a year (0.35). GFAP measured after 24 h and on day 7 could be a promising biomarker of functional outcome after one year (cut-off point ≤ 0.231 ng/mL, sensitivity 75.0%, specificity 61.2%, cut off point ≤ 0.235 ng/mL, sensitivity 75.0%, specificity 73.9%, respectively) and the severity of the patient's neurological condition. At GFAP concentrations above 0.25 ng/mL, measured within 24 hours, a sharp increase in mortality was observed in stroke patients. In the case of NGB, at the time of stroke occurrence (14 ng/mL) and after 24 hours (10– 60 ng/mL). Differences in the concentrations of these biomarkers have been demonstrated in different stroke subtypes. Conclusion: NGB and GFAP are important biomarkers of ischemic brain injury and may also participate in predicting neurological outcomes. [ABSTRACT FROM AUTHOR]

Backgroud: Stroke is a cardiovascular disease classified as a catastrophic and has significant effects on society and the economy. According to data from the World Stroke Organization, 89% of stroke-related death and disabilities occur in low- and middle-income countries (WSO 2022). In Indonesia, stroke continues to be one of the leading causes of mortality and disability. Data from the Global Burden of Diseases Study (2019) and Riskesdas (2018) indicate that 65% of stroke sufferers have a risk of impairment and 15% have a chance of death. Purpose: This study aims to analyze management policies and implementation of acute ischemic stroke patient management in hospitals and evaluate inter-criteria with multi-criteria decision making. Design/methodology/approach: This research method uses a quantitative approach with a total of 15 respondents from 5 hospitals. Data analysis technique used is the Analytical Hierarchy Process (AHP). Finding/Result: The results of the study show that the effective factor has the highest weight (0.276) in improving thrombolysis therapy service (rt-PA) for acute ischemic stroke patients. Meanwhile, the alternative strategy that becomes the priority in this research is standardizing stroke protocols and pathways with a weight value of (0.275). The AHP processing results in private hospitals prioritizing effective factors or criteria as the main priority, and the alternative strategy in the form of standardizing stroke protocols and pathways becomes the first alternative priority strategy. In government hospitals, the AHP data factor or criteria prioritize tariff and time as the main priority, while the alternative strategy is the formation of a stroke team. The policy implications include tariff adjustments, awareness, and the establishment of standardized stroke protocols and clinical pathways, which also have a positive impact on the outcomes of stroke patients. Conclusion: In order to enhance thrombolysis therapy (rt-PA) services for patients with acute ischemic stroke, the most effective factor is the one with the maximum weight, which is (0.276). The alternative strategy that is the top priority in this study outcome is "standardization of stroke protocols and pathways" with a weighted value (0,275). Original/value (State of the art): In this study, analyze management policies, implement acute ischemic stroke patient treatment in hospitals, and assess the criteria using multi-criteria decision-making. Using 6 criteria: efficacy, feasibility, tariff, time, fairness, and acceptance. The multi-criteria combination and alternative strategies are assessed using AHP to determine the criteria that have the greatest influence on thrombolysis therapy recommendations, and the alternative strategy priority that can improve thrombolysis therapy services. [ABSTRACT FROM AUTHOR]

Left atrial appendage occlusion affects systemic coagulation parameters, leading to additional patient-related benefits. The aim of this study was to investigate the differences in coagulation factor changes 6 months after epicardial left atrial appendage occlusion in patients with different LAA morphometries. This is the first study to analyze these relationships in detail. A prospective study of 22 consecutive patients was performed. Plasminogen, fibrinogen, tPA concentration, PAI-1, TAFI and computed tomography angiograms were performed. Patients were divided into subgroups based on left atrial appendage body and orifice diameter enlargement. The results of blood tests at baseline and six-month follow-up were compared. In a population with normal LAA body size and normal orifice diameter size, a significant decrease in analyzed clotting factors was observed between baseline and follow-up for all parameters except plasminogen. A significant decrease between baseline and follow-up was observed with enlarged LAA body size in all parameters except TAFI, in which it was insignificant and plasminogen, in which a significant increase was observed. Occlusion of the left atrial appendage is beneficial for systemic coagulation. Patients with a small LAA may benefit more from LAA closure in terms of stabilizing their coagulation factors associated with potential thromboembolic events in the future.

Chutithep Teekaput,1,2,&ast; Chayasak Wantaneeyawong,1,2,&ast; Chaiwet Jakrachai,3 Sarocha Nuttawut,3 Soraya Nuttawut,3 Saranya Bowornsomboonkun,3 Kanokkarn Teekaput,1 Kitti Thiankhaw1,2 1Division of Neurology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 2The Northern Neuroscience Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 3Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand&ast;These authors contributed equally to this workCorrespondence: Kitti Thiankhaw, Division of Neurology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, 110, Inthawaroros Road, Sriphum, Chiang Mai, 50200, Thailand, Tel +66 (0) 5393 5899, Fax +66 (0) 5393 5481, Email kitti.th@cmu.ac.thPurpose: The association between the Alberta Stroke Programme Early CT Score (ASPECTS) and intracranial hemorrhage (ICH) in acute ischemic stroke (AIS) patients undergoing thrombolysis remains unclear. This study aimed to determine the relationship between ASPECTS and thrombolysis-associated outcomes, focusing on symptomatic (sICH) and asymptomatic (aICH) ICH.Patients and methods: AIS patients with middle cerebral artery (MCA) territory treated with thrombolysis were enrolled. Patients were categorized into favorable (8– 10) and unfavorable (7 or less) ASPECTS. The primary outcomes were sICH and aICH. Secondary outcomes included ICH management, modified Rankin Scale (mRS), and mortality. Multivariable logistic regression analysis evaluated the risk of unfavorable ASPECTS and its association with study outcomes.Results: We included 622 patients (mean age 66.1 ± 13.5 years; 50.5% male); 95 (15.3%) had unfavorable ASPECTS. Patients with unfavorable ASPECTS had higher sICH but not aICH (21.1% vs 4.9%, P < 0.001 and 16.9% vs 17.3%, P = 1.00). Unfavorable ASPECTS was associated with sICH (adjusted odds ratio 5.1; 95% confidence interval 2.7– 9.7, P < 0.001). Factors associated with lower ASPECTS included age ≥ 65 years, body weight < 60 kg, atrial fibrillation, onset-to-needle time ≥ 120 minutes, and anemia. Patients with lower ASPECTS had higher mortality and unfavorable mRS (> 2) at discharge, 14 days, and 90 days (74.7% vs 50.1%, P < 0.001 for 90-day mRS > 2).Conclusion: ASPECTS is a simple tool to predict thrombolysis-associated sICH but not aICH. Patients with unfavorable ASPECTS are at higher risk of complications and poor functional outcomes. Alternative treatments, such as mechanical thrombectomy, might be advisable for these patients.Keywords: ischemic stroke, intracranial hemorrhage, thrombolysis, outcome, neuroimaging, ASPECTS

Abstract Background Pulmonary intravascular thrombus formation has been widely observed in patients with respiratory failure, for example, in patients with SARS-CoV-2 infection (COVID-19). The aim of this study was to evaluate the efficacy/safety of alteplase thrombolysis in COVID-19 severe hypoxemic respiratory failure. In this multicenter, open-label study, patients were randomized to receive alteplase (low- or high-dose) over 5 days plus standard of care (SOC), or SOC alone. The primary endpoint was time to clinical improvement (≥ 2-point decrease on WHO Clinical Progression Scale, or hospital discharge) up to Day 28. Secondary endpoints included all-cause mortality at Day 28, treatment failure at Day 28 and change in arterial oxygen partial pressure/fractional inspired oxygen (PaO2/FiO2) ratio at Day 6 versus baseline. Results Sixty-nine patients were randomized to alteplase (low- or high-dose) and 35 to SOC; 65% were on high-flow oxygen or non-invasive ventilation at baseline. Median time to clinical improvement was 25 days in the alteplase group and > 28 days (median not reached) in the SOC group. All-cause mortality was 8/69 (12%) versus 10/35 (29%) in the alteplase versus SOC groups, respectively (unadjusted risk difference [RD], − 17% [95% confidence interval (CI) − 34 to 0], p = 0.047; adjusted RD, − 16% [95% CI − 31 to 1], p = 0.058). The PaO2/FiO2 ratio (mean [standard deviation]) increased by + 30 (84) mmHg in the alteplase group and decreased by − 12 (59) mmHg in the SOC group (adjusted mean difference vs. SOC, p = 0.052). Differences were greater in patients receiving high-dose alteplase, and in those not receiving invasive ventilation. Eighteen patients (26.1%) in the alteplase group discontinued treatment due to adverse events. Major bleeding was more frequent with alteplase than with SOC (9 vs. 0 patients); no bleeding was fatal. The study closed early due to insufficient patient recruitment. Conclusion Alteplase was not associated with faster clinical recovery from COVID-19 severe hypoxemic respiratory failure. A numerical difference in survival and PaO2/FiO2 ratio was observed, particularly in patients not receiving invasive ventilation. These exploratory findings merit further investigation in larger patient cohorts that are adequately powered to confirm the hypotheses generated in this study regarding the impact of alteplase on treatment outcomes. Trial registration ClinicalTrials.gov: NCT04640194 (November 23, 2020); https://clinicaltrials.gov/study/NCT04640194 (early discontinuation due to insufficient patient recruitment).

Catastrophic spontaneous spinal epidural hematoma (SSEH) following thrombolysis poses a complex intersection of neurosurgical and cardiological challenges. This case report presents the institutional experience of a 66-year-old female who developed rapid-onset compressive myelopathy after thrombolysis for inferior wall myocardial infarction with injection streptokinase. SSEH, although rare, demands prompt recognition due to its potential for permanent neurologic injury and mortality. The discussion highlights the clinical significance, anatomical considerations, and multidisciplinary approach requisite for accurate diagnosis and effective management of SSEH. The conclusion underscores the necessity for clinicians, particularly cardiologists administering thrombolytic therapies, to consider SSEH in postthrombolysis patients presenting with neurological deficits.

Background and Purpose Tenecteplase is a thrombolytic agent with pharmacological advantages over alteplase and has been shown to be noninferior to alteplase for acute ischemic stroke in randomized trials. However, evidence pertaining to the safety and efficacy of tenecteplase in patients from different ethnic groups is lacking. The aim of this systematic review and metaanalysis was to investigate ethnicity-specific differences in the safety and efficacy of tenecteplase versus alteplase in patients with acute ischemic stroke. Methods Following an International Prospective Register of Systematic Reviews (PROSPERO)- registered protocol (CRD42023475038), three authors conducted a systematic review of the PubMed/MEDLINE, Embase, Cochrane Library, and CINAHL databases for articles comparing the use of tenecteplase with any thrombolytic agent in patients with acute ischemic stroke up to November 20, 2023. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Two independent authors extracted data onto a standardized data collection sheet. A pairwise meta-analysis was conducted in risk ratios (RR). Results From 34 studies (59,601 participants), the rate of complete recanalization was significantly higher (P

Background: The incidence of Non communicable diseases (NCDs) including stroke is increasing in India over the past few years. Thrombolysis therapy has revolutionized management of acute ischemic stroke. In spite of such recent advances in stroke therapy, the public remains uninformed about stroke symptoms and management. Objective: To assess the public awareness of stroke risk factors, symptoms, treatment and rehabilitation measures. Methods: The study was a community-based cross-sectional study, designed as an online survey. The tool used for the survey was a semi-structured online questionnaire. Results: Regarding the risk factors of stroke, of the participants, 41 (14.8%) were aware of valvular heart diseases, 18 (6.5%) of lack of exercise, 238 (85.9%) of dyslipedemia, 236 (85.2%) of hypertension, 222 (80.1%) of smoking, and 154 (55.6%) of diabetes. Regarding symptoms of stroke, of the participants, 209 (75.5%) were aware of loss of balance, 240 (86.6%) of speech abnormalities, 261 (94.2%) of facial weakness, and 234 (84.5%) of weakness. Conclusion: Efforts should be made to educate the public regarding uncommon symptoms of stroke, thrombolysis treatment and rehabilitation measures, so that people make beneficial health care decisions in stroke management.

BACKGROUND: We hypothesized that treatment delays might be an effect modifier regarding risks and benefits of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT). METHODS: We used the dataset of the SWIFT-DIRECT trial, which randomized 408 patients to IVT+MT or MT alone. Potential interactions between assignment to IVT+MT and expected time from onset-to-needle (OTN) as well as expected time from door-to-needle (DTN) were included in regression models. The primary outcome was functional independence (modified Rankin Scale (mRS) 0-2) at 3 months. Secondary outcomes included mRS shift, mortality, recanalization rates, and (symptomatic) intracranial hemorrhage at 24 hours. RESULTS: We included 408 patients (IVT+MT 207, MT 201, median age 72 years (IQR 64-81), 209 (51.2%) female). The expected median OTN and DTN were 142 min and 54 min in the IVT+MT group and 129 min and 51 min in the MT alone group. Overall, there was no significant interaction between OTN and bridging IVT assignment regarding either the functional (adjusted OR (aOR) 0.76, 95% CI 0.45 to 1.30) and safety outcomes or the recanalization rates. Analysis of in-hospital delays showed no significant interaction between DTN and bridging IVT assignment regarding the dichotomized functional outcome (aOR 0.48, 95% CI 0.14 to 1.62), but the shift and mortality analyses suggested a greater benefit of IVT when in-hospital delays were short. CONCLUSIONS: We found no evidence that the effect of bridging IVT on functional independence is modified by overall or in-hospital treatment delays. Considering its low power, this subgroup analysis could have missed a clinically important effect, and exploratory analysis of secondary clinical outcomes indicated a potentially favorable effect of IVT with shorter in-hospital delays. Heterogeneity of the IVT effect size before MT should be further analyzed in individual patient meta-analysis of comparable trials. TRIAL REGISTRATION NUMBER: URL: https://www. CLINICALTRIALS: gov ; Unique identifier: NCT03192332.

Background: Stroke is a major global health concern, ranking second in terms of fatality worldwide, following ischaemic heart disease. However, few stroke patients arrive at the hospital within the optimal time for thrombolysis, and even among those who do, not all receive this therapy. Therefore, the objective of the study was to examine the factors that influence the treatment of acute ischaemic stroke (AIS), particularly with intravenous thrombolysis and to evaluate the short-term outcomes. Methods: This prospective observational study was carried out between August 2019 and August 2021 in the emergency department of a tertiary care hospital. Patients with AIS who were eligible for intravenous thrombolysis within 4.5 hours of the beginning of symptoms were included in the study. Comprehensive assessments, including history, examinations and blood investigations, were conducted. Thrombolytic treatment was administered within the specified time frame, while antiplatelets were given in other cases. Follow-up evaluations were conducted at discharge and 90 days. Results: The age distribution, comorbidities and CT-MRI findings were similar between individuals who received thrombolysis and those who did not. Among the thrombolysis group, 84% had no complications, while 8% experienced intracerebral haemorrhage and 8% had an extension of the infarction. The overall mortality rate was 13.33% for non-thrombolysis patients and 12% for thrombolysis recipients, with no statistically significant difference between the two groups. Conclusion: The results highlight the need for careful consideration when deciding to use thrombolysis for AIS cases. Additionally, they emphasise the importance of actively monitoring and effectively managing any potential treatment complications. [ABSTRACT FROM AUTHOR]

The administration of intravenous thrombolysis (IVT) for patients with acute ischemic stroke who have recently ingested direct oral anticoagulants (DOACs) presents a clinical challenge due to the perceived increased risk of intracranial hemorrhage (ICH). Traditional guidelines from the US and European authorities advise against IVT within 48 h of last DOAC ingestion, unless specific coagulation tests indicate safety. However, emerging observational studies suggest that IVT might be safe in selected patients. A US stroke registry study and a global multicenter cohort study both reported no significant increase in symptomatic ICH among patients on DOACs compared to those not on anticoagulants. A systematic review of all published observational studies further supported these findings, showing comparable bleeding rates and functional outcomes in DOAC-treated patients. Reversal agents like idarucizumab for dabigatran have demonstrated potential in facilitating safer IVT administration, though logistical and cost-related barriers limit their widespread use. The variability in global guidelines reflects differing approaches to risk assessment and resource availability, highlighting the need for individualized treatment decisions. In India, the increasing prevalence of atrial fibrillation and stroke as well as prescription of DOACs necessitate adapted guidelines that consider local health-care infrastructure. Despite the promising observational data, the lack of randomized controlled trials underscores the need for further research to establish robust evidence for IVT use in this context. Collaborative international efforts and inclusion of diverse patient populations in future studies will be crucial to refine treatment protocols and improve outcomes for stroke patients on DOACs.

Ruiming Wang, Weiguo Kong, Wenhua Zhang Department of Neurology, Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, People’s Republic of ChinaCorrespondence: Wenhua Zhang, Department of Neurology, Hangzhou Traditional Chinese Medicine Hospital affiliated to Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China, Tel +86-571-85827888, Fax +86-571-85119481, Email zwhzxpz@hotmail.comObjective: This study aimed to explore the relationship between serum lipoprotein(a) (LP(a)) levels and early neurological deterioration (END) in patients with acute ischemic stroke (AIS) after thrombolysis.Methods: In total, 236 patients with AIS after thrombolysis were enrolled in this study. Serum LP(a) levels were measured on admission after thrombolysis. END was defined as an increase of at least two points in the NIHSS score within 48 hours after thrombolysis. Binary logistic regression analysis was used to assess the association between serum LP(a) levels and END.Results: Overall, patients with END had higher LP(a) than those without END (high LP(a): 38.3% vs 22.2%, intermediate LP(a): 40.3% vs 41.8%, low LP(a): 21.3% vs 36.0%, p< 0.005). In the multivariate analysis, high LP(a) (defined as LP(a) level≥ 300 mg/L) was an independent risk factor for END post-thrombolysis (OR=3.154, 95% CI=1.067– 9.322, p=0.038).Conclusion: Our findings demonstrated that LP(a) was an independent risk factor for END post-thrombolysis and that LP(a) level≥ 300 mg/L could be associated with END post-thrombolysis in this study population.Keywords: Lipoprotein(a), early neurological deterioration, acute ischemic stroke, thrombolysis

Yufeng Yao,1,2 Qiyuan Song,3 Jingnan Zhang,2,4 Yingying Wen,2,4 Xiaoyan Dou2 1Shantou University Medical College, Shantou, Guangdong Province, People’s Republic of China; 2Department of Ophthalmology, Shenzhen Second People’s Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong Province, People’s Republic of China; 3Department of Ophthalmology, Shenzhen Children’s Hospital, Shenzhen, Guangdong Province, People’s Republic of China; 4Shenzhen University Medical College, No.1066 Xueyuan Road, Shenzhen University, Shenzhen, Guangdong Province, People’s Republic of ChinaCorrespondence: Xiaoyan Dou, Email douxy08@163.comAbstract: The retina’s similar structure and function to the brain make it a unique visual “window” for studying cerebral disorders. Ophthalmic artery occlusion (OAO) or retinal artery occlusion (RAO) is a severe ophthalmic emergency that significantly affects visual acuity. Studies have demonstrated that patients with OAO or RAO face a notably higher risk of future acute ischemic stroke (AIS). However, ophthalmologists often overlook multidisciplinary approach involving the neurologist, to evaluate the risk of AIS and devise clinical treatment strategies for patients with OAO or RAO. Unlike the successful use of thrombolysis in AIS, the application of thrombolysis for OAO or RAO remains limited and controversial due to insufficient reliable evidence. In this review, we aim to summarize the anatomical and functional connections between the retina and the brain, and the clinical connection between OAO or RAO and AIS, compare and review recent advances in the effectiveness and safety of intravenous and intra-arterial thrombolysis therapy in patients with OAO or RAO, and discuss future research directions for OAO or RAO. Our goal is to advance the development of multidisciplinary diagnosis and treatment strategies for the disease, as well as to establish expedited pathways or thrombolysis guidelines for vascular intervention.Keywords: retina, brain, ophthalmic artery occlusion, retinal artery occlusion, stroke, thrombolysis

Abstract Thrombotic cardiovascular diseases are a prevalent factor contributing to both physical impairment and mortality. Thrombolysis and ischemic mitigation have emerged as leading contemporary therapeutic approaches for addressing the consequences of ischemic injury and reperfusion damage. Herein, an innovative cellular-cloaked spermatozoon-driven microcellular submarine (SPCS), comprised of multimodal motifs, was designed to integrate nano-assembly thrombolytics with an immunomodulatory ability derived from innate magnetic hyperthermia. Rheotaxis-based navigation was utilized to home to and cross the clot barrier, and finally accumulate in ischemic vascular organs, where the thrombolytic motif was “switched-on” by the action of thrombus magnetic red blood cell-driven magnetic hyperthermia. In a murine model, the SPCS system combining innate magnetic hyperthermia demonstrated the capacity to augment delivery efficacy, produce nanotherapeutic outcomes, exhibit potent thrombolytic activity, and ameliorate ischemic tissue damage. These findings underscore the multifaceted potential of our designed approach, offering both thrombolytic and ischemia-mitigating effects. Given its extended therapeutic effects and thrombus-targeting capability, this biocompatible SPCS system holds promise as an innovative therapeutic agent for enhancing efficacy and preventing risks after managing thrombosis. Graphical abstract

Obstructive sleep apnea (OSA) is a common sleep disordered breathing in stroke patients. This case report aimed to show the presence of OSA in stroke can contribute to the increasing chance of mortality and morbidity. We presented a case of first-time stroke in a 64-year-old female with a history of pre-stroke OSA. She underwent intravenous thrombolysis as main therapy within the time limit under 4.5 hours since the stroke onset. She had prolonged hospital stay due to complications from OSA, even though she only had a small ischemic core (9 mL) in follow-up radiological imaging and was discharged with a greater National Institutes of Health Stroke Scale (NIHSS) score than admission (5 to 10). OSA can be one of warning signs for poor prognosis in stroke patients. Understanding the presence of OSA not only can be beneficial toward choosing the next steps of therapy, but also important for the rehabilitation and recovery period of stroke patients.

Abstract Background and purpose Cerebrovascular events during thrombolysis in cardiac arrest (CA) caused by pulmonary embolism (PE) is a life-threatening condition. However, the balance between cerebrovascular events and thrombolytic therapy in PE-induced CA remains a great challenge. Methods In this study, we reported three unique cases regarding main concerns surrounding cerebrovascular events in thrombolytic therapy in PE-induced CA. Results The patient in the case 1 treated with thrombolysis during CPR and finally discharged neurologically intact. The patient in the case 2 received delayed thrombolysis and died eventually. The patient in the case 3 was contraindicated to thrombolysis due to the complication of subarachioid hemorrahage and died within days. Conclusions Our case series highlights three proposed approaches to consider before administering thrombolysis as a treatment option in PE-induced CA patients: (1) prolonging the resuscitation, (2) administering thrombolysis promptly, and (3) ruling out cerebrovascular events.

Introduction: The Hub-and-Spoke stroke system seeks to enhance the efficiency of stroke care by establishing a cohesive network between healthcare facilities providing quality stroke care to patients. This study endeavors to evaluate the effectiveness and characterize the outcomes of acute ischemic stroke patients treated within the Hub-and-Spoke hospital system over 2 years. The assessment focused on thrombolysis rates, mortality, and disability at 3-month follow-up. Methods: We conducted a retrospective single-center review to assess the service delivery and outcomes of acute ischemic stroke patients within the Hub-and-Spoke framework which was implemented in Q3 2021. The Hub-and-Spoke model aimed to provide appropriate neurological care for stroke patients, growing from four to eight spoke hospitals in 2 years. Results: The study consisted of 132 stroke patients transferred to the hub hospital, and 42 (31.8%) of them had acute ischemic stroke. Among these 42 ischemic stroke patients, 76% of them were candidates for thrombolysis with a mean NIHSS of 12 (6–22). Among the subset of 32 patients eligible for intervention within the specified time window, a total of 23 individuals, constituting 72% received r-TPA. Regarding patients administered r-TPA, 91.2% demonstrated favorable functional outcomes with an mRS score of 0–1, while 8.7% exhibited a score of 2–3. Among those not given r-TPA, the mean NIHSS was 17 (ranging from 2 to 32). Their functional outcomes after 3 months revealed 52.5% with an mRS score of 0–1, 16% with a score of 2–3, 21.2% with a score of 4–5, and 10.5% with an mRS score of 6. Conclusion: Hub-and-Spoke networks represent a crucial advancement in stroke treatment, particularly for facilities lacking the capacity to manage strokes effectively. By leveraging added expertise and reducing the time from onset to diagnosis to treatment, these networks have significantly enhanced patient care. This enhancement is particularly evident in the increased rate of thrombolysis, resulting in reduced morbidity and prevention of mortality.

Abstract Cardiovascular diseases (CVDs), mainly caused by thrombosis complications, are the leading cause of mortality worldwide, making the development of alternative treatments highly desirable. In this study, the thrombolytic potential of green kiwifruit (Actinidia deliciosa cultivar Hayward) was assessed using in-vitro and in-silico approaches. The crude green kiwifruit extract demonstrated the ability to reduce blood clots significantly by 73.0 ± 1.12% (P

Abstract **Ischemic stroke remains a leading cause of morbidity and mortality globally. Despite the advances in thrombolytic therapy, notably recombinant tissue plasminogen activator (rtPA), patient outcomes are highly variable. This study aims to introduce a novel predictive model, the Acute Stroke Thrombolysis Non-Responder Prediction Model (ASTN-RPM), to identify patients unlikely to benefit from rtPA within the critical early recovery window. We conducted a retrospective cohort study at Baoding No.1 Central Hospital including 709 adult patients diagnosed with acute ischemic stroke and treated with intravenous alteplase within the therapeutic time window. The ASTN-RPM was developed using Least Absolute Shrinkage and Selection Operator (LASSO) regression technique, incorporating a wide range of biomarkers and clinical parameters. Model performance was evaluated using Receiver Operating Characteristic (ROC) curves, calibration plots, and Decision Curve Analysis (DCA). ASTN-RPM effectively identified patients at high risk of poor response to thrombolysis, with an AUC of 0.909 in the training set and 0.872 in the validation set, indicating high sensitivity and specificity. Key predictors included posterior circulation stroke, high admission NIHSS scores, extended door to needle time, and certain laboratory parameters like homocysteine levels. The ASTN-RPM stands as a potential tool for refining clinical decision-making in ischemic stroke management. By anticipating thrombolytic non-response, clinicians can personalize treatment strategies, possibly improving patient outcomes and reducing the burden of ineffective interventions. Future studies are needed for external validation and to explore the incorporation of emerging biomarkers and imaging data.