Thrombotic microenvironment responsive crosslinking cyclodextrin metal-organic framework nanocarriers for precise targeting and thrombolysis.

Global public health is seriously threatened by thrombotic disorders because of their high rates of mortality and disability. Most thrombolytic agents, especially protein-based pharmaceuticals, have a short half-life in circulation, reducing their effectiveness in thrombolysis. The creation of an intelligent drug delivery system that delivers medication precisely and releases it under regulated conditions at nearby thrombus sites is essential for effective thrombolysis. In this article, we present a unique medication delivery system (MCRUA) that selectively targets platelets and releases drugs by stimulation from the thrombus' microenvironment. The thrombolytic enzyme urokinase-type plasminogen-activator (uPA) and the anti-inflammatory medication Aspirin (acetylsalicylic acid, ASA) are both loaded onto pH-sensitive CaCO3/cyclodextrin crosslinking metal-organic frameworks (MC) that make up the MCRUA system. c(RGD) is functionalized on the surface of MC, which is functionalized by RGD to an esterification reaction. Additionally, the thrombus site's acidic microenvironment causes MCRUA to disintegrate to release uPA for thrombolysis and aiding in vessel recanalization. Moreover, cyclodextrin-encapsulated ASA enables the treatment of the inflammatory environment within the thrombus, enhancing the antiplatelet aggregation effects and promoting cooperative thrombolysis therapy. When used for thrombotic disorders, our drug delivery system (MCRUA) promotes thrombolysis, suppresses rethrombosis, and enhances biosafety with fewer hemorrhagic side effects.

A microthrombus-driven fixed-point cleaved nanosystem for preventing post-thrombolysis recurrence via inhibiting ferroptosis.

Thrombus-induced cardiovascular diseases threaten human health. Current treatment strategies often rely on urokinase plasminogen activator (uPA) for its efficacy, yet it has such limiting factors as short half-life, lack of thrombus targeting, and systemic side effects leading to unintended bleeding. In addition, thrombolytic interventions can trigger inflammation-induced damage at thrombus sites, which affects endothelial function. To address these challenges, Fer-1/uPA@pep-CREKA-Lipo (Fu@pep-CLipo) has been developed. This system achieves precise and efficient thrombolysis while enhancing the thrombus microenvironment and mitigating ischemia-reperfusion injury, with exceptional thrombus targeting ability via the strong affinity of the Cys-Arg-Glu-Lys-Ala (CREKA) peptide for fibrin. The Cys-Nle-TPRSFL-DSPE (pep) could respond to the thrombus microenvironment and fixed-point cleavage. The uPA component linked to the liposome surface is strategically cleaved upon exposure to abundant thrombin at thrombus sites. Importantly, the inclusion of Fer-1 within Fu@pep-CLipo contributes to reactive oxygen species (ROS) scavenging and significantly improves the thrombus microenvironment. This innovative approach not only achieves highly efficient and precise thrombolysis but also positively influences the expression of eNOS protein while suppressing inflammatory factors like TNF-α and IL-6. This dual action contributes to improved thrombus inflammatory microenvironment and mitigated ischemia-reperfusion injury.

Urokinase in the treatment of tuberculous pleurisy: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy of urokinase (UK) treatment for tuberculous pleural effusion (TPE). METHODS: We searched Chinese biomedical literature database, WanFang data, CNKI, PubMed, EMbase, Web of Science and The Cochrane Library for the randomized controlled trials (RCTs) of urokinase treatment for tuberculous pleurisy from January 2000 to February 2023. Pleural tuberculosis, urokinase and randomized controlled trial were used as keywords. The eligible studies were meta-analyzed by using Revman 5.4.1: risk of bias was assessed, mean difference (MD) and 95% CI were used for continuous variables, pooled studies were conducted using random-effects or fixed-effects models, forest plots were drawn to analyze efficacy, and funnel plots were drawn to discuss publication bias. RESULTS: Twenty-nine RCTs were included. The meta-analyzed results showed that, on the basis of routine anti-tuberculosis, comparison between the treatment group treated with urokinase and the control group treated with antituberculosis alone, the time of pleural effusion absorption [MD-5.82, 95%CI (- 7.77, - 3.87); P<0.00001] and the residual pleural thickness [MD-1.31, 95%CI (- 1.70, - 0.91); P<0.00001], pleural effusion drainage volume [MD 822.81, 95%CI (666.46,977.96); P<0.00001], FVC%pred [MD 7.95, 95%CI (4.51,11.40); P<0.00001], FEV1%pred [MD 12.67, 95%CI (10.09,15.24); P<0.00001] were significantly different. CONCLUSION: The clinical effect of urokinase is better than that of antituberculous therapy alone: it can increase total pleural effusion, decrease residual pleural thickness, improve the pulmonary function, and shorten the time of pleural effusion absorption.

Urokinase prophylactic anticoagulation in children with nephrotic syndrome: a multicenter retrospective cohort study.

OBJECTIVE: To analyze the clinical effect of urokinase on the prevention of thrombosis in children with primary nephrotic syndrome. METHODS: A total of 370 children diagnosed with primary nephrotic syndrome (PNS) in the Children's Hospital of Soochow University and Zibo Maternal and Child Health Hospital from January 2018 to December 2022 were selected as the research objects. The patients were divided into a urokinase adjuvant therapy group and non-urokinase adjuvant therapy group according to the application of drugs. The clinical data of the children were collected, including sex, age, drug application, bleeding during treatment, and telephone follow-up, to record whether thromboembolism occurred in the acute stage and remission stage. The clinical pattern of PNS, renal biopsy, histopathological type, and related laboratory indexes before and after treatment were recorded. RESULTS: A total of 313 patients were treated with urokinase and 57 patients were not. More thrombotic events was observed in non-urokinase group compared to the urokinase group(2 versus 0 episodes, p = 0.02). The thrombotic events observed included one patient had pulmonary embolism combined with right ventricular thrombosis, and another had intracranial venous thrombosis. More minor bleeding events occurred in urokinase group compared to the non-urokinase group(7 versus 1 episodes, p = 1.0). No major bleeding events occurred in either group. CONCLUSION: The rational prophylactic use of urokinase anticoagulation in children with PNS can prevent the formation of thromboembolism and has good safety.

Minimally invasive puncture combined with a high frequency of urokinase therapy improves outcomes in patients with HICH.

Minimally invasive puncture combined with urokinase is widely used in the treatment of hypertensive intracerebral hemorrhage (HICH). However, the appropriate frequency of urokinase following minimally invasive puncture in patients is still unclear. In total, 55 patients were enrolled in this study. According to the frequency of urokinase (10.0 â€‹× â€‹104 units) administration, 30 patients received urokinase at Q4h, while the other 25 patients received urokinase at Q8h. In the univariate analysis, preoperative GCS (p â€‹= â€‹0.0002), postoperative GCS (p â€‹= â€‹0.0007), the volume of residual hematoma (p â€‹= â€‹0.0179), and the frequency of urokinase (p â€‹= â€‹0.0110) were associated with unfavorable outcomes in patients with HICH in the basal ganglia. The multivariate analysis revealed that the frequency of urokinase was independently associated with unfavorable outcomes in patients with HICH in the basal ganglia (p â€‹= â€‹0.038, 1.109-35.380). The drainage time was significantly shorter in the Q4h group (14.17 â€‹± â€‹0.86 â€‹h) than in the Q8h group (27.36 â€‹± â€‹1.39 â€‹h) (p â€‹< â€‹0.0001). The GOS (4.37 â€‹± â€‹0.18), BI (75.52 â€‹± â€‹2.39), and mRS (1.67 â€‹± â€‹0.24) in the Q4h group were significantly ameliorated compared to those in the Q8h group (GOS 3.56 â€‹± â€‹0.18, BI 64.13 â€‹± â€‹2.22, and mRS 2.64 â€‹± â€‹0.28, respectively) (p â€‹= â€‹0.0004, p â€‹= â€‹0.0002, and p â€‹= â€‹0.0018) at 3 months of follow-up. Thus, minimally invasive puncture combined with urokinase is safe and efficient. Increasing the frequency of urokinase administration can produce faster and better postoperative recovery for patients with HICH in the basal ganglia.

Continuous intrafemoral artery infusion of urokinase improves diabetic foot ulcers healing and decreases cardiovascular events in a long-term follow-up study.

INTRODUCTION: Diabetic foot ulcer (DFU) is a disabling complication of diabetes mellitus. Here, we attempted to assess whether long-term intrafemoral artery infusion of low-dose urokinase therapy improved DFUs and decreased cardiovascular events in patients with DFUs. RESEARCH DESIGN AND METHODS: This trial was a single-center, randomized, parallel study. A total of 195 patients with DFU were randomized to continuous intrafemoral thrombolysis or conventional therapy groups. The continuous intrafemoral thrombolysis group received continuous intrafemoral urokinase injection for 7 days, and conventional therapy just received wound debridement and dressing change. Then, a follow-up of average 6.5 years was performed. RESULTS: Compared with conventional therapy, at the first 1 month of intervention stage, the ulcers achieved a significant improvement in continuous intrafemoral thrombolysis group including a complete closure (72.4% vs 17.5%), an improved ulcer (27.6% vs 25.8%), unchanged or impaired ulcer (0% vs 56.7%). During the 6.5-year follow-up, for the primary outcome of ulcer closure rate, continuous intrafemoral thrombolysis therapy obtained a better complete healing rate (HR 3.42 (95% CI 2.35 to 4.98, p<0.0001)). For the secondary outcome of cardiovascular disease events, continuous intrafemoral thrombolysis therapy had a lower incidence of cardiovascular events (HR 0.50 (95% CI 0.34 to 0.74, p<0.0001)). Importantly, intrafemoral thrombolysis therapy decreased the incidence of cardiovascular death (HR 0.42 (95%CI 0.20 to 0.89, p=0.0241)). Additionally, continuous intrafemoral thrombolysis therapy improved local skin oxygenation and peripheral neuropathy as well as glycolipid metabolic profiles when compared with conventional therapy group (p<0.05). CONCLUSIONS: Continuous intrafemoral thrombolysis therapy has a better therapeutic efficacy to improve DFUs and decrease cardiovascular events. TRIAL REGISTRATION NUMBER: NCT01108120.

Effect of Intrathecal Urokinase Infusion on Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Vasospasm following an aneurysmal subarachnoid hemorrhage (SAH) causes serious neurological complications, despite surgical clipping of the aneurysm. Intrathecal urokinase (UK) infusion has been shown to effectively prevent symptomatic vasospasm in patients who have undergone endovascular obliteration of the ruptured aneurysms. OBJECTIVE: To investigate whether intrathecal UK infusion can prevent symptomatic vasospasm in patients undergoing surgical or endovascular treatment. METHODS: A total of 90 patients with severe aneurysmal SAH were enrolled and assigned to a surgical neck clipping (n = 56) or an endovascular coil embolization (n = 34) groups. After treatment, UK infusion from the lumbar drain was repeated in 32 patients in the surgical neck clipping group (group B) and all in the endovascular coil embolization group (group C) until complete resolution of the SAH was observed on computed tomography. The remaining 24 of the surgical neck clipping group, without UK infusion, were assigned to group A. RESULTS: Symptomatic vasospasm occurred in 7 (29.2%) patients in group A, 2 (6.3%) in group B, and none in group C (group A vs. group B [P = 0.02]; group B vs. group C [P = 0.14]). Excellent clinical outcomes (modified Rankin score, 0 or 1) were observed in 37.5%, 59.4%, and 76.5% of patients in group A, B, and C, respectively (group A vs. group B [P = 0.11]). CONCLUSION: Clearance of SAH via intrathecal UK infusion significantly reduced symptomatic vasospasm in patients in both UK groups, resulting in better clinical outcomes.

Rational peptide design for targeting cancer cell invasion.

Cell invasion is an important process in cancer progression and recurrence. Invasion and implantation of cancer cells from their original place to other tissues, by disabling vital organs, challenges the treatment of cancer patients. Given the importance of the matter, many molecular treatments have been developed to inhibit cancer cell invasion. Because of their low production cost and ease of production, peptides are valuable therapeutic molecules for inhibiting cancer cell invasion. In recent years, advances in the field of computational biology have facilitated the design of anti-cancer peptides. In our investigation, using computational biology approaches such as evolutionary analysis, residue scanning, protein-peptide interaction analysis, molecular dynamics, and free energy analysis, our team designed a peptide library with about 100 000 candidates based on A6 (acetyl-KPSSPPEE-amino) sequence which is an anti-invasion peptide. During computational studies, two of the designed peptides that give the highest scores and showed the greatest sequence similarity to A6 were entered into the experimental analysis workflow for further analysis. In experimental analysis steps, the anti-metastatic potency and other therapeutic effects of designed peptides were evaluated using MTT assay, RT-qPCR, zymography analysis, and invasion assay. Our study disclosed that the IK1 (acetyl-RPSFPPEE-amino) peptide, like A6, has great potency to inhibit the invasion of cancer cells.

Fiberoptic bronchoscopy combined with urokinase therapy for the treatment of fatal massive hemoptysis: A case report.

BACKGROUND: Fatal massive hemoptysis is a life-threatening emergency in the respiratory system. Currently, the treatment methods and techniques for massive hemoptysis are still limited, and there are often issues of delayed treatment or improper methods in clinical practice, leading to the difficulty of rescuing patients and high mortality rates. When fatal massive hemoptysis occurs, the key to successful treatment lies in whether intrapulmonary blood clots can be effectively cleared and airway patency can be ensured. Our practice of combining fiberoptic bronchoscopy with urokinase treatment to clear intrapulmonary blood clots after fatal massive hemoptysis demonstrates the effectiveness of this method. CASE SUMMARY: We report a 32-year-old female who experienced cough, accompanied by fatal massive hemoptysis with extensive blood clot obstruction in the airway. Considering the difficulty of clearing the airway using conventional methods, it was decided to perform fiberoptic bronchoscopy combined with urokinase therapy after reviewing relevant literature. After treatment, the intrapulmonary blood clots were successfully extracted, thereby relieving airway obstruction. Finally, the patient was successfully weaned off extracorporeal membrane oxygenation, extubated, and evacuated from the ventilator. Currently, the patient's condition is stable, and follow-up chest X-ray as well as computed tomography scans have shown improvement compared to previous assessments. CONCLUSION: Fatal massive hemoptysis is a intractable emergency in clinical practice. In this case, we confirmed that fiberoptic bronchoscopy combined with urokinase therapy may be effective and safe in the treatment of fatal massive hemoptysis.

Urokinase administration for intraventricular hemorrhage in adults: A retrospective analysis of hemorrhage volume reduction and clinical outcomes.

BACKGROUND: Intraventricular hemorrhage (IVH) is a type of ventricular bleeding that results in significant morbidity and mortality. Multiple studies have investigated the use of urokinase in IVH treatment. The use of urokinase may lead to higher rates of hematoma resolution and lower mortality rates. However, further studies are required to determine efficacy of urokinase administration. This study examined the association between urokinase use, IVH volume reduction, and clinical outcomes. METHODS: In total, 94 adult patients with hypertensive intracerebral hemorrhage with ventricular extension or primary IVH were enrolled between 2015 and 2021. Participants were categorized into two groups: "EVD combined with fibrinolysis" and "EVD only." The primary objective was to assess the reduction of IVH severity. Additionally, the study evaluated the functional outcomes and shunt dependency rate as secondary outcomes. Non-contrast computed tomography scans were obtained to measure the severity of IVH using the mGRAEB score. The main outcomes were the association among urokinase administration, reduced IVH severity, and functional outcomes. RESULTS: There were no significant differences in the reduction rate of mGRAEB scores within a 7-day period (-50.0 [-64.4 to -32.5] % vs -44.2 [-59.3 to -7.9] %; p = 0.489). In addition, investigation of the third and fourth ventricles showed similar findings between the two groups. Urokinase treatment was not associated with significant differences in the modified Rankin Scale (5.0 (4.0-5.0) vs. 4.5 (4.0-5.0), p = 0.674) or shunt dependency rate (33.3% vs 39.3%, p = 0.58). CONCLUSION: This study found that intraventricular urokinase use in patients with IVH was not associated with reduced IVH severity. In addition, urokinase use was not associated with better functional outcomes or minor shunt dependency rates.

Association between intrapleural urokinase monotherapy and treatment failure in patients with pleural infection: a retrospective cohort study.

BACKGROUND: Pleural infection, an infection of the pleural space, is frequently treated with antibiotics and thoracic tube drainage. In case of insufficient drainage, an intrapleural fibrinolytic agent is considered before surgical intervention. However, the effectiveness of fibrinolytic monotherapy is still controversial. Therefore, we aimed to examine the association between urokinase monotherapy and treatment failure in patients with pleural infection. METHODS: In this retrospective observational study, patients with pleural infection underwent chest tube insertion were divided into two groups including patients treated with or without intrapleural instillation of urokinase. The propensity score overlap weighting was used to balance the baseline characteristics between the groups. Treatment failure was defined by the composite primary outcome of in-hospital death and referral for surgery. RESULTS: Among the 94 patients, 67 and 27 patients were in the urokinase and non-urokinase groups, respectively. Urokinase monotherapy improved the composite outcome between the groups (19.4% vs. 48.1%, p = 0.01). After adjusting using propensity score overlap weighting, urokinase monotherapy improved the composite outcome compared to the non-urokinase group (19.0% vs. 59.5%, p = 0.003). CONCLUSIONS: Urokinase monotherapy can be an important nonsurgical treatment option for patients with pleural infection. TRIAL REGISTRATION: The participants were retrospectively registered.

A urokinase-associated outbreak of Ralstonia mannitolilytica bloodstream infections in haemodialysis patients in north-eastern Italy, January to April 2023.

An outbreak of Ralstonia mannitolilytica bloodstream infections occurred in four hospitals in north-eastern Italy, involving 20 haemodialysis patients with tunnelled central vascular catheter access. We identified as the outbreak source a batch of urokinase vials imported from India contaminated with R. mannitolilytica. Whole genome sequences of the clinical and urokinase strains were highly related, and only urokinase-treated patients were reported with R. mannitolilytica infections (attack rate = 34%; 95% confidence interval: 22.1-47.4). Discontinuation of the contaminated urokinase terminated the outbreak.

Predictive role of pre-thrombolytic hs-CRP on the safety and efficacy of intravenous thrombolysis in acute ischemic stroke.

PURPOSE: To investigate the predictive role of pre-thrombolytic high sensitivity C-reactive protein (hs-CRP) on the safety and efficacy of intravenous thrombolysis in patients with acute ischemic stroke (AIS). METHODS: Patients with AIS who underwent intravenous thrombolysis with recombinant plasminogen activator (rtPA) or urokinase without endovascular therapy from June 2019 to June 2022 were retrospectively analysed. All patients were grouped into two groups (high or low hs-CRP group) according to the median value of hs-CRP before intravenous thrombolysis. The baseline NIHSS, NIHSS changes before and after thrombolysis (ΔNIHSS), the rate of good thrombolysis response (NIHSS decreased ≥ 2 points from baseline), the rate of any intracranial hemorrhage, age, sex, hypertension, diabetes, uric acid and platelet count were compared between the two groups. Logistic regression analysis was performed to identify possible prognostic factors for a good thrombolysis response. RESULTS: A total of 212 patients were included in the analysis, with a mean age of 66.3 ± 12.5 years. In total, 145 patients received rtPA, and 67 patients received urokinase. Patients were divided into a high hs-CRP group (> 1.60 mg/L) and a low hs-CRP group (≤ 1.60 mg/L) according to the median hs-CRP level (1.60 mg/L). The ΔNIHSS of the high hs-CRP group was significantly smaller than that of the low hs-CRP group (0 [-1 ~ 0] vs. -1 [-2 ~ 0], P < 0.05). The good rate of thrombolysis response in the high hs-CRP group was significantly lower than that in the low hs-CRP group (21.9% vs. 36.5%, P < 0.05). Similar results were shown in the rtPA subgroup between the high and low hs-CRP groups but not in the urokinase subgroup. Logistic regression analysis showed that hs-CRP > 1.60 mg/L was negatively correlated with a good thrombolysis response rate (OR = 0.496, 95% CI = 0.266-0.927, P = 0.028). CONCLUSION: hs-CRP > 1.6 mg/L may serve as a poor prognosis predictive factor for patients with AIS receiving intravenous thrombolysis. However, due to the small sample size of this study, further studies are needed to verify our results.

The role of D-dimer and fibrinogen testing in catheter-directed thrombolysis with urokinase for deep venous thrombosis.

BACKGROUND: During catheter-directed thrombolysis (CDT), D-dimer (D-D) are generated in large quantities and fibrinogen (FIB) is continuously consumed. Reduction of FIB increases the risk of bleeding. However, there are currently few studies on the relationship between D-D and FIB concentrations during CDT. OBJECTIVES: To evaluate the relationship of D-D and FIB concentrations during CDT with urokinase for deep venous thrombosis (DVT). METHOD: 17 patients with lower limb DVT were enrolled and treated with CDT. The concentrations of plasma D-D and FIB were measured every 8 h during thrombolysis. The degree of thrombolysis was evaluated, the change rules of D-D and FIB concentrations were analyzed, and the change curve graphs were drawn. The "thrombus volume," "thrombolysis time," "thrombolysis ratio," "D-D peak," "D-D rising speed," "FIB falling speed," and "duration of D-D elevation" were calculated in each patient. The mixed model was used to simulate the time change trend of the plasma D-D and FIB concentrations. Pearson method and linear regression were used to analyze the correlation and linear relationship, respectively. RESULTS: The D-D concentration first increased rapidly and then decreased gradually, and the FIB concentration continued to decrease during thrombolysis. The rate of the decline of FIB varies with the urokinase dose. The thrombus volume is positively correlated with D-D rising speed, duration of D-D elevation, D-D peak, and FIB falling speed; the D-D rising speed is positively correlated with the D-D peak and FIB falling speed; and the D-D peak is positively correlated with the FIB falling speed. The correlation coefficients were all statistically significant (p < 0.05). Efficacy reached level I-II in 76.5% patients. No major bleeding occurred in any of the patients. CONCLUSION: During CDT with urokinase for DVT, the concentrations of D-D and FIB show specific changes, and there are some specific relationships between each other. Understanding these changes and relationships may be helpful to adjust the thrombolysis time and urokinase dose more rationally.

Safety and Efficacy of Stereotaxic Surgery Combined with Urokinase in the Treatment of Ventricular Hemorrhage: A Retrospective Propensity-Matched Score Analysis.

BACKGROUND: Intraventricular hemorrhage (IVH) is a severe and devastating stroke. Research on existing treatment options has been controversial. Therefore, we aimed to evaluate the safety and efficacy of minimally implanted stereotactic puncture combined with urokinase (uPA) in the treatment of IVH. METHODS: The clinical data of 122 IVH patients admitted to our department from 2018 to 2022 were retrospectively analyzed. According to the modified RanKin score (mRS) after 30 days, the patients were divided into good prognosis (mRS 0-3) and poor prognosis (mRS 4-6), and the factors affecting the prognosis were screened by univariate and multivariate analysis, and then the tendency Score matching and paired patient screening were performed for comparative analysis between uPA and non-uPA groups. RESULTS: Patients' age, uPA usage, initial Glasgow Coma Scale and primary blood volume all could affect the mRS score of patients. One hundred patients were finally included, including 50 cases in the uPA group and 50 cases in the non-uPA group. The analysis showed that at follow-up after 30 days, 46.0% of the patients in the uPA group and 28.0% in the non-uPA group had an mRS score of 0-3; however, they were not statistically significantly different. The postoperative hematoma clearance rate in the uPA group was significantly higher than that in the non-uPA group (P < 0.001), and the incidence of postoperative complications was not increased (P > 0.05). CONCIUSIONS: uPA treatment can improve the treatment efficiency. However, its effect in improving patient outcomes does not appear to be significant.

Comparative Efficacy and Safety of Thrombolytic Agents for Pulmonary Embolism: A Bayesian Network Meta-Analysis.

BACKGROUND: Thrombolytic agents and anticoagulants are the two classes of medication used in the treatment of acute pulmonary embolism (PE). There is continuous renewal and iteration of thrombolytic agents, and the efficacy and adverse effects of different agents have different effects on PE due to their different mechanisms of action. OBJECTIVES: The aim of the study was to evaluate the efficacy and safety of different thrombolytic agents in the treatment of all types of acute PE: hemodynamically unstable PE (massive PE) and hemodynamically stable PE (submassive PE and low-risk PE), using a network meta-analysis. METHODS: A search was conducted of the following databases: PubMed, The Cochrane Library, Embase, and Web of Science to collect randomized controlled trials (RCTs) comparing thrombolytic agents with heparin or other thrombolytic agents in patients with acute PE; the clinical outcomes included patient mortality, recurrent PE, pulmonary artery systolic pressure (PASP) after treatment, and major and minor bleeding. The measurement duration of outcome indicators was the longest follow-up period. Thereafter, a network meta-analysis was performed using a Bayesian network framework. RESULTS: A total of 29 RCTs (3,067 patients) were included, of which 6 studies (304 patients) were massive PE, 14 studies (2,173 patients) were submassive PE, 1 study (83 patients) included massive and submassive PE, and 8 studies (507 patients) were PE of unknown type. The treatment regimens included thrombolytic therapy (alteplase, reteplase, tenecteplase, streptokinase, and urokinase) and anticoagulant therapy alone. The results showed that the mortality using thrombolytic agents (except tenecteplase) was significantly lower compared with heparin. The recurrence of PE with alteplase was significantly lower compared with heparin (RR = 0.23, 95% CI, 0.04, 0.65). The PASP after using alteplase was significantly lower compared with heparin (mean difference = -11.36, 95% CI, -21.45, -1.56). Compared with heparin, the incidence of minor bleeding associated with tenecteplase was higher (RR = 3.27, 95% CI, 1.36, 7.39); compared with streptokinase, the incidence of minor bleeding associated with tenecteplase was higher (RR = 3.22, 95% CI, 1.01, 11.10). CONCLUSION: For patients with acute PE, four thrombolytic agents (alteplase, reteplase, streptokinase, and urokinase) appeared to be superior in efficacy compared with anticoagulants alone due to a reduction in mortality and no increase in bleeding risk. Alteplase may be a better choice because it not only reduced mortality but also reduced PE recurrence rate and treated PASP. Tenecteplase did not reduce mortality compared with anticoagulants alone and may not be a good choice of thrombolytic agent due to an increase in minor bleeding compared with streptokinase and anticoagulants alone. Thrombolytic drugs should be rationally selected to optimize the thrombolytic regimen and achieve as good a balance as possible between thrombolysis and bleeding.

Intraarterial urokinase for thrombus migration after mechanical thrombectomy for large vessel ischemic stroke.

BACKGROUND: Achieving rapid and complete reperfusion is the ultimate purpose for ischemic stroke with large vessel occlusion (LVO). Although mechanical thrombectomy (MT) had been a proverbially important procedure, medium vessel occlusion (MeVO) with thrombus migration can sporadically occur after MT. Moreover, the safe and effective approach for such had been unknown. We reported thrombolysis with intraarterial urokinase for MeVO with thrombus migration after MT. METHODS: We included 122 patients who were treated by MT with LVO stroke at our institution between April 2019 and March 2021. Of 26 patients (21.3%) who developed MeVO with thrombus migration after MT, 11 (9.0%) underwent additional MT (MT group) and 15 (12.3%) received intraarterial urokinase (UK group). The procedure time; angiographically modified Treatment in Cerebral Ischemia Scale (mTICI); functional independence, which was defined as modified Rankin Scale 0-2, on day 30 or upon discharge; and symptomatic and asymptomatic intracerebral hemorrhage (ICH) were compared between the UK and MT groups. RESULTS: The procedure time, mTICI, and asymptomatic ICH did not significantly differ between the groups. In the UK group, 8 of 15 (53.3%) patients obtained functional independence, and the functional independence rate was significantly higher in the UK group than in the MT group (p < 0.05). Symptomatic ICH did not occur in the UK group, and its incidence was significantly smaller than that in the MT group (p < 0.05). CONCLUSION: The results of this study suggest that intraarterial urokinase for MeVO with thrombus migration after MT may safely improve angiographic reperfusion.

Shunt Dependence after Intraventricular Hemorrhage and Intraventricular Fibrinolysis with uPA versus rt-PA.

BACKGROUND: We compare the effect of urokinase (urokinase-type plasminogen activator [uPA]) versus alteplase (recombinant tissue plasminogen activator [rt-PA]) for intraventricular fibrinolysis (IVF) in patients with intraventricular hemorrhage (IVH) on ventriculoperitoneal shunt (VPS) dependence, functional outcome, and complications in the management of IVH. METHODS: We retrospectively reviewed the patients admitted with IVH or intracerebral hemorrhage (ICH) with IVH within 7 years in three different departments and found 102 patients who met the inclusion criteria. The primary end points were VPS dependence and Glasgow outcome score (GOS) at 3 months. Secondary end points were rate of rebleeding under IVF and incidence of treatment-related complications. Patients were divided into three groups: group I comprised patients treated with external ventricular drain (EVD) and IVF with uPA; group II comprised patients treated with EVD and IVF with rt-PA; and group III comprised patients treated with EVD alone. RESULTS: In all, 9.8% patients needed VPS: 12.2% in group I and 15.0% in group II, with no statistically significant difference. VPS patients had higher values of the modified Graeb score (mGS), IVH score, and IVH volume. We saw a trend for a better outcome in group II, with six patients achieving a GOS of 4 or 5 after 3 months. The mortality rate was higher in groups I and III. We found no statistical difference in the complication rate between groups I and II. Logistic regression analysis revealed that higher mGS and age predicted worse prognosis concerning mortality. The risk for death rose by 7.8% for each year of age. Any additional mGS point increased the chances of death by 9.7%. CONCLUSION: Our data suggest that both uPA and rt-PA are safe and comparable regarding incidence of communicating hydrocephalus, and age and mGS are predictive for mortality.