Choice of intrapleural fibrinolytic agents in the treatment of adult complicated parapneumonic effusion and empyema: Network meta-analysis.

BACKGROUND: The appropriate use of intrapleural fibrinolytic agents in patients with complicated parapneumonic effusion and empyema remains unclear, especially regarding the choice of fibrinolytic agents. We conducted a network meta-analysis comparing outcomes of intrapleural fibrinolytic agents in patients with complicated parapneumonic effusion and empyema. METHODS: MEDLINE and EMBASE were searched through April 2022 to identify randomized controlled trials (RCTs) that investigated outcomes in patients with complicated parapneumonic effusion or empyema who were treated with intrapleural fibrinolytic agents. The outcomes of interest were surgical requirements, bleeding, length of hospital stay, and all-cause mortality. RESULTS: Our analysis included 10 RCTs that enrolled 1085 patients treated with intrapleural tissue plasminogen activator (TPA) (n = 138), TPA + deoxyribonuclease (DNase) (n = 52), streptokinase (n = 311), urokinase (n = 75), DNase (n = 51), or placebo (n = 458). The rates of surgical requirement were significantly lower with TPA and TPA + DNase than with placebo (risk ratio [RR]; 95% confidence interval [CI] = 0.36 [0.14-0.97], p = 0.038, RR [95% CI] = 0.25 [0.08-0.78], p = 0.017, respectively). The risk of bleeding was higher with TPA + DNase than with placebo (RR [95% CI] = 10.91 [1.53-77.99], p = 0.017), as well as TPA and TPA + DNase than with urokinase (RR [95% CI] = 17.90 [1.07-299.44], p = 0.044, RR [95% CI] = 89.3 [2.88-2772.49], p = 0.010, respectively). All-cause mortality was similar among the groups. CONCLUSION: TPA and TPA + DNase reduced the rates of surgical requirement compared with placebo. However, TPA + DNase increased the risk of bleeding compared with placebo. Intrapleural agents for complicated parapneumonic effusion and empyema should be selected with an individual risk assessment.

Urokinase Plasminogen Activator Deficiency Aggravates Cationic Bovine Serum Albumin-Induced Membranous Nephropathy Through T Helper Cell Type 2-Prone Immune Response in Mice.

Urokinase plasminogen activator (uPA) is a crucial activator of the fibrinolytic system that modulates tissue remodeling, cancer progression, and inflammation. However, its role in membranous nephropathy (MN) remains unclear. To clarify this issue, an established BALB/c mouse model mimicking human MN induced by cationic bovine serum albumin (cBSA), with a T helper cell type 2-prone genetic background, was used. To induce MN, cBSA was injected into Plau knockout (Plau-/-) and wild-type (WT) mice. The blood and urine samples were collected to measure biochemical parameters, such as serum concentrations of immunoglobulin (Ig)G1 and IgG2a, using enzyme-linked immunoassay. The kidneys were histologically examined for the presence of glomerular polyanions, reactive oxygen species (ROS), and apoptosis, and transmission electron microscopy was used to examine subepithelial deposits. Lymphocyte subsets were determined using flow cytometry. Four weeks post-cBSA administration, Plau-/- mice exhibited a significantly higher urine protein-to-creatine ratio, hypoalbuminemia, and hypercholesterolemia than WT mice. Histologically, compared to WT mice, Plau-/- mice showed more severe glomerular basement thickening, mesangial expansion, IgG granular deposition, intensified podocyte effacement, irregular thickening of glomerular basement membrane and subepithelial deposits, and abolishment of the glycocalyx. Moreover, increased renal ROS levels and apoptosis were observed in Plau-/- mice with MN. B-lymphocyte subsets and the IgG1-to-IgG2a ratio were significantly higher in Plau-/- mice after MN induction. Thus, uPA deficiency induces a T helper cell type 2-dominant immune response, leading to increased subepithelial deposits, ROS levels, and apoptosis in the kidneys, subsequently exacerbating MN progression in mice. This study provides a novel insight into the role of uPA in MN progression.

[Regional catheter thrombolysis for late proximal deep vein thrombosis]. / Rezul'taty lecheniya pozdnego proksimal'nogo tromboza glubokikh ven regionarnym kateternym trombolizisom.

OBJECTIVE: To compare the efficacy of regional catheter thrombolysis with urokinase and alteplase for late proximal deep vein thrombosis. MATERIAL AND METHODS: We analyzed safety and effectiveness of treatment of 38 patients with late proximal deep vein thrombosis divided into 2 statistically homogeneous groups by 19 people. In the first group, regional thrombolysis with urokinase was performed with injection of the drug into thrombosed popliteal, femoral and iliac veins. Alteplase was used in the second group. Patients received rivaroxaban in pre-, perioperative period and throughout 6 months after surgery. Complications of endovascular therapy were recorded. After 12 months, ultrasound and clinical examination were carried out to assess vein recanalization and venous outflow disorders. Vein recanalization was evaluated as follows: <50% - minimal, 50-99% - partial, 100% - complete. RESULTS: Minor hemorrhagic complications of endovascular treatment developed in 31.7 and 21% of patients, respectively. In the first group, complete vein recanalization occurred in 31.6%, partial - in 21%, minimal - in 47.4% of patients. In the second group, these values were 47.4%, 36.8% and 15.8%, respectively. In the first group, no signs of venous outflow disorders were observed in 31.6% of patients, mild disorders - in 15.8%, moderate disorders - in 31.6%, severe - in 21% of patients. In the second group, these values were 47.4%, 31.6%, 10.5% and 10.5%, respectively. CONCLUSION: Thrombolysis with alteplase is safer and more effective compared to urokinase.

Efficacy and safety assessment of urokinase plus tirofiban in acute cerebral infarction patients without clear criminal vessels.

To determine the efficacy and safety assessment of urokinase plus tirofiban in acute cerebral infarction patients without clear criminal vessels. Totally 96 cases of acute cerebral infarction (ACI) patients without clear criminal vessels enrolled in our hospital from July 2017 to July 2020 were randomized to the control group (n=48) with urokinase (n=48) and the observation group (n=48) with urokinase and tirofiban. Clinical efficacy, National Institute of Health Stroke Scale (NIHSS) score, Barthel Index (BI), Clusterin (CLU), tumor necrosis factor-α (TNF-α), serum hypersensitive C-reactive protein (hs - CRP), interleukin-6 (IL-6) and safety were compared. The observation group outperformed the control group in terms of clinical efficacy. Before treatment, the NIHSS scores, BI scores and serum levels of CLU, TNF-α, hs - CRP, and IL-6 in the control group were similar to those in the observation group. After treatment, the above indicators were all decreased, and lower in the observation group. The observation group had a lower incidence of adverse reactions. Arterial thrombolysis of urokinase plus tirofiban in ACI patients without clear responsible vessels effectively reduces postoperative NIHSS score, improves self-care ability, relieves the level of inflammatory factors, with fewer adverse reactions and higher safety profile.

Screening bioactive compounds from Danggui-shaoyao-san for treating sodium retention in nephrotic syndrome using bio-affinity ultrafiltration.

ETHNOPHARMACOLOGICAL RELEVANCE: Danggui-shaoyao-san (DSS), a representative formula of Traditional Chinese Medicine (TCM) for promoting blood circulation and diuresis (Huo-Xue-Li-Shui) therapy, has been used to clinically nephrotic syndrome (NS) and relieve nephrotic edema. AIM OF THE STUDY: To explore the effects and mechanisms of DSS in improving sodium retention and to identify the bioactive compounds from DSS. MATERIALS AND METHODS: DSS prescriptions were disassembled into Yangxue-Huoxue (YXHX) and Jianpi-Lishui (JPLS). A nephrotic rat model was induced with puromycin aminonucleoside (PAN), and the effects on urinary sodium excretion, urinary plasmin(gen) content, and plasmin activity of DSS, YXHX, and JPLS extracts were assessed. The inhibitory effects on urokinase-type plasminogen activator (uPA) and plasmin activity of extracts were evaluated in vitro. Bio-affinity ultrafiltration and high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (BAU-UPLC-Q/TOF-MS) were used to rapidly screen and qualitatively analyze the uPA/plasmin affinity compounds from DSS extract. Additionally, uPA/plasmin inhibition assays and molecular docking were used to verify the activity and affinity mechanisms of the potential bioactive compounds. RESULTS: In vivo, DSS, YXHX, and JPLS prevented sodium retention in nephrotic rats. DSS and YXHX treatment decreased urinary plasmin activity but did not alter urinary plasmin(ogen) concentration, and their extracts showed strong uPA and plasmin inhibitory activity in vitro. These results suggested that uPA and plasmin are direct targets of DSS and YXHX in intervening NS sodium retention. Using BAU-UPLC-Q/TOF-MS, gallic acids, methyl gallate, albiflorin, and 1,2,3,4,6-O-pentagalloylglucose (PGG) were screened as uPA or plasmin affinity compounds. Among them, PGG was found to be a uPA and plasmin dual inhibitor, with an IC50 of 6.861 µM against uPA and an IC50 of 149.0 µM against plasmin. The molecular docking results of PGG with uPA and plasmin were consistent with the verification results. CONCLUSION: Intervening in sodium retention by inhibiting uPA-mediated plasmin generation and plasmin activity in the kidneys could be possible mechanisms for DSS, as indicated by the results in PAN-induced nephrotic rats. We conclude that PGG is a potential bioactive compound responsible for the effect of DSS on natriuresis.

Hemodialysis Arteriovenous Fistula Dysfunction: Retrospective Comparison of Post-thrombotic Percutaneous Endovascular Interventions with Pre-emptive Angioplasty.

BACKGROUND: We aimed to compare the clinical outcomes of pre-emptive angioplasty versus post-thrombotic percutaneous endovascular restoration of dysfunctional arteriovenous fistula (AVF). METHODS: This retrospective study reviewed the data from 80 patients who underwent 114 endovascular interventions for a malfunctioning AVF from July 2016 to August 2019. Stenotic AVFs were treated with pre-emptive angioplasty. Thrombosed AVFs were treated with percutaneous pharmacomechanical fibrinolysis with urokinase used only during the operation or continuously infused. The differences in patency rates were evaluated using the Kaplan-Meier method. In addition, univariate and multivariate regression Cox models were used to determine influential factors on the postintervention primary patency. RESULTS: Post-thrombotic interventions and pre-emptive angioplasty yielded statistically similar rates in clinical success (100 vs. 100%), anatomic success (94 vs. 89%; P = 0.52), complication (4 vs. 11%; P = 0.29), as well as postintervention primary, assisted primary and secondary patency (P = 0.80; 0.57; 0.57). The use of pre-emptive angioplasty was associated with reduced total cost (¥25,108 vs. ¥30,833, P < 0.001). The patients who used urokinase only during the operation prolonged both the primary and assisted primary patency (P = 0.02; 0.002), while those with continuous infusion of urokinase had worst patency rates and high costs (¥39,275 vs. ¥25,108 vs. ¥27,140, P < 0.001). Compared with the other locations, dysfunction in the anastomotic or juxta-anastomotic segment (HR = 0.41, P = 0.001) was associated with prolonged postintervention primary patency. CONCLUSIONS: No clinical outcome differences were found between the post-thrombotic percutaneous endovascular interventions and pre-emptive angioplasty. However, pre-emptive angioplasty decreased access expenditure.

Rationale and design of a phase 3b, prospective, randomized, open label, blinded-endpoint, multicenter trial of the efficacy and safety of urokinase thrombolysis comparing with antiplatelet agents for patients with minor stroke.

RATIONALE: Minor ischemic stroke attack has taken a significant part of cerebrovascular disease burden. Benefits of thrombolysis in minor stroke is under debates and the use of urokinase in developing countries needs to be further explored. AIM: TRUST (ThRombolysis of Urokinase for minor STroke) trial was designed to evaluate the efficacy and safety of intravenous urokinase for the treatment of acute minor ischemic stroke. SAMPLE SIZE ESTIMATES: To reach a double-sided type I error rate of 0.05 to test our hypothesis, with ß = 0.80, sample size of 1002 subjects were determined after further adjustment to account for up to 5% nonadherence. METHODS AND DESIGN: TRUST trial was developed with PROBE design, as a multicenter, randomized, open label, single-blind clinical trial with the stage of phase 3b. STUDY OUTCOMES: The proportion of patients retaining full ability of independent living, which is defined as patients scoring 0-1 on modified Rankin Scale score at 90 days. DISCUSSION: TRUST trial may potentially provide promising and affordable thrombolysis for acute minor ischemic stroke in the developing parts of the world.

Predictors of hemorrhagic complications after intravenous thrombolysis in acute cerebral infarction patients: A single-center study of 391 cases.

ABSTRACT: For patients with ischemic stroke, intravenous (IV) thrombolysis with Urokinase within 6 hours has been accepted as beneficial, but its application is limited by high risk of hemorrhagic complications after thrombolysis. This study aimed to analyze the risk factors of hemorrhagic complications after intravenous thrombolysis using Urokinase in acute cerebral infarction (ACI) patients.Total 391 consecutive ACI patients were enrolled and divided into 2 groups: the hemorrhagic complications group and the non-hemorrhagic complications group. The related data were collected and analyzed.Univariate analysis showed significant differences in prothrombin time, atrial fibrillation (AF), Mean platelet volume, large platelet ratio (L-PLR), triglyceride (TG), Lactate dehydrogenase, alanine aminotransferase (ALT), high-density lipoprotein, and baseline National Institute of Health Stroke Scale score between the hemorrhagic complications and the non-hemorrhagic complications group (P < .1). Multivariate logistic regression analysis indicated that AF (odds ratio [OR] = 2.91, 95% confidence interval [CI] = 1.06-7.99 P = .039) was the risk factor of hemorrhagic complications, while ALT (OR = 0.27, 95% CI = 0.10-0.72 P = .009) and TG (OR = 0.16, 95% CI = 0.06-0.45 P = .000) were protective factors of hemorrhagic complications.For patients with AF and lower levels of ALT or TG, the risk of hemorrhagic complications might increase after ACI.

Effectiveness of intravenous r-tPA versus UK for acute ischaemic stroke: a nationwide prospective Chinese registry study.

BACKGROUND: Intravenous recombinant tissue plasminogen activator (r-tPA) and urokinase (UK) are both recommended for the treatment of acute ischaemic stroke (AIS) in China, but with few comparative outcome data being available. We aimed to compare the outcomes of these two thrombolytic agents for the treatment of patients within 4.5 hours of onset of AIS in routine clinical practice in China. METHODS: A pre-planned, prospective, nationwide, multicentre, real-world registry of consecutive patients with AIS (age ≥18 years) who received r-tPA or UK within 4.5 hours of symptom onset according to local decision-making and guideline recommendations during 2017-2019. The primary effectiveness outcome was the proportion of patients with an excellent functional outcome (defined by modified Rankin scale scores 0 to 1) at 90 days. The key safety endpoint was symptomatic intracranial haemorrhage according to standard definitions. Multivariable logistic regression was used for comparative analysis, with adjustment according to propensity scores to ensure balance in baseline characteristics. RESULTS: Overall, 4130 patients with AIS were registered but 320 had incomplete or missing data, leaving 3810 with available data for analysis of whom 2666 received r-tPA (median dose 0.88 (IQR 0.78-0.90) mg/kg) and 1144 received UK (1.71 (1.43-2.00)×104 international unit per kilogram). There were several significant intergroup differences in patient characteristics: r-tPA patients were more educated, had less history of stroke, lower systolic blood pressure, greater neurological impairment and shorter treatment times from symptom onset than UK patients. However, in adjusted analysis, the frequency of excellent outcome (OR 1.18, 95% CI 1.00 to 1.40, p=0.052) and symptomatic intracranial haemorrhage (OR 0.70, 95% CI 0.33 to 1.47, p=0.344) were similar between groups. CONCLUSIONS: UK may be as effective and carry a similar safety profile as r-tPA in treating mild to moderate AIS within guidelines in China. REGISTRATION: http://www.clinicaltrials.gov. unique identifier: NCT02854592.

Low-dose urokinase thrombolytic therapy for patients with acute intermediate-high-risk pulmonary embolism: A retrospective cohort study.

INTRODUCTION: Patients at intermediate-high risk of developing a pulmonary embolism (PE) are very likely to experience adverse outcomes, such as cardiovascular instability and death. The role of thrombolytic therapy in intermediate-high-risk PE remains controversial. OBJECTIVES: This study aimed to determine the efficacy and safety of low-dose urokinase (UK) thrombolytic therapy for intermediate-high-risk PE. PATIENTS AND METHODS: This retrospective study included 81 consecutive patients with intermediate-high-risk PE from two centers. Patients received low-dose UK or low-molecular-weight heparin (anticoagulant therapy group). The efficacy outcomes were mortality, computed tomography pulmonary angiography (CTPA)-confirmed absorption, and dyspnea. Safety was assessed as the incidence of bleedings. RESULTS: The in-hospital mortality, 9-month mortality, and long-term mortality at the last follow-up were comparable for the low-dose UK group and the anticoagulant therapy group (6.45% vs. 0%, p = 0.144, 9.68% vs. 8.16%, p = 0.815, and 12.90% vs. 12.24%, p = 0.931, respectively). CTPA-confirmed absorption at one month after admission was higher in the low-dose UK group than in the anticoagulant therapy group (p = 0.016). The incidences of short-term dyspnea at discharge and long-term dyspnea at the last follow-up were lower in the low-dose UK group than in the anticoagulant therapy group (27.59% vs. 52%, p = 0.035, 33.33% vs. 58.14%, p = 0.043, respectively). No major bleeding occurred. The incidence of minor bleeding was not significantly different between the two groups (3.23% vs. 6%, p = 0.974). CONCLUSION: In intermediate-high-risk PE, a low-dose UK might increase CTPA-confirmed absorption and improve short-term and long-term dyspnea without affecting mortality or increasing the bleeding risk.

Safety and efficacy study of prourokinase injection during primary percutaneous coronary intervention in acute ST-segment elevation myocardial infarction.

OBJECTIVES: To evaluate the efficacy and safety of intracoronary administration of prourokinase via balloon catheter during primary percutaneous coronary interventions in patients with acute ST-segment elevation myocardial infarction. METHODS: Acute ST-segment elevation myocardial infarction patients underwent primary percutaneous coronary interventions were randomly divided into two groups: intracoronary prourokinase group (n = 125) and control group (n = 135). During primary percutaneous coronary interventions, prourokinase or saline was injected to the distal end of the culprit lesion via balloon catheter after balloon catheter dilatation. Demographic and clinical characteristics, infarct size, myocardial reperfusion, and cardiac functions were evaluated and compared between two groups. Hemorrhagic complications and major averse cardiovascular events (MACE) occurred in the 6-months follow-up were recorded. RESULTS: No significant differences were observed between two groups with respect to baseline demographic, clinical, and thrombolysis in myocardial infarction grade (P > 0.05). In the intracoronary prourokinase group, more patients had ST-segment resolution (>50%) compared with control group (P < 0.05). Patients in the intracoronary prourokinase group showed lower levels of serum CK, creatine kinase-MB fraction, and troponin I than those in control group (P < 0.05). No significant differences in bleeding complications were observed between the two groups (P > 0.05). At 6-months follow-up, there was no statistically different of MACE between the two groups (P > 0.05). CONCLUSIONS: Intracoronary administration of prourokinase via balloon catheter during primary percutaneous coronary interventions effectively improved myocardial perfusion and no increased bleeding in ST-segment elevation myocardial infarction patients.

Outcome of AngioJet mechanical thrombus aspiration in the treatment of acute lower extremities deep venous thrombosis.

OBJECTIVES: The objective of this study was to evaluate the efficacy and safety in patients with acute lower extremity deep venous thrombosis who underwent pharmacomechanical thrombectomy (PMT, AngioJet mechanical thrombus aspiration). METHODS: In this retrospective, 424 consecutive patients with acute lower extremity deep venous thrombosis from three institutions were enrolled in the study from January 2015 to December 2018. Of these, patients were divided into two groups, AngioJet group (n = 186) and catheter-directed thrombolysis (CDT) group (n = 238). Evaluation indexes including limb circumference difference, length of stay (LOS), urokinase dosage, periprocedural complications, follow-up imaging findings and villalta scores were analyzed from the medical records. RESULTS: A total of 424 patients diagnosed with acute lower extremity deep venous thrombosis were collected in this study. These patients were categorized into AngioJet group and CDT group. Significant differences were observed between the two groups with respect to the thigh circumference difference (5.32 ± 1.85 cm vs. 4.69 ± 2.15 cm; p = 0.04), calf circumference difference (2.79 ± 1.54 cm vs. 2.35 ± 1.25 cm; p = 0.01), thigh detumescence rate (72.19 ± 19.55% vs. 65.35 ± 17.26%; p = 0.00) and calf detumescence rate (62.79 ± 18.56% vs. 55.75 ± 17.27%; p = 0.00). The mean dose of urokinase in AngioJet group was 95.16 ± 45.89 million IU significantly less than that in the CDT group 293.76 ± 42.71 million IU (p = 0.00). The overall bleeding complication rate was 9.91% (19 patients in AngioJet group and 23 patients in CDT group), which included three major (0.71%, 3/424) and 39 minor (9.2%,39/424) events. In the AngioJet group, serum creatinine (sCr) concentration and urine erythrocyte from the hemolysis caused by the mechanical process were higher than baseline data at admission (p = 0.00, p = 0.00). The postoperative red blood cell and hemoglobin in two groups were lower than baseline data (p = 0.00, p = 0.00). Compared with CDT, AngioJet thrombectomy has significantly lower estimated incidence of PTS in the follow-up. CONCLUSION: AngioJet thrombectomy has stronger clearance ability for acute lower extremity deep venous thrombosis leading to significant reduction in the consumption of hospital resources, total dose of thrombolytic agents, and infusion time, thereby preventing adverse bleeding events, but patients with renal insufficiency should be careful. Ideal short-term and medium-term efficacy and safety are certain.

Thrombolytic treatment of prosthetic valve thrombosis: a study using Urokinase.

OBJECTIVE: We analysed the efficacy and safety of thrombolytic therapy with urokinase in patients with prosthetic valve thrombosis. METHODS: Twenty-three patients with valve thrombosis received thrombolytic treatment using urokinase. First, a 250,000 IU intravenous bolus injection was administered as a loading dose, followed by intravenous infusion of 100,000 IU/h for 10 h and anticoagulation with low molecular weight heparin every day. The maximum treatment time was 5 days, i.e., until the transvalvular pressure gradient was normal or close to normal. Transthoracic echocardiography (TTE) was used every 12 h to monitor whether the thrombus was reduced and whether there was haemodynamic improvement. Routine blood tests, the prothrombin time (PT), international normalized ratio (INR) and complications were observed every day. RESULTS: Sixteen (69.6%) patients were successfully treated with thrombolytic therapy: 2/2 (100%) aortic valves and 14/21 (66.7%) mitral valves. The partial success rate of this study was 13.0% (3/23). Four patients did not show any improvement in haemodynamics. Two cases had slight urine haemorrhage. One patient died of severe cerebral haemorrhage and shock. The overall mortality was 13.0% (3/23), including two patients who died after subsequent surgery. CONCLUSION: Urokinase is more convenient and successful in the treatment of PVT. More experience may make TT the optimal treatment for PVT, especially in high-risk surgical situations.

The safety and efficacy of pharmaco-mechanical thrombolysis in lower-extremity deep venous thrombosis.

OBJECTIVE: The aim of this study was to investigate the impact of accelerated pharmaco-mechanical thrombolysis (PMT) with low-dose second-generation urokinase for the management of cases with lower-extremity deep venous thrombosis (DVT), and to compare its efficacy in subjects with acute and subacute DVT. METHODS: Thirty-five patients with acute (< 15 days) or subacute (15-30 days) DVT who underwent PMT in a tertiary centre were enrolled in this single-arm, prospective study. Following the placement of a temporary vena cava filter, urokinase (200 000 IU) was administered into the occlusion through a multi-hole catheter for 15 to 20 minutes. Control venography was performed to assess venous flow and the rate of acute recanalisation. Percutaneous balloon dilatation and stent placement were carried out in case of a residual iliac vein stenosis of > 50%. Any residual thrombi were suctioned with an aspiration catheter. The primary outcome measures of this study were the percentages of vessel patency and PTS in the third month after PMT. RESULTS: Complete recanalisation was noted in 23 (66%) patients, while two (6%) had poor recanalisation. The rate of minor complications was 14%. None of the subjects experienced major complications, such as intracranial haemorrhage or pulmonary embolism. No mortality was recorded during the three months of follow up. Control duplex ultrasonography in the third month revealed that the target vein was patent in all subjects. None of the subjects experienced PTS during follow up. In addition, the percentage of acute complete recanalisation was significantly higher in subjects with acute DVT compared to those with subacute DVT (95 vs 27%, p < 0.001). CONCLUSION: PMT with an accelerated regimen of low-dose urokinase provided excellent efficacy in the resolution of thrombus and prevented the development of PTS in the midterm when used for the management of lower-extremity DVT.

Efficacy and safety of intracoronary prourokinase during percutaneous coronary intervention in treating ST-segment elevation myocardial infarction patients: a randomized, controlled study.

BACKGROUND: Prourokinase is a single-chain plasminogen activator presenting with fewer hemorrhagic complications and reduced reocclusion rate compared with the conventional fibrinolytic agents in patients with coronary artery disease. However, prourokinase intracoronary injection during PCI for treating patients with ST-segment elevation myocardial infarction (STEMI) is rarely investigated. Therefore, this study aimed to evaluate the efficacy and safety of intracoronary prourokinase during the percutaneous coronary intervention (PCI) in treating STEMI patients. METHODS: Fifty STEMI patients who underwent primary PCI were consecutively enrolled and randomly assigned to intracoronary prourokinase group (N = 25) or control group (N = 25). During the primary PCI procedure, patients in the intracoronary prourokinase group received 10 ml prourokinase injection, while patients in control group received 10 ml saline injection as control. The primary endpoints were coronary physiological indexes, the secondary endpoints were angiographic assessments, myocardial infarct size/reperfusion assessment, cardiac function evaluations, major adverse coronary events (MACEs) and hemorrhagic complications. All patients were followed up for 3 months. RESULTS: Post PCI, the index of microcirculatory resistance (IMR) was decreased in intracoronary prourokinase group than that in control group (34.56 ± 7.48 vs. 49.00 ± 8.98, P < 0.001), while no difference of coronary flow reserve (CFR) (2.01 ± 0.32 vs. 1.88 ± 0.23, P = 0.267) or fractional flow reserve (FFR) (0.89 ± 0.05 vs. 0.87 ± 0.04, P = 0.121) was found between the two groups. The thrombolysis in myocardial infarction myocardial perfusion grade (TMPG) (P = 0.024), peak values of creatine kinase (CK) (P = 0.028), CK isoenzyme-MB (CK-MB) (P = 0.016), cardiac troponin I (cTnI) (P = 0.032) and complete ST-segment resolution (STR) (P = 0.005) were better in intracoronary prourokinase group compared with control group. At 3-months post PCI, left ventricular ejection fraction (LVEF) and wall motion score index (WMSI) were higher, while left ventricular end-diastolic diameter (LVEDd) was lower in intracoronary prourokinase group compared with control group (all P < 0.05). There was no difference in hemorrhagic complication or total MACE between the two groups. CONCLUSION: Intracoronary prourokinase during PCI is more efficient and equally tolerant compared with PCI alone in treating STEMI patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800016207 . Prospectively registered.

Comparative study of intravenous thrombolysis with rt-PA and urokinase for patients with acute cerebral infarction.

OBJECTIVE: Cerebral infarction has a poor prognosis and causes a serious burden on families and society. Recombinant tissue plasminogen activator (rt-PA) and urokinase (UK) are commonly used thrombolytic agents in the clinic. However, direct and powerful clinical trial evidence to determine the therapeutic effect of rt-PA and UK on intravenous thrombolysis is lacking. METHODS: In this study, 180 patients with acute cerebral infarction were treated with rt-PA or UK. The National Institutes of Health Stroke Scale (NIHSS) scores, Barthel index, bleeding complications, and biomarkers were evaluated. RESULTS: No significant differences in NIHSS or Barthel scores were found between the groups. However, UK increased the risk of intracranial haemorrhage compared with rt-PA. rt-PA had increased activity in reducing serum levels of MMP-9 than UK. CONCLUSION: Intravenous thrombolysis with rt-PA and UK in the time window of acute cerebral infarction can achieve similar therapeutic effects, but rt-PA can further reduce the risk of cerebral haemorrhage and is relatively safer than UK.

Sequential interventional therapy for Budd-Chiari syndrome associated with fresh inferior vena cava thrombosis.

OBJECTIVE: Our study aimed to evaluate the safety and efficacy of sequential interventional therapy for Budd-Chiari syndrome (BCS) caused by obstruction of the inferior vena cava (IVC) with fresh thrombus in the IVC. METHODS: Full medical records were obtained for 20 patients with BCS associated with fresh IVC thrombus who received sequential interventional therapy from 2014 to 2019 at our hospital. All patients underwent small-diameter percutaneous transluminal angioplasty (PTA) balloon catheter predilation combined with sequential catheter-directed thrombolysis and large-diameter PTA balloon dilation. Ultrasound examinations were performed at 1 week, 1 month, 3 months, and every 6 months thereafter. Therapeutic effects and perioperative and postoperative adverse effects were recorded to assess the safety of the treatment. RESULTS: All 20 patients were treated with small PTA balloon catheters (diameter, 10-14 mm) to predilate the occlusive segment of the IVC. Urokinase 400,000 to 600,000 (465,000 ± 93,000) units was administered to patients through the catheter for 6 to 20 (9.7 ± 4.2) consecutive days postoperatively. Ultrasound re-examination showed that the IVC thrombus disappeared completely in 14 patients (70.0%), and a small amount of the old thrombus remained in 6 patients (30.0%). After thrombolysis, all 20 patients received PTA balloon dilation (diameter, 26-30 mm) in the stenosed IVC segment, and blood flow recovered subsequently. No pulmonary embolism or death occurred in the perioperative course. The perioperative survival rate was 100.0%. CONCLUSIONS: Sequential interventional therapy for BCS associated with fresh IVC thrombus is safe and effective.

Intra-arterial thrombolysis in acute popliteal artery occlusion is a safe and effective technique reducing the rate of open surgery.

BACKGROUND: Acute popliteal artery occlusion is a frequent clinical entity with a risk of major amputation. Several attitudes are possible and treatment is not standardized. The purpose of this study is to demonstrate safety and effectiveness of intra-arterial thrombolysis in acute popliteal artery occlusion. METHODS: This is a retrospective analysis of a prospective database of patients treated by intra-arterial thrombolysis for acute lower-limb ischemia due to popliteal artery occlusion between 2001 and 2014.The primary endpoint was technical and clinical success. Etiologies and etiologic treatment, amputation-free survival, in-hospital mortality and bleeding complications rates were secondary endpoints. RESULTS: Seventy-one patients, with a mean 6-day-old ischemic time before thrombolysis, were analyzed. Technical and clinical success was 90% and 87% respectively. Etiology was embolic in 33 patients (cardiac N.=14, aortic=6, unknown=13) and thrombotic in 38 (atheromatous N.=19, entrapment N.= 4, popliteal aneurysm N.=11, Buerger N.=2, thrombophilia N.=1, hyperhomocysteinemia N.=1). Survival and amputation-free survival at 30 days were 97% and 94% respectively. There were no major bleeding complications. CONCLUSIONS: Intra-arterial thrombolysis of acute popliteal artery occlusion is an effective technique which reduces the rate of open surgery. The risk of bleeding complications is very low.

AngioJet Aspiration Thrombectomy Combined with Transcatheter Thrombolysis in Treatment of Acute Portal Venous Systemic Thrombosis.

BACKGROUND: This study set out to assess the feasibility, effectiveness, and safety of percutaneous AngioJet aspiration thrombectomy combined with transcatheter thrombolysis for treating acute portal venous systemic thrombosis (APVST). METHODS: Clinical data of 13 patients with APVST who were treated by AngioJet aspiration thrombectomy combined with transcatheter thrombolysis from March 2017 to July 2018 were analyzed retrospectively. The effect of portal venous recanalization was evaluated by intraoperative angiography and postoperative surveillance of clinical findings, portal venous ultrasound, or computed tomography. RESULTS: Successful puncture of the portal vein (PV) was performed in all patients. The PV was punctured successfully in 7 patients via the transjugular intrahepatic route, 2 patients failed to be punctured and then had successful percutaneous transhepatic puncture, and 4 patients underwent percutaneous transhepatic PV puncture directly. The duration of thrombus aspiration was 238.46 ± 89.89 sec (range, 120-360), and the amount of urokinase in thrombus aspiration was 353,000 ± 87,700 IU (range, 200,000-400,000). Portal venous thrombosis was dissolved by the AngioJet thrombectomy device (Boston Scientific, Marlborough, MA) in all patients. After aspiration, angiography showed that grade III lysis was achieved in 8 patients, grade II lysis in 1 patient, and grade I lysis in 4 patients. The length of transcatheter thrombolysis was 3.07 ± 1.75 days (range, 1-7), and the total urokinase dose via an indwelling catheter was 1,230,000 ± 706,000 IU (range, 200,000-2,800,000). Four patients had a transjugular intrahepatic portosystemic shunt, 1 patient with stenosis of the superior mesenteric vein (SMV) achieved balloon angioplasty, and 1 patient with stenosis of the SMV was stented. Operative complications were transient hematuria (4 patients), palpitation (1 patient), and bowel resection (1 patient). No patients died within 30 days. Patients were discharged at 12.00 ± 5.83 days (range, 6-27) after admission. All patients survived, and no recurrence developed during the follow-up of 9.15 ± 3.18 months (range, 4-15). CONCLUSIONS: Percutaneous AngioJet aspiration thrombectomy combined with thrombolytic therapy is feasible and effective for APVST. This treatment is beneficial for APVST in dissolving thrombus, improving SMV flow, and relieving symptoms of PV hypertension.

Evaluation of Percutaneous Mechanical Thrombectomy via the AngioJet System Combined with Catheter-Directed Thrombolysis for the Treatment of Symptomatic Lower Extremity Deep Venous Thrombosis.

BACKGROUND: Current methods of treating lower extremity deep venous thrombosis (LEDVT), such as catheter-directed thrombolysis (CDT) alone, or percutaneous mechanical thrombectomy (PMT) alone, are accompanied by unacceptably high risks of complications. This preliminary retrospective study evaluated the efficacy of CDT combined with PMT (via the AngioJet system), relative to CDT alone, in treating LEDVT. METHODS: Forty-two patients (43 limbs) with symptomatic deep venous thrombosis received either CDT alone (n = 12) or PMT combined with CDT (PMT + CDT) from May 2012 to December 2016. The groups were compared for clinical outcomes and demographics, LEDVT risk factors, and dosages of urokinase. Thrombus removal, by venographic evidence, was classified as grades I (<50%), II (50 to 99%), or III (>99%). RESULTS: In the CDT (PMT + CDT) cohorts, grades I, II, and III thrombus removal was achieved by 8% (3%), 17% (10%), and 75% (87%) of patients, respectively. The urokinase dosage and hospitalization required by the CDT group (5.29 ± 0.45 million IU, 20.4 ± 4.6 days) were significantly greater than those required by the PMT + CDT group (4.08 ± 1.15 million IU, 16.0 ± 6.0 days; P = 0.001, 0.039). The clinical outcomes of the 2 groups were similar. CONCLUSION: Combined PMT and CDT was effective and safe for LEDVT clinical therapy, and hospital stay, urokinase dosage, and complications were less compared with patients who received CDT only.