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.

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.

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.

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.

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.

Pulmonary Interventional Therapy for Acute Massive and Submassive Pulmonary Embolism in Cases Where Thrombolysis Is Contraindicated.

BACKGROUND: In this study, we sought to analyze the clinical outcomes of pharmacomechanical therapy for massive and submassive acute pulmonary embolism (APE). METHODS: We conducted a retrospective investigation of 97 patients who received pharmacomechanical therapy at out center between January 2013 and June 2018 for acute massive and submassive PE because thrombolysis was contraindicated. RESULTS: Of the 97 patients, 46 (47%) were men, and the mean age of the patients was 56 ± 14 years (median, 58 years; range, 21-84 years). Fifty patients had massive PE, whereas the remaining had submassive PE. Analysis of the site of embolus revealed that 67 (69%) had bilateral emboli in the pulmonary arteries (PAs); 5 (5%) only in the left PA, and 25 (26%) only in the right PA. Seventy-nine (81%) of the 97 patients underwent intraoperative placement of the inferior vena caval filters, whereas 3 (3%) required use of a noninvasive ventilator. Two (2%) patients died within 30 days of the interventional therapy because of severe right ventricular failure. The amount of blood loss was nonsignificant. CONCLUSIONS: Our results indicate that an optimal pharmacomechanical therapy protocol could yield favorable outcomes for rapid clot debulking in cases of massive and submassive APE where thrombolysis is contraindicated. Pending further randomized trials, pharmacomechanical therapy shows promise as an alternative treatment method in cases of acute massive or submassive PE, with minimal risk of major bleeding.

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.

A comprehensive report of long-term outcomes after catheter-directed thrombolysis for occluded infrainguinal bypass grafts.

OBJECTIVE: The objective of this study was to assess the technical and short- and long-term clinical outcomes of catheter-directed thrombolysis (CDT) with urokinase for occluded infrainguinal bypass grafts. In addition, factors associated with technical success and amputation-free survival were assessed. METHODS: A retrospective analysis of a cohort of patients treated with catheter-directed urokinase-based thrombolysis for occluded infrainguinal bypass grafts was conducted between January 2000 and December 2015. Demographics, procedural data, and short- and long-term outcome data, including patency rates of the bypasses, limb salvage, and overall survival, were collected. Statistical models for clustered data were applied to assess predictive factors. RESULTS: In 177 patients, 251 CDTs were performed on 204 bypasses. In 209 procedures (83.3%), the occluded bypass was reopened; clinical disappearance of ischemic symptoms occurred after 157 procedures (62.6%). Premature cessation of thrombolysis occurred in 33 procedures (13.2%), and periprocedural and postprocedural complications were noted in 91 patients (36.3%). Factors associated with long-term limb salvage are fewer vascular interventions before CDT (P = .0003), higher number of patent outflow vessels before start of CDT (P < .0001), and higher number of patent outflow vessels after CDT (P < .0001). The 1- and 5-year patency rates of bypasses after successful CDT were 64.6% and 48.9%; amputation-free survival after 1 year, 5 years, and 7 years was 81.5%, 71.3%, and 70.5%, respectively. CONCLUSIONS: Clinical success after CDT was observed in 62% of procedures with an associated complication rate of 36%. Patent outflow vessels before and after CDT are factors associated with long-term limb salvage. Amputation-free survival after 5 years is 71.3%.

Comparison of myocardial microcirculatory perfusion after catheter-administered intracoronary thrombolysis with anisodamine versus standard thrombus aspiration in patients with ST-elevation myocardial infarction.

OBJECTIVE: To evaluate efficacy, safety and feasibility of targeted intracoronary injection using pro-urokinase combined with anisodamine (TCA) versus thrombus aspiration (TA) in ST-elevation myocardial infarction (STEMI) patients with high thrombus loads. BACKGROUND: The best method of avoiding thrombus detachment and stroke in PCI patients with high thrombus loads has not yet been established. METHODS: STEMI patients receiving coronary artery angiography or percutaneous coronary intervention (CAG/PCI) with thrombus grade ≥ 3 from January 1, 2017 to June 30, 2018 were randomly assigned to targeted intracoronary thrombolysis (pro-urokinase and anisodamine via catheter (TCA) group), or the TA group which followed the standard thrombus aspiration procedure. Parameters compared included thrombus grade, index of microcirculatory resistance (IMR), postoperative myocardial SPECT, thrombosis in myocardial infarction (TIMI) scores including flow grade, corrected TIMI frame counts (CTFCs), and TIMI myocardial perfusion grade (TMPG). Adverse events were followed up within 3 months. RESULTS: Thirty-nine patients were finally enrolled. In primary CAG/PCI, the TCA group had higher percentages of TIMI 3 flow and lower IMR values compared with the TA group. The ratio of TMPG 3 grade in the TCA group was higher in repeat CAG, and the perfusion descending area (PDA) presented by SPECT was lower than in the TA group. No significant difference was seen in major adverse coronary events (MACEs) or bleeding events at follow-up. CONCLUSIONS: TCA appears to be effective, safe, and feasible for repatency and reduction of high thrombus burden in primary PCI and may protect myocardial microcirculation with improved outcomes.

Efficacy of Minimally Invasive Intervention in Patients With Acute Cerebral Infarction.

Our aim was to explore the efficacy of minimally invasive intervention in patients with acute cerebral infarction (ACI). Seventy patients with ACI were randomized into either an experimental group or a control group. In addition to the regular treatment, patients in the control group also received intravenous thrombolysis with urokinase, while patients in the other group underwent percutaneous transluminal cerebral angioplasty and stenting. Metrics included recanalization rate, serum cytokines, fibrinolytic markers, and 36-Item Short Form Health Survey score and were compared between the 2 groups. After treatment, patients in the experimental group had better recanalization rate, higher SF-36 score and greater levels of vascular endothelial growth factors, neurotrophic factors, and nerve growth factors than those in the control group. Moreover, the values of fibrinolytic markers changed significantly in both groups after treatment. Compared with the control group, the experimental group had lower levels of tissue polypeptide antigen and plasminogen activator inhibitor-1 and a higher level of von Willebrand factor after treatment. In sum, the application of minimally invasive intervention can increase both the recanalization rate and concentrations of serum cytokines, can improve the quality of life in patients with ACI, and has small impacts on the fibrinolytic system in patients.

Fibrinolysis: a Misunderstood Natural Defense Whose Therapeutic Potential Is Unknown.

Ever since tissue plasminogen activator (tPA) was approved for therapeutic fibrinolysis in 1987, it has been the fibrinolytic of choice. At the same time, it is also recognized that tPA never lived up to its clinical expectations and has more recently been replaced by percutaneous coronary intervention (PCI) as the treatment of choice for acute myocardial infarction (AMI). For other occlusive vascular diseases and for patients in remote areas, tPA remains an essential option. In view of the continued importance of fibrinolysis, it is disappointing that fibrinolysis never evolved beyond what it was when tPA replaced streptokinase (SK) 32 years ago. The endovascular procedure replacement for AMI treatment suffers from being technically demanding, time-consuming, and costly. An untested alternative fibrinolytic paradigm is that of the endogenous, physiological system, which is initiated by tPA but then is followed by the other natural plasminogen activator, urokinase plasminogen activator (uPA). In this combination, it is uPA rather than tPA that has the dominant function. This is also evident from gene knockout studies where deletion of uPA that it has the dominant effect. The fibrinolytic properties of tPA and uPA are complementary so that their combined effect is synergistic, especially when they are administered sequentially starting with tPA. Endogenous fibrinolysis functions without bleeding side effects and is ongoing. This is evidenced by the invariable presence in blood of the fibrin degradation product, D-dimer (normal concentration 110-250 ng/ml). This activator combination, consisting of a mini bolus of tPA followed by a 90-min proUK infusion, was once used to treat 101 AMI patients. Compared with the best of the tPA mega trials, this regimen resulted in an almost a doubling of the infarct artery patency rate and reduced mortality sixfold. To date, a second trial has not yet been done.

Comparison of clear effect and the complications, and short and mid-term effects between ultrasound-guided and non-guided catheter-directed thrombolysis in the treatment of deep venous thrombosis of lower extremity.

OBJECTIVE: To compare the therapeutic effects of ultrasound-guided and non-guided catheter-directed thrombolysis in the treatment of deep venous thrombosis of lower extremity. METHODS: From August 2015 to April 2016, 60 patients with lower extremity deep venous thrombosis were randomly divided into two groups ( n = 30 for each) to receive catheter-directed thrombolysis. Group A was treated under the ultrasound guidance, while Group B was treated without guidance. RESULTS: Catheter-directed thrombolysis was successfully performed by only one intubate in Group A but by 5.9 intubates in Group B. It took 15.4 ± 3.2 min in Group A, significantly less than that in Group B (30.8 ± 6.6 min, p < 0.05). The incidences of hematoma were also remarkably different between the two groups (3.33% vs. 26.67%, p = 0.026). No pseudoaneurysm or arteriovenous fistula was found in Group A, but there were two cases of pseudoaneurysm and two cases of arteriovenous fistula in Group B (both 6.67%, p = 0.492). The circumference differences of the affected limb between before and after thrombolysis were 49.47 ± 2.484 mm in Group A, significantly higher than that in Group B (28.40 ± 2.856 mm, p < 0.001). After treatment, the venous unobstructed improvement rates and deep vein patency rate were both better than those in Group B (77 + 2.603% vs. 57.23 + 1.828% and 80% vs. 46.67%, respectively; p < 0.001). There were only three cases of PTS in Group A (10%, 3/30), but there were 11 cases in Group B (36.67%, 11/30). CONCLUSION: Ultrasound-guided catheter-directed thrombolysis has advantages, with improvement of venous patency and decrease of the incidence of PTS.

A randomized study of prourokinase 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 (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI). METHODS: Acute STEMI patients underwent primary PCI were randomly divided into two groups: intracoronary prourokinase (IP) group (n = 118) and control group (n = 112). During primary PCI, prourokinase or saline were 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 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 angiographic characteristics (P > 0.05). In IP group, more patients had complete ST segment resolution (>70%) compared with control group (P < 0.05). Patients in IP group showed lower levels of serum CK, CK-MB and TnI, and a much higher myocardial blood flow (MBF) than those in control group (P < 0.05). No significant differences of TIMI major or minor bleeding complications were observed between the two groups (P > 0.05). At 6-months follow-up, there was a trend that patients in the IP group had a less chance to have MACE, though it was not statistically different (8.5% vs 12.5%, P > 0.05). CONCLUSIONS: Intracoronary administration of prourokinase via balloon catheter during primary PCI effectively improved myocardial perfusion in STEMI patients.

Acute Massive Pulmonary Thromboembolism Treated by Selective Catheter-Directed Thrombolysis.

BACKGROUND: To evaluate the safety and efficacy of selective catheter-directed thrombolysis (SCDT) in treating acute massive pulmonary thromboembolism (AMPTE). METHODS: Twenty-six AMPTE patients were enrolled between March 2010 and March 2013. A Uni*Fuse infusion system was inserted into the main pulmonary artery thrombus. The thrombolytic regimen included an intraoperative bolus injection of 250,000 IU urokinase, followed by continuous thrombolytic infusion of 5,000 IU/kg per (every) 24 hr urokinase for 72 hr postoperatively. Clinical symptoms, shock index (SI), systolic pulmonary artery pressure (sPAP), peripheral arterial partial pressure of oxygen (PaO2), and Miller index (MI) were assessed before and after treatment. RESULTS: The patients included 16 men and 10 women (49.9 ± 18.8 years old; time to onset of 50.2 ± 28.5 hr). After thrombolysis, dyspnea and cough were relieved to varying degrees; chest pain, hemoptysis, and syncope disappeared. Importantly, a clinical success rate of 100% was achieved. All objective indices were improved: SI decreased from 1.74 ± 0.38 before operation to 0.71 ± 0.09 postoperatively (P = 0.00); PaO2 increased from 52.78 ± 6.92 mm Hg to 85.98 ± 5.91 mm Hg (P = 0.00); sPAP was reduced from 65.19 ± 8.22 mm Hg to 34.42 ± 4.05 mm Hg (P = 0.00); MI dropped from 0.69 ± 0.09 to 0.33 ± 0.06 (P = 0.00). Mean total urokinase amounts were 1,298,000 IU for each patient. Postoperative complications included 2 cases of puncture-site hematoma (cured by pressure bandage) and 1 case of gastrointestinal hemorrhage (healed by conservative treatment without blood transfusion). CONCLUSIONS: SCDT may be considered a safe and efficacious treatment for AMPTE.

Comparison of Systemic Thrombolysis Versus Indirect Thrombolysis via the Superior Mesenteric Artery in Patients with Acute Portal Vein Thrombosis.

BACKGROUND: The aim of this study was to evaluate the safety and efficacy of indirect thrombolysis via the superior mesenteric artery (SMA) in patients with acute portal vein thrombosis. METHODS: Over 10 years, we studied the safety and efficacy of indirect thrombolysis via the SMA in 34 patients with acute portal vein thrombosis. Eighteen patients were categorized as the systemic thrombolysis (ST) group and 16 as the catheter thrombolysis (CT) group. The ST group was administered low-molecular-weight heparin, and patients in the CT group received catheter thrombolysis. Clinical data, such as comorbidities, laboratory test results, therapeutic methods, and prognosis, were recorded. All the patients underwent a routine clinical follow-up that was performed by inpatient examinations or outpatient visits at a mean follow-up time of 34 months. RESULTS: The thrombus score was significantly higher in the ST group (3.67 ± 1.19) than in the CT group (2.38 ± 0.62) after 2 weeks of treatment (P < 0.05). The average period of symptom alleviated was longer in the ST group (3.29 ± 1.59 days) than in the CT group (2.07 ± 0.73 days, P < 0.05). Five patients (4 in the ST group and 1 in the CT group) underwent a laparotomy because of peritonitis after thrombolysis for 24 hr. One patient died of a malignant tumor after 18 months. CONCLUSIONS: Indirect thrombolysis via the SMA is safer and more effective for patients with portal vein thrombosis compared with systemic thrombolysis.

Flushing the liver with urokinase before transplantation does not prevent nonanastomotic biliary strictures.

The aim of the present study was to assess whether flushing the donor liver with urokinase immediately before implantation reduces the incidence of nonanastomotic biliary strictures (NASs) after liver transplantation, without causing increased blood loss, analyzed as a historical cohort study. Between January 2005 and October 2012, all liver (re-)transplantations were included. Of the 185 liver transplant recipients included, 63 donor livers between January 2010 and October 2012 received urokinase (study group), whereas the donor liver of 122 consecutive recipients, who served as a historical control group, between January 2005 and January 2010 did not receive urokinase. Basic donor (Eurotransplant donor risk index) and recipient (age, body mass index, laboratory Model for End-Stage Liver Disease score) characteristics did not significantly differ in both groups. Thirty-three recipients developed NASs: 22 in the control group (18%) and 11 (17.5%) in the study group (P = 0.68). Analyzed separately for donation after circulatory death (P = 0.42) or donation after brain death (P = 0.89), there was no difference between the groups in incidence of NAS. Of all the recipients developing NAS, 7 (21%) needed retransplantation and all others were treated conservatively. Autologous blood transfusion requirements did not differ significantly between both groups (P = 0.91), whereas interestingly, more heterologous blood transfusions were needed in the control group (P < 0.001). This study has its limitations by its retrospective character. A multi-institutional prospective study could clarify this issue. In conclusion, arterial flushing of the liver with urokinase immediately before implantation did not lead to a lower incidence of NAS in this study, nor did it lead to increased blood loss.

Is it dangerous to treat acute ischemic stroke by thrombolytic therapy in patients with comorbid intracranial aneurysms?

OBJECTIVES: The safety of cerebral ischemic stroke patients with comorbid intracranial aneurysms treated by thrombolysis is still an unsolved mystery. We aimed to perform a secondary analysis and review to provide evidence on whether stroke patients with intracranial aneurysms have worse outcomes after thrombolysis. METHODS: We searched almost all the relevant English articles published before June 21, 2015, using databases such as Medline, Embase, and Cochrane and tracked the acquired references to include the available articles. Data were processed using RevMan5.0 software provided by Cochrane collaboration, and relevant clinical guidelines, theory, retrospective studies, and case reports were summarized. RESULTS: We included 5 retrospective studies totaling 767 patients who met the inclusion and analytical criteria, which included 78 people with intracranial aneurysms. The total relative risk for patients with unruptured intracranial aneurysms developing intracranial hemorrhage after thrombolysis was 0.98 (95% confidence interval [CI], 0.60-1.58; P=.92; I(2)=22%). The total relative risk for symptomatic intracranial hemorrhage was 0.97 (95% CI, 0.37-2.57; P=.95; I(2)=40%). The total relative risk for mortality during hospitalization was 1.09 (95% CI, 0.36-3.31; P=.21; I(2)=36%). We collected 13 case reports for reference. CONCLUSION: The presence of unruptured intracranial aneurysms was not associated with a statistically significant increased risk of intracranial hemorrhage, symptomatic intracranial hemorrhage, and inhospital death after intravenous thrombolysis, although some theories and guidelines had opposite views. We suggest to perform more clinical trials with larger samples, multiple centers, and higher level of evidence to draw more reliable conclusions.

[Regional intraosseous thrombolytic therapy in comprehensive treatment of patients with diabetic foot syndrome]. / Regionarnaia vnutrikostnaia tromboliticheskaia terapiia v kompleksnom lechenii sindroma diabeticheskoi stopy.

The authors assessed efficacy of regional intraosseous administration of urokinase medac in comprehensive treatment of patients with complicated forms of diabetic foot syndrome by means of analysing therapeutic results in a total of 65 patients presenting with pyonecrotic complications of diabetic foot. The patients were subdivided into 2 groups. The control group was composed of 35 patients receiving basic therapy. The study group comprised 30 patients subjected to comprehensive treatment including regional intraosseous (into the heel bone of the affected limb) administration of urokinase medac at a dose of 100 thousand IU for 5 days. Efficacy of treatment was evaluated by the course of the wound process, indices of haemostasis, free radical oxidation, results of surgical treatment. In patients of the Study Group the terms of wound purification from pyonecrotic masses amounted to 9.8±0.3 days, which was by 4.7 days less than in the Control Group patients (p<0.01), marginal epithelialization of wounds also occurred averagely by 6.4 days faster. On day 22 of using the basic therapy alone, the haemostasis system preserved the condition of coagulation activity. The Study Group patients as early as on day 5 of treatment demonstrated shifts towards normocoagulation. In the Control Group by day 22 of treatment, the level of malonic dialdehyde decreased by 18.5%, the index of catalase activity increased by 24.6% (p<0.05); in the Study Group the level of malonic dialdehyde decreased by 42.6% and catalase activity increased by 69.4% (p<0.01). On the background of using urokinase the number of high amputations decreased by 18% and the number of operations with the supporting function preserved decreased by 12% as compared with basic therapy alone. A conclusion was made that additional use of regional intraosseous administration of urokinase medac as compared with basic therapy alone promoted a more significant decrease in the coagulation activity of blood and the level of free-radical lipid oxidation, stimulation of regenerative processes, as well as improvement of outcomes of surgical treatment.