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Cardiology Journal Sep 2023In contemporary clinical practice, there is an increasing need for new clinically relevant biomarkers potentially optimizing management strategies in patients with...
BACKGROUND
In contemporary clinical practice, there is an increasing need for new clinically relevant biomarkers potentially optimizing management strategies in patients with suspected acute coronary syndrome (ACS). This study aimed to determine the diagnostic utility of soluble urokinase-type plasminogen activator receptor (suPAR) levels in individuals with suspected ACS.
METHODS
A literature search was performed in Web of Science, PubMed, Scopus, and the Cochrane Central Register of Controlled Trials databases, for studies comparing suPAR levels among patients with and without ACS groups. The methodological quality of the included papers was assessed using the Newcastle-Ottawa Scale (NOS). A fixed-effects model was used if I² < 50%; otherwise, the random-effects model was performed.
RESULTS
Five studies with 3417 participants were included in the meta-analysis. Pooled analysis showed that mean suPAR levels in the ACS group were statistically significantly higher than in the control group (3.56 ± 1.38 vs. 2.78 ± 0.54 ng/mL, respectively; mean difference: 1.04; 95% confidence interval: 0.64-1.44; I² = 99%; p < 0.001).
CONCLUSIONS
In the context of acute coronary syndrome, suPAR is a potential biomarker for the early identification of medical conditions in individuals who are being treated in emergency rooms.
PubMed: 37772350
DOI: 10.5603/cj.96228 -
Molecular and Clinical Oncology Jan 2018Current relevant research suggests there are significant differences between the expression of the urokinase plasminogen activator (uPA) system in cancer tissues and in...
Current relevant research suggests there are significant differences between the expression of the urokinase plasminogen activator (uPA) system in cancer tissues and in normal tissues. However, the potential effectiveness of the uPA system as a prognostic biomarker of non-small cell lung cancer (NSCLC) remains unclear. In the present study, a systematic review and meta-analysis were performed to evaluate the relevance of the uPA system in the prognosis of patients with NSCLC. Using the PubMed, EMBASE, Web of Science and Cochrane Library databases, data from relevant academic journal articles were extracted and subjected to analysis. Associations between expression profiles pertaining to the uPA system and the overall survival (OS) of patients with NSCLC were analyzed. The study incorporated data from 11 independent journal articles and these reports included a total of 937 patients with NSCLC. The meta-analysis results revealed that increased expression of urokinase plasminogen activator (uPA) and PA inhibitor type 1 (PAI-1) exhibited no significant association with poor OS [hazard ratio (HR)-uPA=1.07 (0.87-1.31), P=0.53; HR-PAI-1=1.02 (0.63-1.65), P=0.94]. Similarly, reduced expression of PAI type 2 (PAI-2) did not significantly correlate with poor OS [HR-PAI-2=1.58 (0.64-3.90); P=0.32]. Notably, however, a significant association was observed between increased expression levels of uPA receptor (uPAR) and poor OS for NSCLC [HR-uPAR=1.50 (1.04-2.15); P=0.03]. Therefore, the expression of uPAR in the uPA system of patients with NSCLC could be used as a novel clinical biomarker to evaluate the prognosis of NSCLC. The utilization of this biomarker may provide a platform for the further development of targeted drugs for the treatment of NSCLC.
PubMed: 29387404
DOI: 10.3892/mco.2017.1484 -
BioMed Research International 2019Chronic kidney disease (CKD) has become a global public health problem with a high prevalence and mortality. There is no sensitive and effective markers for chronic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chronic kidney disease (CKD) has become a global public health problem with a high prevalence and mortality. There is no sensitive and effective markers for chronic kidney disease. Previous studies proposed suPAR as an early predict biomarker for chronic kidney disease, but the results are controversial. Therefore, the purpose of the current meta-analysis is to evaluate the association between suPAR and CKD.
METHODS
We searched the PubMed, Embase, Cochrane Library databases, and Web of Science before May 1, 2019. The search was based on the key words including suPAR and CKD. Data are extracted independently according to standard format, and quality analysis is performed. We extracted the concentration of suPAR and hazard rate (HR) values of mortality, cardiovascular disease, and end-stage renal disease.
RESULTS
There were 14 studies fulfilling the criteria. The concentration of suPAR was higher in patients with CKD than that in the control group ( < 0.001; SMD: -2.17; 95% CI: -2.71, -1.63; = 67.4%). SuPAR had a higher risk of mortality (=0.001; HR: 1.72; 95% CI: 1.24, 2.39; = 68.0%). The higher suPAR level increased the risk of cardiovascular disease ( < 0.001; HR: 3.06; 95% CI: 2.21, 4.22; = 0.0%) and the risk of end-stage renal disease ( < 0.001; HR: 1.40; 95% CI: 1.22, 1.60; = 0.0%).
CONCLUSIONS
Monitoring suPAR concentrations may be used for early diagnosis and prognosis for patients with CKD, and the higher suPAR increased the risk of mortality, cardiovascular events, and end-stage renal disease.
Topics: Biomarkers; Cardiovascular Diseases; Cause of Death; Databases, Factual; Humans; Kidney Failure, Chronic; Mortality; Prognosis; Receptors, Urokinase Plasminogen Activator; Renal Insufficiency, Chronic; Risk Factors
PubMed: 31886242
DOI: 10.1155/2019/6927456 -
European Archives of... Jul 2021To clarify the association between the 4G/5G polymorphism of plasminogen activator inhibitor-1 (PAI-1) and sudden sensorineural hearing loss (SSNHL). (Meta-Analysis)
Meta-Analysis Review
Association between the 4G/5G polymorphism of plasminogen activator inhibitor-1 (PAI-1) gene and sudden sensorineural hearing loss in Caucasian population: a meta-analysis.
PURPOSE
To clarify the association between the 4G/5G polymorphism of plasminogen activator inhibitor-1 (PAI-1) and sudden sensorineural hearing loss (SSNHL).
METHODS
A systematic literature search of related studies up to August 30, 2019 in the PubMed and Embase databases was performed, and the results were displayed by odds ratios (ORs), and their 95% confidence intervals (CIs) were assessed using the STATA12.0 software using an allele model and a recessive model.
RESULTS
Three eligible studies covering 519 subjects (241 cases, 278 controls) were identified. No statistically significant association was detected between the 4G/5G polymorphism and SSNHL in any model (allele model: 5G vs. 4G, OR = 0.952, 95% CI = 0.765-1.185, P = 0.662; recessive model: 5G/5G vs. 4G/5G + 4G/4G, OR = 0.841, 95% CI = 0.415-1.704, P = 0.631).
CONCLUSIONS
There is no statistically significant association between the 4G/5G polymorphism of PAI-1 gene and SSNHL in the Caucasian population, and well-designed studies covering more patients and institutions should be conducted.
Topics: Genetic Predisposition to Disease; Genotype; Hearing Loss, Sensorineural; Humans; Odds Ratio; Plasminogen Activator Inhibitor 1; Polymorphism, Genetic; Risk Factors
PubMed: 32901365
DOI: 10.1007/s00405-020-06305-z -
Journal of Cerebral Blood Flow and... Dec 2010Thrombolysis with recombinant tissue plasminogen activator (rtPA) improves outcome in animal models of stroke and in clinical trial, but is associated with increased... (Meta-Analysis)
Meta-Analysis Review
Thrombolysis with recombinant tissue plasminogen activator (rtPA) improves outcome in animal models of stroke and in clinical trial, but is associated with increased intracranial hemorrhage. Here, we explore the impact of biologic and experimental design factors on efficacy and bleeding. We conducted a systematic review of studies describing the effect of tPA in thrombotic occlusion models of ischemic stroke followed by random effects meta-analysis, meta-regression, and trim and fill. We identified 202, 66, 128, and 54 comparisons reporting infarct volume, neurobehavioral score, hemorrhage, and mortality, respectively. The rtPA reduced infarct volume by 25.2% (95% confidence interval=21.8 to 28.6, 3388 animals), improved neurobehavioral score by 18.0% (12.6% to 23.3%, n=1243), increased the risk of hemorrhage (odds ratio=1.71, 1.42 to 2.07, n=2833) and had no significant effect on mortality (odds ratio=0.82, 0.62 to 1.08, n=1274). There was an absolute reduction in efficacy of 1.1% (0.7% to 1.4%) for every 10 minutes delay to treatment. Cumulative meta-analysis showed that the estimate of efficacy fell as more data became available. Publication bias inflated efficacy by 5.1% (infarct volume) and 8.1% (neurobehavioral score). This data set was large enough to be adequately powered to estimate with precision the impact of biologic and experimental factors on the efficacy and safety of rtPA.
Topics: Animals; Humans; Models, Biological; Stroke; Thrombosis; Tissue Plasminogen Activator
PubMed: 20648038
DOI: 10.1038/jcbfm.2010.116 -
Journal of Stroke and Cerebrovascular... Jul 2024To compare the safety and efficacy of Dual Antiplatelet Therapy (DAPT) and Intravenous (IV) Tissue Plasminogen Activator (t-PA) in minor Acute Ischemic Stroke (AIS). (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To compare the safety and efficacy of Dual Antiplatelet Therapy (DAPT) and Intravenous (IV) Tissue Plasminogen Activator (t-PA) in minor Acute Ischemic Stroke (AIS).
MATERIALS AND METHODS
Following Cochrane and PRISMA guidelines, we analyzed observational studies and clinical trials comparing DAPT and IV t-PA in patients with minor AIS. Databases included PubMed, Scopus, and Web of Science. Data extraction included study characteristics, patient demographics, and analyzed outcomes. RevMan 5.3 and OpenMetaAnalyst 2021 were used to analyze the data and assess heterogeneity, respectively. The risk of bias was determined using RoB 2.0 and the Newcastle-Ottawa scale.
RESULTS
This meta-analysis included five studies with 3,978 DAPT-treated patients and 2,224 IV t-PA-treated patients. We found no significant differences in achieving modified Rankin scale (mRS) scores of 0-1 (OR 1.11, 95 % CI: 0.79, 1.55, p = 0.56) and 0-2 (OR 0.90, 95 % CI: 0.61, 1.31, p = 0.57), as well as combined mRS scores (OR 1.05, 95 % CI: 0.82, 1.34, p = 0.72). Similarly, there were no significant disparities between the two treatment groups in NIHSS score change from baseline (MD 0.32, 95 % CI: -0.35, 0.98, p = 0.35) and in mortality rates (OR 0.87, 95 % CI: 0.26, 2.93, p = 0.83). Notably, in comparison to the IV t-PA group, the DAPT group exhibited a significantly lower incidence of bleeding (OR 0.31, 95 % CI: 0.14, 0.69, p = 0.004) and symptomatic intracranial hemorrhage (sICH) (OR 0.10, 95 % CI: 0.04, 0.26, p < 0.00001).
CONCLUSIONS
Our meta-analysis found no significant differences in efficacy between DAPT and IV t-PA. However, DAPT demonstrated a significantly lower risk of sICH and bleeding compared with IV t-PA.
Topics: Humans; Ischemic Stroke; Tissue Plasminogen Activator; Fibrinolytic Agents; Platelet Aggregation Inhibitors; Treatment Outcome; Dual Anti-Platelet Therapy; Thrombolytic Therapy; Risk Factors; Male; Female; Aged; Middle Aged; Risk Assessment; Disability Evaluation; Administration, Intravenous; Recovery of Function; Observational Studies as Topic; Aged, 80 and over
PubMed: 38561167
DOI: 10.1016/j.jstrokecerebrovasdis.2024.107704 -
Europace : European Pacing,... Feb 2023While atrial fibrillation (AF) is suggested to induce a prothrombotic state, increasing thrombotic risk, it is also hypothesized that coagulation underlies AF onset.... (Meta-Analysis)
Meta-Analysis
AIMS
While atrial fibrillation (AF) is suggested to induce a prothrombotic state, increasing thrombotic risk, it is also hypothesized that coagulation underlies AF onset. However, conclusive evidence is lacking. With this systematic review and meta-analysis, we aimed to summarize and combine the evidence on the associations between coagulation factors with AF in both longitudinal and cross-sectional studies.
METHODS AND RESULTS
We systematically searched for longitudinal cohort and cross-sectional studies investigating AF and thrombosis. For longitudinal studies, pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. For cross-sectional studies, we determined pooled standardized mean differences (SMDs) and 95% CIs. A total of 17 longitudinal and 44 cross-sectional studies were included. In longitudinal studies, we found significant associations between fibrinogen (HR 1.05, 95% CI 1.00-1.10), plasminogen activator inhibitor 1 (PAI-1) (HR 1.06, 95% CI 1.00-1.12), and D-dimer (HR 1.10, 95% CI 1.02-1.19) and AF incidence. In cross-sectional studies, we found significantly increased levels of fibrinogen (SMD 0.47, 95% CI 0.20-0,74), von Willebrand factor (SMD 0.96, 95% CI 0.28-1.66), P-selectin (SMD 0.31, 95% CI 0.08-0.54), ß-thromboglobulin (SMD 0.82, 95% CI 0.61-1.04), Platelet Factor 4 (SMD 0.42, 95% CI 0.12-0.7), PAI-1 (1.73, 95% CI 0.26-3.19), and D-dimer (SMD 1.74, 95% CI 0.36-3.11) in AF patients, as opposed to controls.
CONCLUSION
These findings suggest that higher levels of coagulation factors are associated with prevalent and incident AF. These associations are most pronounced with prevalent AF in cross-sectional studies. Limited evidence from longitudinal studies suggests a prothrombotic state underlying AF development.
Topics: Humans; Atrial Fibrillation; Plasminogen Activator Inhibitor 1; Cross-Sectional Studies; Biomarkers; Blood Coagulation Factors; Fibrinogen; Thrombosis
PubMed: 35942591
DOI: 10.1093/europace/euac130 -
Avicenna Journal of Medicine Oct 2011Hemodialysis catheters are commonly used when renal replacement therapy is initiated. These catheters have significant complications. Among "locking" solutions used in...
BACKGROUND AND OBJECTIVES
Hemodialysis catheters are commonly used when renal replacement therapy is initiated. These catheters have significant complications. Among "locking" solutions used in an attempt to decrease these complications is recombinant tissue plasminogen activator (rt-PA). This systematic review is to determine the efficacy of rt-PA versus heparin, the standard of care.
MATERIALS AND METHODS
A systematic review of randomized controlled trials studying rt-PA alone or rt-PA plus heparin versus heparin alone as locking agents for hemodialysis catheters, which included patients needed a temporary hemodialysis catheter for hemodialysis. We identified relevant trials through electronic databases and correspondence with experts. Two investigators independently reviewed potentially eligible trials and extracted data.
RESULTS
Three trials met the inclusion criteria. One trial reported an improved catheter malfunctioning in patients using rt-PA plus heparin to lock catheters (20.0%) versus heparin alone (34.8%). Another trial reported higher blood flow rate in hemodialysis catheters in patients who received rt-PA (231.6 ± 12.4 mL/min) compared with those who received heparin (206.9 mL/min). The third trial reported formation and weight of clots which were decreased by half in rt-PA group versus heparin group.
CONCLUSIONS
In the few randomized trials that met our inclusion criteria, the use of rt-PA as a locking solution for hemodialysis catheters seems to be associated with fewer adverse events and catheter malfunctioning as compared with heparin. Our systematic review is limited by the few randomized trials addressing our question and the wide variety of outcome measures. Further prospective randomized trials are needed to confirm this conclusion.
PubMed: 23210006
DOI: 10.4103/2231-0770.90913 -
Chest Feb 2001To assess, by systematic review, the efficacy and safety of recombinant tissue plasminogen activator (rt-PA) in the treatment of lower extremity deep venous thrombosis... (Review)
Review
OBJECTIVE
To assess, by systematic review, the efficacy and safety of recombinant tissue plasminogen activator (rt-PA) in the treatment of lower extremity deep venous thrombosis (DVT). A secondary objective is to assess the optimal dose and route of administration of rt-PA.
METHODS
Included studies were randomized, controlled trials comparing rt-PA plus unfractionated heparin (UFH) to UFH alone, rt-PA at different doses, or rt-PA by different routes of administration in the treatment of DVT. Outcomes had to be described in terms of percent change in venographic patency for efficacy (>50% lysis) and in sufficient detail for complications (major and minor hemorrhages and other). The search strategy included searching electronic databases and contacting pharmaceutical agencies and content experts. Study quality was assessed using the Jadad scale. A threshold quality score was used to exclude trials.
RESULTS
Five studies met the following inclusion criteria: three comparing rt-PA plus UFH vs UFH alone (180 patients); one comparing high-dose vs low-dose rt-PA (32 patients); and one comparing systemic vs local administration of rt-PA (151 patients). In studies comparing rt-PA vs placebo, patients assigned to rt-PA were more likely to have > 50% lysis and complications (summary odds ratios [OR], 11.7; 95% confidence interval [CI], 2.61 to 52.5; and OR, 9.95; 95% CI, 2.21 to 44.7, respectively). Major and intracerebral hemorrhages were not significantly increased. One study comparing different doses demonstrated that high-dose and low-dose rt-PA were equally efficacious (OR, 0.88; 95% CI, 0.05 to 14.78). Local rt-PA was neither more efficacious nor riskier than systemic rt-PA.
CONCLUSION
This systematic review does not support routine use of rt-PA for DVT.
Topics: Anticoagulants; Cerebral Hemorrhage; Fibrinolytic Agents; Heparin; Humans; Randomized Controlled Trials as Topic; Streptokinase; Tissue Plasminogen Activator; Venous Thrombosis
PubMed: 11171740
DOI: 10.1378/chest.119.2.572 -
International Journal of Stroke :... Apr 2015There is uncertainty surrounding the influence of prior antiplatelet agent use on outcomes after intravenous thrombolysis with recombinant tissue plasminogen activator... (Meta-Analysis)
Meta-Analysis Review
Prior antiplatelet agent use and outcomes after intravenous thrombolysis with recombinant tissue plasminogen activator in acute ischemic stroke: a meta-analysis of cohort studies and randomized controlled trials.
BACKGROUND
There is uncertainty surrounding the influence of prior antiplatelet agent use on outcomes after intravenous thrombolysis with recombinant tissue plasminogen activator in acute ischemic stroke.
AIM
We performed a systematic review with a final meta-analysis to evaluate the efficacy and safety of prior antiplatelet use before intravenous recombinant tissue plasminogen activator for acute ischemic stroke.
SUMMARY OF REVIEW
We searched PubMed and Embase databases from 1997 to 2014. Primary outcome was functional outcome at the end of follow-up; secondary outcomes were symptomatic intracranial hemorrhage and recanalization rate. The meta-analysis was performed with Review Manager 5.2 (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2012). Eleven studies with a total of 19,453 patients were included. A total of 6517 (33.5%) patients who had received intravenous recombinant tissue plasminogen activator were taking antiplatelet agent before stroke onset. Pooled analysis demonstrated a clear trend that previous antiplatelet users had a reduced probability of good outcome, although it was not conventionally statistically significant (OR 0.86; 95% CI 0.73-1.01; P = 0.06). There was no difference in recanalization rate between two groups (OR 1.23; 95% CI 0.30-4.99; P = 0.77). The risk of symptomatic intracranial hemorrhage was significantly increased in the antiplatelet group (OR 1.65; 95% CI 1.44-1.90; P < 0.01).
CONCLUSIONS
In acute ischemic stroke patients receiving intravenous recombinant tissue plasminogen activator therapy, prior antiplatelet agent use did not lead to a significant difference in functional outcome, although it significantly increased the risk of symptomatic intracranial hemorrhage. Recanalization rate was not different between two groups. In the subgroup analysis, prior clopidogrel mono therapy may not increase the risk of symptomatic intracranial hemorrhage, which will need further studies to confirm.
Topics: Cohort Studies; Databases, Bibliographic; Humans; Injections, Intravenous; Ischemia; Outcome Assessment, Health Care; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Stroke; Thrombolytic Therapy; Tissue Plasminogen Activator
PubMed: 25545076
DOI: 10.1111/ijs.12431