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Thrombosis Research Nov 2013Thromboembolism, including deep venous thrombosis and pulmonary embolism, is a grave threat to patients undergoing total joint replacement. Using a systematic review and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Thromboembolism, including deep venous thrombosis and pulmonary embolism, is a grave threat to patients undergoing total joint replacement. Using a systematic review and meta-analysis we asked whether gene mutations or polymorphisms could be risk factors for thrombosis after arthroplasty.
METHODS
We performed a comprehensive search of Medline, PubMed, Embase, Cochrane databases, China National Knowledge Infrastructure (CNKI), and Google Scholar, and identified 19 studies detailing genetic investigations of patients with thromboembolism following joint replacement.
RESULTS
Our meta-analyses included 5149 patients who underwent arthroplasty surgery. Significant associations with venous thromboembolism were identified for factor G1691A (odds ratio (OR) 1.41, 95% confidence interval (CI) 1.03 - 1.94, p=0.03), prothrombin G20210A (OR 2.16, 95% CI, 1.27- 3.69, p=0.005), and MTHFR/C677T/TT (OR 2.36, 95% CI 1.03 - 5.42, p=0.04) in Caucasian populations. No significant gene mutation was identified in Asian populations.
CONCLUSION
This study suggests a way to identify patients scheduled for arthroplasty who are at higher risk of thrombosis, enabling individualized treatment.
Topics: Arthroplasty, Replacement; Factor V; Humans; Methylenetetrahydrofolate Reductase (NADPH2); Polymorphism, Genetic; Prothrombin; Risk Factors; Thromboembolism
PubMed: 24074702
DOI: 10.1016/j.thromres.2013.09.005 -
Annals of Vascular Surgery Jul 2010To summarize the present evidence for an association between circulating tissue plasminogen activator (tPA) levels and abdominal aortic aneurysm (AAA) presence, we... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
To summarize the present evidence for an association between circulating tissue plasminogen activator (tPA) levels and abdominal aortic aneurysm (AAA) presence, we performed a systematic review and meta-analysis of case-control studies that compared plasma tPA levels between patients with AAA and subjects without AAA.
METHODS
MEDLINE was searched to identify all case-control studies that compared plasma tPA levels between patients with AAA and subjects without AAA. For each study, data regarding plasma tPA levels in both the AAA and control groups were used to generate standardized mean differences and 95% confidence intervals. Study-specific estimates were combined using inverse variance-weighted average of logarithmic standardized mean differences in both fixed- and random-effects models.
RESULTS
Our search identified five eligible case-control studies, including data on 234 patients with AAA and 459 subjects without AAA. Pooled analysis of the five studies demonstrated nonsignificantly higher plasma tPA levels in the AAA group than those in the control group in fixed-effect models (standardized mean differences = 0.07; 95% confidence interval = -0.09-0.24; p = 0.40). There was minimal study heterogeneity of results (p = 0.05) and no evidence of significant publication bias (p = 0.3272).
CONCLUSION
The results of our analysis suggest that plasma tPA levels may not be higher in patients with AAA than those in subjects without AAA. Higher plasma tPA levels may not be associated with AAA presence.
Topics: Aged; Aortic Aneurysm, Abdominal; Biomarkers; Case-Control Studies; Evidence-Based Medicine; Female; Humans; Male; Middle Aged; Risk Assessment; Risk Factors; Tissue Plasminogen Activator; Up-Regulation
PubMed: 20409678
DOI: 10.1016/j.avsg.2010.02.005 -
Reviews in Medical Virology Jul 2023Numerous studies have linked coronavirus disease 2019 (COVID-19) with endothelial dysfunction and reported elevated levels of endothelial biomarkers in this disease. We... (Meta-Analysis)
Meta-Analysis Review
Numerous studies have linked coronavirus disease 2019 (COVID-19) with endothelial dysfunction and reported elevated levels of endothelial biomarkers in this disease. We conducted a systematic review and meta-analysis of the published evidence in this respect. A systematic literature search of PubMed and Scopus databases was performed to find studies investigating biomarkers of endothelial dysfunction in COVID-19 patients. Pooled standardized mean differences and their 95% confidence intervals were calculated for each biomarker using random effect model. 74 studies with 7668 patients were included. In comparison to patients with good outcome, those with poor outcome had higher levels of von Willebrand factor (vWF) (SMD: 0.83, 95% CI: 0.59-1.07, p < 0.00001), vWF:ADAMTS13 (1.23, (0.77-1.7), p < 0.00001), angiopoietin-2 (Ang-2) (1.06 (0.6-1.51), p < 0.0001), E-selectin (1.09 (0.55-1.63), p < 0.0001), P-selectin (0.59 (0.24-0.94), p = 0.001), syndecan-1 (0.99 (0.6-1.37), p < 0.00001), mid-regional pro-adrenomedullin (MR-proADM) (1.52 (1.35-1.68), p < 0.00001), vascular endothelial growth factor (0.27 (0.02-0.53), p = 0.03), soluble fms-like tyrosine kinase-1 (sFLT-1) (1.93 (0.65-3.21), p = 0.03) and lower levels of ADAMTS13 antigen (-0.69 (-0.9 to -0.47) p < 0.00001) and activity (-0.84 (-1.06 to -0.61) p < 0.0000). Plasminogen activator inhibitor-1 and tissue plasminogen activator levels were not different between the two groups (p < 0.05). There were elevated levels of endothelial dysfunction biomarkers in COVID-19 patients with poor outcome, indicating their possible role in disease severity and prognosis. In particular, MR-proADM, vWF, syndecan-1 and sFLT-1 showed a significant association with poor outcome in these patients.
Topics: Humans; Tissue Plasminogen Activator; Syndecan-1; COVID-19; Vascular Endothelial Growth Factor A; von Willebrand Factor; Biomarkers
PubMed: 36943015
DOI: 10.1002/rmv.2442 -
Systematic Reviews May 2013There is currently only one clinically approved drug, tissue plasminogen activator (tPA), for the treatment of acute ischaemic stroke. The RhoA pathway, including RhoA... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There is currently only one clinically approved drug, tissue plasminogen activator (tPA), for the treatment of acute ischaemic stroke. The RhoA pathway, including RhoA and its downstream effector Rho kinase (ROCK), has been identified as a possible therapeutic target. Our aim was to assess the impact of study design characteristics and study quality on reported measures of efficacy and to assess for the presence and impact of publication bias.
METHODS
We conducted a systematic review and meta-analysis on publications describing the efficacy of RhoA and ROCK inhibitors in animal models of focal cerebral ischaemia where outcome was assessed as a change in lesion size or neurobehavioural score, or both.
RESULTS
We identified 25 published papers which met our inclusion criteria. RhoA and ROCK inhibitors reduced lesion size by 37.3% in models of focal cerebral ischaemia (95% CI, 28.6% to 46.0%, 41 comparisons), and reduced neurobehavioural data by 40.5% (33.4% to 47.7%, 30 comparisons). Overall study quality was low (median=4, interquartile range 3-5) and measures to reduce bias were seldom reported. Publication bias was prevalent and associated with a substantial overstatement of efficacy for lesion size.
CONCLUSIONS
RhoA and ROCK inhibitors appear to be effective in animal models of stroke. However the low quality score, publication bias and limited number of studies are areas which need attention prior to conducting clinical trials.
Topics: Animals; Brain Ischemia; Disease Models, Animal; Protein Kinase Inhibitors; Stroke; rho-Associated Kinases; rhoA GTP-Binding Protein
PubMed: 23687965
DOI: 10.1186/2046-4053-2-33 -
Journal of Diabetes and Metabolic... Dec 2020The 4G5G polymorphism of Plasminogen activator inhibitor-1 (PAI-1) gene is reported to be associated with diabetes nephropathy and retinopathy (DNR) risk. However, the... (Review)
Review
BACKGROUND
The 4G5G polymorphism of Plasminogen activator inhibitor-1 (PAI-1) gene is reported to be associated with diabetes nephropathy and retinopathy (DNR) risk. However, the findings are conflicting. Herein, we conducted a case-control and meta-analysis study to explore the association of PAI-1 4G5G polymorphism with risk of DNR.
METHODS
We retrieved PubMed, EMBASE, Web of Knowledge, and CNKI databases and screened eligible studies up to August 15, 2020. The strength of associations was assessed by odd ratio (OR) and the corresponding 95% confidence interval (95% CI).
RESULTS
A total of 27 case-control studies including 16 studies with 1,825 cases case and 1,731 controls on DN and eleven studies with 1,397 cases and 1,545 controls on DR were selected. Pooled data showed that the PAI-1 4G5G polymorphism was significantly associated with DN (allele model: OR = 0.674, 95% CI 0.524-0.865, p = 0.002; homozygote model: OR = 0.536, 95% CI 0.351-0.817, p = 0.004; heterozygote model: OR = 0.621, 95% CI 0.427-0.903, p = 0.013; dominant model: OR = 0.575, 95% CI 0.399-0.831, p = 0.003; and recessive model: OR = 0.711, 95% CI 0.515-0.981, p = 0.038) and DR (homozygote model: OR = 0.770, 95% CI 0.621-0.955, p = 0.0.017) risk. Stratified analyses by ethnicity indicated that PAI-1 4G5G polymorphism was associated with DN and DR risk in Asians and Caucasians, respectively.
CONCLUSIONS
The present meta-analysis revealed that the PAI-1 4G5G polymorphism was associated with increased risk of DN and DR risk. However, well-designed large-scale clinical studies are required to further validate our results.
PubMed: 33520873
DOI: 10.1007/s40200-020-00675-1 -
American Journal of Hematology Apr 2024In the general population, individuals with an inherited thrombophilia have a higher risk of thrombosis, but the effect of inherited thrombophilia on the risk of... (Meta-Analysis)
Meta-Analysis
In the general population, individuals with an inherited thrombophilia have a higher risk of thrombosis, but the effect of inherited thrombophilia on the risk of cancer-associated venous thromboembolism (VTE) remains controversial. Our objective was to determine the risk of VTE in cancer patients with inherited thrombophilia. We conducted a systematic review and meta-analysis of studies reporting on VTE after a cancer diagnosis in adult patients who were tested for inherited thrombophilia. In September 2022, we searched Medline, EMBASE, and Cochrane Central. Two reviewers screened the abstracts/full texts and assessed study quality using the Quality in Prognostic Studies tool. We used Mantel-Haenszel random-effects models to estimate pooled odds ratios (OR) of VTE and 95% confidence intervals (95%CI). We included 37 and 28 studies in the systematic review and meta-analysis, respectively. Most studies focused on specific cancer types and hematologic malignancies were rare. The risk of VTE was significantly higher in cancer patients with non-O (compared with O) blood types (OR: 1.56 [95% CI: 1.28-1.90]), Factor V Leiden, and Prothrombin Factor II G20210A mutations compared with wild types (OR: 2.28 [95% CI: 1.51-3.48] and 2.14 [95% CI: 1.14-4.03], respectively). Additionally, heterozygous and homozygous methylenetetrahydrofolate reductase C677T had ORs of 1.50 (95% CI: 1.00-2.24) and 1.38 (95% CI: 0.87-2.22), respectively. Among those with Plasminogen-Activator Inhibitor-1 4G/5G, Vascular Endothelial Growth Factor (VEGF) A C634G, and VEGF C2578A mutations, there was no significant association with VTE. In conclusion, this meta-analysis provided evidence that non-O blood types, Factor V Leiden, and Prothrombin Factor II G20210A mutations are important genetic risk factors for VTE in cancer patients.
Topics: Adult; Humans; Venous Thromboembolism; Vascular Endothelial Growth Factor A; Prothrombin; Thrombophilia; Mutation; Neoplasms; Factor V; Risk Factors
PubMed: 38291601
DOI: 10.1002/ajh.27222 -
Thrombosis Research Mar 2014According to US Food and Drugs Administration (FDA), 2 hour recombinant tissue plasminogen activator (rt-PA) 100mg infusion is recommended for eligible patients with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
According to US Food and Drugs Administration (FDA), 2 hour recombinant tissue plasminogen activator (rt-PA) 100mg infusion is recommended for eligible patients with acute pulmonary embolism (PE). However,there exists evidence implying that a lower dosage of rt-PA can be equally effective but potentially safer compared with rt-PA 100mg regimen. The aim of this systematic review and meta-analysis is to assess the efficacy and safety of low dose rt-PA in the treatment of acute PE.
MATERIAL AND METHOD
We searched Pubmed, EMBASE, the Cochrane library and CBM Literature Database for randomized controlled trials (RCT) focusing on low dose rt-PA for acute PE. Outcomes were described in terms of changes of image tests and echocardiography, major bleeding events, all-cause death, and recurrence of PE.
RESULTS
Five studies (440 patients) were included, three of which compared low dose rt-PA (0.6 mg/kg, maximum 50mg or 50mg infusion 2h) with standard dose (100mg infusion 2h). There were more major bleeding events in standard dose rt-PA group than in low dose group (OR 0.33, 95%CI 0.12-0.91;P=0.94,I(2)=0%), while there were no statistical differences in recurrent PE or all cause mortality between these two groups. Two studies compared low dose (0.6 mg/kg, maximum 50mg/2 min bolus or 10mg bolus, ≤40 mg/2 h) with heparin. There was no significant difference in major bleeding events (OR 0.73, 95% CI 0.14-3.98;P=0.72), recurrent PE or all cause mortality. No dose-related heterogeneity was found for all the included studies.
CONCLUSIONS
The results of this meta-analysis were hypothesis-generating. Based on the limited data, our systematic review suggested that low dose rt-PA had similar efficacy but was safer than standard dose of rt-PA. In addition, compared with heparin, low dose rt-PA didn't increase the risk of major bleeding for eligible PE patients.
Topics: Dose-Response Relationship, Drug; Humans; Pulmonary Embolism; Recombinant Proteins; Thrombolytic Therapy; Tissue Plasminogen Activator
PubMed: 24412030
DOI: 10.1016/j.thromres.2013.12.026 -
BMJ Open Oct 2019Soluble urokinase plasminogen activated receptor (suPAR) is a biomarker that may predict the occurrence of focal segmental glomerulosclerosis (FSGS); however, there is... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Soluble urokinase plasminogen activated receptor (suPAR) is a biomarker that may predict the occurrence of focal segmental glomerulosclerosis (FSGS); however, there is still controversy about whether suPAR can predict FSGS. In this study, we performed a systematic evaluation and meta-analysis to prove whether suPAR can predict FSGS, and to detect a threshold concentration of suPAR that can be used to diagnose FSGS. In addition, a threshold concentration of suPAR for the diagnosis of FSGS was proposed.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
We systematically searched PubMed, Embase, Cochrane Library, Web of Science and China Biology Medicine databases for studies published from the inception dates to 1 December 2018. ELIGIBILITY CRITERIA: (1) Data involving the suPAR level were from blood samples; (2) FSGS was diagnosed by biopsy; and (3) randomised controlled trials, cohort studies, case-control studies and cross-sectional studies.
DATA EXTRACTION AND SYNTHESIS
Initially, a total of 364 studies were searched, among which 29 studies were finally included. In addition, seven studies described the cut-off value of suPAR, which ranged from 2992.6 to 5500 pg/mL.
RESULTS
The results showed that the suPAR levels in the primary FSGS group were significantly higher when compared with that in the normal control group (p0.001; standard mean difference (SMD): 2.56; 95% CI 1.85 to 3.28), and significant differences were observed in the secondary FSGS and in the normal control group (p0.001; SMD: 1.68; 95% CI 1.37 to 1.98). A suPAR concentration of 3000 pg/mL may be the best threshold for the diagnosis of primary FSGS (sensitivity=0.72; specificity=0.88; area under the curve=0.85).
CONCLUSION
Our results suggested that suPAR might be a potential biomarker for predicting primary and secondary FSGS. In addition, our data showed that a suPAR concentration of 3000 pg/mL might be used as a threshold for the diagnosis of FSGS.
TRIAL REGISTRATION NUMBER
CRD42019120948.
Topics: Biomarkers; Glomerulosclerosis, Focal Segmental; Humans; Predictive Value of Tests; Prognosis; Receptors, Urokinase Plasminogen Activator
PubMed: 31594897
DOI: 10.1136/bmjopen-2019-031812 -
Clinical and Experimental Nephrology Jan 2023Some clinical trials have shown that soluble urokinase-type plasminogen activator receptor (suPAR) has good predictive value for acute kidney injury (AKI), but there is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Some clinical trials have shown that soluble urokinase-type plasminogen activator receptor (suPAR) has good predictive value for acute kidney injury (AKI), but there is still a lack of evidence-based proof. Therefore, we conducted this systematic review and meta-analysis to evaluate the predictive value of suPAR for AKI.
METHODS
Pubmed, EMBASE, Cochrane Library, and Web of Science databases were searched until December 2021 to obtain the literature on the prediction of suPAR for AKI. The quality of the included studies was assessed using the QUADAS-2 scoring system, and a bivariate random-effect model was used for the meta-analysis. The present study has been registered on PROSPERO (Registration No. CRD42022324978).
RESULTS
Seven articles were included, involving 2,319 patients, 635 of whom were AKI patients. The meta-analysis results showed that the combined sensitivity of suPAR in predicting AKI was 0.77 (95% CI 0.67-0.84); the specificity was 0.64 (95% CI 0.53-0.75); the odds ratio of diagnosis was 6 (95% CI 3-10); the pooled positive likelihood ratio was 2.2 (95% CI 1.6-2.9); the pooled negative likelihood ratio was 0.36 (95% CI 0.26-0.52); and the area under the summary receiver-operating characteristic (SROC) curve was 0.77 (95% CI 0.12~0.99). Deek's funnel plot suggested no potential publication bias among included studies.
CONCLUSION
suPAR is a valuable biomarker for the prediction of AKI with relatively high predictive accuracy, but its clinical application needs improvements. SuPAR should be considered as an indicator in the subsequent development of more effective predictive tools for AKI.
Topics: Humans; Receptors, Urokinase Plasminogen Activator; Acute Kidney Injury; Biomarkers; ROC Curve
PubMed: 36469196
DOI: 10.1007/s10157-022-02300-2 -
PloS One 2016Recombinant tissue plasminogen activator (rtPA) is the only effective drug approved by US FDA to treat ischemic stroke, and it contains pleiotropic effects besides... (Meta-Analysis)
Meta-Analysis Review
Recombinant Tissue Plasminogen Activator Induces Neurological Side Effects Independent on Thrombolysis in Mechanical Animal Models of Focal Cerebral Infarction: A Systematic Review and Meta-Analysis.
BACKGROUND AND PURPOSE
Recombinant tissue plasminogen activator (rtPA) is the only effective drug approved by US FDA to treat ischemic stroke, and it contains pleiotropic effects besides thrombolysis. We performed a meta-analysis to clarify effect of tissue plasminogen activator (tPA) on cerebral infarction besides its thrombolysis property in mechanical animal stroke.
METHODS
Relevant studies were identified by two reviewers after searching online databases, including Pubmed, Embase, and ScienceDirect, from 1979 to 2016. We identified 6, 65, 17, 12, 16, 12 and 13 comparisons reporting effect of endogenous tPA on infarction volume and effects of rtPA on infarction volume, blood-brain barrier, brain edema, intracerebral hemorrhage, neurological function and mortality rate in all 47 included studies. Standardized mean differences for continuous measures and risk ratio for dichotomous measures were calculated to assess the effects of endogenous tPA and rtPA on cerebral infarction in animals. The quality of included studies was assessed using the Stroke Therapy Academic Industry Roundtable score. Subgroup analysis, meta-regression and sensitivity analysis were performed to explore sources of heterogeneity. Funnel plot, Trim and Fill method and Egger's test were obtained to detect publication bias.
RESULTS
We found that both endogenous tPA and rtPA had not enlarged infarction volume, or deteriorated neurological function. However, rtPA would disrupt blood-brain barrier, aggravate brain edema, induce intracerebral hemorrhage and increase mortality rate.
CONCLUSIONS
This meta-analysis reveals rtPA can lead to neurological side effects besides thrombolysis in mechanical animal stroke, which may account for clinical exacerbation for stroke patients that do not achieve vascular recanalization with rtPA.
Topics: Animals; Animals, Genetically Modified; Blood-Brain Barrier; Brain Edema; Cerebral Infarction; Data Interpretation, Statistical; Disease Models, Animal; Male; Rats; Recombinant Proteins; Sensitivity and Specificity; Stroke; Thrombolytic Therapy; Tissue Plasminogen Activator
PubMed: 27387385
DOI: 10.1371/journal.pone.0158848