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Journal of the Neurological Sciences Nov 2015The association between chronic kidney disease (CKD) and hemorrhagic complications or clinical outcomes in patients treated with intravenous (IV) thrombolytic agents is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The association between chronic kidney disease (CKD) and hemorrhagic complications or clinical outcomes in patients treated with intravenous (IV) thrombolytic agents is controversial.
METHODS
We searched multiple databases for studies on the association between CKD and symptomatic intracerebral hemorrhage (ICH) and/or clinical outcomes in acute stroke patients treated with IV tissue plasminogen activator (tPA). Observational studies that evaluated the association between CKD and outcomes after adjusting for other confounding factors were eligible. We assessed study quality and performed a meta-analysis. The main outcome was symptomatic ICH. The secondary outcomes were poor functional status at 3 months using the modified Rankin Scale, mortality at 3 months, and any ICH.
RESULTS
Seven studies were selected based on our eligibility criteria. Of 7168 patients treated with IV tPA, 2001 (27.9%) had CKD. Patients with CKD had a higher risk of symptomatic ICH and mortality [pooled odds ratio (OR) 1.56, 95% confidence interval (CI) 1.05-2.33 and pooled OR 1.70, 95% CI 1.03-2.81, respectively]. Patients with CKD were likely to have an increased risk of poor outcome at 3 months. There was no significant association between CKD and any ICH.
CONCLUSIONS
Chronic kidney disease may significantly affect symptomatic hemorrhagic complications and poor clinical outcomes following administration of IV tPA.
Topics: Fibrinolytic Agents; Humans; Outcome Assessment, Health Care; Renal Insufficiency, Chronic; Stroke; Tissue Plasminogen Activator
PubMed: 26434615
DOI: 10.1016/j.jns.2015.09.353 -
World Neurosurgery May 2023Randomized controlled trials comparing endovascular thrombectomy (EVT) versus EVT preceded by intravenous thrombolysis (EVT + IVT) for acute ischemic stroke due to... (Review)
Review
BACKGROUND
Randomized controlled trials comparing endovascular thrombectomy (EVT) versus EVT preceded by intravenous thrombolysis (EVT + IVT) for acute ischemic stroke due to large artery occlusion remain controversial. This systematic review and meta-analysis seek to compare these 2 modalities.
METHODS
Online Protocol is available at PROSPERO (york.ac.uk) (registration# CRD42022357506). MEDLINE, PubMed, and Embase were searched. The primary outcome was 90-day modified Rankin scale (mRS) ≤2. Secondary outcomes were 90-day mRS ≤1, 90-day mean mRS, National Institutes of Health Stroke Scale (NIHSS) at 1-3 and 3-7 days, 90-day Barthel Index, 90-day EQ-5D-5L (EuroQoL Group 5-Dimension 5-Level), the volume of infarction (mL), successful reperfusion, complete reperfusion, recanalization, 90-day mortality, any intracranial hemorrhage (ICH), symptomatic ICH, embolization in new territory, new infarction, puncture site complications, vessel dissection, and contrast extravasation. The certainty in the evidence was determined by the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.
RESULTS
Six randomized controlled trials yielding 2332 patients were included, of which 1163 and 1169 underwent EVT and EVT + IVT, respectively. The relative risk (RR) of 90-day mRS ≤2 was similar between the groups (RR = 0.96[0.88, 1.04]; P = 0.28). EVT was non-inferior to EVT + IVT because the lower bond of 95% confidence interval of the risk difference (RD = -0.02 [-0.06, 0.02]; P = 0.36) exceeded the -0.1 non-inferiority margin. The certainty in the evidence was high. The RR of successful reperfusion (RR = 0.96 [0.93, 0.99]; P = 0.006), any ICH (RR = 0.87 [0.77, 0.98]; P = 0.02), and puncture site complications (RR = 0.47 [0.25, 0.88]; P = 0.02) were lower with EVT. For EVT + IVT, the number needed to treat for successful reperfusion was 25, and the number needed to harm for any ICH was 20. The 2 groups were similar in other outcomes.
CONCLUSION
EVT is non-inferior to EVT + IVT. In centers capable of both EVT and IVT, if timely EVT is feasible, it is reasonable to skip bridging IVT and keep rescue thrombolysis at the discretion of the interventionist for patients presenting within 4.5 hours of anterior ischemic stroke.
PubMed: 37201784
DOI: 10.1016/j.wneu.2023.05.033 -
OncoTargets and Therapy 2015Although the urokinase plasminogen activator receptor (uPAR) is expressed in gastric cancer (GC) and colorectal cancer (CRC), its evaluation as a prognostic biomarker... (Review)
Review
PURPOSE
Although the urokinase plasminogen activator receptor (uPAR) is expressed in gastric cancer (GC) and colorectal cancer (CRC), its evaluation as a prognostic biomarker remains controversial. In this study, we performed a literature review and meta-analysis to evaluate the association of uPAR expression with the prognosis of patients with GC and CRC.
METHOD
The PubMed database was searched for material published in English, and data were then extracted and assessed by two reviewers independently. Correlations between uPAR expression and clinicopathological features and overall survival (OS) of patients with GC or CRC were analyzed.
RESULTS
A total of 2,082 patients with GC and CRC from ten studies were included. The results of the meta-analysis showed that the uPAR expression rate in GC and CRC tissues was higher than that in normal tissues (odds ratio [OR] =3.385; 95% confidence interval [CI] 2.605-4.400; P=0.000). Our meta-analysis also revealed a significant association between uPAR expression and lymph node metastasis (OR =1.366; 95% CI =1.086-1.718; P=0.008) and tumor stage (OR =3.076; 95% CI =2.330-4.061; P=0.000). Furthermore, we found that high uPAR expression correlated with poor OS (OR =1.937; 95% CI =1.570-2.930; P=0.000).
CONCLUSION
The uPAR expression may serve as a novel disease marker in GC and CRC, as well as a therapeutic target.
PubMed: 26150727
DOI: 10.2147/OTT.S80634 -
Ophthalmic Surgery, Lasers & Imaging... Nov 2023Many interventions for nonarteritic central retinal artery occlusion (CRAO) are associated with serious complications and little effect on visual outcomes. We report on... (Review)
Review
Many interventions for nonarteritic central retinal artery occlusion (CRAO) are associated with serious complications and little effect on visual outcomes. We report on the findings of a Cochrane systematic review that searched seven databases for peer-reviewed articles reporting on treatments for acute nonarteritic CRAO. We assessed six randomized controlled trials, including interventions such as tissue plasminogen activator (t-PA), isovolumic hemodilution, eyeball massage, intraocular pressure reduction, anticoagulation, vasodilation, oxygen inhalation, laser embolysis, transcorneal electrical stimulation, thrombolysis, pentoxifylline, and enhanced external counterpulsation. However, none of the randomized controlled trials demonstrated significant improvement in visual acuity at 1 month compared to observation, and some patients treated with t-PA experienced serious adverse effects including intracranial hemorrhage. Proposed interventions for acute nonarteritic CRAO may not be better than observation, but the evidence is uncertain. Larger, well-designed studies are necessary to determine the most effective management option for acute nonarteritic CRAO. .
Topics: Humans; Tissue Plasminogen Activator; Retinal Artery Occlusion; Thrombolytic Therapy; Hemodilution; Eye
PubMed: 37855834
DOI: 10.3928/23258160-20230922-01 -
The Cochrane Database of Systematic... Dec 2020Frostbite is a thermal injury caused when tissue is exposed to sub-zero temperatures (in degrees Celsius) long enough for ice crystals to form in the affected tissue....
BACKGROUND
Frostbite is a thermal injury caused when tissue is exposed to sub-zero temperatures (in degrees Celsius) long enough for ice crystals to form in the affected tissue. Depending on the degree of tissue damage, thrombosis, ischaemia, necrosis (tissue death), gangrene and ultimately amputation may occur. Several interventions for frostbite injuries have been proposed, such as hyperbaric oxygen therapy, sympathectomy (nerve block), thrombolytic (blood-thinning) therapy and vasodilating agents such as iloprost, reserpine, pentoxifylline and buflomedil, but the benefits and harms of these interventions are unclear.
OBJECTIVES
To assess the benefits and harms of the different management options for frostbite injuries.
SEARCH METHODS
On 25 February 2020, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), Embase (OvidSP), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED), Conference Proceedings Citation Index-Science (CPCI-S), as well as trials registers. Shortly before publication, we searched Clinicaltrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform, OpenGrey and GreyLit (9 November 2020) again. We investigated references from relevant articles, and corresponded with a trial author.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that compared any medical intervention, e.g. pharmacological therapy, topical treatments or rewarming techniques, for frostbite injuries to another treatment, placebo or no treatment.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data. We used Review Manager 5 for statistical analysis of dichotomous data with risk ratio (RR) with 95% confidence intervals (CIs). We used the Cochrane 'Risk of bias' tool to assess bias in the included trial. We assessed incidence of amputations, rates of serious and non-serious adverse events, acute pain, chronic pain, ability to perform activities of daily living, quality of life, withdrawal rate from medical therapy due to adverse events, occupational effects and mortality. We used GRADE to assess the quality of the evidence.
MAIN RESULTS
We included one, open-label randomised trial involving 47 participants with severe frostbite injuries. We judged this trial to be at high risk of bias for performance bias, and uncertain risk for attrition bias; all other risk of bias domains we judged as low. All participants underwent rapid rewarming, received 250 mg of aspirin and 400 mg intravascular (IV) buflomedil (since withdrawn from practice), and were then randomised to one of three treatment groups for the following eight days. Group 1 received additional IV buflomedil 400 mg for one hour per day. Group 2 received the prostacyclin, iloprost, 0.5 ng to 2 ng/kg/min IV for six hours per day. Group 3 received IV iloprost 2 ng/kg/min for six hours per day plus fibrinolysis with 100 mg recombinant tissue plasminogen activator (rtPA) for the first day only. The results suggest that iloprost and iloprost plus rtPA may reduce the rate of amputations in people with severe frostbite compared to buflomedil alone, RR 0.05 (95% CI 0.00 to 0.78; P = 0.03; very low-quality evidence) and RR 0.31 (95% CI 0.10 to 0.94; P = 0.04; very low-quality evidence), respectively. Iloprost may be as effective as iloprost plus rtPA at reducing the amputation rate, RR 0.14 (95% CI 0.01 to 2.56; P = 0.19; very low-quality evidence). There were no reported deaths or withdrawals due to adverse events in any of the groups; we assessed evidence for both outcomes as being of very low quality. Adverse events (including flushing, nausea, palpitations and vomiting) were common, but not reported separately by comparator arm (very low-quality evidence). The included study did not measure the outcomes of acute pain, chronic pain, ability to perform activities of daily living, quality of life or occupational effects.
AUTHORS' CONCLUSIONS
There is a paucity of evidence regarding interventions for frostbite injuries. Very low-quality evidence from a single small trial indicates that iloprost, and iloprost plus rtPA, in combination with buflomedil may reduce the need for amputation in people with severe frostbite compared to buflomedil alone. However, buflomedil has been withdrawn from use. High quality randomised trials are needed to establish firm evidence for the treatment of frostbite injuries.
Topics: Amputation, Surgical; Aspirin; Bias; Drug Therapy, Combination; Epoprostenol; Fibrinolytic Agents; Frostbite; Humans; Iloprost; Platelet Aggregation Inhibitors; Pyrrolidines; Recombinant Proteins; Rewarming; Tissue Plasminogen Activator; Vasodilator Agents
PubMed: 33341943
DOI: 10.1002/14651858.CD012980.pub2 -
The Archives of Bone and Joint Surgery Nov 2018The Plasminogen Activator Inhibitor-1 gene 4G/5G (PAI-1 4G/5G) polymorphism has been suggested to be associated with osteonecrosis of the femoral head (ONFH)... (Review)
Review
BACKGROUND
The Plasminogen Activator Inhibitor-1 gene 4G/5G (PAI-1 4G/5G) polymorphism has been suggested to be associated with osteonecrosis of the femoral head (ONFH) susceptibility; however, the results are conflicting and inconclusive. We have carried out a comprehensive meta-analysis to derive a more precise estimation of the association.
METHODS
A comprehensive search in PubMed, EMBASE, Google Scholar, and ISI Web of Knowledge databases was conducted to identify all eligible case-control publications investigating the association between PAI-1 4G/5G polymorphism and ONFH risk. Odds ratios (OR) and corresponding 95% confidence intervals (CI) were used to assess the association.
RESULTS
A total of six studies with 456 cases and 1,019 controls were included in this review. Three studies were from Caucasian descendants and the three others were from East Asian descendants. Overall analysis suggests a significant association between PAI-1 4G/5G polymorphism and ONFH risk under the allele model (4G vs. 5G: OR =1.540, 95% CI =1.055-2.248, ) and the recessive model (4G4G vs. 4G5G+5G5G: OR=1.931, 95% CI: 1.162-3.207, ). When stratified by ethnicity, we have found a significant association between PAI-1 4G/5G polymorphism and ONFH risk among the Caucasian (4G5G vs. 5G5G: OR=1.806, 95% CI: 1.064-3.067, ) and East Asians (4G4G vs. 5G5G: OR=1.619, 95% CI: 1.025-2.556, and 4G4G vs. 4G5G+5G5G: OR=1.665, 95% CI: 1.207-2.297, ).
CONCLUSION
The present meta-analysis suggested that PAI-1 4G/5G (rs1799889) polymorphism is a potential risk factor for development of ONFH. However, large-scale and well-designed case-control studies in different ethnicities are required to validate these results.
PubMed: 30637301
DOI: No ID Found -
Journal of Stroke and Cerebrovascular... Apr 2021To compare outcomes between two models of acute ischemic stroke care. Namely 1) "drip-and-stay", i.e. IV tissue plasminogen activator (tPA) administered at a spoke... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To compare outcomes between two models of acute ischemic stroke care. Namely 1) "drip-and-stay", i.e. IV tissue plasminogen activator (tPA) administered at a spoke hospital in a telestroke network, with the patient remaining at the spoke, versus 2) "drip-and-ship", i.e. tPA administered at a spoke hospital with subsequent patient transfer to a hub hospital, and 3) "hub", i.e. tPA and subsequent treatment at a hub hospital.
MATERIALS AND METHODS
We performed a systematic review and meta-analysis according to PRISMA guidelines. Literature searches of MEDLINE, Embase, and Cochrane from inception-October 2019 included randomized control trials and observational cohort studies comparing the drip-and-stay model to hub and drip-and-ship models. Outcomes of interest were functional independence (modified Rankin Scale ≤ 1), symptomatic intracranial hemorrhage (sICH), mortality, and length of stay. Pooled effect estimates were calculated using a fixed-effects meta-analysis and random-effects Bayesian meta-analysis. Non-inferiority was calculated using a fixed-margin method.
RESULTS
Of 2806 unique records identified, 10 studies, totaling 4,164 patients, fulfilled the eligibility criteria. Meta-analysis found no significant difference in functional outcomes (mRS0-1) (6 studies, RR=1.09, 95%CI 0.98-1.22, p=0.123), sICH (8 studies, RR=0.98, 95%CI 0.64-1.51, p=0.942), or 90-day mortality (5 studies, RR=0.98, 95%CI 0.73-1.32, p=0.911, respectively) between patients treated in a drip-and-stay model compared to patients treated in drip-and-ship or hub models. There was no significant heterogeneity in these outcomes. Drip-and-stay outcomes (mRS 0-1, sICH) were non-inferior when compared to the combined group.
CONCLUSIONS
Our findings indicate that drip-and-stay is non-inferior to current models of drip-and-ship or hub stroke care, and may be as safe and as effective as either.
Topics: Aged; Aged, 80 and over; Female; Fibrinolytic Agents; Humans; Infusions, Intravenous; Intracranial Hemorrhages; Ischemic Stroke; Length of Stay; Male; Middle Aged; Observational Studies as Topic; Patient Transfer; Randomized Controlled Trials as Topic; Recovery of Function; Risk Assessment; Risk Factors; Telemedicine; Thrombolytic Therapy; Time Factors; Time-to-Treatment; Tissue Plasminogen Activator; Treatment Outcome
PubMed: 33540336
DOI: 10.1016/j.jstrokecerebrovasdis.2021.105638 -
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 -
Thrombosis Journal 2018Small studies have implicated plasminogen activator inhibitor-1 (PAI-1) as a predictor of cardiovascular events; however, these findings have been inconsistent.We sought...
BACKGROUND
Small studies have implicated plasminogen activator inhibitor-1 (PAI-1) as a predictor of cardiovascular events; however, these findings have been inconsistent.We sought out to examine the potential role of PAI-1 as a marker for major adverse cardiovascular events (MACE).
METHODS
We systematically reviewed all indexed studies examining the association between PAI-1 and MACE (defined as death, myocardial infarction, or cerebrovascular accident) or restenosis. EMBASE, Web of Science, Medline, and the Cochrane Library were searched through October 2016 to identify relevant studies, supplemented by letters to authors and review of citations. Studies reporting the results of PAI-1 antigen and/or activity levels in association with MACE in human subjects were included.
RESULTS
Of 5961 articles screened, we identified 38 articles published between 1991 to 2016 that reported PAI-1 levels in 11,557 patients. In studies that examined PAI-1 antigen and activity levels, 15.1% and 29.6% of patients experienced MACE, respectively. Patients with MACE had higher PAI-1 antigen levels with a mean difference of 6.11 ng/mL (95% CI, 3.27-8.96). This finding was similar among patients with and without known coronary artery disease. Comparatively, studies that stratified by PAI-1 activity levels were not associated with MACE. In contrast, studies of coronary restenosis suggest PAI-1 antigen and activity levels are negatively associated with MACE.
CONCLUSIONS
Elevated plasma PAI-1 antigen levels are associated with MACE. Definitive studies are needed to ascertain if PAI-1 acts simply as a marker of risk or if it is indeed a bona fide therapeutic target.
PubMed: 29991926
DOI: 10.1186/s12959-018-0166-4 -
Thrombosis and Haemostasis Jul 2016Elevated plasma levels of the pro-thrombotic and pro-inflammatory factor plasminogen activator inhibitor-1 (PAI-1) may contribute to the pathogenesis of atherosclerotic... (Meta-Analysis)
Meta-Analysis Review
Elevated plasma levels of the pro-thrombotic and pro-inflammatory factor plasminogen activator inhibitor-1 (PAI-1) may contribute to the pathogenesis of atherosclerotic cardiovascular disease. Beyond their lipid-lowering effect, statins have been shown to modulate plasma PAI-1 levels but evidence from individual randomised controlled trials (RCTs) is controversial. Therefore, we aimed to assess the potential effects of statin therapy on plasma PAI-1 concentration through a meta-analysis of RCTs. We searched Medline and SCOPUS databases (up to October 3, 2014) to identify RCTs investigating the effect of statin therapy on plasma PAI-1 concentrations. We performed random-effects meta-analysis and assessed heterogeneity (I² test, subgroup and sensitivity analyses) and publication bias (funnel plot, Egger and "trim and fill" tests). Sixteen RCTs (comprising 19 treatment arms) were included and pooled analyses showed a significant effect of statins in reducing plasma PAI-1 concentrations (weighted mean difference WMD: -15.72 ng/ml, 95 % confidence interval [CI]: -25.01, -6.43,). In subgroup analysis, this effect remained significant in with lipophilic statins (atorvastatin and simvastatin) (WMD: -21.32 ng/ml, 95 % CI: -32.73, -9.91, I²=99 %) and particularly atorvastatin (WMD: -20.88 ng/mL, 95 % CI: -28.79, -12.97, I2=97 %). In the meta-regression analysis, the impact of statins on PAI-1 did not correlate with the administered dose, duration of treatment and changes in plasma LDL-cholesterol concentrations. Finally, evidence of publication bias was observed. In conclusion, taking into account the limit of heterogeneity between studies, the present meta-analysis suggests that statin therapy (mainly atorvastatin) significantly lowers plasma PAI-1 concentrations.
Topics: Atorvastatin; Coronary Artery Disease; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Plasminogen Activator Inhibitor 1; Publication Bias; Randomized Controlled Trials as Topic; Regression Analysis; Risk Factors
PubMed: 27009446
DOI: 10.1160/TH15-10-0770