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The Cochrane Database of Systematic... Aug 2022Acute pulmonary embolism (APE) is a major cause of acute morbidity and mortality. APE results in long-term morbidity in up to 50% of survivors, known as post-pulmonary... (Review)
Review
BACKGROUND
Acute pulmonary embolism (APE) is a major cause of acute morbidity and mortality. APE results in long-term morbidity in up to 50% of survivors, known as post-pulmonary embolism (post-PE) syndrome. APE can be classified according to the short-term (30-day) risk of mortality, based on a variety of clinical, imaging and laboratory findings. Most mortality and morbidity is concentrated in high-risk (massive) and intermediate-risk (submassive) APE. The first-line treatment for APE is systemic anticoagulation. High-risk (massive) APE accounts for less than 10% of APE cases and is a life-threatening medical emergency, requiring immediate reperfusion treatment to prevent death. Systemic thrombolysis is the recommended treatment for high-risk (massive) APE. However, only a minority of the people affected receive systemic thrombolysis, due to comorbidities or the 10% risk of major haemorrhagic side effects. Of those who do receive systemic thrombolysis, 8% do not respond in a timely manner. Surgical pulmonary embolectomy is an alternative reperfusion treatment, but is not widely available. Intermediate-risk (submassive) APE represents 45% to 65% of APE cases, with a short-term mortality rate of around 3%. Systemic thrombolysis is not recommended for this group, as major haemorrhagic complications outweigh the benefit. However, the people at higher risk within this group have a short-term mortality of around 12%, suggesting that anticoagulation alone is not an adequate treatment. Identification and more aggressive treatment of people at intermediate to high risk, who have a more favourable risk profile for reperfusion treatments, could reduce short-term mortality and potentially reduce post-PE syndrome. Catheter-directed treatments (catheter-directed thrombolysis and catheter embolectomy) are minimally invasive reperfusion treatments for high- and intermediate-risk APE. Catheter-directed treatments can be used either as the primary treatment or as salvage treatment after failure of systemic thrombolysis. Catheter-directed thrombolysis administers 10% to 20% of the systemic thrombolysis dose directly into the thrombus in the lungs, potentially reducing the risks of haemorrhagic side effects. Catheter embolectomy mechanically removes the thrombus without the need for thrombolysis, and may be useful for people with contraindications for thrombolysis. Currently, the benefits of catheter-based APE treatments compared with existing medical and surgical treatment are unclear despite increasing adoption of catheter treatments by PE response teams. This review examines the evidence for the use of catheter-directed treatments in high- and intermediate-risk APE. This evidence could help guide the optimal treatment strategy for people affected by this common and life-threatening condition.
OBJECTIVES
To assess the effects of catheter-directed therapies versus alternative treatments for high-risk (massive) and intermediate-risk (submassive) APE.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search was 15 March 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of catheter-directed therapies for the treatment of high-risk (massive) and intermediate-risk (submassive) APE. We excluded catheter-directed treatments for non-PE. We applied no restrictions on participant age or on the date, language or publication status of RCTs.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. The main outcomes were all-cause mortality, treatment-associated major and minor haemorrhage rates based on two established clinical definitions, recurrent APE requiring retreatment or change to a different APE treatment, length of hospital stay, and quality of life. We used GRADE to assess certainty of evidence for each outcome.
MAIN RESULTS
We identified one RCT (59 participants) of (ultrasound-augmented) catheter-directed thrombolysis for intermediate-risk (submassive) APE. We found no trials of any catheter-directed treatments (thrombectomy or thrombolysis) in people with high-risk (massive) APE or of catheter-based embolectomy in people with intermediate-risk (submassive) APE. The included trial compared ultrasound-augmented catheter-directed thrombolysis with alteplase and systemic heparinisation versus systemic heparinisation alone. In the treatment group, each participant received an infusion of alteplase 10 mg or 20 mg over 15 hours. We identified a high risk of selection and performance bias, low risk of detection and reporting bias, and unclear risk of attrition and other bias. Certainty of evidence was very low because of risk of bias and imprecision. By 90 days, there was no clear difference in all-cause mortality between the treatment group and control group. A single death occurred in the control group at 20 days after randomisation, but it was unrelated to the treatment or to APE (odds ratio (OR) 0.31, 95% confidence interval (CI) 0.01 to 7.96; 59 participants). By 90 days, there were no episodes of treatment-associated major haemorrhage in either the treatment or control group. There was no clear difference in treatment-associated minor haemorrhage between the treatment and control group by 90 days (OR 3.11, 95% CI 0.30 to 31.79; 59 participants). By 90 days, there were no episodes of recurrent APE requiring retreatment or change to a different APE treatment in the treatment or control group. There was no clear difference in the length of mean total hospital stay between the treatment and control groups. Mean stay was 8.9 (standard deviation (SD) 3.4) days in the treatment group versus 8.6 (SD 3.9) days in the control group (mean difference 0.30, 95% CI -1.57 to 2.17; 59 participants). The included trial did not investigate quality of life measures. AUTHORS' CONCLUSIONS: There is a lack of evidence to support widespread adoption of catheter-based interventional therapies for APE. We identified one small trial showing no clear differences between ultrasound-augmented catheter-directed thrombolysis with alteplase plus systemic heparinisation versus systemic heparinisation alone in all-cause mortality, major and minor haemorrhage rates, recurrent APE and length of hospital stay. Quality of life was not assessed. Multiple small retrospective case series, prospective patient registries and single-arm studies suggest potential benefits of catheter-based treatments, but they provide insufficient evidence to recommend this approach over other evidence-based treatments. Researchers should consider clinically relevant primary outcomes (e.g. mortality and exercise tolerance), rather than surrogate markers (e.g. right ventricular to left ventricular (RV:LV) ratio or thrombus burden), which have limited clinical utility. Trials must include a control group to determine if the effects are specific to the treatment.
Topics: Acute Disease; Anticoagulants; Hemorrhage; Humans; Pulmonary Embolism; Thrombolytic Therapy; Tissue Plasminogen Activator
PubMed: 35938605
DOI: 10.1002/14651858.CD013083.pub2 -
Medicine Nov 2023Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory biomarker that is used to predict mortality, readmission, early discharge, and LOS, thus,... (Meta-Analysis)
Meta-Analysis
Role of soluble urokinase type plasminogen activator receptor (suPAR) in predicting mortality, readmission, length of stay and discharge in emergency patients: A systematic review and meta analysis.
BACKGROUND
Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory biomarker that is used to predict mortality, readmission, early discharge, and LOS, thus, serves as a useful tool for ED physicians. Our study aims to analyze the efficacy of suPAR in predicting these prognostic markers in ED.
METHODS
We performed a comprehensive search on 6 databases from the inception to 30th November 2022, to select the following eligibility criteria; a) observation or triage trial studies investigating the role of suPAR levels in predicting: 30 day and 90-day mortality, 30-day readmission, early discharge (within 24hr), and LOS in patients coming to AMU.
RESULTS
A total of 13 studies were included, with a population size of 35,178, of which 52.9% were female with a mean age of 62.93 years. Increased risk of 30-day mortality (RR = 10.52; 95% CI = 4.82-22.95; I2 = 38%; P < .00001), and risk of 90-day mortality (RR = 5.76; 95% CI = 3.35-9.91; I2 = 36%; P < .00001) was observed in high suPAR patients. However, a slightly increased risk was observed for 30-day readmission (RR = 1.50; 95% CI = 1.16-1.94; I2 = 54%; P = .002). More people were discharged within 24hr in the low suPAR level group compared to high suPAR group (RR = 0.46; 95% CI = 0.40-0.53; I2 = 41%; P < .00001). LOS was thrice as long in high suPAR level patients than in patients with low suPAR (WMD = 3.20; 95% CI = 1.84-4.56; I2 = 99%; P < .00001).
CONCLUSION
suPAR is proven to be a significant marker in predicting 30-day and 90-day mortality in ED patients.
Topics: Humans; Female; Middle Aged; Male; Receptors, Urokinase Plasminogen Activator; Patient Discharge; Patient Readmission; Length of Stay; Biomarkers; Prognosis
PubMed: 37960735
DOI: 10.1097/MD.0000000000035718 -
VASA. Zeitschrift Fur Gefasskrankheiten Mar 2020A 4G/5G polymorphism in the promoter region of the plasminogen activator inhibitor type 1 (PAI-1) gene has been reported to enhance the plasma levels of PAI-1, which... (Meta-Analysis)
Meta-Analysis
A 4G/5G polymorphism in the promoter region of the plasminogen activator inhibitor type 1 (PAI-1) gene has been reported to enhance the plasma levels of PAI-1, which plays an important role in fibrinolysis disorders and venous thromboembolism, but a large number of studies have reported inconclusive results. Therefore, we performed a meta-analysis to analysis these associations. We performed a publication search for articles published before April 2019 by using the electronic databases of web of Science, Embase, PubMed, CNKI, CBM and WanFang data with the following terms "PAI-1", "polymorphism", "Venous Thromboembolism". Two investigators independently extracted data and assessed study quality. Statistical analyses were undertaken using Stata 14.0. A total of 27 studies, with 3135 patients and 5346 controls were included. Overall, the variant PAI-1 4G/4G and PAI-1 4G/5G was associated with venous thromboembolism risk, compared with the PAI-1 5G/5G allele in the populations included in the analysis. Stratified analysis revealed that PAI-1 4G/4G and PAI-1 4G/5G genotypes were associated with an increased VTE risk among Asia populations in all five genetic models. The PAI-1 4G/5G polymorphism may be a potential biomarker of VTE risk, particularly in Asia populations. Further larger studies with multi-ethnic populations are required to further assess the association between PAI-1 4G/4G polymorphisms and VTE risk.
Topics: Genetic Predisposition to Disease; Humans; Plasminogen; Plasminogen Activator Inhibitor 1; Polymorphism, Genetic; Promoter Regions, Genetic; Venous Thromboembolism
PubMed: 31920171
DOI: 10.1024/0301-1526/a000839 -
Neurology Sep 2016The aim of this systematic review and meta-analysis was to evaluate the safety and efficacy of IV thrombolysis (IVT) with tissue plasminogen activator (tPA) delivered... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The aim of this systematic review and meta-analysis was to evaluate the safety and efficacy of IV thrombolysis (IVT) with tissue plasminogen activator (tPA) delivered through telestroke networks in patients with acute ischemic stroke.
METHODS
We conducted a systematic review and meta-analysis according to PRISMA guidelines. Literature searches on MEDLINE, Embase, and CENTRAL databases covered prospective randomized controlled and nonrandomized studies comparing telemedicine-guided IVT to IVT administered at stroke centers and were published from the earliest date available until April 1, 2015. Outcomes of interest were symptomatic intracerebral hemorrhage, mortality, and functional independence (modified Rankin Scale scores 0-1) at 3 months. Random-effects meta-analysis was used to compute pooled effect estimates and the I(2) statistic to assess heterogeneity.
RESULTS
Of 529 records identified, 7 studies totaling 1,863 patients fulfilled our eligibility criteria. Among these, thrombolysis was largely restricted to the 3-hour time window. Symptomatic intracerebral hemorrhage rates were similar between patients subjected to telemedicine-guided IVT and those receiving tPA at stroke centers (risk ratio [RR] = 1.01, 95% confidence interval [CI] 0.37-2.80; p = 0.978) with low evidence of heterogeneity (I(2) = 37%; p = 0.189). There was no difference in mortality (RR = 1.04, 95% CI 0.74-1.48; p = 0.806) or in functional independence (RR = 1.11, 95% CI 0.78-1.57; p = 0.565) at 3 months between telemedicine-guided and stroke center thrombolysis. No heterogeneity was identified (I(2) = 0%, p = 0.964 and I(2) = 52%, p = 0.123, respectively).
CONCLUSIONS
Our findings indicate that IV tPA delivery through telestroke networks is safe and effective in the 3-hour time window. Lack of prospective trials, however, emphasizes the need to further substantiate these findings in the 3- to 4.5-hour time window.
PROSPERO REGISTRATION INFORMATION
URL: http://www.crd.york.ac.uk/PROSPERO. Unique identifier: CRD42015017232.
Topics: Fibrinolytic Agents; Humans; Stroke; Telemedicine; Thrombolytic Therapy; Tissue Plasminogen Activator
PubMed: 27566746
DOI: 10.1212/WNL.0000000000003148 -
Hormone and Metabolic Research =... Apr 2020Different adipokines secreted from adipose tissue, exert a range of physiological effects. The aim of present systematic review and meta-analysis was to critically... (Meta-Analysis)
Meta-Analysis
Effect of Bariatric Surgery on the Circulating Level of Adiponectin, Chemerin, Plasminogen Activator Inhibitor-1, Leptin, Resistin, and Visfatin: A Systematic Review and Meta-Analysis.
Different adipokines secreted from adipose tissue, exert a range of physiological effects. The aim of present systematic review and meta-analysis was to critically investigate the consequence of bariatric surgery on circulating adipokines, that is, adiponectin, leptin, visfatin, resistin, plasminogen activator inhibitor, and chemerin. After systematically checking the following electronic databases: ISI web of Science, Scopus and PubMed without limitation in time and language up to February 2019, a pool based on a random effect model was established. Eighty-five eligible studies were entered for quantitative analysis. Our meta-analysis revealed that circulating adiponectin increased significantly after bariatric surgery [Standardized mean difference (SMD)=1.401, 95% CI: 1.101, 1.701, p<0.001]; whilst leptin (SMD=-2.178, 95% CI: -2.433, -1.923, p<0.001), PAI-1 (-14.928 ng/ml 95% CI: -21.794, -8.063, p<0.001), and chemerin (-50.238 ng/ml 95% CI: -85.708, -14.768, p<0.001) decreased. However, serum visfatin (2.05 ng/ml, 95% CI: -5.07, 9.17, p=0.573) and resistin (-2.080 ng/ml, 95% CI: -5.352, 1.192, p=0.21) were unchanged. In conclusion, bariatric surgery is associated with a reduction in specific adipokines including leptin, chemerin, and PAI-1, whereas adiponectin is raised, adaptations that could be indicative of improved fat mass and function.
Topics: Adiponectin; Adipose Tissue; Bariatric Surgery; Chemokines; Cytokines; Diabetes Mellitus, Type 2; Humans; Leptin; Nicotinamide Phosphoribosyltransferase; Obesity; Organ Size; Plasminogen Activator Inhibitor 1; Postoperative Period; Resistin; Weight Loss
PubMed: 32268422
DOI: 10.1055/a-1129-6785 -
Stroke Nov 2012Recombinant tissue plasminogen activator (rtPA) is an effective treatment for acute ischemic stroke but is associated with an increased risk of intracranial hemorrhage... (Meta-Analysis)
Meta-Analysis Review
Risk factors for intracranial hemorrhage in acute ischemic stroke patients treated with recombinant tissue plasminogen activator: a systematic review and meta-analysis of 55 studies.
BACKGROUND AND PURPOSE
Recombinant tissue plasminogen activator (rtPA) is an effective treatment for acute ischemic stroke but is associated with an increased risk of intracranial hemorrhage (ICH). We sought to identify the risk factors for ICH with a systematic review of the published literature.
METHODS
We searched for studies of rtPA-treated stroke patients that reported an association between a variable measured before rtPA infusion and clinically important ICH (parenchymal ICH or ICH associated with clinical deterioration). We calculated associations between baseline variables and ICH with random-effect meta-analyses.
RESULTS
We identified 55 studies that measured 43 baseline variables in 65 264 acute ischemic stroke patients. Post-rtPA ICH was associated with higher age (odds ratio, 1.03 per year; 95% confidence interval, 1.01-1.04), higher stroke severity (odds ratio, 1.08 per National Institutes of Health Stroke Scale point; 95% confidence interval, 1.06-1.11), and higher glucose (odds ratio, 1.10 per mmol/L; 95% confidence interval, 1.05-1.14). There was approximately a doubling of the odds of ICH with the presence of atrial fibrillation, congestive heart failure, renal impairment, previous antiplatelet agents, leukoaraiosis, and a visible acute cerebral ischemic lesion on pretreatment brain imaging. Little of the variation in the sizes of the associations among different studies was explained by the source of the cohort, definition of ICH, or degree of adjustment for confounding variables.
CONCLUSIONS
Individual baseline variables were modestly associated with post-rtPA ICH. Prediction of post-rtPA ICH therefore is likely to be difficult if based on single clinical or imaging factors alone. These observational data do not provide a reliable method for the individualization of treatment according to predicted ICH risk.
Topics: Age Factors; Aged; Aged, 80 and over; Brain Ischemia; Fibrinolytic Agents; Humans; Intracranial Hemorrhages; Risk Factors; Stroke; Tissue Plasminogen Activator
PubMed: 22996959
DOI: 10.1161/STROKEAHA.112.665331 -
Seminars in Thrombosis and Hemostasis Jul 2022Plasminogen activator inhibitor type 1 (PAI-1) is a main inhibitor of fibrinolysis. The PAI-1 gene () harbors genetic variants with the potential of modifying plasma...
Plasminogen activator inhibitor type 1 (PAI-1) is a main inhibitor of fibrinolysis. The PAI-1 gene () harbors genetic variants with the potential of modifying plasma levels of PAI-1. A delicate balance exists between the coagulation and fibrinolytic system, and changes in PAI-1 have been suggested to compromise establishment of a successful pregnancy. Therefore, this systematic review investigated the association between genetic variants and/or plasma levels of PAI-1 and placenta-mediated pregnancy complications. An extensive literature search was conducted in PubMed, Embase, and Web of Science on the 29 of April 2021. All studies underwent quality rating according to The Study Quality Assessment Tools checklist provided by National Heart, Lung and Blood Institute. A total of 71 studies were included, among which 60 studies investigated PAI-1 genotypes and 11 studies measured PAI-1 plasma levels. In 32 out of 59 studies, no association was found between the PAI-1 4G/5G polymorphism (rs1799768) and placenta-mediated pregnancy complications, which was stated as no significant difference in the genotype distribution comparing women with and without placenta-mediated pregnancy complications or no significantly increased odds of placenta-mediated pregnancy complications carrying the 4G/4G or 4G/5G genotype. Eight out of 11 studies reported significantly higher PAI-1 plasma levels in preeclamptic women than in women without preeclampsia. In conclusion, no clear evidence indicates that PAI-1 polymorphisms are associated with placenta-mediated pregnancy complications, and the possible association between high PAI-1 plasma levels and preeclampsia needs further investigations. Thus, investigation of PAI-1 genotypes and PAI-1 plasma levels does not currently seem to have a place in daily clinical practice managing placenta-mediated pregnancy complications.
Topics: Female; Humans; Placenta; Plasminogen Activator Inhibitor 1; Polymorphism, Genetic; Pre-Eclampsia; Pregnancy
PubMed: 35021249
DOI: 10.1055/s-0041-1742082 -
Stroke Research and Treatment 2013Background. Intravenous tPA (tissue plasminogen activator) therapy remains underutilized in patients with Acute Ischemic Stroke (AIS). Anecdotal data indicates that... (Review)
Review
Background. Intravenous tPA (tissue plasminogen activator) therapy remains underutilized in patients with Acute Ischemic Stroke (AIS). Anecdotal data indicates that physicians are increasingly liable for administering and for failure to administer tPA. Methods. An extensive search of Medline, Embase, Westlaw, LexisNexis Legal, and Google Scholar databases was performed. Case studies that involved malpractice litigation in ischemic stroke and thrombolytic therapy were analyzed systematically. Results. We identified 789 ischemic stroke litigation cases, of which 46 cases were related to intravenous tPA and stroke litigation. Case descriptions of 40 cases were available. Data for verdicts were available for 38 patients. The most frequent plaintiff claim was related to failure to administer intravenous tPA (38, 95%). Only 2 (5.0%) claim involved complications of treatment with tPA. Hospitals were defendants in majority of the 36 cases. Physicians were involved in 33 cases. While ED physicians were involved in 25 (60.52%) cases, neurologists were involved in 8 (20.0%) cases. There were 26 (65%) defendant-favored and 12 (30%) plaintiff-favored verdicts. Conclusion. Physicians and hospitals are at an increased risk of litigation in patients with AIS when in IV-tPA is being considered for treatment. While majority of the cases litigated were cases where tPA was not administered, only about 1 in 20 cases was litigated when complications occurred.
PubMed: 24083048
DOI: 10.1155/2013/562564 -
Journal of Assisted Reproduction and... Jul 2023Recurrent pregnancy loss (RPL) is affecting 1-4% of women who conceive approximately, and no cause could be found in more than 50% of women suffering from RPL. Inherited... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Recurrent pregnancy loss (RPL) is affecting 1-4% of women who conceive approximately, and no cause could be found in more than 50% of women suffering from RPL. Inherited thrombophilias have got increasing attention in women with unexplained RPL, so we aim to explore the relationship among these most common thrombophilic polymorphisms and RPL through a literature review and meta-analysis.
METHODS
Observational studies from PubMed, Embase, Cochrane, and Web of Science from 1997 to 7 April 2022 were searched. For each genetic variant, a fixed or random-effect model was used according to the heterogeneity test to calculate pooled ORs and 95% CIs for both dominant and recessive genetic models. Egger's line regression test was used to assess publication bias. The quality of the included articles was assessed by the Newcastle Ottawa scale.
RESULTS
A total of 124 articles comprising 17,278 RPL patients and 16,021 controls were included. Results showed that hyperhomocysteinemia (MTHFR) C677T (dominant model: OR, 1.43; 95% CI, 1.25-1.64; recessive model: OR, 1.60; 95% CI, 1.36-1.87), MTHFR A1298C (dominant model: OR, 1.66; 95% CI, 1.26-2.18; recessive model: OR, 1.79; 95% CI, 1.42-2.26), PAI-1 4G/5G (dominant model: OR, 1.67; 95% CI, 1.36-2.06; recessive model: OR, 1.80; 95% CI, 1.39-2.32), angiotensin-converting enzyme I/D (OR, 1.23; 95% CI, 1.00-1.53), Factor XIII V34L (OR, 1.38; 95% CI, 1.02-1.87), and β-fibrinogen-455G/A (OR, 1.60; 95% CI, 1.02-2.51) were significantly associated with RPL.
CONCLUSION
This study provides potentially useful clinical markers to evaluate the risk of RPL or to help unexplained RPL patients identify possible causes, which may allow for targeted treatment.
Topics: Pregnancy; Humans; Female; Genetic Predisposition to Disease; Polymorphism, Genetic; Thrombophilia; Plasminogen Activator Inhibitor 1; Abortion, Habitual; Methylenetetrahydrofolate Reductase (NADPH2); Observational Studies as Topic
PubMed: 37248348
DOI: 10.1007/s10815-023-02823-x -
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