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European Journal of Medical Research Feb 2023At the end of 2021, the European Medicines Agency (EMA) expanded its approval for the recombinant human interleukin-1 (IL-1) receptor antagonist Anakinra for the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
At the end of 2021, the European Medicines Agency (EMA) expanded its approval for the recombinant human interleukin-1 (IL-1) receptor antagonist Anakinra for the treatment of COVID-19 patients with elevated soluble urokinase plasminogen activator receptor (suPAR). However, the role of Anakinra in COVID-19 remains unanswered, especially in patients receiving different forms of respiratory support. Therefore, the objective of this systematic review is to assess the safety and effects of Anakinra compared to placebo or standard care alone on clinical outcomes in adult hospitalized patients with SARS-CoV-2 infection.
METHODS
We searched the Cochrane COVID-19 Study Register (comprising MEDLINE, Embase, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, medRxiv, and the Cochrane Central Register of Controlled Trials (CCSR)) and the WHO COVID-19 Global literature on coronavirus disease database to identify completed and ongoing studies from inception of each database to December 13, 2021. Since then, we monitored new published studies weekly up to June 30, 2022 using the CCSR. We included RCTs comparing treatment with Anakinra to placebo or standard care alone in adult hospitalized patients with SARS-CoV-2 infection.
RESULTS
We included five RCTs with 1,627 patients (n = 888, n = 739, mean age 59.63 years, 64% male). Random-effects meta-analysis was used to pool data. We found that Anakinra makes little or no difference to all-cause mortality at up to day 28 compared to placebo or standard care alone (RR 0.96, 95% CI 0.64-1.45; RD 9 fewer per 1000, 95% CI 84 fewer to 104 more; 4 studies, 1593 participants; I = 49%; low certainty of evidence).
CONCLUSIONS
Anakinra has no effect on adult hospitalized patients with SARS-CoV-2 infection regarding mortality, clinical improvement and worsening as well as on safety outcomes compared to placebo or standard care alone.
TRIAL REGISTRATION
PROSPERO Registration Number: CRD42021257552.
Topics: Adult; Humans; Male; Middle Aged; Female; COVID-19; Interleukin 1 Receptor Antagonist Protein; SARS-CoV-2
PubMed: 36841793
DOI: 10.1186/s40001-023-01072-z -
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 -
Trends in Psychiatry and Psychotherapy 2023Major depressive disorder (MDD) is a severe mental health condition that affects millions of people worldwide. Etiologically, several factors may play a role in its... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Major depressive disorder (MDD) is a severe mental health condition that affects millions of people worldwide. Etiologically, several factors may play a role in its development. Previous studies have reported elevated plasminogen activator inhibitor-1 (PAI-1) levels in patients with depression, suggesting that PAI-1 levels might be linked to the etiology of MDD.
METHODS
We systematically searched the following online databases: MEDLINE, Scopus, and Web of Science up to September 10, 2020, to identify studies in which PAI-1 levels were reported in subjects with MDD. Subsequently we used RevMan 5.3 to perform a meta-analysis of data extracted from the included studies using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and PICO criteria for the search and analysis.
RESULTS
Six studies that reported mean ± standard deviation (SD) were included in the analysis, with a total of 507 MDD patients and 3,453 controls. The overall standardized mean difference (SMD) was 0.27 (95% confidence interval [95% CI] 0.01-0.53). PAI-1 serum levels were 0.27 SDs higher in MDD patients than in controls. The test for overall effect was significant (z = 2.04, p = 0.04). Substantial heterogeneity was detected among the studies, demonstrated by the inconsistency test (I² = 72%) and the chi-square test (χ² = 18.32; p = 0.003).
CONCLUSIONS
This systematic review and meta-analysis showed that MDD might be related to elevated PAI-1 levels. We propose larger prospective clinical studies to further investigate this clinical correlation and validate the clinical significance of these observations.
Topics: Humans; Depressive Disorder, Major; Plasminogen Activator Inhibitor 1; Prospective Studies
PubMed: 34798692
DOI: 10.47626/2237-6089-2021-0338 -
Annals of Agricultural and... Jun 2023The global impact of acute kidney injury (AKI) has not been thoroughly investigated. With the development of new techniques, soluble urokinase plasminogen activator... (Meta-Analysis)
Meta-Analysis
INTRODUCTION AND OBJECTIVE
The global impact of acute kidney injury (AKI) has not been thoroughly investigated. With the development of new techniques, soluble urokinase plasminogen activator receptor (suPAR) has become increasingly important in the diagnosis of AKI. Therefore, a systematic review and meta-analysis was carried out to evaluate the predictive value of suPAR for AKI.
MATERIAL AND METHODS
The review and meta-analysis investigated the relationship between suPAR levels and acute kidney injury. Pubmed, Scopus, Cochrane Controlled Register of Trials, and Embase were searched for relevant studies from inception to 10 January 2023. Stata (Ver. 16 StataCorp, College Station, TX, USA) was used for all statistical analyses. A random effects model using the Mantel-Haenszel approach was employed, and odds ratios (OR) and standard mean differences (SMD) with 95% confidence intervals (CI) were calculated for binary and continuous outcomes, respectively.
RESULTS
Nine studies reported suPAR levels among patients with and without AKI. Pooled analysis showed that suPAR levels in patients with and without AKI varied and amounted to 5.23 ± 4.07 vs. 3.23 ±0.67 ng/mL (SMD = 3.19; 95%CI: 2.73 to 3.65; p<0.001). The results from the sensitivity analysis did not alter the direction.
CONCLUSIONS
This results show that increasing suPAR levels are associated with the occurrence of AKI. SuPAR might act as a novel biomarker for CI-AKI in clinical practice.
Topics: Humans; Receptors, Urokinase Plasminogen Activator; Acute Kidney Injury; Odds Ratio; Universities
PubMed: 37387388
DOI: 10.26444/aaem/167464 -
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 -
Biomedicines Jun 2022Autoimmune pancreatitis (AIP) is a rare etiological type of chronic pancreatitis. The clinical and radiological presentation of AIP often resembles that of pancreatic... (Review)
Review
Autoimmune pancreatitis (AIP) is a rare etiological type of chronic pancreatitis. The clinical and radiological presentation of AIP often resembles that of pancreatic cancer. Identifying non-invasive markers for their early distinction is of utmost importance to avoid unnecessary surgery or a delay in steroid therapy. Thus, this systematic review was conducted to revisit all current evidence on the clinical utility of different serum biomarkers in diagnosing AIP, distinguishing AIP from pancreatic cancer, and predicting disease course, steroid therapy response, and relapse. A systematic review was performed for articles published up to August 2021 by searching electronic databases such as MEDLINE, Web of Science, and EMBASE. Among 5123 identified records, 92 studies were included in the qualitative synthesis. Apart from immunoglobulin (Ig) G4, which was by far the most studied biomarker, we identified autoantibodies against the following: lactoferrin, carboanhydrase II, plasminogen-binding protein, amylase-α2A, cationic (PRSS1) and anionic (PRSS2) trypsinogens, pancreatic secretory trypsin inhibitor (PSTI/SPINK1), and type IV collagen. The identified novel autoantigens were laminin 511, annexin A11, HSP-10, and prohibitin. Other biomarkers included cytokines, decreased complement levels, circulating immune complexes, -glycan profile changes, aberrant miRNAs expression, decreased IgA and IgM levels, increased IgE levels and/or peripheral eosinophil count, and changes in apolipoprotein isoforms levels. To our knowledge, this is the first systematic review that addresses biomarkers in AIP. Evolving research has recognized numerous biomarkers that could help elucidate the pathophysiological mechanisms of AIP, bringing us closer to AIP diagnosis and its preoperative distinction from pancreatic cancer.
PubMed: 35884816
DOI: 10.3390/biomedicines10071511 -
World Neurosurgery Nov 2017The safety and efficacy of intraventricular fibrinolysis (IVF) in patients with intraventricular hemorrhage (IVH) are unclear. We aimed to determine these issues and to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The safety and efficacy of intraventricular fibrinolysis (IVF) in patients with intraventricular hemorrhage (IVH) are unclear. We aimed to determine these issues and to evaluate whether there are differences between recombinant tissue-plasminogen activator (rt-PA) and urokinase according to subgroup analyses.
METHODS
A meta-analysis was undertaken of randomized controlled trials in patients with IVH that compared the administration of rt-PA or urokinase through extraventricular drainage (EVD) with normal saline through EVD or EVD placement alone.
RESULTS
Six randomized controlled trials involving 607 patients with IVH were included; 2 trials investigated urokinase and 4 rt-PA. IVF reduced death from any cause at the end of follow-up (risk ratio [RR] 0.63, 95% confidence interval [CI] 0.47-0.83), which was driven mostly by rt-PA (RR 0.65, 95% CI 0.48-0.86). Urokinase did not reduce mortality (RR 0.30, 95% CI 0.06-1.53). However, rt-PA did not reduce the proportion of survivors with poor functional outcome (RR 1.36, 95% CI 1.04-1.77), or the composite endpoint of death and poor functional outcome (RR 0.96, 95% CI 0.83-1.11). IVF neither reduced the need for shunt placement (RR 1.06, 95% CI 0.75-1.49) nor increased ventriculitis (RR 0.57, 95% CI 0.35-0.93) and rebleeding (RR 1.65, 95% CI 0.79-3.45).
CONCLUSIONS
Although the use of IVF in patients with IVH appears generally safe, its benefit is limited to a reduction in mortality at the expense of an increased number of survivors with moderately-severe to severe disability. Subgroup analyses do not suggest an advantage of IVF with urokinase over rt-PA.
Topics: Cerebral Hemorrhage; Fibrinolytic Agents; Humans; Injections, Intraventricular; Randomized Controlled Trials as Topic; Thrombolytic Therapy; Tissue Plasminogen Activator
PubMed: 28778779
DOI: 10.1016/j.wneu.2017.07.135 -
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 -
Current Problems in Cardiology Oct 2023Twelve CCI patients were studied with confirmed or suspected COVID-19 infection. The majority of these patients were males (83.3%) with a median age of 55 years from... (Review)
Review
Twelve CCI patients were studied with confirmed or suspected COVID-19 infection. The majority of these patients were males (83.3%) with a median age of 55 years from three geographical locations, constituting the Middle East (7), Spain (3), and the USA (1). In 6 patients, IgG/IgM was positive for COVID-19, 4 with high pretest probability and 2 with positive RT-PCR. Type 2 DM, hyperlipidemia, and smoking were the primary risk factors. Right-sided neurological impairments and verbal impairment were the most common symptoms. Our analysis found 8 (66%) synchronous occurrences. In 58.3% of cases, neuroimaging showed left Middle Cerebral Artery (MCA) infarct and 33.3% right. Carotid artery thrombosis (16.6%), tandem occlusion (8.3%), and carotid stenosis (1%) were also reported in imaging. Dual antiplatelet therapy (DAPT) and anticoagulants were conservative therapies (10). Two AMI patients had aspiration thrombectomy, while three AIS patients had intravenous thrombolysis/tissue plasminogen activator (IVT-tPA), 2 had mechanical thrombectomy (MT), and 1 had decompressive craniotomy. Five had COVID-19-positive chest X-rays, whereas 4 were normal. four of 8 STEMI and 3 NSTEMI/UA patients complained chest pain. LV, ICA, and pulmonary embolism were further complications (2). Upon discharge, 7 patients (70%) had residual deficits while 1 patient unfortunately died.
Topics: Female; Humans; Male; Middle Aged; Anticoagulants; COVID-19; Infarction, Middle Cerebral Artery; Stroke; Thrombectomy; Thrombolytic Therapy; Tissue Plasminogen Activator; Treatment Outcome; Case Reports as Topic
PubMed: 37209804
DOI: 10.1016/j.cpcardiol.2023.101814 -
Cerebrovascular Diseases (Basel,... 2022Hemorrhagic transformation (HT) is a complication that occurs spontaneously or after thrombolysis in acute ischemic stroke (AIS) and can increase morbidity and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hemorrhagic transformation (HT) is a complication that occurs spontaneously or after thrombolysis in acute ischemic stroke (AIS) and can increase morbidity and mortality. The association of biomarkers with the risk of HT has been variably reported. We conducted a systematic review of the literature and meta-analysis and sought to compare blood biomarkers associated with HT and its subtypes by evaluating its predictability and correlation with outcome in AIS.
METHODS
The study protocol was registered in the PROSPERO database (CRD42020201334) and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Among 2,230 articles identified from Cochrane Library, PubMed, and Web of Science databases, 30 quality-appraised articles were found eligible. Meta-analysis was conducted for matrix metalloproteinase-9 (MMP-9), cellular fibronectin (c-Fn), ferritin, S100 calcium-binding protein B (S100B), and neutrophil-lymphocyte ratio (NLR). We also reviewed biomarkers for correlation with the functional outcome at 90 days from stroke onset (poor outcome modified Rankin scale >2).
RESULTS
The pooled diagnostic odds ratio (DORpooled) was the highest for baseline c-Fn levels (299.253 [95% CI, 20.508-4,366.709]), followed by MMP-9 (DORpooled, 29.571 [95% CI 17.750-49.267]) and ferritin (DORpooled, 24.032 [95% CI 2.557-225.871]). However, wide confidence intervals for ferritin and c-Fn suggested lesser reliability of the markers. Patients with MMP-9 levels ≥140 ng/mL were 29.5 times at higher risk of developing symptomatic HT after AIS (area under the curve = 0.881). S100B (DORpooled, 6.286 [95% CI, 1.861-21.230]) and NLR (DORpooled, 5.036 [95% CI, 2.898-8.749]) had lower diagnostic accuracies. Among the markers not included for meta-analysis, caveolin-1, thrombin-activated fibrinolysis inhibitor, plasminogen activator inhibitor-1, and soluble ST2 were highly sensitive. Elevated levels of MMP-9, ferritin, and NLR were found to be associated with poor functional outcomes and mortality.
CONCLUSION
Of the 5 biomarkers, there was enough evidence that MMP-9 has higher diagnostic accuracy for predicting the risk of HT before thrombolysis. MMP-9, ferritin, and NLR also predicted poor short-term outcomes.
Topics: Biomarkers; Brain Ischemia; Ferritins; Hemorrhage; Humans; Ischemic Stroke; Matrix Metalloproteinase 9; Prognosis; Reproducibility of Results; Stroke
PubMed: 34569521
DOI: 10.1159/000518570