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Journal of the American Heart... May 2017Plasminogen activator inhibitor type 1 (PAI-1) plays an essential role in the fibrinolysis system and thrombosis. Population studies have reported that blood PAI-1... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Plasminogen activator inhibitor type 1 (PAI-1) plays an essential role in the fibrinolysis system and thrombosis. Population studies have reported that blood PAI-1 levels are associated with increased risk of coronary heart disease (CHD). However, it is unclear whether the association reflects a causal influence of PAI-1 on CHD risk.
METHODS AND RESULTS
To evaluate the association between PAI-1 and CHD, we applied a 3-step strategy. First, we investigated the observational association between PAI-1 and CHD incidence using a systematic review based on a literature search for PAI-1 and CHD studies. Second, we explored the causal association between PAI-1 and CHD using a Mendelian randomization approach using summary statistics from large genome-wide association studies. Finally, we explored the causal effect of PAI-1 on cardiovascular risk factors including metabolic and subclinical atherosclerosis measures. In the systematic meta-analysis, the highest quantile of blood PAI-1 level was associated with higher CHD risk comparing with the lowest quantile (odds ratio=2.17; 95% CI: 1.53, 3.07) in an age- and sex-adjusted model. The effect size was reduced in studies using a multivariable-adjusted model (odds ratio=1.46; 95% CI: 1.13, 1.88). The Mendelian randomization analyses suggested a causal effect of increased PAI-1 level on CHD risk (odds ratio=1.22 per unit increase of log-transformed PAI-1; 95% CI: 1.01, 1.47). In addition, we also detected a causal effect of PAI-1 on elevating blood glucose and high-density lipoprotein cholesterol.
CONCLUSIONS
Our study indicates a causal effect of elevated PAI-1 level on CHD risk, which may be mediated by glucose dysfunction.
Topics: Biomarkers; Blood Glucose; Coronary Disease; Fibrinolysis; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Incidence; Lipoproteins, HDL; Mendelian Randomization Analysis; Multivariate Analysis; Observational Studies as Topic; Odds Ratio; Plasminogen Activator Inhibitor 1; Polymorphism, Single Nucleotide; Risk Assessment; Risk Factors
PubMed: 28550093
DOI: 10.1161/JAHA.116.004918 -
HPB : the Official Journal of the... Aug 2016Pancreatic ductal adenocarcinoma (PDAC) continues to be associated with a poor prognosis. This systematic review aimed to summarize the literature regarding potential... (Review)
Review
BACKGROUND
Pancreatic ductal adenocarcinoma (PDAC) continues to be associated with a poor prognosis. This systematic review aimed to summarize the literature regarding potential prognostic biomarkers to facilitate validation studies and clinical application.
METHODS
A systematic review was performed (2004-2014) according to PRISMA guidelines. Studies were ranked using REMARK criteria and the following outcomes were examined: overall/disease free survival, nodal involvement, tumour characteristics, metastasis, recurrence and resectability.
RESULTS
256 biomarkers were identified in 158 studies. 171 biomarkers were assessed with respect to overall survival: urokinase-type plasminogen activator receptor, atypical protein kinase C and HSP27 ranked the highest. 33 biomarkers were assessed for disease free survival: CD24 and S100A4 were the highest ranking. 17 biomarkers were identified for lymph node involvement: Smad4/Dpc4 and FOXC1 ranked highest. 13 biomarkers were examined for tumour grade: mesothelin and EGFR were the highest ranking biomarkers. 10 biomarkers were identified for metastasis: p16 and sCD40L were the highest ranking. 4 biomarkers were assessed resectability: sCD40L, s100a2, Ca 19-9, CEA.
CONCLUSION
This review has identified and ranked specific biomarkers that should be a primary focus of ongoing validation and clinical translational work in PDAC.
Topics: Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Disease Progression; Disease-Free Survival; Humans; Lymphatic Metastasis; Neoplasm Grading; Neoplasm Recurrence, Local; Pancreatectomy; Pancreatic Neoplasms; Predictive Value of Tests; Risk Factors; Time Factors; Treatment Outcome
PubMed: 27485059
DOI: 10.1016/j.hpb.2016.05.004 -
International Journal of Cardiology.... Jun 2024In compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we conducted this systemic review on the prevalence, mechanism, and therapy of... (Review)
Review
In compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we conducted this systemic review on the prevalence, mechanism, and therapy of sleep disorder in patients with cardiovascular disease (CVD). After searching PubMed and Embase, 78 articles were selected for this review. This review discusses the bidirectional relationship between CVD and sleep disorders. Sleep impairment is highly prevalent in patients with CVD and mainly involves insomnia and sleep-breathing disorders. Several valuable biomarkers could be implicated in predicting sleep disorders in CVD patients, such as placental growth factor, vascular endothelial growth factor family, high sensitivity C-reactive protein, endoglin, fms-like tyrosine kinase-1, plasminogen activator inhibitor-1, erythropoietin. Moreover, non-drug therapies, namely physical exercise, cognitive behavioral therapy for insomnia (CBT-I), and continuous positive airway pressure benefit the prognosis of patients with CVD. In conclusion, this study highlights the importance of sleep quality, which is responsible for long- and short-term cardiac outcomes in patients with CVD.
PubMed: 38549735
DOI: 10.1016/j.ijcrp.2024.200257 -
Journal of Sports Sciences Feb 2020High-intensity-interval-training (HIIT) has been suggested to have beneficial effects in multiple populations across individual systematic reviews, although there is a... (Meta-Analysis)
Meta-Analysis
High-intensity-interval-training (HIIT) has been suggested to have beneficial effects in multiple populations across individual systematic reviews, although there is a lack of clarity in the totality of the evidence whether HIIT is effective and safe across different populations and outcomes. The aim of this meta-review was to establish the benefits, safety and adherence of HIIT interventions across all populations from systematic reviews and meta-analyses. Major databases were searched for systematic reviews (with/without meta-analyses) of randomised & non-randomised trials that compared HIIT to a control. Thirty-three systematic reviews (including 25 meta-analyses) were retrieved encompassing healthy subjects and people with physical health complications. Evidence suggested HIIT improved cardiorespiratory fitness, anthropometric measures, blood glucose and glycaemic control, arterial compliance and vascular function, cardiac function, heart rate, some inflammatory markers, exercise capacity and muscle mass, versus non-active controls. Compared to active controls, HIIT improved cardiorespiratory fitness, some inflammatory markers and muscle structure. Improvements in anxiety and depression were seen compared to pre-training. Additionally, no acute injuries were reported, and mean adherence rates surpassed 80% in most systematic reviews. Thus, HIIT is associated with multiple benefits. Further large-scale high-quality studies are needed to reaffirm and expand these findings. ACSM: American College of Sports Medicine; BMI: Body Mass Index; BNP: Brain Natriuretic Peptide; BP: Blood Pressure; CAD: Coronary Artery Disease; CHD: Coronary Heart Disease; COPD: Chronic Obstructive Pulmonary Disease; CRP: c- reactive Protein; CVD: Cardiovascular Disease; DBP: Diastolic Blood Pressure; ES: Effect Size; FAS: Reduced Fatty Acid Synthase; FATP-1: Reduced Fatty Acid Transport Protein 1; FMD: Flow Mediated Dilation; Hs-CRP: High-sensitivity c- reactive Protein; HDL: High Density Lipoprotein; HIIT: High-Intensity Interval Training; HOMA: Homoeostatic Model Assessment; HR: Heart Rate; HTx: Heart Transplant Recipients; IL-6: Interleukin-6; LDL: Low Density Lipoprotein; LV: Left Ventricular; LVEF: Left Ventricular Ejection Fraction; MD: Mean Difference; MetS: Metabolic Syndrome; MPO: Myeloperoxidase; MICT: Moderate-Intensity Continuous Training; NO: Nitric Oxide; NRCT: Non-Randomised Controlled Trial; PA: Physical Activity; PAI-1: Plasminogen-activator-inhibitor-1; QoL: Quality of Life; RCT: Randomised Controlled Trial; RoB: Risk of Bias; RPP: Rate Pressure Product; RT: Resistance Training; SBP: Systolic Blood Pressure; SD: Standardised Difference; SMD: Standardised Mean Difference; TAU: Treatment-As-Usual; T2DM: Type 2 Diabetes Mellitus; TC: Total Cholesterol; TG: Triglycerides; TNF-alfa: Tumour Necrosis Factor alpha; UMD: Unstandardised Mean Difference; WC: Waist Circumference; WHR: Waist-to-Hip Ratio; WMD: Weighted Mean Difference: HIIT may improve cardiorespiratory fitness, cardiovascular function, anthropometric variables, exercise capacity, muscular structure and function, and anxiety and depression severity in healthy individuals and those with physical health disorders.Additionally, HIIT appears to be safe and does not seem to be associated with acute injuries or serious cardiovascular events.
Topics: Anthropometry; Anxiety; Biomarkers; Cardiorespiratory Fitness; Depression; Exercise Tolerance; High-Intensity Interval Training; Humans; Inflammation; Mental Health; Muscle, Skeletal; Quality of Life
PubMed: 31889469
DOI: 10.1080/02640414.2019.1706829 -
Seminars in Thrombosis and Hemostasis Jul 2023Observational studies indicate a relationship between vitamin D deficiency and an increased risk of venous and arterial thrombotic events, but the underlying mechanisms...
Observational studies indicate a relationship between vitamin D deficiency and an increased risk of venous and arterial thrombotic events, but the underlying mechanisms behind this association are uncertain. This systematic review explores if there is an association between decreased vitamin D levels and a prothrombotic profile. The systematic literature search initially identified 3,214 studies (published until December 21, 2021) investigating the relationship between vitamin D and numerous hemostatic parameters. After the screening process, 18 observational and intervention studies fulfilled the inclusion criteria and were included in this systematic review. Parameters of primary hemostasis, secondary hemostasis, and fibrinolysis were investigated in six, thirteen, and fifteen of these studies, respectively. Most of the eligible studies did not identify significant associations between decreased vitamin D levels and hemostatic parameters. Some conflicting results were found between decreased vitamin D levels and thrombin generation parameters and the tissue factor pathway inhibitor. Conflicting results were also found between decreased vitamin D levels and fibrinolytic parameters, although the evidence may point toward weak associations with some regulators of fibrinolysis, mostly decreased tissue type plasminogen activator. Overall, our systematic review did not identify any definitive link between vitamin D deficiency and a prothrombotic profile, which might otherwise help explain the observed association between vitamin D deficiency and increased risk of thrombotic events. Moreover, there is no clinical evidence to confirm or refute a possible antithrombotic effect of vitamin D. Larger high-quality randomized controlled trials are needed to better elucidate the link between vitamin D deficiency and a prothrombotic risk profile.
Topics: Humans; Fibrinolysis; Hemostasis; Vitamin D Deficiency; Thrombosis; Vitamin D; Hemostatics
PubMed: 36174611
DOI: 10.1055/s-0042-1756701 -
Aging Dec 2023Tenecteplase (TNK), a newer fibrinolytic agent with greater fibrin specificity and longer half-life than alteplase, may has practical advantages over alteplase in acute... (Meta-Analysis)
Meta-Analysis
Tenecteplase (TNK), a newer fibrinolytic agent with greater fibrin specificity and longer half-life than alteplase, may has practical advantages over alteplase in acute ischemic stroke (AIS) thrombolysis. We aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare different doses of TNK (0.1, 0.25, 0.4 mg/kg) and alteplase in acute ischemic stroke patients. We systematically searched PubMed, Embase and https://clinicaltrials.gov/ for RCTs comparing TNK with alteplase in this population eligible for thrombolysis. The Cochrane Risk of Bias Tool was used to assess study quality. Random-effects or fixed-effects meta-analysis models were used for evaluating all outcomes. Total 10 RCTs with 5097 patients were included. Compared with alteplase, TNK at doses of 0.25 mg/kg may associated with the greatest odds to achieve 90-day excellent independence (mRS score ≤1), but there were no significant differences between other doses of TNK (0.1 mg/kg and 0.4 mg/kg) and alteplase. Among secondary outcomes, no significant differences were found in functional outcome (mRS score ≤2) and mortality at 90 days between any dose of TNK and alteplase. Compared with alteplase, TNK was effective at doses of 0.1 mg/kg and 0.25 mg/kg without increased risk of symptomatic intracerebral hemorrhage (sICH), but patients treated with TNK 0.4 mg/kg showed increased odds of sICH. In conclusion, compared with alteplase, intravenous thrombolysis with TNK at dose of 0.25 mg/kg has a better efficacy and similar safety profile and is a reasonable option for patients with AIS.
Topics: Humans; Tissue Plasminogen Activator; Tenecteplase; Stroke; Brain Ischemia; Randomized Controlled Trials as Topic; Ischemic Stroke; Cerebral Hemorrhage; Treatment Outcome
PubMed: 38149983
DOI: 10.18632/aging.205315 -
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 -
Journal of Orthopaedic Surgery and... Jul 2023Calcaneal fractures are a common orthopedic disease, account for approximately 2% of all bone fractures, and represent 60% of fractures of tarsal bones. Tranexamic acid... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Calcaneal fractures are a common orthopedic disease, account for approximately 2% of all bone fractures, and represent 60% of fractures of tarsal bones. Tranexamic acid (TXA) is a synthetic antifibrinolytic drug that competitively blocks the lysine-binding sites of plasminogen, plasmin, and tissue plasminogen activator, delaying fibrinolysis and blood clot degradation. However, the effect of TXA on patients with calcaneal surgery remains controversial. Our objective was to evaluate the effectiveness of TXA in calcaneal fractures surgeries.
METHODS
The electronic literature databases of Pubmed, Embase, and Cochrane library were searched in December 2022. The data on blood loss, the stay in the hospital, the duration of surgery, hemoglobin, hematocrit, platelet count, prothrombin time, activated partial thromboplastin time, and wound complication were extracted. The Stata 22.0 software was used for the meta-analysis.
RESULTS
Four randomized controlled studies met our inclusion criteria. This meta-analysis showed that TXA significantly reduced postoperative blood loss during the first 24 h (p < 0.001), improved the level of hemoglobin (p < 0.001) and hematocrit (p = 0.03), and reduced the risk of wound complications (p = 0.04). There was no significant difference between the two groups regarding total and intraoperative blood loss, hospital stay, duration of surgery, platelet count, activated partial thromboplastin time, and prothrombin time.
CONCLUSION
TXA significantly reduced blood loss during the first 24 h postoperatively, improved the level of hemoglobin and hematocrit, and reduced the risk of wound complications. Given the evidence, TXA can be used in patients with calcaneal fractures and had the potential benefit of blood reduction.
PROTOCOL REGISTRATION
The protocol was registered in PROSPERO (registration No. CRD42023391211).
Topics: Humans; Tranexamic Acid; Tissue Plasminogen Activator; Randomized Controlled Trials as Topic; Calcaneus; Tarsal Bones; Ankle Injuries
PubMed: 37438798
DOI: 10.1186/s13018-023-03924-0 -
Stroke Sep 2016After the demonstration of efficacy of bridging therapy, reliably predicting early recanalization (ER; ≤3 hours after start of intravenous thrombolysis) would be... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
After the demonstration of efficacy of bridging therapy, reliably predicting early recanalization (ER; ≤3 hours after start of intravenous thrombolysis) would be essential to limit futile, resource-consuming, interhospital transfers. We present the first systematic review on the incidence and predictors of ER after intravenous thrombolysis alone.
METHODS
We systematically searched for studies including patients solely treated by intravenous thrombolysis that reported incidence of ER and its association with baseline variables. Using meta-analyses, we estimated pooled incidence of ER, including according to occlusion site, and summarized the available evidence regarding predictors of no-ER.
RESULTS
We identified 26 studies that together included 2063 patients. The overall incidence of partial or complete ER was 33% (95% confidence interval, 27-40). It varied according to occlusion site: 52% (39-64) for distal middle cerebral artery, 35% (28-42) for proximal middle cerebral artery, 13% (6-22) for intracranial carotid artery, and 13% (0-35) for basilar occlusion. Corresponding rates for complete ER were 38% (22-54), 21% (15-29), 4% (1-8), and 4% (0-22), respectively. Proximal occlusion and higher National Institute of Health Stroke Scale were the most consistent no-ER predictors. Other factors, such as long or totally occlusive thrombus and poor collateral circulation, emerged as potential predictors but will need confirmation.
CONCLUSION
The overall incidence of ER after intravenous thrombolysis is substantial, highlighting the importance of reliably predicting ER to limit futile, interhospital transfers. Incidence of no-ER is particularly high for proximal occlusion and severe strokes. Given the scarcity of published data, further studies are needed to improve no-ER prediction accuracy.
Topics: Administration, Intravenous; Angiography, Digital Subtraction; Brain; Brain Ischemia; Fibrinolytic Agents; Humans; Magnetic Resonance Angiography; Neuroimaging; Stroke; Thrombolytic Therapy; Time Factors; Tissue Plasminogen Activator; Treatment Outcome
PubMed: 27462117
DOI: 10.1161/STROKEAHA.116.014181 -
Phytotherapy Research : PTR Sep 2022We perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to quantify the effect of resveratrol supplementation on endothelial function. A... (Meta-Analysis)
Meta-Analysis Review
We perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to quantify the effect of resveratrol supplementation on endothelial function. A comprehensive search was performed in electronic databases including PubMed, Scopus, Web of Science, and Cochrane Library up to February 2021 with no limitation in time and language. A meta-analysis of eligible studies was performed using a random-effects model to estimate the pooled effect size of flow-mediated dilation (FMD), intracellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), fibrinogen, and plasminogen activator inhibitor-1 (PAI-1). In total, 21 arms from 17 studies were included. The meta-analysis results showed that resveratrol significantly change the concentrations of FMD (WMD: 1.43%; 95% CI: 0.98 to 1.88, p < .001) and ICAM-1 (WMD: -7.09 ng/ml, 95% CI: -7.45 to -6.73, p < .001). However, VCAM-1, fibrinogen, and PAI-1 did not change significantly after resveratrol supplementation. In conclusion, the results of this study suggest that resveratrol supplementation can improve endothelial function which could be important, especially in patients with cardiovascular diseases.
Topics: Dietary Supplements; Fibrinogen; Humans; Intercellular Adhesion Molecule-1; Plasminogen Activator Inhibitor 1; Randomized Controlled Trials as Topic; Resveratrol; Vascular Cell Adhesion Molecule-1
PubMed: 35833325
DOI: 10.1002/ptr.7562