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Cerebrovascular Diseases (Basel,... 2014The use of thrombolytics is frequently considered in patients with cerebral venous and dural sinus thrombosis (CVT) who deteriorate despite anticoagulant therapy. (Review)
Review
BACKGROUND
The use of thrombolytics is frequently considered in patients with cerebral venous and dural sinus thrombosis (CVT) who deteriorate despite anticoagulant therapy.
PURPOSE
To collect all the published information about the use of systemic thrombolysis in CVT in order to assess its efficacy and safety.
METHODS
We performed a PubMed search, checked all reference lists of studies found and used data from the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Outcome was classified at the last available follow-up by the modified Rankin Scale (mRS). The cases were stratified according to variables that might influence outcome.
RESULTS
A total of 16 reports (26 patients, 2 from the ISCVT and 24 from the systematic review of the literature) were included. No randomized clinical trial was found. Seven patients presented with isolated intracranial hypertension syndrome (26.9%), 17 with encephalopathy (65.4%) and 2 were comatose (7.7%). The superior sagittal sinus was the one most often affected (n = 21; 80.8%), and there was thrombosis of the deep cerebral venous system in 5 patients (19.2%). Urokinase was the thrombolytic agent most frequently administered (n = 19; 73.1%), whereas streptokinase and recombinant tissue plasminogen activator were used in 2 cases each (7.7%). Intracranial hemorrhages occurred in 3 cases (11.5%). Extracranial hemorrhages occurred in 5 cases (19.2%), and overall there were 3 cases of serious bleeding (11.5%), including 2 deaths (7.7%). Partial or complete recanalization was verified in most patients (n = 16; 61.5%). The survival rate was 92.3% (24/26 patients). At the last available follow-up, 22/25 patients regained independency (mRS scores 0-2; 88%), 2/25 died (mRS score 6; 8%) and 1/25 was severely dependent (mRS scores 3-5; 4%).
CONCLUSIONS
In all, 88% of the CVT patients treated with systemic thrombolysis regained their independency, but 2 deaths associated with intracranial hemorrhage occurred. The mortality rate and disability at the last available follow-up were similar to those found in 2 previous systematic reviews concerning the use of thrombolytics in CVT. Due to the small sample size and lack of controls, the efficacy of systemic thrombolysis in acute CVT cannot be assessed from the published information. Concerning safety, a nonnegligible proportion of bleedings was reported.
Topics: Activities of Daily Living; Adolescent; Adult; Aged; Brain Damage, Chronic; Cerebral Hemorrhage; Cerebral Veins; Child; Child, Preschool; Coma; Disease Susceptibility; Female; Fibrinolytic Agents; Follow-Up Studies; Humans; Infant; Infusions, Intravenous; Intracranial Hypertension; Intracranial Thrombosis; Male; Middle Aged; Recombinant Proteins; Sinus Thrombosis, Intracranial; Streptokinase; Thrombolytic Therapy; Thrombophilia; Tissue Plasminogen Activator; Treatment Outcome; Urokinase-Type Plasminogen Activator; Venous Thrombosis; Young Adult
PubMed: 24356180
DOI: 10.1159/000356840 -
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 -
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 -
The Lancet. Infectious Diseases Apr 2010Various genes regulate the intensity of the inflammatory and coagulation response to infection and therefore might determine the severity and outcome of meningococcal... (Meta-Analysis)
Meta-Analysis Review
Various genes regulate the intensity of the inflammatory and coagulation response to infection and therefore might determine the severity and outcome of meningococcal disease. We systematically reviewed the published work for case-control studies on the influence of host genetics on severity and outcome in meningococcal disease and identified 27 studies including 7245 patients, with an overall mortality of 10% (range 1-19%). Despite flaws in the methods of the studies there was a clear association of host genetics with mortality and severity in meningococcal disease. Polymorphisms in SERPINE1 (odds ratio [OR] 2.23, 95% CI 1.48-3.35), IL1RN (OR 1.85, 95% CI 1.25-2.76) and IL1B (OR 1.81, 95% CI 1.09-2.97) were associated with mortality in our meta-analyses. In conclusion, gene variation influences severity and mortality in meningococcal disease. Polymorphisms might have potential as prognostic markers or to determine tailor-made adjunctive therapy. Carefully designed, prospective, whole-genome association studies and randomised clinical trials of treatments in specific genetic subgroups are needed.
Topics: Case-Control Studies; Genome-Wide Association Study; Humans; Meningococcal Infections; Plasminogen Activator Inhibitor 1; Polymorphism, Genetic; Publishing; Randomized Controlled Trials as Topic; Severity of Illness Index; Tumor Necrosis Factor-alpha
PubMed: 20334849
DOI: 10.1016/S1473-3099(10)70045-1 -
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 -
Frontiers in Neurology 2021Mechanical thrombectomy (MT) is now the standard-of-care treatment for acute ischemic stroke (AIS) of the anterior circulation and may be performed irrespective of...
Mechanical thrombectomy (MT) is now the standard-of-care treatment for acute ischemic stroke (AIS) of the anterior circulation and may be performed irrespective of intravenous tissue plasminogen activator (IV-tPA) eligibility prior to the procedure. This study aims to understand better if tPA leads to higher rates of reperfusion and improves functional outcomes in AIS patients after MT and to simultaneously evaluate the functionality and efficiency of a novel semi-automated systematic review platform. The Nested Knowledge AutoLit semi-automated systematic review platform was utilized to identify randomized control trials published between 2010 and 2021 reporting the use of mechanical thrombectomy and IV-tPA (MT+tPA) vs. MT alone for AIS treatment. The primary outcome was the rate of successful recanalization, defined as thrombolysis in cerebral infarction (TICI) scores ≥2b. Secondary outcomes included 90-day modified Rankin Scale (mRS) 0-2, 90-day mortality, distal embolization to new territory, and symptomatic intracranial hemorrhage (sICH). A separate random effects model was fit for each outcome measure. We subjectively found Nested Knowledge to be highly streamlined and effective at sourcing the correct literature. Four studies with 1,633 patients, 816 in the MT+tPA arm and 817 in the MT arm, were included in the meta-analysis. In each study, patient populations consisted of only tPA-eligible patients and all imaging and clinical outcomes were adjudicated by an independent and blinded core laboratory. Compared to MT alone, patients treated with MT+tPA had higher odds of eTICI ≥2b (OR = 1.34 [95% CI: 1.10; 1.63]). However, there were no statistically significant differences in the rates of 90-day mRS 0-2 (OR = 0.98 [95% CI: 0.77; 1.24]), 90-day mortality (OR = 0.94 [95% CI: 0.67; 1.32]), distal emboli (OR = 0.94 [95% CI: 0.25; 3.60]), or sICH (OR = 1.17 [95% CI: 0.80; 1.72]). Administering tPA prior to MT may improve the rates of recanalization compared to MT alone in tPA-eligible patients being treated for AIS, but a corresponding improvement in functional and safety outcomes was not present in this review. Further studies looking at the role of tPA before mechanical thrombectomy in different cohorts of patients could better clarify the role of tPA in the treatment protocol for AIS.
PubMed: 34975722
DOI: 10.3389/fneur.2021.759759 -
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 -
Thrombosis and Haemostasis Dec 2012Several coagulation and fibrinolytic parameters appear to be affected by thyroid hormone excess; however, the net effect on the haemostatic system remains unclear. We... (Meta-Analysis)
Meta-Analysis Review
Several coagulation and fibrinolytic parameters appear to be affected by thyroid hormone excess; however, the net effect on the haemostatic system remains unclear. We aimed to update our previous review and systematically summarise and meta-analyse the data by assessing the effects of thyrotoxicosis on the coagulation and fibrinolytic system in vivo . Data sources included MEDLINE (2006-2012), EMBASE (2006-2012), and reference lists. The sources were combined with our previous search containing studies from 1980-2006. Eligible studies were all observational or experimental studies. Two investigators independently extracted data and rated study quality. Weighted mean proportion and 95% confidence intervals were calculated and pooled using a fixed and a random-effects model. A total of 29 articles consisting of 51 studies were included, as in several articles more than one study was described. We included four intervention (before and after treatment in hyperthyroid patients), five cross-sectional (hyperthyroid subjects and euthyroid controls), and four experimental (before and after use of thyroid hormone in euthyroid subjects) medium/high quality studies for meta-analysis. We found that thyrotoxicosis shifts the haemostatic balance towards a hypercoagulable and hypofibrinolytic state with a rise in factors VIII and IX, fibrinogen, von Willebrand factor, and plasminogen activator inhibitor-1. This was observed in endogenous and exogenous thyrotoxicosis, and in subclinical as well as overt hyperthyroidism. We conclude that both subclinical and overt hyperthyroidism induce a prothrombotic state, which is therefore likely to be a risk factor for venous thrombosis.
Topics: Blood Coagulation; Blood Coagulation Factors; Fibrinolysis; Humans; Hyperthyroidism; Risk Factors; Thrombosis; Thyrotoxicosis
PubMed: 23014708
DOI: 10.1160/TH12-07-0496 -
Journal of Neurology Feb 2023Hemorrhagic transformation (HT) is a common complication of alteplase treatment. However, the prevalence rate, risk factors, and clinical outcomes of remote... (Meta-Analysis)
Meta-Analysis Review
Prevalence, risk factors, and clinical outcomes of remote intracerebral hemorrhage after intravenous thrombolysis in acute ischemic stroke: a systematic review and meta-analysis.
BACKGROUND
Hemorrhagic transformation (HT) is a common complication of alteplase treatment. However, the prevalence rate, risk factors, and clinical outcomes of remote intracerebral hemorrhage (rICH) after intravenous thrombolysis in acute ischemic stroke are not well understood.
METHODS
Following a previously registered protocol, the PubMed, Web of Science, and Embase databases were systematically searched to identify relevant literature up to June 2022. Cohort studies reporting thrombolysis-related rICH in patients with acute ischemic stroke were included. Random effects models were used to calculate pooled prevalence rate, mean difference (MD) or odds ratio (OR) with corresponding 95% confidence interval (CI).
RESULTS
Fourteen studies with 52,610 patients were included in this meta-analysis. The pooled rICH prevalence was 3.2% (95% CI 3.1-3.4%). Compared to patients without intracerebral hemorrhage (ICH), those with rICH were older, more likely to be female, and had a higher proportion of prior stroke, chronic heart failure and cardioembolism, and higher diastolic blood pressure. Small vessel disease markers (e.g., white matter hyperintensities and cerebral microbleeds) were strongly associated with rICH. The presence of rICH decreased the likelihood of favorable outcomes (OR 0.36, 95% CI 0.31-0.41) and increased the risk of mortality (OR 4.37, 95% CI 2.86-6.67).
CONCLUSIONS
Although rICH is uncommon after intravenous thrombolysis, its presence can lead to worse functional outcomes and higher mortality in acute ischemic stroke. Patients at high risk of rICH must be identified based on potential risk factors.
Topics: Female; Humans; Male; Brain Ischemia; Cerebral Hemorrhage; Fibrinolytic Agents; Ischemic Stroke; Prevalence; Risk Factors; Thrombolytic Therapy; Tissue Plasminogen Activator; Treatment Outcome
PubMed: 36198828
DOI: 10.1007/s00415-022-11414-2 -
Journal of Thrombosis and Haemostasis :... Dec 2020Retinal vascular occlusion is a leading cause of sight loss. Both retinal artery occlusion (RAO) and retinal vein occlusion (RVO) have been associated with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Retinal vascular occlusion is a leading cause of sight loss. Both retinal artery occlusion (RAO) and retinal vein occlusion (RVO) have been associated with hypercoagulable states; however, the burden of thrombophilia in these patients is unclear.
OBJECTIVES
This study aims at estimating the prevalence of inherited and acquired thrombophilias in adults with RAO or RVO through a systematic review and meta-analysis of the literature.
PATIENTS/METHODS
PubMed and EMBASE were systematically searched from inception to 29 February 2020. All studies reporting prevalences of factor V Leiden (FVL) and prothrombin (F-II) G20210A mutations, methylenetetrahydrofolate reductase (MTHFR) C677T and plasminogen activator inhibitor (PAI) 4G polymorphisms, antithrombin III (AT-III), protein C (PC) and protein S (PS) activity deficiencies, hyperhomocysteinemia, and antiphospholipid (APL) antibodies in adults with RAO or RVO were included. Pooled prevalences and 95% confidence intervals (CI) were calculated.
RESULTS
Ninety-five studies were included; FVL and F-II mutations were found in 6% (95% CI: 5-8) and 3% (95% CI: 2-4) of individuals with RVO, respectively, whereas AT-III, PC, and PS activity deficiencies were found in <2%. The MTHFR C677T and PAI 4G homozygous polymorphism were observed in 13% (95% CI: 10-17) and 23% (95% CI: 16-31) of RVO, respectively; 8% presented APL antibodies. Similar findings were observed in individuals with RAO.
CONCLUSIONS
Compared with healthy subjects, patients with retinal vascular occlusion showed similar prevalences of inherited and acquired thrombophilias. These findings do not support routine thrombophilia screening in individuals with RAO or RVO.
Topics: Adult; Factor V; Humans; Methylenetetrahydrofolate Reductase (NADPH2); Prothrombin; Retinal Vein Occlusion; Risk Factors; Thrombophilia
PubMed: 32805772
DOI: 10.1111/jth.15068