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Thrombosis Research Apr 2024Hormone replacement therapy is associated with an increased thromboembolic risk. The effects of testosterone (T) on coagulation markers in people assigned female at... (Meta-Analysis)
Meta-Analysis
Effects of gender affirming hormone therapy with testosterone on coagulation and hematological parameters in transgender people assigned female at birth: A systematic review and meta-analysis.
BACKGROUND
Hormone replacement therapy is associated with an increased thromboembolic risk. The effects of testosterone (T) on coagulation markers in people assigned female at birth (AFAB) under gender affirming hormone therapy (GAHT) are not well described.
METHODS
Systematic review and meta-analysis on English-language articles retrieved from PubMed, Scopus and Cochrane Library up to April 2023 investigating T therapy in AFAB people. Coagulation parameters included international normalized ratio (INR), fibrinogen, activated partial thromboplastin clotting time (aPTT), plasminogen activator inhibitor-1 (PAI-1); hematological variables included hemoglobin (Hb) and hematocrit (HCT). We also reported the rate of thromboembolic events. Data were combined as mean differences (MD) with a 95 % confidence interval (CI) of pre- vs post-follow-up values, using random-effects models.
RESULTS
We included 7 studies (6 prospective and 1 retrospective) providing information on 312 subjects (mean age: 23 to 30 years) who underwent GAHT with variable T preparation. T therapy was associated with a significant increase in INR values [MD: 0.02, 95 % confidence interval (CI): 0.01-0.03; p = 0.0001], with negligible heterogeneity (I = 4 %). T therapy was associated with increased Hb (MD: 1.48 g/dL, 95%CI: 1.17 to 1.78; I = 9 %) and HCT (4.39 %, 95%CI: 3.52 to 5.26; I = 23 %) values. No effect on fibrinogen, aPTT and PAI-1 was found. None of the study reported thromboembolic events during the follow-up.
CONCLUSION
Therapy with T increased blood viscosity in AFAB men. A slight increase in INR values was also found, but the clinical relevance and mechanism(s) of this finding needs to be clarified.
Topics: Adult; Female; Humans; Male; Young Adult; Fibrinogen; Plasminogen Activator Inhibitor 1; Prospective Studies; Retrospective Studies; Testosterone; Thromboembolism; Transgender Persons
PubMed: 38457996
DOI: 10.1016/j.thromres.2024.02.029 -
Expert Review of Anticancer Therapy 2024To provide an overview of the available literature data on clinical applications of positron emission tomography (PET) targeting the urokinase-type plasminogen activator... (Review)
Review
INTRODUCTION
To provide an overview of the available literature data on clinical applications of positron emission tomography (PET) targeting the urokinase-type plasminogen activator receptor in oncology.
METHODS
A literature search was conducted in PubMed, Web of Science and Scopus databases up to June 2023. The results were presented according to the PRISMA guidelines. The quality of the studies was assessed using the Critical Appraisal Skill Program checklist.
RESULTS
Seven papers were selected for final analysis, involving 266 patients with solid tumors who underwent PET with uPAR-ligands. Thematic areas identified include feasibility studies ( = 2) on the safety, pharmacokinetics, and dosimetry of uPAR-targeting radiopharmaceuticals; uPAR-directed imaging in head and neck cancer ( = 2); uPAR PET in prostate cancer ( = 2); and the investigation of uPAR in neuroendocrine neoplasms ( = 1). Six of the seven studies used the radiopharmaceutical [Ga]Ga-NOTA-AE105 while one study used [Cu]Cu-DOTA-AE105. The studies showed protocol homogeneity, with static PET imaging at 20 minutes. The quality assessment revealed limitations such as small cohorts and the fact that all studies were performed by a single research group.
CONCLUSIONS
uPAR-PET appears to be a promising imaging tool in well-selected oncological settings, but it needs to be validated by multicentre collaboration.
PubMed: 38451196
DOI: 10.1080/14737140.2024.2328167 -
Journal of Neurology May 2024Alteplase is the current standard of care for acute ischemic stroke. Tenecteplase is a newer fibrinolytic agent with preferable administration and lower costs; however,... (Meta-Analysis)
Meta-Analysis Comparative Study Review
OBJECTIVE
Alteplase is the current standard of care for acute ischemic stroke. Tenecteplase is a newer fibrinolytic agent with preferable administration and lower costs; however, its comparative effectiveness to alteplase remains uncertain. We set out to perform a systematic review and meta-analysis to establish the benefits and harms of tenecteplase versus alteplase for acute ischemic stroke.
METHODS
We searched PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov from inception to April 2023 for randomized and non-randomized studies that compared tenecteplase versus alteplase for acute ischemic stroke. Paired reviewers independently assessed risk of bias and extracted data. We performed both conventional meta-analyses and Bayesian network meta-analyses (NMA) with random-effects models and used the GRADE approach to evaluate the certainty of evidence. Our primary efficacy outcome was excellent functional outcome at 3 months, defined as a score of 0-1 on the modified Rankin Scale. Our primary safety outcomes were symptomatic intracranial hemorrhage and all-cause mortality.
RESULTS
Thirty-six studies were eligible for review, including 12 randomized (n = 5533) and 24 non-randomized studies (n = 44,956). Moderate certainty evidence showed that there was no difference between tenecteplase and alteplase in increasing the proportion of patients achieving excellent functional outcome at 3 months (odds ratio [OR], 1.10; 95% CI 0.98-1.23; risk difference [RD] 2.4%, 95% CI - 0.5 to 5.2), while moderate certainty evidence from NMA suggested that 0.25 mg/kg tenecteplase significantly improved excellent functional outcome at 3 months (OR, 1.16; 95% credible interval 1.02-1.32). Moderate certainty evidence showed that, compared to alteplase, tenecteplase may make little to no difference in the prevalence of symptomatic intracranial hemorrhage (OR, 1.12; 95% CI 0.79-1.59; RD 0.3%, 95% CI - 0.5 to 1.4), and probably reduces all-cause mortality (adjusted odds ratio [aOR], 0.44; 95% CI 0.30-0.64; RD - 4.6%; 95% CI - 5.8 to - 2.9).
CONCLUSIONS
Moderate certainty evidence suggested that there was little to no difference between tenecteplase and alteplase in increasing the proportion of patients achieving excellent functional outcome at 3 months and the risk of symptomatic intracranial hemorrhage, while compared to alteplase, tenecteplase probably reduce all-cause mortality. Administration of 0.25 mg/kg tenecteplase after acute ischemic stroke is suggestive of increasing the proportion of patients that achieve excellent functional outcome at 3 months.
Topics: Humans; Tenecteplase; Ischemic Stroke; Tissue Plasminogen Activator; Fibrinolytic Agents; Randomized Controlled Trials as Topic; Outcome Assessment, Health Care
PubMed: 38436679
DOI: 10.1007/s00415-024-12243-1 -
Advances in Simulation (London, England) Feb 2024Ischaemic strokes are medical emergencies, and reperfusion treatment, most commonly intravenous thrombolysis, is time-critical. Thrombolysis administration relies on...
BACKGROUND
Ischaemic strokes are medical emergencies, and reperfusion treatment, most commonly intravenous thrombolysis, is time-critical. Thrombolysis administration relies on well-organised pathways of care with highly skilled and efficient clinicians. Simulation training is a widespread teaching modality, but results from studies on the impact of this intervention have yet to be synthesised. This systematic review and meta-analysis aimed to synthesise the evidence and provide a recommendation regarding the effects of simulation training for healthcare professionals on door-to-needle time in the emergency thrombolysis of patients with ischaemic stroke.
METHODS
Seven electronic databases were systematically searched (last updated 12th July 2023) for eligible full-text articles and conference abstracts. Results were screened for relevance by two independent reviewers. The primary outcome was door-to-needle time for recombinant tissue plasminogen activator administration in emergency patients with ischaemic stroke. The secondary outcomes were learner-centred, improvements in knowledge and communication, self-perceived usefulness of training, and feeling 'safe' in thrombolysis-related decision-making. Data were extracted, risk of study bias assessed, and analysis was performed using RevMan™ software (Web version 5.6.0, The Cochrane Collaboration). The quality of the evidence was assessed using the Medical Education Research Study Quality Instrument.
RESULTS
Eleven studies were included in the meta-analysis and nineteen in the qualitative synthesis (n = 20,189 total patients). There were statistically significant effects of simulation training in reducing door-to-needle time; mean difference of 15 min [95% confidence intervals (CI) 8 to 21 min]; in improving healthcare professionals' acute stroke care knowledge; risk ratio (RR) 0.42 (95% CI 0.30 to 0.60); and in feeling 'safe' in thrombolysis-related decision-making; RR 0.46 (95% CI 0.36 to 0.59). Furthermore, simulation training improved healthcare professionals' communication and was self-perceived as useful training.
CONCLUSION
This meta-analysis showed that simulation training improves door-to-needle times for the delivery of thrombolysis in ischaemic stroke. However, results should be interpreted with caution due to the heterogeneity of the included studies.
PubMed: 38424568
DOI: 10.1186/s41077-024-00283-6 -
PloS One 2024The effectiveness of administering argatroban as a treatment approach following antiplatelet therapy or alteplase thrombolytic therapy in patients with acute stroke is... (Meta-Analysis)
Meta-Analysis
Can the combination of antiplatelet or alteplase thrombolytic therapy with argatroban benefit patients suffering from acute stroke? a systematic review, meta-analysis, and meta-regression.
BACKGROUND
The effectiveness of administering argatroban as a treatment approach following antiplatelet therapy or alteplase thrombolytic therapy in patients with acute stroke is presently uncertain. However, it is important to highlight the potential benefits of combining this medication with known thrombolytics or antiplatelet therapy. One notable advantage of argatroban is its short half-life, which helps minimize excessive anticoagulation and risk of bleeding complications in inadvertent cases of hemorrhagic stroke. By conducting a meticulous review and meta-analysis, we aim to further explore the common use of argatroban and examine the plausible advantages of combining this medication with established thrombolytic and antiplatelet therapies.
METHOD
In this study, we performed a rigorous and methodical search for both randomized controlled trials and retrospective analyses. Our main objective was to analyze the impact of argatroban on the occurrence of hemorrhagic events and the mRS scores of 0-2. We utilized a meta-analysis to assess the relative risk (RR) associated with using argatroban versus not using it.
RESULTS
In this study, we analyzed data from 11 different studies, encompassing a total of 8,635 patients. Out of these patients, 3999(46.3%) received argatroban treatment while the remaining 4636(53.7%)did not. The primary outcome of 90-day functional independence (modified Rankin scale (mRS) score≤2) showed that the risk ratio (RR) for patients using argatroban after alteplase thrombolytic therapy compared to those not using argatroban was(RR, 1.00 ([95% CI, 0.92-1.09]; P = 0.97), indicating no statistical significance. However, for patients using argatroban after antiplatelet therapy, was (RR,1.09 [95% CI, 1.04-1.14]; P = 0.0001), which was statistically significant. In terms of hemorrhagic events, the RR for patients using argatroban compared to those not using argatroban was (RR,1.08 [95% CI, 0.88-1.33]; P = 0.46), indicating no statistical significance.
CONCLUSION
The results of this study suggest that further research into combination therapy with argatroban and antiplatelet agents may be warranted, however more rigorous RCTs are needed to definitively evaluate the effects of combination treatment.
Topics: Humans; Platelet Aggregation Inhibitors; Tissue Plasminogen Activator; Retrospective Studies; Stroke; Hemorrhage; Fibrinolytic Agents; Thrombolytic Therapy; Treatment Outcome; Randomized Controlled Trials as Topic; Arginine; Pipecolic Acids; Sulfonamides
PubMed: 38412157
DOI: 10.1371/journal.pone.0298226 -
BMC Infectious Diseases Feb 2024To evaluate the efficacy of urokinase (UK) treatment for tuberculous pleural effusion (TPE). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the efficacy of urokinase (UK) treatment for tuberculous pleural effusion (TPE).
METHODS
We searched Chinese biomedical literature database, WanFang data, CNKI, PubMed, EMbase, Web of Science and The Cochrane Library for the randomized controlled trials (RCTs) of urokinase treatment for tuberculous pleurisy from January 2000 to February 2023. Pleural tuberculosis, urokinase and randomized controlled trial were used as keywords. The eligible studies were meta-analyzed by using Revman 5.4.1: risk of bias was assessed, mean difference (MD) and 95% CI were used for continuous variables, pooled studies were conducted using random-effects or fixed-effects models, forest plots were drawn to analyze efficacy, and funnel plots were drawn to discuss publication bias.
RESULTS
Twenty-nine RCTs were included. The meta-analyzed results showed that, on the basis of routine anti-tuberculosis, comparison between the treatment group treated with urokinase and the control group treated with antituberculosis alone, the time of pleural effusion absorption [MD-5.82, 95%CI (- 7.77, - 3.87); P<0.00001] and the residual pleural thickness [MD-1.31, 95%CI (- 1.70, - 0.91); P<0.00001], pleural effusion drainage volume [MD 822.81, 95%CI (666.46,977.96); P<0.00001], FVC%pred [MD 7.95, 95%CI (4.51,11.40); P<0.00001], FEV1%pred [MD 12.67, 95%CI (10.09,15.24); P<0.00001] were significantly different.
CONCLUSION
The clinical effect of urokinase is better than that of antituberculous therapy alone: it can increase total pleural effusion, decrease residual pleural thickness, improve the pulmonary function, and shorten the time of pleural effusion absorption.
Topics: Humans; Tuberculosis, Pleural; Urokinase-Type Plasminogen Activator; Pleural Effusion; Exudates and Transudates; Drainage
PubMed: 38402168
DOI: 10.1186/s12879-024-08975-0 -
European Review For Medical and... Jan 2024The aim of this study was to perform a systematic review of the usefulness of suPAR as a prognostic marker in non-critical COVID-19 patients.
OBJECTIVE
The aim of this study was to perform a systematic review of the usefulness of suPAR as a prognostic marker in non-critical COVID-19 patients.
MATERIALS AND METHODS
We carried out a literature search in MEDLINE, Embase, and Web of Science using the following keywords: ("soluble urokinase receptor" OR "urokinase plasminogen activator receptor" OR "suPAR" OR "soluble uPAR" OR "soluble uPA receptor") AND ("COVID-19" OR "SARS-CoV-2"). We included observational studies (descriptive or analytic) that measured plasma suPAR on COVID-19 patients 18 years old or older, with non-critical disease at the beginning of the study.
RESULTS
After screening and eligibility assessment, a total of 16 articles were included in the review. Most studies that measured mean differences found that suPAR levels were higher in patients with worse outcomes. The studies that measured diagnostic accuracy concluded that suPAR was highly sensitive and moderately specific to predicting bad outcomes. Studies that performed a survival analysis found that patients with high suPAR levels were more at risk of bad outcomes. Most of the studies included in this review were performed before extensive vaccination and omicron wave.
CONCLUSIONS
COVID-19 patients with moderate initial disease and elevated suPAR levels are more at risk of poor outcomes. Larger prospective clinical trials are needed to confirm the results obtained in this review.
Topics: Humans; Biomarkers; COVID-19; Prognosis; Prospective Studies; Receptors, Urokinase Plasminogen Activator; Urokinase-Type Plasminogen Activator
PubMed: 38305628
DOI: 10.26355/eurrev_202401_35086 -
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 -
Archives of Medical Research Feb 2024Fibrates are widely used in the treatment of dyslipidemia and associated metabolic abnormalities; however, their effects on adipokines are unclear. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Fibrates are widely used in the treatment of dyslipidemia and associated metabolic abnormalities; however, their effects on adipokines are unclear.
AIM OF THE STUDY
This meta-analysis of clinical trials aimed to evaluate the effect of fibrates on circulating adipokine levels.
METHODS
Only randomized controlled trials investigating the impact/effect of fibrate treatment on circulating adipokine levels were included from searches in PubMed-Medline, SCOPUS, ClinicalTrials.gov, Web of Science, and Google Scholar databases. A random effects model and the generic inverse variance method were used for the meta-analysis. Sensitivity analysis was conducted using the leave-one-out method.
RESULTS
This meta-analysis of 22 clinical trials showed a significant reduction on/in leptin (WMD: -1.58 ng/mL, 95% CI: -2.96, -0.20, p = 0.02, I = 0%), plasminogen activator inhibitor-1 (PAI-1) (WMD: -13.86 ng/mL, 95% CI: -26.70, -1.03, p = 0.03, I = 99%), and visfatin (WMD: -1.52 ng/mL, 95% CI: -2.49, -0.56, p = 0.002, I = 0%) after fibrate therapy; no significant effect was observed on adiponectin (WMD: -0.69 µg/ml, 95% CI: -1.40, 0.02, p = 0.06, I = 83%) and resistin (WMD: -2.27 ng/mL, 95% CI: -7.11, 2.57, p = 0.36, I = 0%). The sensitivity analysis was robust only for visfatin, while the effect size was sensitive to one arm for leptin, four for adiponectin, and two for PAI-1.
CONCLUSION
This meta-analysis showed that fibrate treatment significantly improves adipokine levels with a decrease in leptin, PAI-1, and visfatin, suggesting potential additional clinical therapeutic benefits through/of fibrate treatment on adipose tissue.
Topics: Leptin; Fibric Acids; Adipokines; Plasminogen Activator Inhibitor 1; Nicotinamide Phosphoribosyltransferase; Adiponectin; Randomized Controlled Trials as Topic
PubMed: 38266418
DOI: 10.1016/j.arcmed.2024.102957 -
Journal of Clinical Medicine Jan 2024: Subretinal macular hemorrhage (SRMH) secondary to age-related macular degeneration (AMD) is a relatively rare condition in ophthalmology characterized by blood... (Review)
Review
: Subretinal macular hemorrhage (SRMH) secondary to age-related macular degeneration (AMD) is a relatively rare condition in ophthalmology characterized by blood collection between the neurosensory retina and the retinal pigment epithelium (RPE). Without prompt treatment, visual prognosis is poor. A plethora of treatment approaches have been tried over the past years ranging from intravitreal anti-vascular endothelial growth factor (anti-VEGF) monotherapy to direct subretinal surgery, with no conclusive superiority of one over the other. : We conducted a systematic review of the outcomes and treatment modalities of SRMH from inception to 14 June 2022, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA). The level of evidence was assessed for all included articles according to the quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. : A total of 2745 articles were initially extracted, out of which 1654 articles were obtained after duplicates were removed and their abstracts screened. A total of 155 articles were included for full-text review. Finally, 81 articles remained that fulfilled the inclusion criteria. : Even though there are solid results supporting a variety of treatments for SRMH, the best treatment modality has still not been conclusively demonstrated and further research is needed.
PubMed: 38256501
DOI: 10.3390/jcm13020367