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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 -
Frontiers in Pharmacology 2020Recanalization with tissue plasminogen activator (tPA) is the only approved agent available for acute ischemic stroke. But delayed treatment of tPA may lead to lethal...
The Protective Role of Immunomodulators on Tissue-Type Plasminogen Activator-Induced Hemorrhagic Transformation in Experimental Stroke: A Systematic Review and Meta-Analysis.
Recanalization with tissue plasminogen activator (tPA) is the only approved agent available for acute ischemic stroke. But delayed treatment of tPA may lead to lethal intracerebral hemorrhagic transformation (HT). Numerous studies have reported that immunomodulators have good efficacy on tPA-induced HT in ischemic stroke models. The benefits of immunomodulators on tPA-associated HT are not clearly defined. Here, we sought to conduct a systematic review and meta-analysis of preclinical studies to further evaluate the efficacy of immunomodulators. The PubMed, Web of Science, and Scopus electronic databases were searched for studies. Studies that reported the efficacy of immunomodulators on tPA-induced HT in animal models of stroke were included. Animals were divided into two groups: immunomodulators plus tPA (intervention group) or tPA alone (control group). The primary outcome was intracerebral hemorrhage, and the secondary outcomes included infarct volume and neurobehavioral score. Study quality was assessed by the checklist of CAMARADES. We used standardized mean difference (SMD) to assess the impact of interventions. Regression analysis and subgroup analysis were performed to identify potential sources of heterogeneity and evaluate the impact of the study characteristics. The evidence of publication bias was evaluated using trim and fill method and Egger's test. We identified 22 studies that met our inclusion criteria involving 516 animals and 42 different comparisons. The median quality checklist score was seven of a possible 10 (interquartile range, 6-8). Immunomodulators improved cerebral hemorrhage (1.31 SMD, 1.09-1.52); infarct volume (1.35 SMD, 0.95-1.76), and neurobehavioral outcome (0.9 SMD, 0.67-1.13) in experimental stroke. Regression analysis and subgroup analysis indicated that control of temperature and time of assessment were important factors that influencing the efficacy of immunomodulators. Our findings suggested that immunomodulators had a favorable effect on tPA-associated intracerebral hemorrhage, cerebral infarction, and neurobehavioral impairments in animal models of ischemic stroke.
PubMed: 33424615
DOI: 10.3389/fphar.2020.615166 -
Frontiers in Pharmacology 2022This meta-analysis aimed to assess the efficacy and safety of ginkgo terpene lactone preparations including ginkgo diterpene lactone meglumine injection, ginkgolide...
This meta-analysis aimed to assess the efficacy and safety of ginkgo terpene lactone preparations including ginkgo diterpene lactone meglumine injection, ginkgolide injection, and ginkgolide B injection for ischemic stroke (IS). We searched the randomized controlled trials (RCTs) with publication date earlier than 31 August 2021 in PubMed, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Journals Database (VIP), Chinese Biomedical Literature Database (CBM), Wanfang Database, Embase, and the Cochrane Library. RevMan 5.3 software was applied to analyze the data and generate the forest plot and funnel plot. Meanwhile, publication bias was also assessed by Egger's test with STATA 12 software. A total of 28 RCTs were eligible for inclusion. Among them, 23 RCTs were used to evaluate the efficacy of ginkgo terpene lactone preparations as the main treatment intervention for IS. To be specific, ginkgo diterpene lactone meglumine injection was superior to control drug in improving clinical efficacy [RR = 1.18, 95% CI (1.12, 1.24), Z = 6.36, < 0.001] and neurological function [MD = -1.42, 95% CI (-1.91, -0.93), Z = 5.66, < 0.001]. However, the effectiveness of the ginkgolide B injection group was equivalent to that of the control group. Additionally, ginkgolide injection achieved better clinical efficacy [RR = 1.10, 95% CI (1.02, 1.18), Z = 2.36, = 0.02], but the changes of neurological function deficit was not obviously different between two groups [MD = -0.43, 95% CI (-4.32, 3.46), Z = 0.22, = 0.83]. Furthermore, meta-analysis of five trials on ginkgo diterpene lactone meglumine injection combined with recombinant tissue plasminogen activator (rt-PA) thrombolytic therapy for acute IS showed that combination therapy was better in improving clinical efficacy [OR = 1.91, 95% CI (1.13, 3.22), Z = 2.41, = 0.02] and neurological function [MD = -3.31, 95% Cl (-3.64,-2.98), Z = 19.63, < 0.001]. Importantly, no serious adverse drug reactions/adverse drug events (ADRs/ADEs) were reported. Ginkgo terpene lactone preparations have good therapeutic effects on patients with IS. For acute IS, ginkgo diterpene lactone meglumine injection can be used as a complementary therapy to improve the clinical efficacy of rt-PA.
PubMed: 35392576
DOI: 10.3389/fphar.2022.821937 -
Frontiers in Neurology 2022The available literature on mobile stroke units (MSU) has focused on clinical outcomes, rather than operational performance. Our objective was to establish normalized...
BACKGROUND
The available literature on mobile stroke units (MSU) has focused on clinical outcomes, rather than operational performance. Our objective was to establish normalized metrics and to conduct a meta-analysis of the current literature on MSU performance.
METHODS
Our MSU in upstate New York serves 741,000 people. We present prospectively collected, retrospectively analyzed data from the inception of our MSU in October of 2018, through March of 2021. Rates of transportation/dispatch and MSU utilization were reported. We also performed a meta-analysis using MEDLINE, SCOPUS, and Cochrane Library databases, calculating rates of tPA/dispatch, tPA-per-24-operational-hours ("per day"), mechanical thrombectomy (MT)/dispatch and MT/day.
RESULTS
Our MSU was dispatched 1,719 times in 606 days (8.5 dispatches/24-operational-hours) and transported 324 patients (18.8%) to the hospital. Intravenous tPA was administered in 64 patients (3.7% of dispatches) and the rate of tPA/day was 0.317 (95% CI 0.150-0.567). MT was performed in 24 patients (1.4% of dispatches) for a MT/day rate of 0.119 (95% CI 0.074-0.163). The MSU was in use for 38,742 minutes out of 290,760 total available minutes (13.3% utilization rate). Our meta-analysis included 14 articles. Eight studies were included in the analysis of tPA/dispatch (342/5,862) for a rate of 7.2% (95% CI 4.8-9.5%, I = 92%) and 11 were included in the analysis of tPA/day (1,858/4,961) for a rate of 0.358 (95% CI 0.215-0.502, I = 99%). Seven studies were included for MT/dispatch (102/5,335) for a rate of 2.0% (95% CI 1.2-2.8%, I = 67%) and MT/day (103/1,249) for a rate of 0.092 (95% CI 0.046-0.138, I = 91%).
CONCLUSIONS
In this single institution retrospective study and meta-analysis, we outline the following operational metrics: tPA/dispatch, tPA/day, MT/dispatch, MT/day, and utilization rate. These metrics are useful for internal and external comparison for institutions with or considering developing mobile stroke programs.
PubMed: 35614916
DOI: 10.3389/fneur.2022.868051 -
Therapeutic Advances in Respiratory... 2020Soluble urokinase-type plasminogen activator receptor (suPAR) is positively correlated with immune system activity. Inflammation can promote the development of chronic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Soluble urokinase-type plasminogen activator receptor (suPAR) is positively correlated with immune system activity. Inflammation can promote the development of chronic obstructive pulmonary disease (COPD). Therefore, this study conducted a systematic review and meta-analysis to assess the association between suPAR levels and the pathogenesis of COPD, and further assess the exact clinical value of suPAR in COPD.
METHODS
PubMed, Excerpt Medica Database (Embase), Web of Science (WOS), and Cochrane Library databases were searched for studies that reported the value of suPAR diagnosis for adult COPD patients.
RESULTS
A total of 11 studies were included, involving 4520 participants. Both COPD patients with predicted forced expiratory volume in 1 s (FEV1)⩾80% [weighted mean difference (WMD) = 320.25; 95% confidence interval (CI): 99.79-540.71] and FEV1 < 80% (WMD = 2950.74; 95% CI: 2647.06-3254.43) showed higher suPAR level. The sensitivity and specificity of suPAR for diagnosis of COPD were 87% and 79%, respectively, and AUC was 84%. This can not only effectively identify acute exacerbation of COPD (AECOPD) in a healthy population (WMD = 3114.77; 95% CI: 2814.66-3414.88), but also has the potential to distinguish AECOPD from stable COPD (WMD = 351.40; 95% CI: 215.88-486.93). There was a significant decrease of suPAR level after treatment [WMD = -1226.97; 95% CI: -1380.91- (-1073.03)].
CONCLUSION
suPAR as a novel biomarker has potential for early diagnosis of COPD and prediction of AECOPD. There is a potential correlation between the level of suPAR and the state of COPD, which may also indicate the early state and severity of COPD. When the suPAR level of COPD patients is further increased, the risk of acute exacerbation increases and should be highly valued. This also shows potential as a measure of treatment response, and as a guide to the clinical management in COPD.
Topics: Aged; Biomarkers; Early Diagnosis; Female; Forced Expiratory Volume; Humans; Lung; Male; Middle Aged; Predictive Value of Tests; Prognosis; Pulmonary Disease, Chronic Obstructive; Receptors, Urokinase Plasminogen Activator; Vital Capacity
PubMed: 32643535
DOI: 10.1177/1753466620938546 -
Frontiers in Pharmacology 2022Inflammatory biomarkers may play vital roles in the pathophysiology of diabetes and diabetic cardiorenal complications. Sodium-glucose cotransporter-2 (SGLT2)... (Review)
Review
Inflammatory biomarkers may play vital roles in the pathophysiology of diabetes and diabetic cardiorenal complications. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have a potential cardiovascular and renal protective effect in type 2 diabetes. The aim of this meta-analysis was to quantify the effects of SGLT2 inhibitors on biomarkers of inflammation in randomized controlled trials (RCTs). PubMed, Cochrane Library, EMBASE, and Web of Science were searched for eligible RCTs of adults with type 2 diabetes (T2D) with no time limit (updated to 12 October 2022). The biomarkers selected included C-reactive protein (CRP), interleukin-6, tumor necrosis factor-alpha, leptin, adiponectin, ferritin, plasminogen activator inhibitor (PAI)-1, and vascular cell adhesion molecule-1. Data were analyzed using a random-effect model in Review Manager 5.4. Thirty-four studies with 6,261 patients (68.6% male) were eligible for this meta-analysis. The mean age of the participants was 62.57(±11.13) years old, and the median treatment duration length with follow-up was 24 weeks. Generally, the included trials were of good methodological quality. The meta-analysis revealed that ferritin levels were significantly reduced in SGLT2 inhibitor treatment groups placebo or standard diabetes therapies (SMD: -1.21; 95% CI: -1.91, -0.52, < 0.001). The effects of CRP (SMD: 0.25; 95% CI: -0.47, -0.03, = 0.02) and leptin (SMD: -0.22; 95% CI: -0.43, -0.01, = 0.04) were reduced, and the effects of adiponectin were improved (SMD: 0.28; 95% CI: 0.15, 0.41, < 0.001) in placebo-controlled studies. PAI-1 levels were significantly reduced in studies controlled for diabetes therapies (SMD: -0.38; 95% CI: -0.61, -0.15, = 0.001). This analysis provides strong evidence supporting anti-inflammatory effects of SGLT2 inhibitors in T2D subjects. The mechanisms and possible targets for the inflammation reducing and cardiorenal protective properties of SGLT2 inhibitors remain to be explored.
PubMed: 36467062
DOI: 10.3389/fphar.2022.1045235 -
International Journal of Molecular... Sep 2020Stroke is the leading cause of disability, and stroke survivors suffer from long-term sequelae even after receiving recombinant tissue plasminogen activator therapy and...
Stroke is the leading cause of disability, and stroke survivors suffer from long-term sequelae even after receiving recombinant tissue plasminogen activator therapy and endovascular intracranial thrombectomy. Increasing evidence suggests that exosomes, nano-sized extracellular membrane vesicles, enhance neurogenesis, angiogenesis, and axonal outgrowth, all the while suppressing inflammatory reactions, thereby enhancing functional recovery after stroke. A systematic literature review to study the association of stroke recovery with exosome therapy was carried out, analyzing species, stroke model, source of exosomes, behavioral analyses, and outcome data, as well as molecular mechanisms. Thirteen studies were included in the present systematic review. In the majority of studies, exosomes derived from mesenchymal stromal cells or stem cells were administered intravenously within 24 h after transient middle cerebral artery occlusion, showing a significant improvement of neurological severity and motor functions. Specific microRNAs and molecules were identified by mechanistic investigations, and their amplification was shown to further enhance therapeutic effects, including neurogenesis, angiogenesis, axonal outgrowth, and synaptogenesis. Overall, this review addresses the current advances in exosome therapy for stroke recovery in preclinical studies, which can hopefully be preparatory steps for the future development of clinical trials involving stroke survivors to improve functional outcomes.
Topics: Animals; Axons; Disease Models, Animal; Exosomes; Humans; Mesenchymal Stem Cells; MicroRNAs; Neovascularization, Physiologic; Neurogenesis; Stroke; Synapses
PubMed: 32962207
DOI: 10.3390/ijms21186894 -
Stroke Mar 2022Stroke disproportionately affects racial minorities, and the level to which stroke treatment practices differ across races is understudied. Here, we performed a...
Stroke disproportionately affects racial minorities, and the level to which stroke treatment practices differ across races is understudied. Here, we performed a systematic review of disparities in stroke treatment between racial minorities and White patients. A systematic literature search was performed on PubMed to identify studies published from January 1, 2010, to April 5, 2021 that investigated disparities in access to stroke treatment between racial minorities and White patients. A total of 30 studies were included in the systematic review. White patients were estimated to use emergency medical services at a greater rate (59.8%) than African American (55.6%), Asian (54.7%), and Hispanic patients (53.2%). A greater proportion of White patients (37.4%) were estimated to arrive within 3 hours from onset of stroke symptoms than African American (26.0%) and Hispanic (28.9%) patients. A greater proportion of White patients (2.8%) were estimated to receive tPA (tissue-type plasminogen activator) as compared with African American (2.3%), Hispanic (2.6%), and Asian (2.3%) patients. Rates of utilization of mechanical thrombectomy were also lower in minorities than in the White population. As shown in this review, racial disparities exist at key points along the continuum of stroke care from onset of stroke symptoms to treatment. Beyond patient level factors, these disparities may be attributed to other provider and system level factors within the health care ecosystem.
Topics: Healthcare Disparities; Humans; Racial Groups; Stroke; Thrombectomy; Tissue Plasminogen Activator; United States
PubMed: 35105178
DOI: 10.1161/STROKEAHA.121.036263 -
BioMed Research International 2019Chronic kidney disease (CKD) has become a global public health problem with a high prevalence and mortality. There is no sensitive and effective markers for chronic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chronic kidney disease (CKD) has become a global public health problem with a high prevalence and mortality. There is no sensitive and effective markers for chronic kidney disease. Previous studies proposed suPAR as an early predict biomarker for chronic kidney disease, but the results are controversial. Therefore, the purpose of the current meta-analysis is to evaluate the association between suPAR and CKD.
METHODS
We searched the PubMed, Embase, Cochrane Library databases, and Web of Science before May 1, 2019. The search was based on the key words including suPAR and CKD. Data are extracted independently according to standard format, and quality analysis is performed. We extracted the concentration of suPAR and hazard rate (HR) values of mortality, cardiovascular disease, and end-stage renal disease.
RESULTS
There were 14 studies fulfilling the criteria. The concentration of suPAR was higher in patients with CKD than that in the control group ( < 0.001; SMD: -2.17; 95% CI: -2.71, -1.63; = 67.4%). SuPAR had a higher risk of mortality (=0.001; HR: 1.72; 95% CI: 1.24, 2.39; = 68.0%). The higher suPAR level increased the risk of cardiovascular disease ( < 0.001; HR: 3.06; 95% CI: 2.21, 4.22; = 0.0%) and the risk of end-stage renal disease ( < 0.001; HR: 1.40; 95% CI: 1.22, 1.60; = 0.0%).
CONCLUSIONS
Monitoring suPAR concentrations may be used for early diagnosis and prognosis for patients with CKD, and the higher suPAR increased the risk of mortality, cardiovascular events, and end-stage renal disease.
Topics: Biomarkers; Cardiovascular Diseases; Cause of Death; Databases, Factual; Humans; Kidney Failure, Chronic; Mortality; Prognosis; Receptors, Urokinase Plasminogen Activator; Renal Insufficiency, Chronic; Risk Factors
PubMed: 31886242
DOI: 10.1155/2019/6927456 -
Journal of the American Heart... Dec 2020Background tPA (tissue-type plasminogen activator) remains the only approved drug for acute ischemic stroke, with a potentially serious adverse effect: hemorrhagic... (Meta-Analysis)
Meta-Analysis
Background tPA (tissue-type plasminogen activator) remains the only approved drug for acute ischemic stroke, with a potentially serious adverse effect: hemorrhagic transformation. The effects of antithrombotic agents on tPA-induced hemorrhagic transformation after ischemic stroke are not clearly defined. We performed a systematic review and meta-analysis in preclinical studies aiming to evaluate the efficacy of antithrombotic agents on tPA-induced hemorrhagic transformation after ischemic stroke. Methods and Results We conducted a systematic review and meta-analysis of studies testing antithrombotic agents in animal models of tPA-induced hemorrhagic transformation. The pooled effects were calculated using random-effects models, and heterogeneity was explored through meta-regression and subgroup analyses. Publication bias was assessed using trim and fill method and the Egger test. The efficacy of 18 distinct interventions was described in 22 publications. The pooled data showed a significant improvement in cerebral hemorrhage, infarct size, and neurobehavioral outcome in treated compared with control animals (standardized mean difference, 0.45 [95% CI, 0.11-0.78]; standardized mean difference, 1.18 [95% CI, 0.73-1.64]; and standardized mean difference, 0.91 [95% CI, 0.49-1.32], respectively). Subgroup analysis indicated that quality score, random allocation, control of temperature, anesthetic used, stroke model used, route of drug delivery, time of drug administration, and time of assessment were significant factors that influenced the effects of interventions. Conclusions Administration with antiplatelet agents revealed statistically significant improvement in all the outcomes. Anticoagulant agents showed significant effects in infarct size and neurobehavioral score, but fibrinolytic agents did not show any significant improvement in all the outcomes. The conclusions should be interpreted cautiously given the heterogeneity and publication bias identified in this analysis.
Topics: Animals; Case-Control Studies; Cerebral Hemorrhage; Disease Models, Animal; Fibrinolytic Agents; Ischemic Stroke; Male; Mental Status and Dementia Tests; Mice; Platelet Aggregation Inhibitors; Rabbits; Rats; Tissue Plasminogen Activator; Treatment Outcome
PubMed: 33283576
DOI: 10.1161/JAHA.120.017876