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Thrombosis Journal May 2024We conducted this systematic review and meta-analysis to better understand the association between rs1799762 PAI-1 gene polymorphism and the risk of RPL. (Review)
Review
BACKGROUND
We conducted this systematic review and meta-analysis to better understand the association between rs1799762 PAI-1 gene polymorphism and the risk of RPL.
METHODS
A systematic search for studies that assessed the association between PAI-1 4G/5G polymorphism and RPL risk published in search sources, PubMed/Medline, ISI Web of Knowledge, Scopus, and Google Scholar till January 2024 was conducted.
RESULTS
There were 23 case-control studies in total, with a high degree of statistical heterogeneity among them which indicated the need for subgroup analysis. We found a significant positive association between the risk of RPL and 4G/4G PAI-1 (OR: 2.57; 95% CI: 1.69-3.90), likewise 4G/5G (OR: 2/02 95% CI: 1.39-2.92) and mixed genotype (4G/4G+4G/5G) (OR: 2.31 95% CI: 1.81-2.93). Considering the ethnicity, the 4G/4G polymorphism is significantly associated with Asian descent (OR: 2.10; CI: 1.65-2.69) while the strong association (OR: 6.47; CI: 3.23-12.97) observed in the Greater Middle East descent is not statistically significant (P=0.16). PAI-1 4G/5G polymorphism association with RPL was only significant in Greater Middle East descent (OR: 2.93; CI: 2.41-3.56), and mixed genotype was significantly associated with RPL in Asian (OR: 2.37; CI: 1.55-3.61), Greater Middle East (OR: 3.01; CI: 2.16-4.19), and European populations (OR: 1.38; CI: 0.91-2.10). The association between RPL and PAI-1 4G/4G was significant for RPLs both under 12 weeks (OR: 1.82; 95% CI: 1.34-2.47), and under 24 weeks (OR: 1.46; 95% CI: 1.11-1.92), while considering heterozygote form the association was only significant for RPLs under 24 weeks (OR: 1.91; 95% CI: 1.58-2.31). Regarding the mixed genotype, there is a significant positive association between PAI-1 and RPL for RPLs under 12 weeks (OR: 2.09; 95% CI: 1.49-2.93), and under 24 weeks (OR: 2.10; 95% CI: 1.52-2.92).
CONCLUSIONS
Our findings indicate a significant association between the rs1799762 PAI-1 polymorphism and the risk of RPL.
PubMed: 38807142
DOI: 10.1186/s12959-024-00612-9 -
Journal of Assisted Reproduction and... Jul 2023Recurrent pregnancy loss (RPL) is affecting 1-4% of women who conceive approximately, and no cause could be found in more than 50% of women suffering from RPL. Inherited... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Recurrent pregnancy loss (RPL) is affecting 1-4% of women who conceive approximately, and no cause could be found in more than 50% of women suffering from RPL. Inherited thrombophilias have got increasing attention in women with unexplained RPL, so we aim to explore the relationship among these most common thrombophilic polymorphisms and RPL through a literature review and meta-analysis.
METHODS
Observational studies from PubMed, Embase, Cochrane, and Web of Science from 1997 to 7 April 2022 were searched. For each genetic variant, a fixed or random-effect model was used according to the heterogeneity test to calculate pooled ORs and 95% CIs for both dominant and recessive genetic models. Egger's line regression test was used to assess publication bias. The quality of the included articles was assessed by the Newcastle Ottawa scale.
RESULTS
A total of 124 articles comprising 17,278 RPL patients and 16,021 controls were included. Results showed that hyperhomocysteinemia (MTHFR) C677T (dominant model: OR, 1.43; 95% CI, 1.25-1.64; recessive model: OR, 1.60; 95% CI, 1.36-1.87), MTHFR A1298C (dominant model: OR, 1.66; 95% CI, 1.26-2.18; recessive model: OR, 1.79; 95% CI, 1.42-2.26), PAI-1 4G/5G (dominant model: OR, 1.67; 95% CI, 1.36-2.06; recessive model: OR, 1.80; 95% CI, 1.39-2.32), angiotensin-converting enzyme I/D (OR, 1.23; 95% CI, 1.00-1.53), Factor XIII V34L (OR, 1.38; 95% CI, 1.02-1.87), and β-fibrinogen-455G/A (OR, 1.60; 95% CI, 1.02-2.51) were significantly associated with RPL.
CONCLUSION
This study provides potentially useful clinical markers to evaluate the risk of RPL or to help unexplained RPL patients identify possible causes, which may allow for targeted treatment.
Topics: Pregnancy; Humans; Female; Genetic Predisposition to Disease; Polymorphism, Genetic; Thrombophilia; Plasminogen Activator Inhibitor 1; Abortion, Habitual; Methylenetetrahydrofolate Reductase (NADPH2); Observational Studies as Topic
PubMed: 37248348
DOI: 10.1007/s10815-023-02823-x -
Clinical Neurology and Neurosurgery Oct 2023Alteplase is the standard medical therapy for acute ischemic stroke (AIS) patients who present within 4.5 h of symptom onset. Tenecteplase is a modified alteplase... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Alteplase is the standard medical therapy for acute ischemic stroke (AIS) patients who present within 4.5 h of symptom onset. Tenecteplase is a modified alteplase variant with pharmacological and practical advantages over alteplase. Many trials have investigated the efficacy and safety of tenecteplase against alteplase. This systematic review and meta-analysis aimed to compare the efficacy and safety of tenecteplase to alteplase across randomized controlled trials.
METHOD
Medline, Embase, and Cochrane CENTRAL were used to search the related articles until February 20, 2023. Randomized controlled trials (RCTs) that compared the effectiveness and safety of tenecteplase against alteplase for AIS patients were included. Screening, risk of bias assessment, and data extraction were performed following PRISMA guidelines. Data were pooled using a random-effect model.
RESULTS
Ten RCTs were included, with a total of 5123 patients. There was no significant difference between the two interventions in modified rankin scale 0-1 (mRS 0-1) (RR= 1.04, 95% CI [0.99-1.10], P = 0.11, I =0%) and early neurological improvement (RR= 1.06, 95% CI [0.97-1.15], P = 0.21, I =35). There was no difference in the rates of symptomatic intracranial hemorrhage (RR= 1.18, 95% CI [0.84-1.65], P = 0.35, I = 0%). Tenecteplase was associated with significantly higher complete recanalization rate compared to alteplase (RR= 1.17, 95% CI [1.00-1.36], P = 0.05, I =0%). For large vessel occlusion (LVO) patients assigned to tenecteplase, there was a significant improvement in mRS 0-1 (RR= 1.28, 95% CI [1.07-1.52], P = 0.006, I =0%).
CONCLUSION
Based on our meta-analysis, tenecteplase has similar efficacy and safety to alteplase, with a more promising effect in patients with LVO.
Topics: Humans; Tissue Plasminogen Activator; Tenecteplase; Fibrinolytic Agents; Stroke; Brain Ischemia; Randomized Controlled Trials as Topic; Ischemic Stroke; Treatment Outcome
PubMed: 37713743
DOI: 10.1016/j.clineuro.2023.107961 -
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 -
Ophthalmic Surgery, Lasers & Imaging... Nov 2023Many interventions for nonarteritic central retinal artery occlusion (CRAO) are associated with serious complications and little effect on visual outcomes. We report on... (Review)
Review
Many interventions for nonarteritic central retinal artery occlusion (CRAO) are associated with serious complications and little effect on visual outcomes. We report on the findings of a Cochrane systematic review that searched seven databases for peer-reviewed articles reporting on treatments for acute nonarteritic CRAO. We assessed six randomized controlled trials, including interventions such as tissue plasminogen activator (t-PA), isovolumic hemodilution, eyeball massage, intraocular pressure reduction, anticoagulation, vasodilation, oxygen inhalation, laser embolysis, transcorneal electrical stimulation, thrombolysis, pentoxifylline, and enhanced external counterpulsation. However, none of the randomized controlled trials demonstrated significant improvement in visual acuity at 1 month compared to observation, and some patients treated with t-PA experienced serious adverse effects including intracranial hemorrhage. Proposed interventions for acute nonarteritic CRAO may not be better than observation, but the evidence is uncertain. Larger, well-designed studies are necessary to determine the most effective management option for acute nonarteritic CRAO. .
Topics: Humans; Tissue Plasminogen Activator; Retinal Artery Occlusion; Thrombolytic Therapy; Hemodilution; Eye
PubMed: 37855834
DOI: 10.3928/23258160-20230922-01 -
Brain, Behavior, and Immunity Jun 2024There is some evidence of an association between inflammation in the pathogenesis of mental disorders. Soluble urokinase plasminogen activator receptor (suPAR) is a... (Review)
Review
BACKGROUND
There is some evidence of an association between inflammation in the pathogenesis of mental disorders. Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker of chronic inflammation, which provides a more stable index of systemic inflammation than more widely used biomarkers. This review aims to synthesise studies that measured suPAR concentrations in individuals with a psychiatric disorder, to determine if these concentrations are altered in comparison to healthy participants.
METHOD
Comprehensive literature searches from inception to October 2023 were conducted of five relevant databases (PubMed, Web of Science, Embase, Scopus, APA PsychInfo). Random-effects meta-analyses were performed to compare the standardised mean difference of blood suPAR levels (i.e. plasma or serum) for individuals with any psychiatric disorder relative to controls. Separate meta-analyses of suPAR levels were conducted for individuals with schizophrenia or other psychotic disorder and depressive disorder. Risk of bias was assessed using the Newcastle Ottawa Scale. Post-hoc sensitivity analyses included excluding studies at high risk of bias, and analyses of studies that measured suPAR concentrations either in serum or in plasma separately.
RESULTS
The literature search identified 149 records. Ten full-text studies were screened for eligibility and 9 studies were included for review. Primary analyses revealed no significant difference in suPAR levels between individuals with any psychiatric disorder compared to controls (k = 7, SMD = 0.42, 95 % CI [-0.20, 1.04]). However, those with depressive disorder had elevated suPAR levels relative to controls (k = 3, SMD = 0.61, 95 % CI [0.34, 0.87]). Similarly, secondary analyses showed no evidence of a significant difference in suPAR levels in individuals with any psychiatric disorder when studies at high risk of bias were excluded (k = 6, SMD = 0.54, 95 % CI [-0.14, 1.22]), but elevated suPAR concentrations for those with schizophrenia or other psychotic disorder were found (k = 3, SMD = 0.98, 95 % CI [0.39, 1.58]). Furthermore, studies that analysed plasma suPAR concentrations found elevated plasma suPAR levels in individuals with any psychiatric disorder relative to controls (k = 5, SMD = 0.84, 95 % CI [0.38, 1.29]), while studies measuring serum suPAR levels in any psychiatric disorder did not find a difference (k = 2, SMD = -0.61, 95 % CI [-1.27, 0.04]). For plasma, elevated suPAR concentrations were also identified for those with schizophrenia or other psychotic disorder (k = 3, SMD = 0.98, 95 % CI [0.39, 1.58]).
DISCUSSION
When studies measuring either only serum or only plasma suPAR were considered, no significant difference in suPAR levels were observed between psychiatric disorder groups, although significantly elevated suPAR levels were detected in those with moderate to severe depressive disorder. However, plasma suPAR levels were significantly elevated in those with any psychiatric disorder relative to controls, while no difference in serum samples was found. A similar finding was reported for schizophrenia or other psychotic disorder. The plasma findings suggest that chronic inflammatory dysregulation may contribute to the pathology of schizophrenia and depressive disorder. Future longitudinal studies are required to fully elucidate the role of this marker in the psychopathology of these disorders.
PubMed: 38857636
DOI: 10.1016/j.bbi.2024.06.003 -
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 -
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 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 -
Neurological Sciences : Official... Sep 2023We aimed to evaluate the available evidence on the efficacy and safety outcomes of intravenous tenecteplase (TNK) compared with intravenous alteplase(ALT) for patients... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
We aimed to evaluate the available evidence on the efficacy and safety outcomes of intravenous tenecteplase (TNK) compared with intravenous alteplase(ALT) for patients with acute ischemic stroke (AIS) in randomized controlled trials (RCTs).
METHODS
The MEDLINE/PubMed, Embase, Springer, Web of Science, Cochrane Collaboration database, China National Knowledge Infrastructure (CNKI) database, and Wanfang database were comprehensively searched for RCTs regarding the effects of TNK versus ALT among AIS patients in these English and Chinese electronic databases from inception dates to August 1, 2022. This meta-analysis followed PRISMA guidelines. Two reviewers independently retrieved RCTs and extracted relevant information. The methodological quality of the included trials was estimated using the Cochrane risk of bias tool. The pooled analyses were performed using RevMan 5.3 software. The primary outcome was functional outcome on the modified Rankin Scale (mRS) (range 0 to 5) and mortality at 90 days. The secondary outcomes included successful recanalization, early neurologic improvement < 48 h, any intracranial hemorrhage (ICH), and symptomatic ICH. The follow-up time of all studies was at least 3 months.
RESULTS
A total of nine RCTs involving 1958 patients in TNK group and 1731 patients in ALT group were finally included. For the efficacy outcomes, there were no significant differences between the two groups in terms of mRS score 0 ~ 2 (RR 1.00; 95% CI 0.88-1.13; P = 0.96), mRS score 0 ~ 1 (RR 1.03; 95% CI 0.96-1.10; P = 0.36), successful recanalization (RR 1.25; 95% CI 0.88-1.76; P = 0.21), and early neurologic improvement < 48 h (RR 1.08; 95% CI 0.92-1.26; P = 0.37). Similar results were seen for the safety outcomes, which have no statistical differences in terms of any ICH (RR 1.01; 95% CI 0.72-1.41; P = 0.96), symptomatic ICH (RR 1.19; 95% CI 0.81-1.76; P = 0.37), and mortality at 90 days (RR 0.99; 95% CI 0.83-1.19; P = 0.94).
CONCLUSION
Overall, the efficacy and safety outcomes of intravenous thrombolysis with TNK versus ALT for AIS were not statistically different. However, TNK at a dose of 0.25 mg/kg may be a reasonable alternative to ALT for thrombolysis.
Topics: Humans; Tissue Plasminogen Activator; Tenecteplase; Fibrinolytic Agents; Stroke; Intracranial Hemorrhages; Ischemic Stroke; Thrombolytic Therapy; Treatment Outcome; Brain Ischemia
PubMed: 37061572
DOI: 10.1007/s10072-023-06801-0