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International Journal of Molecular... May 2020Oxidative stress reflects a disturbance in the balance between the production and accumulation of reactive oxygen species (ROS). ROS are scavenged by the antioxidant... (Meta-Analysis)
Meta-Analysis
Oxidative stress reflects a disturbance in the balance between the production and accumulation of reactive oxygen species (ROS). ROS are scavenged by the antioxidant system, but when in excess concentration, they can oxidize proteins, lipids, and DNA. DNA damage is usually repaired, and the oxidized products are excreted in urine. 8-hydroxy-2-deoxyguanosine is considered a biomarker for oxidative damage of DNA. It is needed to define background ranges for 8-OHdG, to use it as a measure of oxidative stress overproduction. We established a standardized protocol for a systematic review and meta-analysis to assess background ranges for urinary 8-OHdG concentrations in healthy populations. We computed geometric mean (GM) and geometric standard deviations (GSD) as the basis for the meta-analysis. We retrieved an initial 1246 articles, included 84 articles, and identified 128 study subgroups. We stratified the subgroups by body mass index, gender, and smoking status reported. The pooled GM value for urinary 8-OHdG concentrations in healthy adults with a mean body mass index (BMI) ≤ 25 measured using chemical methods was 3.9 ng/mg creatinine (interquartile range (IQR): 3 to 5.5 ng/mg creatinine). A significant positive association was observed between smoking and urinary 8-OHdG concentrations when measured by chemical analysis. No gender effect was observed.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; Female; Humans; Male; Meta-Analysis as Topic; Oxidative Stress; Smoking
PubMed: 32466448
DOI: 10.3390/ijms21113743 -
Therapeutic Advances in Cardiovascular... 2023Currently, no pharmacological or device-based intervention has been fully proven to reverse the no-reflow phenomenon.
BACKGROUND
Currently, no pharmacological or device-based intervention has been fully proven to reverse the no-reflow phenomenon.
OBJECTIVES
To assess the efficacy and safety of intracoronary (IC) epinephrine in the management of no-reflow phenomenon following percutaneous coronary intervention (PCI), either as first-line treatment or after the failure of conventional agents.
DESIGN
Systematic review.
DATA SOURCES AND METHODS
PubMed and Scopus databases were systematically searched up to 28 May 2022, with additional manual search on the Google Scholar and review of the reference lists of the relevant studies to identify all published studies. Cohort studies, case series, and interventional studies written in English which evaluated the efficacy and safety of IC epinephrine in patients with no-flow phenomenon were included in our review.
RESULTS
Six of the 646 articles identified in the initial search met our inclusion criteria. IC epinephrine was used either as a first-line treatment [two randomized clinical trials (RCTs)] or after the failure of conventional agents (two cohort studies and two case series) for restoring the coronary flow, mainly after primary PCI. As first-line therapy, IC epinephrine successfully restored coronary flow in over 90% of patients in both RCTs, which significantly outperformed IC adenosine (78%) but lagged behind combination of verapamil and tirofiban (100%) in this regard. In the refractory no-flow phenomenon, successful reperfusion [thrombolysis in myocardial infarction (TIMI) flow grade = 3] was achieved in three out of four patients after the administration of IC epinephrine based on the results from both case series. Their findings were confirmed by a recent cohort study that further compared IC epinephrine with IC adenosine and found significant differences between them in terms of efficacy [% TIMI flow grade 3: (69.1% 52.7%, respectively; value = 0.04)] and 1-year major adverse cardiac event (MACE) outcomes (11.3% 26.7%, respectively; value ⩽ 0.01). Overall, malignant ventricular arrhythmias were reported in none of the patients treated with IC epinephrine.
CONCLUSION
Results from available evidence suggest that IC epinephrine might be an effective and safe agent in managing the no-reflow phenomenon.
Topics: Humans; Adenosine; Epinephrine; Heart; No-Reflow Phenomenon; Percutaneous Coronary Intervention
PubMed: 36852839
DOI: 10.1177/17539447231154654 -
Journal of Thrombosis and Thrombolysis Jul 2019De-escalation from ticagrelor to clopidogrel in acute coronary syndrome (ACS) may occur for a variety of reasons, including side effects (bleeding and non-bleeding) and... (Meta-Analysis)
Meta-Analysis
De-escalation from ticagrelor to clopidogrel in acute coronary syndrome (ACS) may occur for a variety of reasons, including side effects (bleeding and non-bleeding) and costs. This study sought to assess the prevalence of de-escalation from ticagrelor to clopidogrel and the occurrence of adverse clinical outcomes following de-escalation. We conducted a systematic review of clinical trials and real-world studies in ACS patients treated with ticagrelor. Real-world data on the prevalence of de-escalation during hospitalization or at discharge, after hospital discharge, and during the whole study period were included for meta-analysis. Major adverse cardiovascular events (MACE) and bleeding events occurring after de-escalation were also assessed. A total of 12 studies were eligible for meta-analysis of the prevalence of de-escalation. De-escalation from ticagrelor to clopidogrel therapy occurred with a mean prevalence of 19.8% [95% confidence interval (CI) 11.2-28.4%]. De-escalation occurred more frequently in-hospital or at discharge than after hospital discharge (23.7% vs. 15.8%). For assessment of clinical outcomes, a total of six studies were eligible for meta-analysis. Mean rate of MACE for patients with de-escalation was 2.1% (95% CI 1.1-4.1%) and the rate of major bleeding events was 1.3% (95% CI 0.4-4.5%). In conclusion, de-escalation commonly occurs in real-world practice. Although rates of major cardiovascular and bleeding events in this analysis were generally low, the profile of patients suitable for de-escalation, the impact of de-escalation on adverse clinical outcomes and how this is affected by the timing after index ACS warrants further large-scale investigation.
Topics: Acute Coronary Syndrome; Cardiovascular Diseases; Clopidogrel; Hemorrhage; Hospitalization; Humans; Patient Discharge; Prevalence; Ticagrelor
PubMed: 31004312
DOI: 10.1007/s11239-019-01860-7 -
BMC Cardiovascular Disorders Oct 2020This meta-analysis aimed to compare the effects of prasugrel and ticagrelor on high (HTPR) and low on-treatment platelet reactivity (LTPR) in patients with acute... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This meta-analysis aimed to compare the effects of prasugrel and ticagrelor on high (HTPR) and low on-treatment platelet reactivity (LTPR) in patients with acute coronary syndrome (ACS).
METHODS
Eligible studies were retrieved from PubMed, Embase, and the Cochrane Library. HTPR and LTPR were evaluated on the basis of the vasodilator-stimulated phosphoprotein platelet reactivity index (VASP-PRI) and P2Y12 reaction units (PRUs). HTPR and LTPR were analyzed using risk ratios (RRs) and their 95% confidence intervals (CIs). Weighted mean difference (WMD) and 95% CI were used to calculate the pooled effect size of platelet reactivity (PR).
RESULTS
Fourteen eligible studies were obtained, which included 2629 patients treated with ticagrelor (n = 1340) and prasugrel (n = 1289). The pooled results showed that the prasugrel-treated patients had higher platelet reactivity than the ticagrelor-treated patients (PRU: WMD = - 32.26; 95% CI: - 56.48 to - 8.76; P < 0.01; VASP-PRI: WMD = - 9.61; 95% CI: - 14.63 to - 4.60; P = 0.002). No significant difference in HTPR based on PRU was identified between the ticagrelor and prasugrel groups (P = 0.71), whereas a lower HTPR based on VASP-PRI was found in the ticagrelor-treated patients than in the prasugrel-treated patients (RR = 0.30; 95% CI: 0.12-0.75; P = 0.010). In addition, the results showed a lower LTPR was observed in the prasugrel group than in the ticagrelor group (RR = 1.40; 95% CI: 1.08-1.81; P = 0.01).
CONCLUSIONS
Prasugrel might enable higher platelet reactivity than ticagrelor. Ticagrelor could lead to a decrease in HTPR and increase in LTPR. However, this result was only obtained in pooled observational studies. Several uncertainties such as the nondeterminancy of the effectiveness of ticagrelor estimated using VASP-PRI or the definition of HTPR (a high or modifiable risk factor) might have affected our results.
Topics: Acute Coronary Syndrome; Aged; Blood Platelets; Cell Adhesion Molecules; Female; Humans; Male; Microfilament Proteins; Middle Aged; Phosphoproteins; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Ticagrelor; Treatment Outcome
PubMed: 33004000
DOI: 10.1186/s12872-020-01603-0 -
BMC Cancer Oct 2019High level of reactive oxygen species (ROS) has been detected in almost all cancers, which make it become one of the best-characterized phenotypes in cancers. Though ROS... (Meta-Analysis)
Meta-Analysis
BACKGROUND
High level of reactive oxygen species (ROS) has been detected in almost all cancers, which make it become one of the best-characterized phenotypes in cancers. Though ROS plays an important role in tumors, the degree of oxidative stress can be better evaluated by assessing stable metabolites of oxidative reactions because of its high instability. 8-hydroxy-2'-deoxyguanosine (8-OHdG), a product of oxidative damage to 2'-deoxyguanosine, is known as a useful marker for assessing oxidative DNA damage and has been a feature of carcinogenesis in several researches. But the exact prognostic value of 8-OHdG expression in patients with cancer is still unclear.
METHODS
A comprehensive search was performed in PubMed, Web of Science, EMBASE. Eligible studies were included based on defined exclusion and inclusion criteria to perform a meta-analysis. STATA 14.0 was used to estimate pooled hazard ratios (HRs) with 95% confidence interval (95% CI), the heterogeneity among studies and publication bias to judge the prognostic value.
RESULTS
A total of 2121 patients from 21 eligible studies were included in the meta-analysis. A significant association was found between elevated 8-OHdG expression and poor OS (overall survival) in cancer patients (pooled HR 1.921, 95% CI: 1.437-2.570); In the subgroup analysis, race of sample, cancer types, detection method of 8-OHdG, sample classification, detection location of 8-OHdG and paper quality (score more or less than 7) did not alter the association between 8-OHdG expression and cancer prognosis. Furthermore, 8-OHdG expression was an independent prognostic marker for overall survival in patients with cancer (pooled HR 2.110, 95% CI: 1.482-3.005) using Cox multivariate analyses.
CONCLUSIONS
This meta-analysis found that highly expressed 8-OHdG in tumor tissues may be a predictor of prognosis in most solid tumors. However, especially in breast cancer, low 8-OHdG expression is associated with poor prognosis, which is partly because of the increased antioxidant mechanisms in breast cancer tissues. This study demonstrates for the first time that 8-OHdG expression is associated with the prognosis of cancer patients. In the future, whether the expression level of 8-OHdG can be used as a biomarker for the prognosis of all human cancers requires more research.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Biomarkers, Tumor; DNA Damage; Disease-Free Survival; Humans; Neoplasms; Oxidative Stress; Prognosis; Proportional Hazards Models; Reactive Oxygen Species
PubMed: 31651287
DOI: 10.1186/s12885-019-6189-9 -
F1000Research 2020There is controversy among physicians regarding the use of dual antiplatelet therapy (DAPT) in acute coronary syndrome (ACS) patients treated with coronary artery... (Comparative Study)
Comparative Study Meta-Analysis
Comparison of major bleeding in patients with acute coronary syndrome that underwent coronary artery bypass grafting treated with clopidogrel or ticagrelor: a systematic review and meta-analysis.
There is controversy among physicians regarding the use of dual antiplatelet therapy (DAPT) in acute coronary syndrome (ACS) patients treated with coronary artery bypass grafting (CABG). Moreover, the evidence of previous studies about this topic remained inconclusive. This study aimed to perform a meta-analysis concerning the relation between the risk of major bleeding and the use of different DAPT (clopidogrel or ticagrelor) in ACS patients treated with CABG. A meta-analysis was conducted during March to October 2019. Searches were carried out in Pubmed, Embase, Cochrane, and Web of Science. The predictor covariate in our present study was DAPT (clopidogrel or ticagrelor), and the outcome measure was the risk of major bleeding. Sub-group analysis was also performed, where data were classified into pre- and post-CABG. Furthermore, to determine the correlation and effect estimation, data were analyzed using fixed or random effect model. A total of 13 studies consisting 34,015 patients treated with clopidogrel and 32,661 patients treated with ticagrelor was included in our study. Our pooled calculation revealed that the incidence of major bleeding was not different significantly between clopidogrel and ticagrelor. In pre- and post-CABG sub-groups, our results also found no significant difference in major bleeding incidence between clopidogrel and ticagrelor groups. Our meta-analysis clarifies that clopidogrel, compared to ticagrelor, or vice versa, is not associated with the risk of major bleeding in ACS patients treated with CABG.
Topics: Acute Coronary Syndrome; Clopidogrel; Coronary Artery Bypass; Humans; Platelet Aggregation Inhibitors; Postoperative Hemorrhage; Ticagrelor
PubMed: 33732438
DOI: 10.12688/f1000research.21925.2 -
Medicine Nov 2021Bleeding is an untoward outcome in the management of elderly patients with acute coronary syndrome (ACS). Although the potent oral P2Y12 inhibitor, ticagrelor is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bleeding is an untoward outcome in the management of elderly patients with acute coronary syndrome (ACS). Although the potent oral P2Y12 inhibitor, ticagrelor is clinically beneficial, its association with bleeding events in elderly ACS patients (≥75 years) is poorly understood.
METHODS
We conducted a systematic search of 7 databases up to May 20, 2020 to identify studies which examined the risk of bleeding (defined according to each study) among elderly ACS patients (≥75 years) receiving ticagrelor compared to clopidogrel. Summary risk ratios (RR) were estimated using the random effects model.
RESULTS
Eight studies consisting of 5 observational studies and 3 randomized controlled trials involving 7032 elderly patients met the eligibility criteria. The mean age of the patients was 77.8 years, and the mean follow-up duration was 12 months. Overall, the pooled RRs showed higher risk of a bleeding event with ticagrelor compared to clopidogrel (RR 1.20, 95% confidence interval [95% CI] 1.03-1.40; P = .017). No statistically significant heterogeneity was observed among the studies (Q = 6.93; P = .44; I2 = 0). Also, pooled RRs did not show a higher risk of major bleeding (RR 1.32, 95% CI 0.91-1.92; P = .15) or minor bleeding (RR 1.09, 95% CI 0.76-1.58; P = .64) when comparing the ticagrelor to the clopidogrel group.
CONCLUSIONS
There is a 20% increased risk of a bleeding event in elderly ACS patients treated with ticagrelor compared to clopidogrel; for such patients, clopidogrel may be considered as an alternative agent to ticagrelor due to its lower risk of bleeding.
Topics: Acute Coronary Syndrome; Aged; Clopidogrel; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Saudi Arabia; Ticagrelor; Treatment Outcome
PubMed: 34871206
DOI: 10.1097/MD.0000000000027398 -
Cancer Control : Journal of the Moffitt... 2021Recent studies have shown that methyltransferase-like 3, a catalytic enzyme that is predominant in the N6-methyladenosine methyltransferase system, is abnormally... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Recent studies have shown that methyltransferase-like 3, a catalytic enzyme that is predominant in the N6-methyladenosine methyltransferase system, is abnormally expressed in various types of carcinoma and is correlated with poorer prognosis. However, the clinical functions of methyltransferase-like 3 in the prognosis of tumors are not fully understood.
METHODS
We identified studies by searching PubMed, Web of Science, and MedRvix for literature (up to June 30, 2020), and collected a total of 9 studies with 1257 patients for this meta-analysis. The cancer types included gastric cancer, breast cancer, non-small cell lung cancer, bladder cancer, colorectal cancer and ovarian. We further used The Cancer Genome Atlas dataset to validate the results.
RESULTS
High methyltransferase-like 3 expression clearly predicted a worse outcome (high vs. low methyltransferase-like 3 expression group; hazard ratio = 2.09, 95% confidence interval 1.53-2.89, = 0.0001). Moreover, methyltransferase-like 3 expression was associated with differentiation (moderate + poor vs. well, pooled odds ratio = 1.76, 95% confidence interval 1.32-2.35, = 0.0001), and gender (male vs. female, pooled odds ratio = 0.73, 95% confidence interval 0.55-0.97, = 0.029).
CONCLUSION
Our results suggest that methyltransferase-like 3 upregulation is significantly associated with poor prognosis and could potentially function as a tumor biomarker in cancer prognosis.
Topics: Adenosine; Female; Humans; Male; Methyltransferases; Neoplasms; Prognosis; Survival Analysis
PubMed: 33631954
DOI: 10.1177/1073274821997455 -
Current Problems in Cardiology Aug 2024Debates persist regarding the optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in coronary artery disease (CAD).... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Debates persist regarding the optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in coronary artery disease (CAD). Recent trials have introduced a novel approach involving P2Y12 inhibitor monotherapy with ticagrelor or clopidogrel, after a short DAPT. However, the effectiveness and safety of this strategy remains to be established. We aimed to perform a meta-analysis comparing monotherapy with P2Y12 inhibitors versus standard DAPT in patients undergoing PCI at 12 months.
METHODS
Multiple databases were searched. Six RCTs with a total of 24877 patients were included. The primary endpoint was all-cause mortality at 12 months of follow-up. The secondary endpoints were cardiovascular mortality, myocardial infarction, probable or definite stent thrombosis, stroke events, and major bleeding. The study is registered with PROSPERO (CRD42024499529).
RESULTS
Monotherapy with P2Y12 inhibitor ticagrelor significantly reduced both allcause mortality (HR 0.71, 95 CI [0.55-0.91], P = 0.007) and cardiovascular mortality (HR 0.66, 95% CI [0.49-0.89], P = 0.006) compared to standard DAPT. In contrast, clopidogrel monotherapy did not demonstrate a similar reduction. The decrease in mortality associated with ticagrelor was primarily due to a lower risk of major bleeding (HR 0.56, 95% CI [0.43-0.72], P < 0.001), while the risk of myocardial infarction (MI) remained unchanged (HR 0.90, 95% CI [0.73-1.11], P = 0.32). The risk of stroke was found to be similar across treatments.
CONCLUSIONS
In comparison to standard DAPT, P2Y12 inhibitor monotherapy with ticagrelor may lead to a reduced mortality. The clinical benefits are driven by a reduction of bleeding risk without ischemic risk trade-off.
Topics: Humans; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Purinergic P2Y Receptor Antagonists; Coronary Artery Disease; Platelet Aggregation Inhibitors; Treatment Outcome; Dual Anti-Platelet Therapy; Ticagrelor
PubMed: 38750991
DOI: 10.1016/j.cpcardiol.2024.102635 -
BMC Cardiovascular Disorders Mar 2020For patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI), the efficacy and safety of novel P2Y... (Meta-Analysis)
Meta-Analysis
Prasugrel or ticagrelor relative to clopidogrel in triple-antiplatelet treatment combined with glycoprotein IIb/IIIa inhibitor for patients with STEMI undergoing PCI: a meta-analysis.
BACKGROUND
For patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI), the efficacy and safety of novel P2Y antagonists, including prasugrel or ticagrelor, has not been established relative to that of the clopidogrel-based triple-antiplatelet treatments (TAPTs; in combination with glycoprotein IIb/IIIa inhibitor). The present meta-analysis evaluated the efficacy and safety of prasugrel- or ticagrelor-based TAPTs relative to that of clopidogrel TAPTs in patients with STEMI undergoing PCI.
METHODS
The databases PubMed, Embase, and Cochrane's Library were systematically searched for relevant randomized controlled trials concerning prasugrel or ticagrelor (test) relative to clopidogrel (control). Depending on heterogeneity, studies were pooled with a random effects or a fixed effects model. Outcomes of blood flow after PCI were evaluated, including TIMI (thrombolysis in myocardial infarction), bleeding events, and major adverse cardiovascular events (MACEs).
RESULTS
Seven studies comprising 11,874 patients conformed to the inclusion criteria. The pooled results with the fixed effects model indicated that after PCI patients in the prasugrel or ticagrelor groups were as likely as those treated with clopidogrel to achieve TIMI grade 3 flow or experience bleeding events. However, compared with the control, the test groups had significantly less risk of MACE (OR: 0.81, 95% CI: 0.70-0.94, P = 0.004), especially at the 1-year follow-up (OR: 0.79, 95% CI: 0.66-0.95, P = 0.01).
CONCLUSIONS
A prasugrel- or ticagrelor-based TAPT may reduce the rate of MACEs, without increasing bleeding in STEMI patients undergoing PCI. However, due to the limited RCT studies and variations in study weight, results of this meta-analysis should be confirmed in a large RCT with adequate sample size and follow-up duration.
Topics: Aged; Aged, 80 and over; Clopidogrel; Drug Therapy, Combination; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Recurrence; Risk Factors; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome
PubMed: 32164560
DOI: 10.1186/s12872-020-01403-6