adverse effects may occur with the use of metformin 8. Alternatively, the potential role of modifications in the gut microbiome had been explored as a new complementary therapeutic strategy 9. Clinical evidence supports the hypothesis that the modulation of the gut microbiota by probiotics could be effective in prevention and management of diabetes 10,11. Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. The healthy human body contains such microbes physiologically; and they can be obtained in forms of over-the-counter food supplements as well. Over the last few years, probiotics, especially the lactobacillus species were shown to be effective in the therapy of type 2 diabetes 12. In type 2 diabetes, gut microbiome is found to be different from that in the healthy population. In a human study, the amount of Firmicutes bacteria was lower, whereas the number of Bacteroides and Proteobacteria is higher in the gastrointestinal tract of patients with type 2 diabetes compared to non-diabetic persons 13. According to the study 13 , the ratio of Bacteriodes and Firmicutes species had positive correlation with decreased insulin resistance, however, causality has not been proven yet. Following innovative dietary strategies, it seems possible to maintain euglycemia by normalizing the altered microbiome, and to prevent long-term micro-and macrovascular complications of type 2 diabetes 9. Although, there have been numerous bacterial species investigated in the therapy of type 2 diabetes, no consensus has been obtained regarding the effectivity and the most effective species. For instance, an earlier meta-analysis suggested, that the intake of certain Lactobacillus species, such as L. fermentum, L. ingluviei and L. acidophilus can lead to weight gain, while the ingestion of L. gasseri and L. plantarum might end up in weight loss both in animal and human studies 14. Previous meta-analysis in this field were not conducted with assessment of the evidence quality levels and the number of identified trials that met their inclusion criteria was relatively low (7-12 trials) 15-19. Two meta-analysis found no significant effects of probiotics on lipid profile 16,19 and two meta-analysis found decreased indexes of lipid profiles 17,18. These contradictory reports on the effect of probiotics inspired us to conduct an updated meta-analysis to assess the effect of probiotic therapies in diabetes mellitus type 2 exclusively from randomized controlled trials. Materials and methods Protocol and registration. This meta-analysis was reported according to the recommendation of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines 20. Pre-specified protocol of this meta-analysis was published in the Prospero Center for Reviews and Dissemination (PROSPERO) under the registration number of CRD42019137997.

Purpose The most common complications of electrophysiology (EP) procedures are related to vascular access. Our study aims to conduct a meta-analysis comparing ultrasound (US)-guided vs. palpation-based technique for femoral venous access in EP procedures. Methods Electronic databases were searched and systematically reviewed for studies comparing femoral vein puncture with/ without US in EP procedures. The primary outcome was the rate of major vascular complications; secondary outcomes were minor vascular complications, inadvertent artery puncture, postprocedural groin pain, and puncture time. Predefined subgroup analysis was conducted separately for patients undergoing pulmonary vein isolation procedure (PVI). A random-effects model was used to derive risk ratios (RR) with 95% confidence interval (CI). Results Nine studies involving 8232 patients met our inclusion criteria. Compared with the standard technique, the use of US reduced major vascular complications (from 2.01 to 0.71%, p < 0.0001). The rate of minor vascular complications (RR = 0.30, 95% CI, 0.14-0.62, p = 0.001) and inadvertent artery puncture were lower with US-guided puncture (RR = 0.31, 95% CI, 0.17-0.58, p = 0.0003). Puncture time was shorter (mean difference = − 92.1 s, 95% CI, − 142.12-− 42.07 s, p = 0.0003) and postprocedural groin pain was less frequent (RR = 0.57, 95% CI, 0.41-0.79, p = 0.0008) in the US group. Subgroup analysis of patients undergoing PVI also showed significant reduction of major vascular complications (RR = 0.27, 95% CI, 0.12-0.64, p = 0.003) and inadvertent artery puncture (RR = 0.35, 95% CI, 0.21-0.59, p < 0.0001). Conclusion Real-time US-guidance of femoral vein puncture in EP procedures is beneficial: it reduces major and minor vascular complications, inadvertent artery puncture, postprocedural groin pain, and puncture time.

We assessed the cardiovascular safety of long-term direct-acting oral anticoagulant (DOAC) treatment. A search of the medical literature was performed from inception until May 31, 2019. Inclusion criteria were (1) randomized trial that assessed the clinical efficacy and/or safety of 1 or more DOAC, (2) control group including oral anticoagulation and/or antiplatelet and/or placebo treatment, and (3) the incidence of acute coronary syndrome during follow-up was reported. Fixed-effect and random-effects models were applied. The analyzed outcomes were myocardial infarction (MI), major bleeding, and mortality. Twenty-eight randomized clinical trials (196 761 patients) were included. Rivaroxaban was associated with a 21% reduction in the relative risk of MI when compared to placebo (relative risk [RR]: 0.79 [95% credible interval, CrI: 0.65-0.94]) and a 31% reduction (RR: 0.70 [95% CrI: 0.53-0.89]) when compared to dabigatran. Apixaban resulted in 24% (RR: 0.76 [95% CrI: 0.58-0.99]) and vitamin K antagonists anticoagulation resulted in 19% (RR: 0.81 [95% CrI: 0.65-0.98]) risk reduction compared to dabigatran. The computed probability of being the first best choice of treatment was 61.8% for rivaroxaban. Cardiovascular safety shows considerable heterogeneity among oral anticoagulants. Treatment with rivaroxaban is associated with reduced rate of MI.

Stroke embodies one of the leading causes of death and disability worldwide. We aimed to provide a comprehensive insight into the effectiveness and safety of antiplatelet agents and anticoagulants in the secondary prevention of ischemic stroke or transient ischemic attack. A systematic search for randomized controlled trials, comparing antiplatelet or anticoagulant therapy versus aspirin or placebo among patients with ischemic stroke or transient ischemic attack, was performed in order to summarize data regarding the different regimens. Keyword-based searches in the MEDLINE, EMBASE, and Cochrane Library databases were conducted until the 1st of January 2021. Our search explored 46 randomized controlled trials involving ten antiplatelet agents, six combinations with aspirin, and four anticoagulant therapies. The review of the literature reflects that antiplatelet therapy improves outcome in patients with ischemic stroke or transient ischemic attack. Monotherapy proved to be an effective and safe choice, especially in patients with a high risk of bleeding. Intensified antiplatelet regimens further improve stroke recurrence; however, bleeding rate increases while mortality remains unaffected. Supplementing the clinical judgment of stroke treatment, assessment of bleeding risk is warranted to identify patients with the highest benefit of treatment intensification.

Background and Purpose: Preventive antiplatelet therapy is recommended for patients with cardiac or cerebrovascular atherosclerosis. Ticagrelor has an improved safety and efficacy profile in patients with acute coronary syndrome; however, data regarding stroke prevention remain controversial. We conducted a network meta-analysis to compare ticagrelor with other receptor antagonists (P2Y12) inhibitors and aspirin in monotherapy or combination in the treatment of patients with high risk for cardiovascular or cerebrovascular disease, defined as coronary artery disease, acute coronary syndrome, stroke or transient ischemic attack, or peripheral artery disease. Methods: Systematic searches of MEDLINE, EMBASE, and the Cochrane Library were conducted until August 1, 2020. Search terms included ticagrelor, AZD 6140, and stroke. The risk of bias was assessed using the Cochrane Collaboration assessment tool. Random-effects model was used to combine risk estimates across trials and risk ratio with 95% CIs served as summary statistics. The influence of individual components was evaluated in an additive network meta-analysis model. The primary efficacy end point was the occurrence of stroke. The safety end points included bleeding and all-cause mortality. Results: Twenty-six randomized clinical trials comprising 124 495 patients were analyzed. When compared with controls, ticagrelor plus aspirin significantly reduced the risk of ischemic stroke by 20% (risk ratio, 0.80 [95% CI, 0.71–0.89]). Treatment with ticagrelor monotherapy did not significantly affect ischemic stroke (risk ratio, 0.88 [95% CI, 0.77–1.00]; P =0.05). Compared with aspirin alone, major bleeding was in similar ranges with antiplatelet monotherapies while the relative risk was twice higher with combined antiplatelet therapies. There was no considerable difference in the risk of mortality with ticagrelor plus aspirin (risk ratio, 0.99 [95% CI, 0.91–1.07]). Conclusions: Ticagrelor on top of aspirin may provide more favorable outcomes on secondary stroke prevention in patients with vascular risk factors; however, this benefit may come with the price of increased bleeding risk including intracranial bleeding.