Impact of CYP2C19 Gene Variants on Long-Term Treatment with Atorvastatin in Patients with Acute Coronary Syndromes.

The effectiveness of lipid-lowering therapies may be insufficient in high-risk cardiovascular patients and depends on the genetic variability of drug-metabolizing enzymes. Customizing statin therapy, including treatment with atorvastatin, may improve clinical outcomes. Currently, there is a lack of guidelines allowing the prediction of the therapeutic efficacy of lipid-lowering statin therapy. This study aimed to determine the effects of clinically significant gene variants of CYP2C19 on atorvastatin therapy in patients with acute coronary syndromes. In total, 92 patients with a confirmed diagnosis of ST-elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction (NSTEMI) were sequenced for target regions within the CYP2C19 gene on the Illumina Miniseq system. The CYP2C19 poor metabolizer phenotype (carriers of CYP2C19*2, CYP2C19*4, and CYP2C19*8 alleles) was detected in 29% of patients. These patients had significantly lower responses to treatment with atorvastatin than patients with the normal metabolizer phenotype. CYP2C19-metabolizing phenotype, patient age, and smoking increased the odds of undertreatment in patients (∆LDL-C (mmol/L) < 1). These results revealed that the CYP2C19 phenotype may significantly impact atorvastatin therapy personalization in patients requiring LDL lipid-lowering therapy.

Impact of Coronary Microvascular Dysfunction on Functional Left Ventricular Remodeling and Diastolic Dysfunction.

BACKGROUND: Coronary microvascular dysfunction (CMD) is a common complication of ST-segment-elevation myocardial infarction (STEMI) and can lead to adverse cardiovascular events. Whether CMD after STEMI is associated with functional left ventricular remodeling (FLVR) and diastolic dysfunction, has not been investigated. METHODS AND RESULTS: This is a nonrandomized, observational, prospective study of patients with STEMI with multivessel disease. Coronary flow reserve and index of microcirculatory resistance of the culprit vessel were measured at 3 months post-STEMI. CMD was defined as index of microcirculatory resistance ≥25 or coronary flow reserve <2.0 with a normal fractional flow reserve. We examined the association between CMD, LV diastolic dysfunction, FLVR, and major adverse cardiac events at 12-month follow-up. A total of 210 patients were enrolled; 59.5% were men, with a median age of 65 (interquartile range, 58-76) years. At 3-month follow-up, 57 patients (27.14%) exhibited CMD. After 12 months, when compared with patients without CMD, patients with CMD had poorer LV systolic function recovery (-10.00% versus 8.00%; P<0.001), higher prevalence of grade 2 LV diastolic dysfunction (73.08% versus 1.32%; P<0.001), higher prevalence of group 3 or 4 FLVR (11.32% versus 7.28% and 22.64% versus 1.99%, respectively; P<0.001), and higher incidence of major adverse cardiac events (50.9% versus 9.8%; P<0.001). Index of microcirculatory resistance was independently associated with LV diastolic dysfunction and adverse FLVR. CONCLUSIONS: CMD is present in ≈1 of 4 patients with STEMI during follow-up. Patients with CMD have a higher prevalence of LV diastolic dysfunction, adverse FLVR, and major adverse cardiac events at 12 months compared with those without CMD. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT05406297.

Effects of Combined Treatment with Sodium Dichloroacetate and Sodium Valproate on the Genes in Inflammation- and Immune-Related Pathways in T Lymphocytes from Patients with SARS-CoV-2 Infection with Pneumonia: Sex-Related Differences.

The study presents data on the anti-inflammatory effects of a combination of sodium dichloroacetate and sodium valproate (DCA-VPA) on the expression of inflammation- and immune response-related genes in T lymphocytes of SARS-CoV-2 patients. The study aimed to assess the effects of DCA-VPA on the genes of cytokine activity, chemokine-mediated signaling, neutrophil chemotaxis, lymphocyte chemotaxis, T-cell chemotaxis, and regulation of T-cell proliferation pathways. The study included 21 patients with SARS-CoV-2 infection and pneumonia: 9 male patients with a mean age of 68.44 ± 15.32 years and 12 female patients with a mean age of 65.42 ± 15.74 years. They were hospitalized between December 2022 and March 2023. At the time of testing, over 90% of sequences analyzed in Lithuania were found to be of the omicron variant of SARS-CoV-2. The T lymphocytes from patients were treated with 5 mmol DCA and 2 mmol VPA for 24 h in vitro. The effect of the DCA-VPA treatment on gene expression in T lymphocytes was analyzed via gene sequencing. The study shows that DCA-VPA has significant anti-inflammatory effects and apparent sex-related differences. The effect is more potent in T cells from male patients with SARS-CoV-2 infection and pneumonia than in females.

Enterobacterales Biofilm-Specific Genes and Antimicrobial and Anti-Inflammatory Biomarkers in the Blood of Patients with Ischemic Heart Disease.

BACKGROUND: Ischemic heart disease (IHD) is the most prevalent type of cardiovascular disease. The main cause of IHD is atherosclerosis, which is a multifactorial inflammatory disease of blood vessels. Studies show that bacteria might have a significant impact on the pathogenesis of atherosclerosis and plaque rupture. This study aimed to evaluate the complexity of interactions between bacteria and the human body concerning metabolites and bacterial genes in patients with ischemic heart disease. METHODS: Bacterial 16S rDNA and wcaF, papC, and sdhC genes were detected in whole blood using a real-time PCR methodology. An enzyme-linked immunosorbent assay was used to measure the concentration of the LL-37 protein. An analysis of ARA in blood plasma was performed. RESULTS: Bacterial 16S rDNA was detected in 31% of the study patients, and the genes wcaF and sdhC in 20%. Enterobacterales genes were detected more frequently in patients younger than 65 years than in patients aged 65 years and older (p = 0.018) and in patients with type 2 diabetes (p = 0.048). Concentrations of the human antimicrobial peptide LL-37 and 12S-HETE concentrations were determined to be higher if patients had 16S rDNA and biofilm-specific genes. CONCLUSIONS: The results of this study enhance the understanding that Enterobacterales bacteria may participate in the pathogenesis of atherosclerosis and IHD. Bacterial DNA and host metabolites in higher concentrations appear to be detected.

Precise Therapy Using the Selective Endogenous Encapsidation for Cellular Delivery Vector System.

Interindividual variability in drug response is a major problem in the prescription of pharmacological treatments. The therapeutic effect of drugs can be influenced by human genes. Pharmacogenomic guidelines for individualization of treatment have been validated and used for conventional dosage forms. However, drugs can often target non-specific areas and produce both desired and undesired pharmacological effects. The use of nanoparticles, liposomes, or other available forms for drug formulation could help to overcome the latter problem. Virus-like particles based on retroviruses could be a potential envelope for safe and efficient drug formulations. Human endogenous retroviruses would make it possible to overcome the host immune response and deliver drugs to the desired target. PEG10 is a promising candidate that can bind to mRNA because it is secreted like an enveloped virus-like extracellular vesicle. PEG10 is a retrotransposon-derived gene that has been domesticated. Therefore, formulations with PEG10 may have a lower immunogenicity. The use of existing knowledge can lead to the development of suitable drug formulations for the precise treatment of individual diseases.

The Effect of Platelet Activity, ABCB1 Genetic Polymorphism, and Renal Function on the Development of Ticagrelor-Related Dyspnea in Patients with Acute Coronary Syndrome.

Purpose: The aim of this study was to determine the effect of ABCB1 genetic polymorphism and renal function on the occurrence of ticagrelor-related dyspnea. Patients and Methods: A total of 299 patients with acute with type 1, 2, or 3 myocardial infarction (with and without ST-segment elevation), who underwent coronary angiography and PTCA with stent implantation and were treated with antiplatelet drugs (ticagrelor and aspirin), were enrolled in this prospective study. For all enrolled patient's platelet aggregation (induction with high-sensitivity adenosine diphosphate, ADP HS) testing was performed using a MULTIPLATE® analyzer. Venous blood was also collected for genotyping. Results: Patients experiencing ticagrelor-related dyspnea had lower ADP HS value (ADP HS ≤ 19.5 U; OR = 2.254; P = 0.009), higher creatinine concentration (>90 µmol/l; OR = 3.414; P = 0.019), and lower GFR value (<60 mL/min/1.73 m2; OR = 2.211; P = 0.035). ABCB1 T allele was associated with ticagrelor-related dyspnea (OR = 2.550; P = 0.04). Conclusion: Ticagrelor-related dyspnea was found to be related to low platelet aggregation, increased plasma creatinine concentration, decreased GFR, and ABCB1 T allele. Carriers of the ABCB1 T allele had a higher plasma creatinine concentration that could be associated with an inhibitory effect of ticagrelor on P-glycoprotein function.

Coronary artery disease, its associations with ocular, genetic and blood lipid parameters.

BACKGROUND/OBJECTIVES: To investigate the associations between ophthalmic parameters, CYP4F2 (rs2108622) and ABCA1 (rs1883025) polymorphisms and coronary artery disease, considering the accessibility, non-invasive origin of retinal examination and its possible resemblance to coronary arteries. SUBJECTS/METHODS: Overall 165 participants divided into groups based on the coronary angiography results and clinical status: control group (N = 73), MI group (N = 63), 3VD (three vessel disease) (N = 24). All the participants underwent total ophthalmic examination - optical coherence tomography (OCT) and OCT angiography of the macula region were performed and evaluated. Total cholesterol, high-density lipoprotein, low-density lipoprotein and triglyceride cholesterol (Tg-C) were tested. A standard manufacturer's protocol for CYP4F2 (rs2108622) and ABCA1 (rs1883025) was used for genotyping with TaqMan probes. RESULTS: GCL+ layer was thicker in control group vs. 3VD group (74.00; 62.67-94.67 (median; min.-max.) vs. 71.06; 51.33-78.44, p = 0.037). T allele carriers under ABCA1 rs1883025 dominant model were shown to have ticker retina and smaller foveal avascular zone in superficial capillary plexus and smaller Tg-C concentration. ABCA1 rs1883025 was associated with retinal thickness (OR = 0.575, 95% CI 0.348-0.948, p = 0.030). Univariate logistic regression showed that ABCA1 rs1883025 CT genotype is associated with decreased risk for coronary artery disease development under overdominant genetic model (OR = 0.498, 95% CI 0.254-0.976; p = 0.042) and codominant genetic model (OR = 0.468, 95% CI 0.232-0.945, p = 0.034). CONCLUSIONS: Results of this study confirmed that non-invasive methods such as OCT of eye might be used for identification of patients at risk of CAD.

The impact of primary percutaneous coronary intervention strategies during ST-elevation myocardial infarction on the prevalence of coronary microvascular dysfunction.

Coronary microvascular dysfunction (CMD) is a common complication of ST-segment elevation myocardial infarction (STEMI) and can lead to adverse cardiovascular events. This is a non-randomized, observational, prospective study of STEMI patients with multivessel disease who underwent primary PCI, grouped based on whether they underwent balloon pre-dilatation stenting or direct stenting of the culprit lesion. Coronary physiology measurements were performed 3 months post-PCI including coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) measurements at the culprit vessel. The primary endpoint was the prevalence of CMD at 3 months, defined as IMR ≥ 25 or CFR < 2.0 with a normal fractional flow reserve. Secondary endpoints included major adverse cardiovascular events (MACE) at 12 months. Two hundred ten patients were enrolled; most were men, 125 (59.5%), with a median age of 65 years. One hundred twelve (53.2%) underwent balloon pre-dilatation before stenting, and 98 (46.7%) underwent direct stenting. The prevalence of CMD at 3 months was lower in the direct stenting group than in the balloon pre-dilatation stenting group (12.24% vs. 40.18%; p < 0.001). Aspiration thrombectomy and administration of intracoronary glycoprotein IIb/IIIa inhibitors were associated with lower odds of CMD (OR = 0.175, p = 0.001 and OR = 0.113, p = 0.001, respectively). Notably, MACE in patients who underwent direct stenting was lower than in those who underwent balloon pre-dilatation before stenting (14.29% vs. 26.79%; p = 0.040). In STEMI patients with multivessel disease, direct stenting of the culprit lesion, aspiration thrombectomy and administration of intracoronary glycoprotein IIb/IIIa inhibitors were associated with a lower prevalence of CMD at 3 months and lower incidence of MACE at 12 months compared with balloon pre-dilatation stenting.This trial is registered at https://ichgcp.net/clinical-trials-registry/NCT05406297 .

The Impact of Trimethylamine N-Oxide and Coronary Microcirculatory Dysfunction on Outcomes following ST-Elevation Myocardial Infarction.

INTRODUCTION: Persistent coronary microcirculatory dysfunction (CMD) and elevated trimethylamine N-oxide (TMAO) levels after ST-elevation myocardial infarction (STEMI) may drive negative structural and electrical cardiac remodeling, resulting in new-onset atrial fibrillation (AF) and a decrease in left ventricular ejection fraction (LVEF). AIMS: TMAO and CMD are investigated as potential predictors of new-onset AF and left ventricular remodeling following STEMI. METHODS: This prospective study included STEMI patients who had primary percutaneous coronary intervention (PCI) followed by staged PCI three months later. Cardiac ultrasound images were obtained at baseline and after 12 months to assess LVEF. Coronary flow reserve (CFR), and index of microvascular resistance (IMR) were assessed using the coronary pressure wire during the staged PCI. Microcirculatory dysfunction was defined as having an IMR value ≥25 U and CFR value <2.5 U. RESULTS: A total of 200 patients were included in the study. Patients were categorized according to whether or not they had CMD. Neither group differed from the other with regards to known risk factors. Despite making up only 40.5% of the study population, females represented 67.4% of the CMD group p < 0.001. Similarly, CMD patients had a much higher prevalence of diabetes than those without CMD (45.7% vs. 18.2%; p < 0.001). At the one-year follow-up, the LVEF in the CMD group had decreased to significantly lower levels than those in the non-CMD group (40% vs. 50%; p < 0.001), whereas it had been higher in the CMD group at baseline (45% vs. 40%; p = 0.019). Similarly, during the follow-up, the CMD group had a greater incidence of AF (32.6% vs. 4.5%; p < 0.001). In the adjusted multivariable analysis, the IMR and TMAO were associated with increased odds of AF development (OR: 1.066, 95% CI: 1.018-1.117, p = 0.007), and (OR: 1.290, 95% CI: 1.002-1.660, p = 0.048), respectively. Similarly, elevated levels of IMR and TMAO were linked with decreased odds of LVEF improvement, while higher CFR values are related to a greater likelihood of LVEF improvement. CONCLUSIONS: CMD and elevated TMAO levels were highly prevalent three months after STEMI. Patients with CMD had an increased incidence of AF and a lower LVEF 12 months after STEMI.

A prospective observational study on impact of epinephrine administration route on acute myocardial infarction patients with cardiac arrest in the catheterization laboratory (iCPR study).

BACKGROUND: Epinephrine is routinely utilized in cardiac arrest; however, it is unclear if the route of administration affects outcomes in acute myocardial infarction patients with cardiac arrest. OBJECTIVES: To compare the efficacy of epinephrine administered via the peripheral intravenous (IV), central IV, and intracoronary (IC) routes. METHODS: Prospective two-center pilot cohort study of acute myocardial infarction patients who suffered cardiac arrest in the cardiac catheterization laboratory during percutaneous coronary intervention. We compared the outcomes of patients who received epinephrine via peripheral IV, central IV, or IC. RESULTS: 158 participants were enrolled, 48 (30.4%), 50 (31.6%), and 60 (38.0%) in the central IV, IC, and peripheral IV arms, respectively. Peripheral IV epinephrine administration route was associated with lower odds of achieving return of spontaneous circulation (ROSC, odds ratio = 0.14, 95% confidence interval = 0.05-0.36, p < 0.0001) compared with central IV and IC administration. (There was no difference between central IV and IC routes; p = 0.9343.) The odds of stent thrombosis were significantly higher with the IC route (IC vs. peripheral IV OR = 4.6, 95% CI = 1.5-14.3, p = 0.0094; IC vs. central IV OR = 6.0, 95% CI = 1.9-19.2, p = 0.0025). Post-ROSC neurologic outcomes were better for central IV and IC routes when compared with peripheral IV. CONCLUSION: Epinephrine administration via central IV and IC routes was associated with a higher rate of ROSC and better neurologic outcomes compared with peripheral IV administration. IC administration was associated with a higher risk of stent thrombosis. Trial registration This trial is registered at NCT05253937 .

Pleiotropic Effects of Ticagrelor: Influence on CYP4F2 Gene and Protein Expression in HUVEC and HepG2, and Escherichia coli Bacterial Survival.

Background: Antiplatelet drugs, such as ticagrelor, which target platelet P2Y12 receptors, are used for prevention of ischemic heart disease. Ticagrelor is also known to have pleiotropic effects of unknown mechanisms. Ticagrelor could influence the expression of molecules involved in resolution of inflammation. This study aimed to investigate if ticagrelor could change the expression of CYP4F2 and its encoded protein concentration and, additionally, to determine ticagrelor possible antibacterial activity against gram-negative bacteria. Methods: CYP4F2 expression was determined in HUVEC and HepG2 cell lines by qPCR. CYP4F2 protein concentration was determined by ELISA. Antibiotic susceptibility testing was performed using a disc diffusion method. Results: Ticagrelor was observed to reduce the expression of CYP4F2 in HUVEC and HepG2 cell lines. It also reduced CYP4F2 protein levels in HUVEC cells. Ticagrelor had no bactericidal activity against gram-negative third generation cephalosporin resistant E. coli. Conclusion: Ticagrelor reduced CYP4F2 protein concentration in HUVEC, and CYP4F2 expression in HUVEC and HepG2 cells, but had no effect on third-generation cephalosporin-resistant E. coli strains.

Retinal and Choroidal Thinning-A Predictor of Coronary Artery Occlusion?

Introduction. Optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) allowed visualization of retina and choroid to nearly the capillary level; however, the relationship between systemic macrovascular status and retinal microvascular changes is not yet known well. Aim. Our purpose was to assess the impact of retinal optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) parameters on prediction of coronary heart disease (CHD) in acute myocardial infarction (MI) and chronic three vessel disease (3VD) groups. Methods. This observational study included 184 patients-26 in 3VD, 76 in MI and 82 in healthy participants groups. Radial scans of the macula and OCTA scans of the central macula (superficial (SCP) and deep (DCP) capillary plexuses) were performed on all participants. All participants underwent coronary angiography. Results. Patients in MI groups showed decreased parafoveal total retinal thickness as well as GCL+ retinal thickness. Outer circle total retinal thickness and GCL+ retinal thickness were lowest in the 3VD group. The MI group had thinner, while 3VD the thinnest, choroid. A decrease in choroidal thickness and vascular density could predict 3VD. Conclusions. A decrease in retinal and choroidal thickness as well as decreased vascular density in the central retinal region may predict coronary artery disease. OCT and OCTA could be a significant, safe, and noninvasive tool for the prediction of coronary artery disease.

SARS-CoV-2 Infection, Sex-Related Differences, and a Possible Personalized Treatment Approach with Valproic Acid: A Review.

Sex differences identified in the COVID-19 pandemic are necessary to study. It is essential to investigate the efficacy of the drugs in clinical trials for the treatment of COVID-19, and to analyse the sex-related beneficial and adverse effects. The histone deacetylase inhibitor valproic acid (VPA) is a potential drug that could be adapted to prevent the progression and complications of SARS-CoV-2 infection. VPA has a history of research in the treatment of various viral infections. This article reviews the preclinical data, showing that the pharmacological impact of VPA may apply to COVID-19 pathogenetic mechanisms. VPA inhibits SARS-CoV-2 virus entry, suppresses the pro-inflammatory immune cell and cytokine response to infection, and reduces inflammatory tissue and organ damage by mechanisms that may appear to be sex-related. The antithrombotic, antiplatelet, anti-inflammatory, immunomodulatory, glucose- and testosterone-lowering in blood serum effects of VPA suggest that the drug could be promising for therapy of COVID-19. Sex-related differences in the efficacy of VPA treatment may be significant in developing a personalised treatment strategy for COVID-19.

CTX-M-producing Escherichia coli strains: resistance to temocillin, fosfomycin, nitrofurantoin and biofilm formation.

Aim: ESBL-producing and bacterial biofilms-forming Escherichia coli are associated with antimicrobial treatment failure. This study aimed to investigate the phenotypic resistance mechanisms of CTX-M E. coli against old antibiotics - cell wall synthesis inhibitors temocillin, nitrofurantoin and fosfomycin. Materials & Methods: Susceptibility to old antibiotics testing was performed using disk diffusion method, biofilm formation was evaluated spectrophotometrically, and PCR was used for the determination of CTX-M type. Results & conclusion: Temocillin was active against nearly 93%, nitrofurantoin and fosfomycin, respectively, 91.7% and 98.6% of tested E. coli. Thus, it demonstrated to be a good alternative therapeutic option against ESBL infections. Bacteria resistant to old antibiotics had CTX-M-15 or CTX-M-15, TEM-1 and OXA-1 combinations. No significant association was found between CTX-M E. coli resistance to temocillin, nitrofurantoin and fosfomycin; however, the level of biofilm formation was found as not affected by the type of CTX-M ß-lactamases.

Blood direct PCR: impact of CYP2C19 and CYP4F2 variants for bleeding prediction in ST-elevation myocardial infarction patients with ticagrelor.

Aims: The goals of this study were to develop a new technique that could pave the way for a quicker determination of CYP4F2 rs3093135 and CYP2C19 rs4244285 variants directly from a patient's blood and to attempt to apply this technique in clinical practice. Patients & methods: The study included 144 consecutive patients admitted with ST elevation myocardial infarction. A blood-direct PCR and real-time PCR were used to detect variants of interest. Results & conclusion: Patients with bleeding events had the CYP2C19 GG (*1*1) variant more frequently than patients without bleeding events. The CYP4F2 TT variant was more frequently detected in patients with bleeding events 3 months after hospitalization.

Ticagrelor is one of the main antiplatelet drugs used for prevention of coronary blood clots after interventional procedures in patients with acute coronary syndromes. It has previously been shown that gene variants of CYP2C19 and CYP4F2 may affect antiplatelet therapy. This paper reports a novel instrument and the results of genetic tests obtained using this instrument. Our instrument can detect variants of the genes associated with ticagrelor antiplatelet therapy in only 40 min. These findings might facilitate individualized treatment with ticagrelor of patients with ST-elevation myocardial infarction.

Assessment of Absorption of Glycated Nail Proteins in Patients with Diabetes Mellitus and Diabetic Retinopathy.

Background and objectives: Glycation occurs in a variety of human tissues and organs. Knowledge about the relationship between predictive biochemical factors such as absorption of glycated nail proteins and severity of type 2 diabetes mellitus (DM) and diabetic retinopathy (DR) remains limited. Materials and Methods: The study group consisted of patients with type 2 DM and DR (n = 32) and a control group (n = 28). Each patient underwent a comprehensive ophthalmic examination. The glycation process in nail clippings was evaluated in stages of in vitro glycation and deglycation stages. ATR-FTIR spectroscopy was used to calculate the infrared absorption in the region of interest. The absorption of solutions with nail clippings was evaluated by NanoDrop spectrophotometry. Absorption spectra differences before and after the exposure to fructosamine 3-kinase were compared between DM patients with DR and the control group. Results: The absorption of glycated nail protein greater than 83.00% increased the chance of developing DM and DR (OR = 15.909, 95% CI 3.914-64.660, p < 0.001). Absorption of glycated nail protein by ATR-FTIR spectroscopy in patients with DM and DR in vitro glycation was statistically significantly higher than in the control group; also absorption of solution with nails by NanoDrop spectroscopy was statistically significantly higher than in controls in vitro glycation and in vitro deglycation. After exposure to fructosamine 3-kinase, absorption of nail protein in DM + severe/proliferative DR group was statistically significantly lower in comparison with DM + mild/moderate group DR. Conclusions: Evaluation of glycated nail protein could be applied to evaluate the risk of having DM and for long-term observation of DM control.

Factors associated with platelet reactivity during dual antiplatelet therapy in patients with diabetes after acute coronary syndrome.

Antiplatelet drugs are prescribed without considering the diabetic status of the patient. The objective of the current investigation was to determine the impact of clinical factors, CYP4F2 enzyme and 20-hydroxyeicosatetraenoic acid (20-HETE) concentrations on high on-treatment platelet reactivity in patients with diabetes treated with antiplatelet drugs following acute coronary syndromes. A total of 667 patients were included in the study. Dual antiplatelet drug loading dosages with aspirin (300 mg) and ticagrelor (180 mg) or clopidogrel (600 mg) were prescribed to all the studied patients. Testing of platelet aggregation was performed the day after loading antiplatelet drug dosages. Platelet aggregation test was done according to the classical Born method. Multivariate binary regression analysis demonstrated that insulin use and higher 20-HETE concentration increased the odds of high on-treatment platelet reactivity during the initiation of antiplatelet drug therapy (OR: 3.968, 95% CI: 1.478-10.656, p = 0.006 and OR: 1.139, 95% CI: 1.073-1.210, respectively, p < 0.001). Ticagrelor use decreased the odds of developing high on-treatment platelet reactivity (OR: 0.238, 95% CI: 0.097-0.585, p = 0.002). Data from this study revealed that high on-treatment platelet reactivity during dual antiplatelet therapy in patients with diabetes may depend on such factors as insulin prescription and 20-HETE concentration.

New potential modulators of CYP4F2 enzyme activity in angina pectoris: hsa-miR-24-3p and hsa-miR-34a-5p.

Purpose: To find an association of relative expression of hsa-miR-24-3p and hsa-miR-34a-5p molecules and CYP4F2 enzyme activity in blood plasma of stable angina pectoris (AP) patients'.Materials and Methods: MiRNA gene expression analysis was performed on total RNA extracted from blood plasma, using quantitative real-time polymerase chain reaction. CYP4F2 enzyme levels were determined using commercial ELISA kit. In total, 32 AP and 15 control samples were examined.Results: The relative expression of hsa-miR-24-3p and hsa-miR-34a-5p was upregulated by 4.4 (p = 0.0001) and 3.8 (p = 0.005) -fold in AP patient's blood plasma compared to control subjects. CYP4F2 enzyme level in blood plasma were 2.1 (p = 0.001) times lower in AP patients. Circulating hsa-miR-24-3p was negatively associated with CYP4F2 enzyme level (Spearman correlation coefficient rank r= -0.32; p = 0.03). Moreover, patients that were taking atorvastatin, had 1.5 (p = 0.04) times higher hsa-miR-24-3p expression in blood plasma.Conclusions. Our data suggest that hsa-miR-24-3p might have an effect on CYP4F2 activity during atherosclerosis.

The impact of CYP2C19 and CYP4F2 variants and clinical factors on treatment outcomes during antiplatelet therapy.

Aim: The aim of this study was to determine the impact of genetic and nongenetic factors on treatment outcomes in patients receiving dual antiplatelet therapy after percutaneous coronary intervention and stent implantation. Materials & methods: Patients (n = 628) used clopidogrel or ticagrelor for at least 1 week before platelet aggregation test. Results: Multivariate binary regression analysis demonstrated that aspirin use and CYP4F2 T allele significantly increased odds for bleeding in clopidogrel users (OR: 2.488, 95% CI: 1.452-4.265; p = 0.001 and OR: 1.573, 95% CI: 1.066-2.320; respectively; p = 0.022). CYP4F2 T allele significantly increased odds for bleeding in ticagrelor users (OR: 8.270, 95% CI: 3.917-17.462; p < 0.001). Conclusion: Aspirin use and CYP4F2 T allele were significantly associated with bleeding during dual antiplatelet therapy.

Current antimicrobial susceptibility testing for beta-lactamase-producing Enterobacteriaceae in clinical settings.

The worldwide prevalence of beta-lactamase-producing Enterobacteriaceae (BL-E) is increasing. Bacterial infections involving ESBLs can be more difficult to treat because of antibiotic resistance, as there are fewer effective antibiotics left to be used. Moreover, treatment failure is often observed. Thus, quick and accurate identification of ß-lactamases is imperative to minimize it. This review article describes most commonly used phenotypic techniques and molecular methods for the detection of ESBLs, acquired AmpC ß-lactamases, and carbapenemases produced by Enterobacteriaceae. Phenotypic detection tests remain useful and relevant in clinical laboratories while molecular diagnostic methods are less affordable, more technically demanding, and not standardized. Molecular methods could be used to speed up results of bacterial antibiotic resistance or to clarify the results of phenotypic ß-lactamases confirmation tests.