Prognostic Value of Redox Status Biomarkers in Patients Presenting with STEMI or Non-STEMI: A Prospective Case-Control Clinical Study.

(1) Background: The aim of our study was to determine the role of oxidative stress (OS) during early evaluation of acute ST-elevated myocardial infarction (STEMI) and non-ST-elevated myocardial infarction (NSTEMI) patients in order to define the role of redox balance in profiling the development of myocardial infarction (MI). (2) Methods: This prospective observational case-control study included 40 consecutive STEMI and 39 NSTEMI patients hospitalized in the coronary care unit of the cardiology clinic at the Kragujevac Clinical Center, Serbia, between 1 January 2016 and 1 January 2017. Blood samples were collected from all patients for measuring cardio-specific enzymes at admission and 12 h after admission to evaluate systemic oxidative stress biomarkers and the activity of antioxidant enzymes. (3) Results: In this study, participants were predominately female (52%), with a mean age of 56.17 ± 1.22 years old in the STEMI group and 69.17 ± 3.65 in the non-STEMI group. According to the Killip classification, the majority of patients (>50%) were at the second and third level. We confirmed the elevation of superoxide anion radicals in the non-STEMI group 6 h after admission in comparison with the STEMI and CTRL groups, but levels had decreased 12 h after admission. Levels of hydrogen peroxide were statistically significantly increased in the NSTEMI group. A positive correlation of superoxide anion radicals and levels of troponin I at admission was observed (r = 0.955; p = 0.045), as well as an inverse correlation between reduced glutathione and levels of NT-pBNP measured 6 h after admission (r = -0.973; p = 0.027). (4) Conclusions: We confirmed that superoxide anion radicals and reduced glutathione observed together with hs-troponin I at admission and NT-pBNP during hospital treatment could be predictors of ST evolution.

Kounis Syndrome Associated With the Use of Diclofenac.

BACKGROUND: Diclofenac is a widely used analgesic, anti-inflammatory, antipyretic drug. In several case reports, its use was associated with the occurrence of Kounis syndrome. The aim of this review was to investigate and summarize published cases of Kounis syndrome suspected to be associated with the use of diclofenac. METHODS: Electronic searches were conducted in PubMed/MEDLINE, Scopus, Web of Science, Google Scholar, and the Serbian Citation Index. RESULTS: Twenty publications describing the 20 patients who met inclusion criteria were included in the systematic review. Specified patient ages ranged from 34 to 81 years. Eighteen (90.0%) patients were male. Five patients (25.0%) reported a previous reaction to diclofenac. Reported time from the used dose of diclofenac to onset of the first reaction symptoms ranged from immediately to 5 hours. Diclofenac caused both type I and type II Kounis syndrome, with the presence of various cardiovascular, gastrointestinal, dermatologic, and respiratory signs and symptoms. Most patients experienced hypotension (n = 15 [75.0%]) and chest pain (n = 12 [60.0%]). The most frequently reported finding on electrocardiogram was ST-segment elevations (n = 17 [85.0%]). Coronary angiogram showed normal coronary vessels in 9 patients (45.0%), with some pathologic findings in 8 patients (40.0%). CONCLUSION: Clinicians should be aware that Kounis syndrome may be an adverse effect of diclofenac. Prompt recognition and withdrawal of the drug, with treatment of both allergic and cardiac symptoms simultaneously, is important.

OnabotulinumtoxinA Reduces Health Resource Utilization in Chronic Migraine: PREDICT Study.

BACKGROUND: PREDICT was a Canadian, multicenter, prospective, observational study in adults naïve to onabotulinumtoxinA treatment for chronic migraine (CM). We descriptively assess health resource utilization, work productivity, and acute medication use. METHODS: OnabotulinumtoxinA (155-195 U) was administered every 12 weeks over 2 years (≤7 treatment cycles). Participants completed a 4-item health resource utilization questionnaire and 6-item Work Productivity and Activity Impairment Questionnaire: Specific Health Problem V2.0. Acute medication use was recorded in daily headache diaries. Treatment-emergent adverse events were recorded throughout the study. RESULTS: A total of 197 participants were enrolled, and 184 received ≥1 treatment with onabotulinumtoxinA and were included in the analysis. Between baseline and the final visit, there were decreases in the percentage of participants who reported headache-related healthcare professional visit(s) (96.2% to 76.8%) and those who received headache-related diagnostic testing (37.5% to 9.9%). Reductions from baseline were also observed in the mean number of headache-related visits to an emergency room/urgent care clinic (2.5 to 1.4) and median headache-related hospital admissions (4.0 to 1.0). OnabotulinumtoxinA improved work productivity and reduced the mean (standard deviation) number of hours missed from work over a 7-day period (6.1 [9.7] to 3.0 [6.8]). Mean (standard deviation) acute medication use decreased from baseline (15.2 [7.6] to 9.1 [6.5] days). No new safety signals were identified. CONCLUSIONS: Real-world evidence from PREDICT demonstrates that onabotulinumtoxinA treatment for CM in the Canadian population reduces health resource utilization and acute medication use and improves workplace productivity, supporting the long-term benefits of using onabotulinumtoxinA for CM.

OnabotulinumtoxinA Improves Quality of Life in Chronic Migraine: The PREDICT Study.

BACKGROUND: The PREDICT study assessed real-world, long-term health-related quality of life in adults with chronic migraine (CM) receiving onabotulinumtoxinA. METHODS: Canadian, multicenter, prospective, observational study in adults naïve to onabotulinumtoxinA for CM. OnabotulinumtoxinA (155-195 U) was administered every 12 weeks over 2 years (≤7 treatment cycles). Primary endpoint: mean change in Migraine-Specific Quality of Life Questionnaire (MSQ) at treatment 4 (Tx4) versus baseline. Secondary endpoints: mean change in MSQ at final visit versus baseline, and headache days. RESULTS: 184 participants (average age 45 years; 84.8% female; 94.6% Caucasian) received ≥1 onabotulinumtoxinA treatment; 150 participants completed 4 treatments (1 year) and 123 completed all 7 treatment cycles (2 years). Mean (SD) onabotulinumtoxinA dose per treatment cycle was 171 (18) U and treatment interval was 13.2 (1.8) weeks. Baseline mean (SD) 20.9 (6.7) headache days/month decreased (Tx1: -3.5 [6.3]; Tx4: -6.5 [6.6]; p < 0.0001 versus baseline). Mean (SD) increased from baseline in MSQ at Tx4 (restrictive: 21.5 [24.3], preventive: 19.5 [24.7], emotional: 22.9 [32.9]) and the final visit (restrictive: 21.3 [23.0], preventive: 19.2 [23.7], emotional: 27.4 [30.7]), exceeding minimal important differences (all p < 0.0001). Seventy-seven (41.8%) participants reported 168 treatment-emergent adverse events (TEAEs); 38 TEAEs (12.0%) were considered treatment-related. Four (2.2%) participants reported six serious TEAEs; none were considered treatment-related. No new safety signals were identified. CONCLUSIONS: Real-world evidence from PREDICT demonstrates that onabotulinumtoxinA for CM in Canada improved MSQ scores and reduced headache frequency and severity, adding to the body of evidence on the long-term safety and effectiveness of onabotulinumtoxinA for CM.

SGLT2 inhibitors: a focus on cardiac benefits and potential mechanisms.

This paper highlights the cardioprotective potential of sodium-glucose cotransporter 2 inhibitors (SLGT2i), as well as several most discussed mechanisms responsible for their cardioprotection. Cardiovascular diseases are considered a primary cause of death in nearly 80% of type 2 diabetes mellitus (T2DM) patients, with a 2-4-fold greater incidence of heart failure (HF) among diabetics. As novel hypoglycemics, SGLT2i showed exceptional cardiovascular benefits, reflected through robust reductions of cardiovascular mortality and hospitalization for HF in T2DM patients. Recently, those effects have been reported even in patients with HF and reduced ejection fraction irrespectively of diabetic status, suggesting that cardioprotective effects of SGLT2i are driven independently of their hypoglycemic actions. SGLT2i exerted hemodynamic and metabolic effects, partially driven by natriuresis and osmotic diuresis. However, those systemic effects are modest, and therefore cannot be completely related to the cardiac benefits of these agents in T2DM patients. Hence, increased circulating ketone levels during SGLT2i administration have brought out another hypothesis of a cardiac metabolic switch. Moreover, SGLT2i influence ion homeostasis and exert anti-inflammatory and antifibrotic effects. Their enviable influence on oxidative stress markers, as well as anti- and pro-apoptotic factors, have also been reported. However, since the main mechanistical contributor of their cardioprotection has not been elucidated yet, a joint action of systemic and molecular mechanisms has been suggested. In the light of ongoing trials evaluating the effects of SGLT2i in patients with HF and preserved ejection fraction, a new chapter of beneficial SGLT2i mechanisms is expected, which might resolve their main underlying action.

Risk factors for potential drug-drug interactions of statins in patients with acute coronary syndrome

Abstract The aim of our study was to assess risk factors for potential drug-drug interactions (pDDIs) of statins across different phases of treatment of acute coronary syndrome (ACS) patients: from the point of first medical contact to the coronary angiography (first phase), after coronary angiography to the last day of hospitalization (second phase) and at discharge from hospital (third phase). This was a post hoc analysis of the data collected during the retrospective observational cohort study conducted at the Clinic for Cardiology of the Clinical Centre Kragujevac, Serbia. Patients prescribed statins were identified from the original study population: 156, 240 and 236 patients for the first, second and third phases, respectively. At least one statin pDDI was present in 113 (72.4%), 161 (67.1%) and 139 (58.9%) patients in the first, second and third phases, respectively. Heart failure, arrhythmias after ACS, CRP, triglycerides, length of hospitalization, number of prescribed drugs, antiarrhythmic drugs, and clopidogrel seem to increase the risk of statin pDDIs in at least one treatment phase. Physicians should be vigilant to the possibility of statin pDDIs in ACS patients who have factors that may increase their rate.

Smoking and sex differences in first manifestation of cardiovascular disease.

BACKGROUND AND AIMS: An increasing proportion of women believe that smoking few cigarettes daily substantially reduces their risk of developing cardiovascular (CV) related disorders. The effect of low intensity smoking is still largely understudied. We investigated the relation among sex, age, cigarette smoking and ST segment elevation myocardial infarction (STEMI) as initial manifestation of CV disease. METHODS: We analyzed data of 50,713 acute coronary syndrome patients with no prior manifestation of CV disease from the ISACS-Archives (NCT04008173) registry. We compared the rates of STEMI in current smokers (n = 11,530) versus nonsmokers (n = 39,183). RESULTS: In the young middle age group (<60 years), there was evidence of a more harmful effect in women compared with men (RR ratios: 1.90; 95% CI: 1.69-2.14 versus 1.68; 95% CI: 1.56-1.80). This association persisted even in women who smoked 1 to 10 packs per year (RR ratios: 2.02; 95% CI: 1.65 to 2.48 versus 1.38; 95% CI: 1.22 to 1.57). In the older group, rates of STEMI were similar for women and men (RR ratios: 1.36; 95% CI: 1.22-1.53 versus 1.39; 95% CI: 1.28-1.50). STEMI was associated with a twofold higher 30-day mortality rate in young middle age women compared with men of the same age (odds ratios, 5.54; 95% CI, 3.83-8.03 vs. 2.93; 95% CI, 2.33-3.69). CONCLUSIONS: Low intensity smoking provides inadequate protection in young - middle age women as they still have a substantially higher rate of STEMI and related mortality compared with men even smoking less than 10 packs per year. This finding is worrying as more young - middle age women are smoking, and rates of smoking among young-middle age men continue to fall.

Improvement in Quality of Life with OnabotulinumtoxinA for Cervical Dystonia: POSTURe.

INTRODUCTION: Symptoms of cervical dystonia (CD) can vary in severity and cause significant pain. OnabotulinumtoxinA is an approved treatment for CD. This study assessed health-related quality of life (HRQoL) in patients with CD who received multiple onabotulinumtoxinA treatments. METHODS: This prospective, observational standard-of-care study was conducted at multiple neurology centers in Québec, Canada. Patients reported the health impact of CD using the Cervical Dystonia Impact Profile (CDIP)-58, before and after up to eight onabotulinumtoxinA treatments. Other measures included the Cervical Dystonia Severity Rating Scale by physician, employment status using the Work Productivity Questionnaire and pain using the Pain Numeric Rating Scale (PNRS). Adverse events (AEs) were recorded. RESULTS: Sixty-two patients were enrolled (safety population, n = 61; modified efficacy population, n = 58). Participants were mostly females who were employed; most (79.3%) had torticollis. In all, 21/62 patients (33.9%) discontinued the study. At the final visit, there was a statistically significant (p < 0.001) improvement in all eight CDIP-58 subscales, particularly head and neck symptoms (-31.0) and psychosocial functioning (-28.2). Employment increased from baseline (55%) to the end of the study (64%), and there was improvement in work productivity. There was a significant (p < 0.0001) reduction in pain measured by the PNRS, from -0.5 post-treatment 1 to -2.4 at end of study. AEs (neck pain, muscular weakness, dysphagia, nausea) were consistent with onabotulinumtoxinA use. CONCLUSION: These real-world data indicate that after repeated, long-term use, onabotulinumtoxinA continues to be a safe and effective treatment for CD, improving HRQoL and work productivity.

2,4-Diketo esters: Crucial intermediates for drug discovery.

Convenient structures such as 2,4-diketo esters have been widely used as an effective pattern in medicinal chemistry and pharmacology for drug discovery. 2,4-Diketonate is a common scaffold that can be found in many biologically active and naturally occurring compounds. Also, many 2,4-diketo ester derivatives have been prepared due to their suitable synthesis. These synthetic drugs and natural products have shown numerous interesting biological properties with clinical potential as a cure for the broad specter of diseases. This review aims to highlight the important evidence of 2,4-diketo esters as a privileged scaffold in medicinal chemistry and pharmacology. Herein, numerous aspects of 2,4-diketo esters will be summarized, including synthesis and isolation of their derivatives, development of novel synthetic methodologies, the evaluation of their biological properties as well as the mechanisms of action of the diketo ester derivates. This paperwork is expected to be a comprehensive, trustworthy, and critical review of the 2,4-diketo ester intermediate to the chemistry community.

Drug-drug interactions in patients with acute coronary syndrome across phases of treatment.

The objective of this study is to evaluate potential drug-drug interactions (pDDIs) and risk factors for pDDIs in three phases of an acute coronary syndrome (ACS) treatment: from the point of first medical contact to the coronary angiography (first phase), after coronary angiography to the last day of hospitalization (second phase), and at discharge from hospital (third phase). This retrospective observational cohort clinical study was conducted at the Clinic for Cardiology of the Clinical Centre Kragujevac, a public tertiary care hospital in Kragujevac, Serbia. Micromedex® interaction checker was used to detect pDDIs. This study included 245 ACS patients. All patients were exposed to at least one pDDI in all the phases of treatment. Mean total number of pDDIs was 9.47 ± 6.07, 10.11 ± 6.92, and 6.29 ± 3.66 in first, second, and third phases, respectively. Age, > 6 h from the beginning of the symptoms to admission, primary PCI, STE-ACS, COPD, delirium, hyperlipidemia, hypertension, obesity, systolic blood pressure at admission, TIMI risk score at admission, ALT, LDL, number of physicians who prescribed drugs to a single patient, number of prescribed drugs, and various pharmacological classes increased risk of pDDIs. Mechanical ventilation, dementia, and drug allergy noted in the medical documentation protected against them. Effects of heart failure, diabetes, and aPTT depended on phase of treatment and severity of pDDI. In conclusion, physicians should be vigilant to the possibility of pDDIs in patients harbouring factors that may increase their rate.

Delayed Care and Mortality Among Women and Men With Myocardial Infarction.

BACKGROUND: Women with ST-segment-elevation myocardial infarction (STEMI) have higher mortality rates than men. We investigated whether sex-related differences in timely access to care among STEMI patients may be a factor associated with excess risk of early mortality in women. METHODS AND RESULTS: We identified 6022 STEMI patients who had information on time of symptom onset to time of hospital presentation at 41 hospitals participating in the ISACS-TC (International Survey of Acute Coronary Syndromes in Transitional Countries) registry (NCT01218776) from October 2010 through April 2016. Patients were stratified into time-delay cohorts. We estimated the 30-day risk of all-cause mortality in each cohort. Despite similar delays in seeking care, the overall time from symptom onset to hospital presentation was longer for women than men (median: 270 minutes [range: 130-776] versus 240 minutes [range: 120-600]). After adjustment for baseline variables, female sex was independently associated with greater risk of 30-day mortality (odds ratio: 1.58; 95% confidence interval, 1.27-1.97). Sex differences in mortality following STEMI were no longer observed for patients having delays from symptom onset to hospital presentation of ≤1 hour (odds ratio: 0.77; 95% confidence interval, 0.29-2.02). CONCLUSIONS: Sex difference in mortality following STEMI persists and appears to be driven by prehospital delays in hospital presentation. Women appear to be more vulnerable to prolonged untreated ischemia. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01218776.

Kinetic and mechanistic study on the reactions of ruthenium(ii) chlorophenyl terpyridine complexes with nucleobases, oligonucleotides and DNA.

In this study, we investigated the ability of Ru(ii) polypyridyl complexes to act as DNA binders. The substitution reactions of three Ru(ii) chlorophenyl terpyridine complexes, i.e. [Ru(Cl-Ph-tpy)(en)Cl]Cl (1), [Ru(Cl-Ph-tpy)(dach)Cl]Cl (2) and [Ru(Cl-Ph-tpy)(bpy)Cl]Cl (3) (Cl-Ph-tpy = 4'-(4-chlorophenyl)-2,2':6',2''-terpyridine, en = 1,2-diaminoethane, dach = 1,2-diaminocyclohexane, bpy = 2,2'-bipyridine), with a mononucleotide guanosine-5'-monophosphate (5'-GMP) and oligonucleotides such as fully complementary 15-mer and 22-mer duplexes with a centrally located GG-binding site for DNA, and fully complementary 13-mer duplexes with a centrally located GG-binding site for RNA were studied quantitatively by UV-Vis spectroscopy. Duplex RNA reacts faster with complexes 1-3 than duplex DNA, while shorter duplex DNA (15mer GG) reacts faster compared with 22mer GG duplex DNA. The measured enthalpies and entropies of activation (ΔH≠ > 0, ΔS≠ < 0) support an associative mechanism for the substitution process. 1H NMR spectroscopy studies performed on complex 3 demonstrated that after the hydrolysis of the Cl ligand, it is capable to interact with guanine derivatives (i.e., 9-methylguanine (9MeG) and 5'-GMP) through N7, forming monofunctional adducts. The molecular structure of the cationic compound [Ru(Cl-Ph-tpy)(bpy)Cl]Cl (3) was determined in the solid state by X-ray crystallography. The interactions of 1-3 with calf thymus (CT) and herring testes (HT) DNA were examined by stopped-flow spectroscopy, in which HT DNA was sensibly more reactive than CT DNA. The reactivity towards the formation of Ru-DNA adducts was also revealed by a gel mobility shift assay, showing that complexes 1 and 2 have a stronger DNA unwinding ability compared to complex 3. Overall, the complexes with bidentate aliphatic diamines proved to be superior to those with bpy in terms of capability to bind to the here studied biomolecules.

Fulminant myocarditis as a primary manifestation of H1N1 infection: A first reported case from Serbia.

A 19-year-old male was admitted to our clinic with a diagnosis of suspected acute pericarditis and acute coronary syndrome. The initial diagnostics at our clinic revealed fulminant myocarditis. Twenty-four hours after admission, the patient's condition deteriorated, and he required mechanical ventilation and cardiopulmonary resuscitation. Unfortunately, the patient died. Clinical course, postmortem pathohistological findings and virus serology indicated that an H1N1 viral caused fulminant myocarditis and was the primary manifestation.

Synthesis, characterization, biological activity, DNA and BSA binding study: novel copper(ii) complexes with 2-hydroxy-4-aryl-4-oxo-2-butenoate.

A serie of novel square pyramidal copper(ii) complexes [Cu(L)2H2O] (3a-d) with O,O-bidentate ligands [L = ethyl-2-hydroxy-4-aryl-4-oxo-2-butenoate; aryl = 3-methoxyphenyl-2a, (E)-2-phenylvinyl-2b, (E)-2-(4'-hydroxy-3'-methoxyphenyl)vinyl-2c, 3-nitrophenyl-2d, 2-thienyl-2e] were synthesized and characterized by spectral (UV-Vis, IR, ESI-MS and EPR), elemental and X-ray analysis. The antimicrobial activity was estimated by the determination of the minimal inhibitory concentration (MIC) using the broth microdilution method. The most active antibacterial compounds were 3c and 3d, while the best antifungal activity was showed by complexes 3b and 3e. The lowest MIC value (0.048 mg mL-1) was measured for 3c against Proteus mirabilis. The cytotoxic activity was tested using the MTT method on human epithelial carcinoma HeLa cells, human lung carcinoma A549 cells and human colon carcinoma LS174 cells. All complexes showed extremely better cytotoxic activity compared to cisplatin at all tested concentrations. Compound 3d expressed the best activity against all tested cell lines with IC50 values ranging from 7.45 to 7.91 µg mL-1. The type of cell death and the impact on the cell cycle for 3d and 3e were evaluated by flow cytometry. Both compounds induced apoptosis and S phase cell cycle arrest. The interactions between selected complexes (3d and 3e) and CT-DNA or bovine serum albumin (BSA) were investigated by the fluorescence spectroscopic method. Competitive experiments with ethidium bromide (EB) indicated that 3d and 3e have a propensity to displace EB from the EB-DNA complex through intercalation suggesting strong competition with EB [Ksv = (1.4 ± 0.2) and (2.9 ± 0.1) × 104 M-1, respectively]. Ksv values indicate that these complexes bind to DNA covalently and non-covalently. The achieved results in the fluorescence titration of BSA with 3d and 3e [Ka = (2.9 ± 0.2) × 106 and (2.5 ± 0.2) × 105 M, respectively] showed that the fluorescence quenching of BSA is a result of the formation of the 3d- and 3e-BSA complexes. The obtained Ka values are high enough to ensure that a significant amount of 3d and 3e gets transported and distributed through the cells.

Primary percutaneous coronary intervention in octogenarians.

BACKGROUND: Limited data are available on the outcome of primary percutaneous coronary intervention (PCI) in octogenarian patients, as the elderly are under-represented in randomized trials. This study aims to provide insights on clinical characteristics, management and outcome of the elderly and very elderly presenting with STEMI. METHODS: 2225 STEMI patients ≥70years old (mean age 76.8±5.1years and 53.8% men) were admitted into the network of the ISACS-TC registry. Of these patients, 72.8% were ≥70 to 79years old (elderly) and 27.2% were ≥80years old (very-elderly). The primary end-point was 30-day mortality. RESULTS: Thirty-day mortality rates were 13.4% in the elderly and 23.9% in the very-elderly. Primary PCI decreased the unadjusted risk of death both in the elderly (OR: 0.32, 95% CI: 0.24-0.43) and very-elderly patients (OR: 0.45, 95% CI 0.30-0.68), without significant difference between groups. In the very-elderly hypertension and Killip class ≥2 were the only independent factors associated with mortality; whereas in the elderly female gender, prior stroke, chronic kidney disease and Killip class ≥2 were all factors independently associated with mortality. Factors associated with the lack of use of reperfusion were female gender and atypical chest pain in the very-elderly and in the elderly; in the elderly, however, there were some more factors, namely: history of diabetes, current smoking, prior stroke, Killip class ≥2 and history chronic kidney disease. CONCLUSIONS: Age is relevant in the prognosis of STEMI, but its importance should not be considered secondary to other major clinical factors. Primary PCI appears to have beneficial effects in the octogenarian STEMI patients.

Sex and age differences and outcomes in acute coronary syndromes.

BACKGROUND: There is conflicting information about sex differences in presentation, treatment, and outcome after acute coronary syndromes (ACS) in the era of reperfusion therapy and percutaneous coronary intervention. The aim of this study was to examine presentation, acute therapy, and outcomes of men and women with ACS with special emphasis on their relationship with younger age (≤65years). METHODS: From January 2010 to June 2015, we enrolled 5140 patients from 3 primary PCI capable hospitals. Patients were registered according to the International Survey of Acute Coronary Syndrome in Transitional Countries (ISACS-TC) registry protocol (ClinicalTrials.gov: NCT01218776). The primary outcome was the incidence of in-hospital mortality. RESULTS: The study population was constituted by 2876 patients younger than 65years and 2294 patients older. Women were older than men in both the young (56.2±6.6 vs. 54.1±7.4) and old (74.9±6.4 vs. 73.6±6.0) age groups. There were 3421 (66.2%) patients with ST elevation ACS (STE-ACS) and 1719 (33.8%) patients without ST elevation ACS (NSTE-ACS). In STE-ACS, the percentage of patients who failed to receive reperfusion was higher in women than in men either in the young (21.7% vs. 15.8%) than in the elderly (35.2% vs. 29.6%). There was a significant higher mortality in women in the younger age group (age-adjusted OR 1.52, 95% CI: 1.01-2.29), but there was no sex difference in the older group (age-adjusted OR 1.10, 95% CI: 0.87-1.41). Significantly sex differences in mortality were not seen in NSTE-ACS patients. CONCLUSIONS: In-hospital mortality from ACS is not different between older men and women. A higher short-term mortality can be seen only in women with STEMI and age of 65 or less.

Influence of Different ß-Blockers on Platelet Aggregation in Patients With Coronary Artery Disease on Dual Antiplatelet Therapy.

INTRODUCTION: The use of ß-blockers in the treatment of patients with coronary heart disease is associated with a decrease in the frequency of angina pectoris and mortality of patients. Due to the severity of the disease and previous cardiovascular interventions, many patients with coronary artery disease (CAD) use dual antiplatelet therapy to achieve greater inhibition of platelet aggregation. The influence of ß-blockers on platelet aggregation in patients using antiplatelet therapy is not well understood. OBJECTIVE: To examine the effect of different ß-blockers on platelet aggregation in patients on dual antiplatelet therapy. METHODOLOGY: The study included 331 patients who were treated at the Department of Cardiology, Clinical Center Kragujevac during 2011. Patients were divided into 4 groups depending on the type of ß-blockers that were used (bisoprolol, nebivolol, metoprolol, and carvedilol). Platelet aggregation was measured using the multiplate analyzer and expressed through the value of adenosine diphosphate (ADP) test (to assess the effect of clopidogrel), ASPI test (to assess the effect of acetyl salicylic acid), TRAP test (to assess baseline platelet aggregation), and the ratio of ADP/TRAP and ASPI/TRAP ASPI/TRAP (ASPI - aranchidonic acid induced aggregation, TRAP - thrombin receptor activating peptide) representing the degree of inhibition of platelet aggregation compared to the basal value. In consideration were taken the representation of demographic, clinical characteristics, laboratory parameters, and cardiovascular medications between the groups. RESULTS: Patients who used nebivolol had a significantly lower value of the ratio of ADP/TRAP (0.39 ± 0.30) compared to patients who used bisoprolol (0.48 ± 0.26; P = .038), and trend toward the lower values of ADP test (328.0 ± 197.3 vs 403.7 ± 213.2; P = .059), while there was no statistically significant difference in values of other laboratory parameters of platelet function between other groups. CONCLUSION: Patients with CAD on dual antiplatelet therapy who used nebivolol had significantly lower levels of residual ADP-induced platelet aggregation compared to baseline than patients who used bisoprolol.

Kounis syndrome, two case reports from Kragujevac, Serbia.

It is well-established that acute coronary syndromes occurs when thrombus formation from atheromatous plaques erode or rupture in the advanced stage of atherosclerotic process with severe reduction of coronary blood flow. Also, some conditions may trigger acute coronary syndrome even in the absence of prior cardiovascular disease, and with normal coronary vessels. One of the most important is Kounis syndrome, also known as "allergic angina" or "allergic myocardial infarction" in which the release of mediators during allergic insults has been incriminated to induce coronary artery spasm and/or atheromatous plaque erosion or rupture. The accurate incidence of Kounis syndrome is not known, but since it was described, many clinical cases have been reported, showing the occurence due to various allergens. Here we present two cases of most probable Kounis syndrome, first in patients after multiple stings by non-venomous insect called "black-fly".