ANTICOAGULANT THERAPY FOR CHRONIC KIDNEY DISEASE AND ATRIAL FIBRILLATION: THE AXIS OF ROTATION BETWEEN THE POLES OF RISK

The frequent comorbidity of atrial fibrillation (AF) and chronic kidney disease (CKD) in the general population is demonstrated in many epidemiological studies. Most patients with an established diagnosis of AF are recommended to use constant anticoagulant therapy (ACT) to prevent ischemic stroke and thromboembolic complications (TEC). With renal dysfunction, changes in the hemostatic system are observed at all stages of CKD, both related to an increase in prothrombogenic activity as well as to development of coagulopathy, which increases the threat of bleeding. Therefore, in patients with CKD and AF, an important aspect of ACT is the choice of the optimal anticoagulant, that will provide a balance between the risks of stroke and hemorrhagic complications, to which this article is dedicated

Review of the European standard for postgraduate training of medical specialists in internal medicine and prospects for implementation in Russian Federation

Relevance. Residency remains an integral part of quality postgraduate education in Russia. Improving the education system of medical workers and creating a system of motivation for their quality work is one of the priority tasks implemented within the framework of the Concept of development of the healthcare system in the Russian Federation until 2020.Objective. Comparison of the European standard of postgraduate training of medical specialists in the field of “internal diseases” with the existing training system in the Russian Federation.Results. The residency program of the Russian Federation pursues a similar aim to the European standard — the training of a qualified general practitioner. The program is based on a modular system and includes the study of various disciplines, an extensive practice program and state final certification. An analysis of the content of the work programs of the disciplines indicates that the training is aimed at the formation of both universal (general cultural) competencies, which are essentially similar to CanMEDS, and professional competencies. There is no significant difference between the list of knowledge, skills and practical skills that a general practitioner must possess after graduation from residency in Europe and Russian Federation. However, the development of a similar program in the Russian Federation takes much less time (2 years or 4,320 hours), which raises a logical question about the quality of training.Conclusion. Despite the diff erence in the programs for postgraduate training of internist (primarily in terms of hours), the learning goal is the formation of similar competencies. It should also be noted a well-structured control system, which makes it possible to objectively evaluate the acquired competencies and adjust the individual learning process

MANIFESTATIONS OF FRAILTY IN ELDERLY PATIENTS WITH ACUTE CORONARY SYNDROME

Background. Frailty is a high-priority issue in cardiovascular medicine because of the aging of patients. It reflects the complex functional disorders and is associated with high morbidity and adverse outcomes. The aim of the study was to examination prevalence of frailty, its associations with mortality and hemorrhagic risk in elderly patients with ACS. Materials and methods. In 130 patients ≥ 75 years (82,7 ± 4,7 years, arterial hypertension (AH) 91,5%, previous myocardial infarction (MI) 32,3%, atrial fibrillation 32,3%, diabetes 26,9%, admitted with MI 75,4% or unstable angina 24,6%, frailty (national validated questionnaire), nutritional status (Mini Nutrition Assessment), cognitive function (Mini Mental State Examination) were assessed. Results. Mean score on a national validated questionnaire was 2,9 ± 1,4 points. Only 8.5% of patients responded negatively to all questionnaire questions. None of the patients had 7 points. 6,2, 19,2, 32,3, 23,8, 6,9 and 3,1% patients had 1, 2, 3, 4, 5 and 6 points. 8,5% of the patients were non-frail, 25,4% pre-frail and 66,1% frail. Patients with frailty were more likely women, had higher incidence of AH, MI in this hospitalization, GFR < 60 ml/min/1,73 m2. Conclusion. Frailty occured in 66,1% of elderly patients with ACS, was associated with increased prevalence of cardiovascular diseases

Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients

Background Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown. Methods Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days. We performed sequential analyses in three prespecified, progressively inclusive cohorts: patients with an elevated d-dimer level (cohort 1), patients with an elevated d-dimer level or an age of at least 75 years (cohort 2), and all the enrolled patients (overall population cohort). The statistical analysis plan specified that if the between-group difference in any analysis in this sequence was not significant, the other analyses would be considered exploratory. The primary efficacy outcome was a composite of asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism. The principal safety outcome was major bleeding. Results A total of 7513 patients underwent randomization. In cohort 1, the primary efficacy outcome occurred in 6.9% of patients receiving betrixaban and 8.5% receiving enoxaparin (relative risk in the betrixaban group, 0.81; 95% confidence interval [CI], 0.65 to 1.00; P=0.054). The rates were 5.6% and 7.1%, respectively (relative risk, 0.80; 95% CI, 0.66 to 0.98; P=0.03) in cohort 2 and 5.3% and 7.0% (relative risk, 0.76; 95% CI, 0.63 to 0.92; P=0.006) in the overall population. (The last two analyses were considered to be exploratory owing to the result in cohort 1.) In the overall population, major bleeding occurred in 0.7% of the betrixaban group and 0.6% of the enoxaparin group (relative risk, 1.19; 95% CI, 0.67 to 2.12; P=0.55). Conclusions Among acutely ill medical patients with an elevated d-dimer level, there was no significant difference between extended-duration betrixaban and a standard regimen of enoxaparin in the prespecified primary efficacy outcome. However, prespecified exploratory analyses provided evidence suggesting a benefit for betrixaban in the two larger cohorts. (Funded by Portola Pharmaceuticals; APEX ClinicalTrials.gov number, NCT01583218. opens in new tab.

Prognostic Significance of Echocardiographic Characteristics in Patients with Type 2 Myocardial Infarction: comparison with Type 1 Myocardial Infarction

Aim. To outline echocardiographic features and assess their prognostic significance for major cardiovascular adverse events (MACEs) within 12 months in patients with type 2 myocardial infarction (MI), compared to type 1 MI (T1MI).Material and methods. The prospective observational study included 161 MI patients who underwent coronary angiography within 24 hours of admission. Type 2 MI (T2MI) diagnosis aligned with the Fourth Universal Definition. Echocardiography and speckle-tracking echocardiography were performed within 72 hours of hospitalization. MACEs encompassed cardiovascular death, non-fatal MI, non-fatal stroke, and HF-related readmissions. Logistic regression analysis was conducted  to evaluate their associations with the outcomes.Results. T2MI were diagnosed in 74 patients (median age, 65 years; males, 55,4%). During follow up, 18 patients for each MI type experienced at least one MACE event. Left ventricular (LV) systolic dysfunction (LV ejection fraction [LVEF] &lt;50%) was observed in 41 (55.4%) T2MI patients, compared with 66 (75.9%) T1MI patients (p=0.014). Median LVEF and global longitudinal strain [GLS] were 47.5% and 13.4%, respectively, for T2MI, compared to 45% and 13.9%, respectively, for T1MI (p=0.032 and p=0.332, respectively). LV diastolic dysfunction [DD] was observed in 56 (75.7%) T2MI and 77 (88.5%) T1MI patients. Grade III was more frequent in T2MI in comparison with T1MI (14.9% vs 1.1%, p=0.001, respectively), whereas grade I was more common in T1MI patients (75.9% vs 43.2%, p=0.004, respectively). Right ventricular (RV) dysfunction was observed more frequent in T2MI patients, compared to those with T2MI (52.7% vs. 35.6%, p=0.025, respectively). In univariate analysis, grade III DD was significantly associated with MACEs in T2MI (odds ratio [OR] 5.1, 95% confidence interval [CI], 1.3–18.5, p=0.017). In multivariate analysis, GLS ≤ 9.6% (OR = 17.3, 95% CI 3.0-99.5, p=0.001), and prior MI (OR = 16.6, 95% CI 1.7–157.6, p=0.015) were significantly associated with a heightened risk of MACEs in T2MI patients.Conclusion. Patients with T2MI had high prevalence of LV and RV dysfunction. Echocardiographic assessments, particularly speckle-tracking echocardiography, hold promise in predicting adverse outcomes for these individuals

Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Coagulation disorders in myocardial infarction with nonobstructive coronary arteries

Aim. To investigate the state of the platelet and plasma components of hemostasis in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA).Material and methods. The study included 42 patients with non-ST-segment elevation myocardial infarction (NSTEMI): MINOCA (n=24) and MI-CAD (n=18). Platelet aggregation ability in response to activation was evaluated using Solar AP2110 and LASCA aggregometers. Platelet functional activity and calcium signaling were assessed using flow cytometry methods. The plasma component of hemostasis, in addition to routine coagulation tests was evaluated using the global coagulation test "Thrombodynamics". The control groups for tests consisted of healthy volunteers.Results. When analyzing the ability of platelets to form aggregates by the aggregometry tests, it was found that platelets in the MINOCA group formed aggregates significantly worse upon ADP stimulation at various concentrations compared to the MI-CAD group. However, when platelets were stimulated with collagen, the opposite effect was observed: in the MI-CAD group, there was a noticeable decrease in aggregate formation in terms of light scattering amplitude compared to the MINOCA group. Flow cytometry using the functional platelet activity test protocol revealed that both groups showed a significantly increased platelet size after activation, reduced platelet granularity) both at rest and upon activation, significantly decreased number of procoagulant phosphatidylserine-positive platelets, and reduced dense granule release upon activation compared to healthy volunteers. The calcium signaling test showed a weakened calcium release in response to ADP in the MINOCA group compared to the MI-CAD group. In the study of the plasma component, no significant differences between the groups or deviations were found according to both routine tests and the "Thrombodynamics" test.Conclusion. Platelet activity did not differ significantly between the MINOCA and MI-CAD groups; however, in the MINOCA group, platelet activity was lower in some tests compared to the MI-CAD group. In the study of the plasma hemostasis component, normocoagulation was recorded in both groups

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

BACKGROUND: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. METHODS: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P=0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P=0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P=0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P=0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P=0.31). CONCLUSIONS: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846 .)