Cardioprotective effect of thiotriazoline in cancer patients

Aim. To evaluate the effectiveness of morpholinium-methyl-triazolyl-thioacetate (thiotriazoline) as a cardioprotector in patients with non-Hodgkin’s lymphomas who received chemotherapy with the inclusion of anthracyclines.Material and methods. Fifty patients with non-Hodgkin’s lymphomas were examined on the background of antitumor therapy. The patients were divided into 2 following groups: group 1 (n=27) — standard chemotherapy; group 2 (n=23) — thiotriazoline as a cardioprotector. The quality of life was assessed using the SF-36 questionnaire; the level of troponin I and the natriuretic peptide NT-proBNP was determined; an electrocardiography and echocardiography were performed.Results. In the course of the study, significant differences (p<0,05) were found in following parameters: the severity of dyspnea and lower limb edema, alanine aminotransferase, aspartate aminotransferase, creatine phosphokinase, troponin I level, NT-proBNP, corrected QT interval, end systolic volume, left ventricular ejection fraction, E/A ratio. The results obtained indicate the clinical and paraclinical advantage of thiotriazoline and reflect its cardioprotective effect. Conclusion. The use of thiotriazoline makes it possible to prevent and slow down the cardiovascular disease continuum, leading to the development of heart failure or decompensation that exists in this category of patients. Keywords: cardio-oncology, thiotriazoline, heart failure, anthracyclines, cardiotoxicity>˂0,05) were found in following parameters: the severity of dyspnea and lower limb edema, alanine aminotransferase, aspartate aminotransferase, creatine phosphokinase, troponin I level, NT-proBNP, corrected QT interval, end systolic volume, left ventricular ejection fraction, E/A ratio. The results obtained indicate the clinical and paraclinical advantage of thiotriazoline and reflect its cardioprotective effect.Conclusion. The use of thiotriazoline makes it possible to prevent and slow down the cardiovascular disease continuum, leading to the development of heart failure or decompensation that exists in this category of patients

Optimal choice of prophylactic anticoagulant therapy for nonvalvular atrial fibrillation in the context of COVID-19 pandemic

Already at the very beginning of COVID-19 pandemic, it became known about the key clinical and pathogenetic significance of immunopathological reactions and disorders of hemostasis. Specific coagulopathy, microvascular thromboinflammatory organ damage, macrothrombosis and thromboembolism in the acute period of COVID-19, as well as secondary hemostasis disorders in convalescents, actualize the issues of caring patients with cardiovascular disease. COVID-19 not only increases the risk of thromboembolic events for patients with previously identified arrhythmias, but can also indirectly cause it (as a complication of infection or therapy). The aim of this work was to summarize the data and substantiate the optimal choice of prophylactic anticoagulant therapy for nonvalvular atrial fibrillation during the COVID-19 pandemic. Atrial fibrillation is not only the most common type of supraventricular tachyarrhythmia, but it is also the main underlying cause of more than half of cardioembolic stroke cases, which requires effective thromboprophylaxis. While maintaining the infectious danger for patients, the anticoagulant selection should take into account the possible dysfunctions and drug interactions during the initial infection or reinfection of COVID-19, as well as the possibility of rapid anticoagulant action reverse if surgery is required or bleeding develops. The optimal choice seems to be the use of dabigatran, which is characterized by the best safety profile for hepato- and nephrotoxicity, cytochrome P450-independent metabolism, and the presence of an antidote

NEW APPROACHES TO THERAPY OF CLASSICAL PH-NEGATIVE MYELOPROLIFERATIVE DISEASES: THE EXPERIENCE OF EARLY THERAPY WITH CEPEGINTERFERON ALPHA-2B

Background. Even 100 years after the first attempts to introduce the chemotherapeutic approaches (in 1918) and despite the completely formed notions of myeloproliferative diseases as a group of malignant neoplasms, in the majority of patients with Ph-negative myeloproliferative neoplasms (MPN), a symptomatic, in fact, therapy approach – the impact on peripheral blood indices and nonspecific thromboprophylaxis – is allowed. The limitations of classical cytoreduction and current targeted therapy, as well as the conviction of most specialists in the impossibility of adequately containment of disease progression, continue to be the main factors that keep physicians from the early start of pathogenetic therapy.Objective: to study the efficacy and safety of cepeginterferon alpha-2b (cePEG-IFN alpha-2b) in early (non-risk-adjusted) therapy of classical Ph-negative myeloproliferative neoplasms in initial use and after therapy with other pegylated interferons (PEG-IFN).Materials and methods. Twenty seven patients with polycythemia vera or essential thrombocythemia, without considering risk, received cePEG-IFN alpha-2b: initially, or after 6 or 12 months of other pegylated interferon therapy, in a dosage of 200 μg per week, with a decrease to 100 μg per week if 2 degree hematological toxicity developed. Hematological and molecular responses were assessed. Follow-up – from 20 to 46 months.Results. In all groups, a hematologic response comparable in depth and dynamics, as well as a molecular response as a steady decrease in the JAK2V617F allelic load, was achieved. There was no effect on the results of change to therapy with cePEG-IFN alpha-2b. CePEGIFN alpha-2b showed less dose-limiting toxicity for neutropenia and better pharmacoeconomic feasibility.Discussion. New data about mechanisms of antiproliferative effects of interferon alfa preparations are given. The pharmacological advantages of cePEG-IFN alpha-2b are discussed: superiority in pharmacokinetic parameters, the presence of one position isomer purity of the drug substance, the convenience of self-application. Conclusion. Early administration of an effective pathogenic therapy is an independent preventive measure to prevent the MPN progression and complications development. The use of cePEG-IFN alpha-2b may help to improve the care of MPN patients

Изменения факторов сердечно-сосудистогориска и особенностей клиническойкартины у мужчин с подагрой за прошедшие 20 лет

Objective. To study the prevalence and degree of risk factors for cardiovascular diseases (CVD) and the transformation of the clinical picture of gout in the past 20 years. Material and methods. The case histories of 305 male gouty patients (mean age 45.6+11.7years) treated at the Rheumatology Department, S.P. Botkin Faculty Therapy Clinic, S.M. Kirov Military Medical in 1990 to 1994 and 2005 to 2009 were retrospectively analyzed. The pattern and prevalence of CVD and the presence of risk factors were studied in patients with gout. Results. The currently ill patients were found to have high body mass index, high arterial hypertension, more pronounced metabolic changes and carbohydrate metabolic disturbances, and a high atherogenic blood lipid profile, which were correlated with elevated uric acid levels. There was also a high frequency of chronic CVD. Conclusion. The found changes point to the transformation of the disease over a number of years and the steady increase in the degrees of a cardiovascular risk in gouty patients with metabolic disturbances.Цель исследования - изучить распространенность и степень выраженности факторов риска сердечно-сосудистых заболеваний (ССЗ), а также трансформацию клинической картины заболевания у больных подагрой за прошедшие 20лет. Материал и методы. Проведен ретроспективный анализ историй болезней 305 пациентов (все мужчины, средний возраст - 45,6+11,7 года) с подагрой, находившихся на лечении в ревматологическом отделении клиники факультетской терапии им. СИ. Боткина Военно-медицинской академии им. СМ. Кирова с 1990 по 1994 г. и с 2005по 2009 г. Изучены структура, распространенность ССЗ, наличие факторов риска у больных подагрой. Результаты и их обсуждение. Установлено, что для пациентов, заболевших в настоящее время, характерны более высокие индекс массы тела, степень артериальной гипертензии, более выраженные изменения метаболизма и нарушения углеводного обмена, высокая атерогенность липидного спектра крови, коррелирующие с повышением уровня мочевой кислоты. Установлена и большая встречаемость хронических ССЗ. Заключение. Обнаруженные особенности свидетельствуют о трансформации заболевания на протяжении ряда лет и неуклонном возрастании степени сердечно-сосудистого риска у больных подагрой с нарушениями метаболизма

Долгосрочное влияние нетакимаба на качество жизни, боль в спине и работоспособность пациентов с анкилозирующим спондилитом: результаты международного многоцентрового рандомизированного двойного слепого клинического исследования III фазы BCD-085-5/ASTERA

The article contains the data obtained during the 156-week follow-up of patients with ankylosing spondylitis (AS) in the ASTERA phase III study.Objective: to evaluate the effect impact of netakimab (NTK) on quality of life (QoL), back pain and work capacity in patients with active AS.Material and methods. The study enrolled 228 patients with active AS who were randomized 1:1 to receive NTK 120 mg or placebo. At week 52, patients in Group 1 (NTK) who achieved ASAS20 continued therapy (NTK at a dose of 120 mg once every 2 weeks) until week 156. Patients in Group 2 (placebo/NTK) received the study drug at a dose of 120 mg subcutaneously every 2 weeks from week 20 until week 68, after which the efficacy of therapy was determined (by achieving an ASAS20 response). Patients who achieved ASAS20 received treatment (NTK at a dose of 120 mg once every 2 weeks) until week 172.Results and discussion. Under NTK therapy, a significant improvement in QoL was observed in the assessment of the physical and psychological components of the SF-36 questionnaire, which was maintained during the three years of therapy: increase in indicator by 12.68±9.92; 13.27±10.14; 12.92±10.03; 14.10±10.35; 14.76±9.77 and 6.10±11.59; 5.50±11.82; 6.32±11.01; 5.87±11.45; 5.25±11.98 points at week 52, 76, 104, 128 and 156, respectively. During the extended therapy period, a reduction in the proportion of working hours missed for health reasons, an improvement in work capacity and work efficiency and an increase in daily activity were observed. Back pain (BASDAI question 2) and nocturnal back pain decreased steadily during the entire follow-up period compared to the screening values.Conclusion. NTK is an effective therapy for active AS that improves QoL scores, significantly reduces pain intensity and improves work productivity.В статье приведены данные, полученные в ходе 156 нед наблюдения за пациентами с анкилозирующим спондилитом (АС) в исследовании III фазы ASTERA.Цель исследования – оценить влияние нетакимаба (НТК) на качество жизни (КЖ), боль в спине и работоспособность пациентов с активным АС.Материал и методы. В исследование включено 228 больных активным АС, которые были рандомизированы в соотношении 1:1 в группу НТК 120 мг или группу плацебо. На неделе 52 пациенты группы 1 (НТК), достигшие ASAS20, продолжили получать терапию (НТК в дозе 120 мг 1 раз в 2 нед) до недели 156. Пациенты группы 2 (плацебо/НТК), начиная с недели 20, использовали исследуемый препарат в дозе 120 мг подкожно 1 раз в 2 нед до недели 68, после которой у них была определена эффективность терапии (по достижению ответа ASAS20). Пациенты, достигшие ASAS20, получали лечение (НТК в дозе 120 мг 1 раз в 2 нед) до недели 172.Результаты и обсуждение. На фоне лечения НТК наблюдалось значимое улучшение КЖ при оценке физического и психологического компонентов опросника SF-36, которое сохранялось на протяжении 3 лет терапии: повышение показателя на 12,68±9,92; 13,27±10,14; 12,92±10,03; 14,10±10,35; 14,76±9,77 и 6,10±11,59; 5,50±11,82; 6,32±11,01; 5,87±11,45; 5,25±11,98 балла на неделях 52, 76, 104, 128, 156 соответственно. В течение продленного периода терапии было выявлено снижение доли рабочего времени, пропущенного по состоянию здоровья, улучшение работоспособности и эффективности труда, а также повышение повседневной активности. Боль в спине (вопрос 2 BASDAI) и ночная боль в спине стойко уменьшались на протяжении всего периода наблюдения по сравнению с их показателями на момент скрининга.Заключение. НТК является эффективным методом терапии активного АС. Под действием НТК улучшаются показатели КЖ, в том числе значимо снижается интенсивность боли и улучшается производительность труда

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

The case of hemoglobinopathy E

Abnormal unstable hemoglobins are common in certain geographic areas (Hb S, Hb C, Hb E, Hb D). The clinical manifestations in carriers of abnormal hemoglobins may be absent or expressed in the form of severe hemolytic anemia with high mortality. The article describes the case with the combination of Hb E and erythrocytosis, which caused some difficulties in the diagnosis of disease