Risk factors for cardiovascular diseases in patients received complex treatment for cranial and craniospinal tumors in childhood

Aim. To study the traditional risk factors for cardiovascular disease (CVD), indicators of endothelial function and exercise tolerance in patients received complex treatment for cranial and craniospinal tumors in childhood, including radiation therapy.Material and methods. We compared examination data of 48 patients who underwent treatment for brain tumors using cranial and craniospinal irradiation in childhood (mean age, 21,7±4,3 years, mean period after the end of treatment, 6,9±5,4 years), and 20 healthy volunteers. Examination methods included assessment of lipid profile, vascular stiffness and endothelial function using the Photoplethysmography and occlusion test, cardiopulmonary test, and in patients who underwent craniospinal irradiation, also echocardiography and duplex ultrasound of extracranial arteries.Results. Compared to healthy individuals, patients after a brain tumor were found to have lower blood pressure, higher heart rate (HR), significantly lower exercise performance (peak oxygen consumption, 19,8±6,4 ml×min-1×kg vs 30,3±5,8 ml×min-1×kg, p<0,0001) and a higher prevalence of dyslipidemia (56% vs 5%, p<0,0001), as well as an increase in the augmentation index, indicating higher stiffness of large vessels (-7,3±16,3 vs -20,3±7,9, p=0,001), and a trend towards a decrease in the occlusion index (p=0,051). Echocardiography and duplex ultrasound revealed no radiation-associated abnormalities.Conclusion. Determining the mechanisms and prognostic significance of the identified risk factors for CVD (dyslipidemia, decreased exercise tolerance, increased heart rate and vascular stiffness) in this category of patients requires further research. Regular monitoring of risk factors, primarily the lipid profile, and the use of preventive measures for individuals with an increased risk of CVD should be recommended

Early echocardiographic alterations in cancer patients during chemotherapy

Aim. To evaluate the early manifestation of cardiotoxicity after the first course of multiagent chemotherapy (MAC) using echocardiography with an assessment of the left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS).Material and methods. The study included 49 cancer patients with elective MAC.Results. After the first administration of a therapeutic dose of chemotherapy, a decrease in LVEF ≥10 and GLS >15 was demonstrated in more than 6,1% of patients, as well as a subclinical decrease in LVEF ≥5% in 22,4% and a decrease in GLS ≥12% in 24,5%.Conclusion. In cancer patients, after the first course of chemotherapy, GLS dynamics should be assessed during echocardiography as a marker of myocardial dysfunction

High-sensitivity troponin I as a predictor of left ventricular dysfunction in the use of cardiotoxic anticancer agents for breast cancer in patients with predominantly low and moderate risk of cardiotoxicity

Aim. To study the significance of monitoring high-sensitivity troponin I (hs-cTnI) for predicting anthracycline-induced left ventricular (LV) dysfunction in the treatment of breast cancer in patients with moderate and low risk of cardiotoxicity (CT).Material and methods. The study involved 49 patients with breast cancer aged 50±10 years who underwent neoadjuvant or adjuvant chemotherapy, which included doxorubicin at a course dose of 60 mg/m2 and an average cumulative dose of 251±60 mg/m2. The level of hs-cTnI was determined by an ultrasensitive method before the start of chemotherapy, after each course of anthracyclines and in 18 patients before the administration of anthracyclines. The level of hscTnI >0,017 ng/ml was considered elevated. Echocardiography was performed before the start of chemotherapy, after the end of anthracycline therapy, and every 3 months for 12 months thereafter. CT was defined as a decrease in LV ejection fraction (EF) by ≥10% to <53%.Results. CT risk before chemotherapy was considered low and moderate in 96% of patients. An increase in hs-сTnI was detected ≥1 times in 56,8% of patients: before chemotherapy — in 13,5%, after 1 and 2 courses of anthracycline therapy — in 13,9%, after 3, 4, 5 and 6 courses — in 44%, 62%, 71% and 66% of patients, respectively. The levels of hs-cTnI before and after administration of anthracyclines did not differ significantly. The development of LV dysfunction was observed in 16,3% of patients. There were following prognostic significance of an increase in hs-cTnI at any time of chemotherapy for a decrease in LV EF: sensitivity — 87,5%, specificity — 50%, the positive predictive value — 28%, the negative predictive value — 94,7%. The closest relationship was noted between CT and hs-cTnI value before the start of chemotherapy (β=0,45, p=0,005) and after the 3rd course of anthracycline therapy (β=0,56, p=0,002).Conclusion. An increase in hs-cTnI level before and during anthracycline thera py in patients with a low risk of cardiotoxicity has a prognostic value in relation to the development of left ventricular dysfunction. Hs-cTnI assessment should be performed before the start of therapy, and then starting from the 3rd course of anthracycline therapy in all patients, regardless of the risk of cardiotoxicity

Клинический случай применения тоцилизумаба у пациента с системным ювенильным идиопатическим артритом

This article describes a case of successfully used tocilizumab (interleukin 6 receptors monoclonal antibodies) in a two-year patient with severe systemic juvenile idiopathic arthritis resistant to oral and parenteral glucocorticoids, nonsteroidal anti-inflammatory drugs, and methotrexate. Just after the first injection of tocilizumab, fever and pain ceased, morning stiffness decreased significantly; laboratory disease activity indices normalized by the 4th week of drug use; by the 16th week inflammatory changes in the joints regressed completely, the disease entered its inactive phase. After using tocilizumab, remission duration was 20 months for articular syndrome and systemic manifestations. No adverse reactions have been registered.В статье описан случай успешного применения моноклональных антител к рецепторам интерлейкина 6 тоцилизумаба у двухлетнего пациента с тяжелым течением системного ювенильного идиопатического артрита, резистентного к пероральным и парентеральным глюкокортикостероидам, нестероидным противовоспалительным препаратам, метотрексату. Уже после первого введения тоцилизумаба купировались лихорадка и болевой синдром, значительно уменьшилась утренняя скованность, к 4-й нед введения препарата нормализовались лабораторные показатели активности болезни, к 16-й нед полностью регрессировали воспалительные изменения в суставах, была констатирована фаза неактивной болезни. Длительность ремиссии суставного синдрома и системных проявлений после применения тоцилизумаба составила 20 мес. Нежелательных реакций на фоне проводимой терапии не зарегистрировано

Treating Systemic Juvenile Idiopathic Arthritis with Tocilizumab: Clinical Case

This article describes a case of successfully used tocilizumab (interleukin 6 receptors monoclonal antibodies) in a two-year patient with severe systemic juvenile idiopathic arthritis resistant to oral and parenteral glucocorticoids, nonsteroidal anti-inflammatory drugs, and methotrexate. Just after the first injection of tocilizumab, fever and pain ceased, morning stiffness decreased significantly; laboratory disease activity indices normalized by the 4th week of drug use; by the 16th week inflammatory changes in the joints regressed completely, the disease entered its inactive phase. After using tocilizumab, remission duration was 20 months for articular syndrome and systemic manifestations. No adverse reactions have been registered

Efficacy of Pneumococcal Polysaccharide Conjugate Vaccine (13-valent, Adsorbed) in Patients with Systemic Juvenile Idiopathic Arthritis Treated with Genetically Engineered Biologic Drugs (Tocilizumab or Canakinumab): Prospective Cohort Study

Background. Immunological potency of 13-valent pneumococcal vaccine (PCV-13) in children with systemic juvenile idiopathic arthritis (SJIA) is still unstudied. Estimates of the genetically engineered biologic drugs (GEBD) effects on pneumococcal vaccination results also remain controversial.Objective. The aim of the study was to explore the PCV-13 efficacy in patients with SJIA and who is on treatment with monoclonal antibodies against interleukin 6 receptor (tocilizumab) and interleukin 8 receptor beta (canakinumab).Methods. The study included patients under the age of 18 with SJIA in remission or active form of disease vaccinated with PCV-13. The vaccine was administered in single dose of 0.5 ml intramuscularly in patients on treatment with GEBD or 3 weeks before GEBD administration for the first time (for patients with active disease). Vaccination was considered effective at achievement of the minimum protective level of antibodies to capsular polysaccharide of pneumococcus (anti-SPP IgG; ≥ 7 U/ml) or increase of anti-SPP IgG level ≥ 2 times in 4 weeks after vaccination. The anti-SPP IgG levels were measured with enzyme immunoassay.Results. The study included 53 patients (27 girls) in remission of SJIA and 25 (16 girls) in active disease. Median age was 13.3 and 10.8 years respectively. Tocilizumab/canakinumab was administrated in 43/10 and 18/7 patients respectively. Minimum significant anti-SPP IgG level and two-fold increase in anti-SPP IgG level were recorded in 49/53 (92%) and 32/53 (60%) patients with SJIA in remission, as well as in 22/25 (88%) and 18/25 (72%) patients in active disease respectively. PCV-13 immunological potency in patients with SJIA in remission and in active disease (in those who were initially administrated and who did not receive GEBD) did not differ.Conclusion. PCV-13 vaccination allows to achieve protective antibodies level in most of the patients with SJIA in children population regardless of the disease stage and the history of GEBD administration

КЛИНИЧЕСКИЙ СЛУЧАЙ ПРИМЕНЕНИЯ КАНАКИНУМАБА У ПАЦИЕНТА С СИСТЕМНЫМ ЮВЕНИЛЬНЫМ ИДИОПАТИЧЕСКИМ АРТРИТОМ, РЕЗИСТЕНТНЫМ К ИММУНОДЕПРЕССАНТАМ И ГЕННО-ИНЖЕНЕРНЫМ БИОЛОГИЧЕСКИМ ПРЕПАРАТАМ

The article presents a case of successful use of an interleukin-1 monoclonal antibody drug (canakinumab) for severe systemic juvenile idiopathic arthritis refractory to treatment with classic immunosuppressants and genetically engineered biopharmaceuticals with a different mode of action. Canakinumab treatment shortly provided reduction in clinical and laboratory parameters of the disease activity, life quality improvement, development of an inactive disease stage and allowed reducing the prednisolone dose by 90% and avoiding intravenous and intraarticular administration of glucocorticoids.В статье приведен случай успешного применения препарата моноклональных антител к интерлейкину 1 (канакинумаб) при тяжелом системном варианте ювенильного идиопатического артрита, рефрактерного к терапии классическими иммунодепрессантами и генно-инженерными биологическими препаратами с другим механизмом действия. Лечение канакинумабом в короткие сроки обеспечило снижение клинических и лабораторных показателей активности болезни, повышение качества жизни, развитие стадии неактивной болезни, позволило снизить дозу преднизолона на 90% и воздержаться от внутривенного и внутрисуставного введения глюкокортикоидов.