Цель. Целью исследования явилась оценка эффективности и приверженности гиполипидемической терапии, частоты развития сердечно-сосудистых осложнений у пациентов с гомо- и гетерозиготной семейной гиперхолестеринемией (СГХС) в течение пятилетнего периода наблюдения в регистре РЕНЕССАНС (Регистр пациентов с СГХС и пациентов очень высокого сЕрдечно-Сосудистого риска с недоСтАточной эффективНоСтью, проводимой гиполипидемической терапии). Материал и методы. РЕНЕССАНС является открытым, национальным, наблюдательным исследованием и включает больных с СГХС. Учитывали наличие факторов риска атеросклероза, анамнез сердечно-сосудистых заболеваний, гиполипидемическую терапию. В каждом центре выполняли определение концентрации: общего холестерина, триглицеридов, холестерина липопротеидов высокой плотности в сыворотке крови. Содержание холестерина липопротеидов низкой плотности (ХС ЛНП) рассчитывали по формуле Фридвальда. В некоторых центрах проводили измерение уровня липопротеида(а). При оценке частоты конечной точки, включавшей фатальные и нефатальные сердечно-сосудистые осложнения (ССО), проводили анализ Каплана-Майера. Результаты. В регистр включено 17 больных с гомозиготной СГХС (средний возраст 22±13 лет, 65% женского пола, 29% дети) и 2288 пациентов с гетерозиготной СГХС (48±16 лет, 57% женского пола, 6% дети). В группе гомозиготной СГХС за период наблюдения 74±13 месяцев ССО зарегистрированы у 5 (29%) пациентов, многокомпонентную гиполипидемическую терапию получали 94% и ни один больной не достиг целевого уровня ХС ЛНП. В группе гетерозиготной СГХС динамическое наблюдение проведено у 1067 (47%) пациентов в течение 32±27 месяцев, конечная точка зарегистрирована у 10% больных. Мужской пол (относительный риск 1,7; 95% доверительный интервал 1,2-2,6 p<0,01), гипертония (3,8; 2,3–6,2; p<0,001), ишемическая болезнь сердца (9,3; 5,6–15,3; p<0,001), отягощенный анамнез по сердечно-сосудистым заболеваниям (ССЗ) (2,6; 1,5–4,5; p<0,001) и концентрация липопротеида(а)≥30 мг/дл (2,2; 1,0–4,7; p<0,05) явились предикторами развития ССО. Частота назначения трехкомпонентной гиполипидемической терапии с ингибиторами PCSK9 возросла с 2 до 9%, а достижение целевого уровня ХС ЛНП − с 2 до 14% (р <0,001 для обоих). Заключение. Пятилетнее наблюдение за участниками регистра РЕНЕССАНС демонстрирует увеличение использования многокомпонентных схем лечения. Мужской пол, гипертония, ишемическая болезнь сердца, отягощенный анамнез по ССЗ и концентрация липопротеида(а) ≥30 мг/дл остаются ведущими факторами, ассоциированными с увеличением риска развития ССО.
The Russian Society of Cardiology (RKO) With the participation of: The National Society for the Study of Atherosclerosis (NOA), the Russian Association of Endocrinologists (RAE), the Russian Society of Cardiosomatic Rehabilitation and Secondary Prevention (RosOKR), the Russian Scientific Medical Society of Therapists (RNMOT), the Eurasian Association of Cardiologists, the Eurasian Association of Therapists (EAT), the Russian Association of Gerontologists and Geriatricians
Rare diseases continue to present numerous challenges for the medical field worldwide. Understanding innovative mechanisms of service provision for patients with rare conditions through shared communication across different healthcare systems should be encouraged. This study presents the organization of medical care for people with rare diseases in Russia, while also exploring the epidemiology of both life-threatening and chronic, progressive, rare diseases. Further, the regulation of medical care provision is examined, including the preferential provision of medicines in different Russian regions and potential role of compulsory medical insurance. The principles guiding patient referrals to appropriate specialist centres for rare diseases are outlined, including considering the increased role that public-patient organizations have in developing healthcare systems. In reviewing the specialized resources available for patients with rare diseases, medical genetics services offering diagnostics and counselling are discussed. Additionally, population-level preventive care necessitates significant investment, principally in diagnostic technology and screening programs. As seen elsewhere, these initiatives involve forming reference centres and tertiary-level pediatric departments staffed by multidisciplinary specialists in rare diseases. Numerous challenges are highlighted relating to Russian healthcare systems, including the financing of expensive treatments and ensuring equitable access to medical care for those patients with rare diseases outside of State-subsidized programs. Recommendations are made on creating international registries for knowledge sharing, quality appraisal, newborn screening, diagnostic challenges, available treatments and rehabilitation services. Given the high cost of rare diseases, cost-effective interventions are advisable, particularly developing preventive programs and targeting the most common and severe mutations in patients planning pregnancies.
Anti‑NMDA encephalitis is a rare autoimmune disease of the central nervous system caused by the synthesis of autoantibodies to the NR1/NR2 subunits of the NMDA receptor, characterized by the development of acute mental, cognitive, motor, autonomic disorders, epileptic syndrome and central hypoventilation.The article presents a three‑year observation of patient 34 years old with anti‑NMDA ncephalitis associated with late‑ stage ovarian teratoma, accompanied by an increase titer of antibodies to NMDA receptors in serum to 1:640.Based on a detailed analysis of clinical, neurological, neuropsychological (MMSE, MoСA, FAB, 10 words test A.R. Luria) and laboratory‑instrumental characteristics of the disease (titer anti‑NMDA, level of IgG, IgM, IgA, lymphocyte subpopulations, EEG, MRI of the brain, pelvis) suggested a combination scheme of first and second line therapy. The sequential use of two cycles of medium‑volume membrane plasmapheresis (25–30 % of the circulating plasma volume, No. 5 + 5) was carried out in combination with pulse therapy with methylprednisolone 1.0 (No. 4 + 3) and cyclophasphamide 1.0 (No. 2 + 1) on background of persistent ovarian teratoma. Symptom regression was achieved by the end of the first cycle, and full recovery to the initial level of cognitive functions occurred after the second cycle, while maintaining the anti‑NMDA antibody titer to 1:160. After removal of ovarian teratoma, the level of anti‑NMDA decreased in a month to 1:40, and after 7 months it reached normal values (<1:10) against the background of basic pill therapy with methotrexate 12.5 mg/week.Thus, a rational combination and sequence of first and second line therapy and therapeutic apheresis, taking into account the pathogenetic features of each phase of the disease, can quickly achieve complete stable remission in patient with anti‑NMDA encephalitis.
Project of the Russian National Atherosclerosis SocietyIn 2016, Guidelines on the medical care organization to the patients with hereditary atherogenic lipid disorders in the regions of Russia were published, which described and presented the principles of routing patients with hereditary dyslipidemia and the organization of medical care for them within the current regulatory documents. In December 2018, the Russian Ministry of Health approved clinical guidelines for the diagnosis and treatment of familial hypercholesterolemia. Thus, persons with a severe hereditary dyslipidemia were able to get free medication with expensive lipid-lowering drugs and receive apheresis. Following the European ones, the Russian guidelines on the management of lipid metabolism disorders were updated: lower target low density lipoprotein cholesterol levels were adopted. In the Russian population, there is a high prevalence of hypercholesterolemia, including familial monogenic and polygenic types. Therefore, timely detection and routing to a lipid center or an office to a specialist (cardiologist, lipidologist), adequate and modern prescription of lipid-lowering therapy will make an important contribution not only to secondary, but also to primary prevention of atherosclerotic cardiovascular complications.
Programmed immunoadsorption (IA) with regeneration of adsoption columns is a promising and safe technique to treat lupus nephritis (LN) in case of ineffective immunosuppressive therapy and its severe adverse reactions. This technique makes it possible to control disease activity, to maintain kidney function, and to ensure a normal quality of life. Due to the reusability of IA columns, it is possible to remove any required amount of IgG and to reduce the cost of an extracorporeal procedure.The paper describes a clinical case of 3-year prolonged IA in a female patient with systemic lupus erythematosus (SLE) and LN with the insufficient efficacy of drug therapy and related complications. Seventy IA sessions were performed during a follow-up period. Combined treatment with glucocorticoids, cytotoxic drugs, and IA resulted in improved clinical and laboratory parameters, lower SLE activity according to SELENA-SLEDAI scores, and better quality of life according to the SF-36 scale. No adverse reactions were recorded during IA sessions.
Disclaimer РThe EAC/RNAS Guidelines represent the views of the EAC and RNAS, and were produced after careful consideration of the scientific and medical knowledge, and the evidence available at the time of their publication. The EAC and RNAS is not responsible in the event of any contradiction, discrepancy, and/or ambiguity between the EAC/RNAS Guidelines and any other official recommendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies. Health professionals are encouraged to take the EAC/RNAS Guidelines fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic, or therapeutic medical strategies; however, the EAC/RNAS Guidelines do not override, in any way whatsoever, the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient’s health condition and in consultation with that patient and, where appropriate and/or necessary, the patient’s caregiver. Nor do the EAC/RNAS Guidelines exempt health professionals from taking into full and careful consideration the relevant official updated recommendations or guidelines issued by the competent public health authorities, in order to manage each patient’s case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations. It is also the health professional’s responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription.Members of the Working Group confirmed the lack of financial support / conflict of interest. In the event of a conflict of interest being reported, the member (s) of the Working Group was (were) excluded from the discussion of sections related to the area of conflict of interest.
Background and Aims: The aim of the present analysis of RENAISSANCE registry (Registry of patients with familial hypercholesterolemia (FH) and very high cardiovascular risk with lack of efficiency of lipid-lowering therapy) is the assessment of adherence and efficiency of the lipid-lowering therapy of patients with FH.
Цель. Целью исследования явилась оценка эффективности и приверженности гиполипидемической терапии, частоты развития сердечно<со< судистых осложнений в течение 3<летнего периода наблюдения в рамках регистра РЕНЕССАНС (Регистр пациентов с СГХС и пациентов очень высокого сЕрдечно<Сосудистого риска с недоСтАточной эффективНоСтью проводимой гиполипидемической терапии). Материал и методы. РЕНЕССАНС является открытым национальным наблюдательным исследованием и включает больных с семейной ги< перхолестеринемией (СГХС), а также пациентов очень высокого сердечно<сосудистого риска (ОВССР). Учитывали наличие факторов риска атеросклероза, анамнез сердечно<сосудистых заболеваний, гиполипидемическую терапию. В каждом центре выполняли определение концен< трации: общего холестерина (ОХС), триглицеридов (ТГ), холестерина липопротеидов высокой плотности (ХС ЛВП) в сыворотке крови. Содер< жание холестерина липопротеидов низкой плотности (ХС ЛНП) рассчитывали по формуле Фридвальда. Уровень липопротеида(а) измеряли методом иммуноферментного анализа в некоторых центрах. При оценке частоты конечной точки, включавшей фатальные и нефатальные сердечно<сосудистых осложнения (ССО), проводили анализ Каплана — Майера. Результаты. В регистр включено 1570 (средний возраст 54,0±14,6 лет) пациентов с СГХС и 121 (63,5±10,9 лет) больной с ОВССР. В группе СГХС динамическое наблюдение проведено у 594 пациентов (38%) в течение 23,6±14,6 месяцев, конечная точка зарегистрирована у 9% больных. Мужской пол (относительный риск 2,1; 95% доверительный интервал 1,13–3,66; p<0,01), гипертония (2,8; 1,4–5,2; p<0,01), ишеми< ческая болезнь сердца (6,8; 3,5–13,2; p<0,0001), отягощенный анамнез по сердечно<сосудистым заболеваниям (ССЗ) (2,1; 1,1–3,9; p<0,05) и концентрация липопротеида(а) ≥ 30 мг/дл (2,8; 1,1–7,7; p<0,05) явились предикторами развития ССО. В группе СГХС отмечено снижение уровня ОХС от исходного на 19%, ХС ЛНП на 25% (р<0,001 для обоих), целевых значений ХС ЛНП достигли 2% больных. В группе ОВССР динамическое наблюдение проведено у 72 (60%) пациентов в течение 19,7±5,8 месяцев. Ни один больной не достиг целевого уровня ХС ЛНП менее 1,4 ммоль/л. Заключение. Трехлетнее наблюдение за участниками регистра РЕНЕССАНС демонстрирует усиление приверженности гиполипидемической терапии. С увеличением риска развития сердечно<сосудистых осложнений при СГХС ассоциированы мужской пол, наличие гипертонии, ише< мической болезни сердца, отягощенного анамнеза по ССЗ и высокий уровень липопротеида(а). The aim of the study was to evaluate the effectiveness and adherence to hypolipidemic therapy, the frequency of cardiovascular events (CVE) during the 3!year follow!up in the RENAISSANCE registry (Registry of patients with familial hypercholesterolemia and very high cardiovascular risk with insufficient effect of hypolipidemic therapy). Methods. The RENAISSANCE registry is an open, national, observational study and includes patients with familial hypercholesterolemia (FH), as well as patients of very high cardiovascular risk (VHR). We took into consideration atherosclerosis risk factors and history of cardiovascular diseases (CVD), adherence to hypolipidemic therapy. Concentrations of total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL!C) were measured in blood serum in all centers. Low density lipoprotein cholesterol (LDL!C) level was defined according to Friedewald formula. The concentration of lipoprotein(a) was measured by enzyme!linked immunosorbent assay in serum in some centers. Kaplan!Mayer analysis was performed to assess the frequency of fatal and nonfatal CVE. Results. The Registry consisted of 1570 (mean age 54.0±14.6 years) FH patients and 121 (63.5±10.9 years) VHR patients. Data of 594 patients (38%) who had follow!up visits were obtained in FH patients, follow!up duration 23.6±14.6 months, 54 (9%) patients experienced CVE. Male sex (hazard ratio 2.1; 95% confidence interval 1.13!3.66, p<0.01), hypertension (2.8;1.4–5.2; p<0.01), ischemic heart disease (6.8;3.5!13.2; p<0.0001), family history of CVD (2.1;1.1–3.9, p<0.05) and lipoprotein(a) level ≥30 mg/dl (2.8;1.1–7.7; p<0.05) were predictors of CVE. In FH patients the level of TC decreased by 19%, LDL!C by 25% (p<0.001 for both). Data on 72 VHR patients (60%) were obtained with follow!up duration of 19.7±5.8 months. No patient achieved the target LDL!C level of less than 1.4 mmol/L. Conclusion. Three!year follow!up of participants in the RENAISSANCE registry shows an enhanced adherence to hypolipidemic therapy. In FH patients the increased risk of new CVE is associated with male sex, hypertension, CHD, family history of CVD and lipoprotein(a) level ≥30 mg/dl
In the process of developing the recommendations, the publications of the official websites of the Russian Federation, the electronic databases of the RSCI, PubMed, MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) were analyzed by the developers independently of each other. The date of the last search query was November 1, 2021. To develop the recommendations for the Guidelines, documents were used that directly describe the features of the management of patients with a new coronavirus infection COVID-19 (recommendations and guidelines - 35; randomized clinical trials and Cochrane Reviews - 23; observational and comparative studies - 134; other documents, notes and comments - 72). Compared to the previous, 5th, version of the recommendations, 35 provisions have been corrected in 10 sections. The provisions of the current version of the recommendations highlight the specifics of anesthesia, intensive care, rehabilitation, resuscitation measures, manipulation, transportation, prevention of the spread of COVID-19 in the implementation of these activities. Methods of protecting personnel from infection with COVID-19 during manipulations, anesthesia and intensive care are considered. The features of respiratory support, extracorporeal detoxification, extracorporeal membrane oxygenation, thromboprophylaxis, drug interactions are described. The features of the management of pregnant women, children, patients with concomitant diseases, the principles of the formation of stocks of drugs and consumables are considered. For management of COVID-19 patients, the following were specified and supplemented: 1) indications and contraindications for the administration of drugs (acetaminophen, glucocorticosteroids, remdesevir, tocilizumab, baricitinab, statins, convalescent plasma), depending on the severity of the disease; 2) features of intensive care for concomitant diseases (cardiovascular system, inflammatory bowel disease, cancer, arrhythmia); 3) the timing of elective surgery in patients who survive COVID-19, and post vaccination; 4) thromboprophylaxis and management of coagulation disorders; 5) regulatory and legal documents concerning the activities of healthcare workers facing COVID-19.
Aim. Russian multicenter register of familial hypercholesterolemia (FH) was transformed into Register of patients with FH and very high cardiovascular risk with insufficient effect of hypolipidemic therapy (RENESSANS Registry) in 2017 The aim of RENESSANS was maximal inclusion of patients not only with FH, but also those with atherosclerotic cardiovascular diseases (CVD), who did not achieve targeted level of low density lipoprotein cholesterol (LDL-C) using hypolipidemic drug therapy.Material and methods. The RENESSANS Registry is an open, national, observing study that includes patients with definite and probable (according to Dutch lipid clinic network and Simon Broome Registry criteria) heterozygous and homozygous FH, as well as patients of very high cardiovascular risk. There were designed two register forms: for patients with FH and for very high cardiovascular risk patients. Doctors filled out forms in paper and electronic variants. They took into consideration the risk factors of atherosclerosis and anamnesis of CVD, adherence to diet and hypolipidemic therapy. Concentrations of total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C) were measured in blood serum in all centers. LDL-C level was defined according to Friedewald formula: LDL-C=TC-HDL-C-TG/2,2 (mmol/l).Results. The Registry consisted of 1208 FH patients and 497 patients with very high risk (average age 54±13 and 61±8, respectively, 37% men). Baseline levels of lipids were 9,4±2,3 and 6,9±1,5 mmol/l for TC, 6,6±2,1 and 4,5±1,3 mmol/l for LDL-C, respectively. The frequency of hypolipidemic therapy in both groups is 70%, while targeted level of LDL-C was achieved extremely rarely.Conclusion. The results show insufficient adherence and low effectiveness of standard hypolipidemic therapy both in patients with FH and very high cardiovascular risk. PCSK9 inhibitors are recommended for resistant hypercholesterolemia treatment. The RENESSANS Registry allows to improve FH diagnostics, to assess treatment effectiveness and choose patients who need treatment with PCSK9 inhibitors.
The article describes ethical, social, psychological and medical problems in the families raising children with rare diseases. It is quite difficult to diagnose a rare disease. It leads to financial deprivation of the family, social isolation and marginalization. Patient organizations play a large role in public awareness of rare diseases. It is of crucial importance to make treatment accessible, to provide qualified medical care, social support of families, to improve cooperation between research centers, medical institutions and patients.
These guidelines represent all current aspects of etiology, diagnosis, and treatment of the clinical and statistical group of familial hypercholesterolemia in both adults and children in accordance with the requirements of the Ministry of Health of Russia.
The Guidelines are designed to demonstrate possible approaches to routing patients with hereditary atherogenic lipid disorders in accordance with existing legal documents. The Guidelines define the stages of medical care of this group of patients. For each stage the possible types of medical care, conditions of its provision and hospitals, on the basis of which it can be provided, as well as ways of payment are established. Criteria for the detailed examination of patients with suspected hereditary atherogenic lipid metabolism are shown. Recommendations reassigned for health care managers, chief-hospital physicians, cardiologists, internists and other physicians.
Objective and methods: Endothelial dysfunction and inflammatory reaction at the site of damage plays a key role in the formation of neointimal hyperplasia, and in the progression of atherosclerosis. The initiating role in these processes is assigned to adhesion molecules. We studied the dynamics of the level of adhesion molecules soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), soluble form of the molecule platelet adhesion and endothelial type-1 (sPECAM-1), sL-, sP-, sE-selectins during double filtration plasmapheresis (DFPP) with use of plasma fractionators (PF) Cascadeflo EC-50W and EC-40W (Asahi Kasei Medical Co., Japan) in patients with stable coronary heart disease and hyperlipidemia-(a) in the early post-implantation period after coronary stenting. Results: DFPP reduces the level of plasma adhesion molecules. When using PF Cascadeflo EC-40W, a more pronounced decrease occurs. The rejection coefficient (RC) of adhesion molecules has been identified for these PF. These RCs reflect the immediate removal efficiency of adhesion molecules in the perfusion of plasma through PF. The removal effectiveness of adhesion molecules when using PF Cascadeflo EC-40W is higher than when using the PF Cascadeflo EC-50W (sICAM-1 - 2.5 times, sVCAM-1 - 2.2 times, sPECAM-1.6 times, sL-selectin - 5 times, sP-selectin - 2.8 times, sE - selectin - 3 times). Conclusion: Reducing adhesion molecule levels when using DFPP may play an important role in correcting of endothelial dysfunction in response to damage to the arterial wall in percutaneous coronary intervention (PCI) during the early post-implantation period after coronary stenting. DFPP is a promising approach to prevent in-stent restenosis (ISR). (C) 2017 Elsevier B.V. All rights reserved.
Family hypercholesterolemia is a monogenic autosomal dominant disease accompanied by significant increase of blood cholesterol, and as a result, premature development and progressive course of atherosclerosis, usually at young age.Even in case of the absence of diseases caused by atherosclerosis the patients with family hypercholesterolmia belong to the high-risk group and to a group of a very high risk of cardiovascular complications development if relevant.Aim.These practical recommendations are developed for physicians and represent the definition, diagnostic criteria and modern approaches to the treatment of family hypercholesteremia.Material and methods.The recommendations contain the stages of providing medical care to this group of patients, depending on the age and sex.Results and discussion.Possible types of medical care were indicated for each stage.An algorithm of identification, management and treatment of patients with family hypercholesterolemia were presented.Conclusion.The main principles of methodological recommendations presented for the organization of medical care for patients with family hypercholesterolemia in the subjects of the Russian Federation are intended for general practitioners, pediatricians and cardiologists, as well as for physicians of other specialties.
The paper considers the topical problems arising in children with the most severe form of type I galactosemia. It describes the specific features of neonatal screening for galactosemia. Diagnostic criteria for the classic, clinical, and biochemical variants of galactosemia are presented. The basic characteristics of the clinical picture and late sequels of the disease are identified. Particular emphasis is placed on management tactics for ill children via dietary correction, complication treatments, preventive measures, and a follow-up.
One of the main causes of mortality of human immunodeficiency virus (HIV)-infected patients are complications of chronic hepatitis C virus (HCV). Combining drug therapy for HCV with double filtration plasmapheresis (DFPP) has significantly increased the effectiveness of treatment for these patients. However, there are no data on the use of this method for the treatment of patients co-infected with HIV and HCV. We demonstrated that positive clinical effect in the treatment of HCV patients by DFPP (previously demonstrated) is also achieved in the treatment of HIV infected patients, co-infected with HCV. The obtained efficiency of 62.5% is almost two times higher than the predicted treatment efficiency. We can conclude that the complex therapy of hepatitis C, including DFPP and medication by PEG-IFN + RBV is an effective and safe approach for the treatment of HCV in patients co-infected with HCV and HIV.
On 15 February 2013 (2 February on the Julian Calendar) we celebrated the 100-year anniversary of the world's first successful experimental plasmapheresis. Scientific research projects in this field were carried out by the Department of Infectious Disease, Russian Imperial Medical Surgical Academy located in Saint-Petersburg. Doctor of Medical Sciences and Professor Vadim A. Yurevich was a Principal Investigator for this research, which in 1913 resulted in the discovery of a new way of treatment. The results were published in Russki Vratch (Russian Physician) Journal no. 18 (1914) - V.A. Yurevich and N.K. Rosenberg For the Question Regarding Washing of Blood Outside of the Body and the Vitality of Red Blood Cells. There was no terminology offered for this medical innovation at that time. Plasma removal was performed not solely, but in combination with washing of blood cells returned to the patient. Nowadays this combination is still considered to be more effective than separate plasmapheresis. According to the published experimental protocols this new treatment was done on 15 February (2 February on the Julian Calendar or old style). One year later in 1914 a famous researcher, John Abel and coauthors, repeated a separate plasma removal treatment with retransfusion of the blood cells and suggested the term plasmapheresis, which is now official. The article entitled Plasma Removal With Return of Corpuscles (Plasmapheresis), written by Abel was published 3 months later than the article by Professor Yurevich. In 1924, Dr Ivan P. Mikhailovskiy repeated experiments by Yurevich and Rosenberg in vivo on a dog model, confirmed the clinical efficiency and developed the methodology in his article Washing of Blood In Vivo, the Methodology, Problems, and Importance for the Treatment of Toxic Conditions.