Aim. To perform comparative analysis of the diagnostic efficacy of sCD40L, PDGF-BB, VEGF-A and ST2 in recipients with cardiac rejection in different periods after transplantation. Materials and methods. The study included 144 cardiac recipients aged from 12 to 71 (mean age 44 ± 14) years old, among those 112 were men. Venous blood plasma taken on the same day with endomyocardial biopsy was used for the study. The concentrations of soluble CD40 ligand (sCD40L), vascular endothelial growth factor (VEGF-A), platelet-derived growth factor (PDGF-BB) were measured using xMAP technology. The concentrations of ST2 were measured by ELISA. Results. Men had significantly higher levels of ST2 and VEGF-A compared to women (p = 0.03). No correlation was found between the levels of biomarkers (sCD40L, PDGF-BB, VEGF-A, ST2) and age, diagnosis before transplantation, presence of arterial hypertension and diabetes mellitus. Comparative analysis of the biomarkers’ levels didn’t show significant difference between patients with heart transplant rejection and without it in the first month and in the first year after transplantation. The ST2 level was significantly higher in patients with heart rejection (p = 0.01) in the long term period (1–5 years) after transplantation compared to patients without rejection. Relative risk of cardiac transplant rejection was significantly higher in patients with high (>22.8 ng/ml) ST2 level (RR = 2.59 ± 0.33; Se – 35%, Sp – 93%). However, its combination with other biomarkers improved their diagnostic value. Relative risk for panel including ST2, VEGF-A and PDGF-BB 3.47 ± 0.55, Se – 57%, Sp – 91%; relative risk for panel including ST2, sCD40L and PDGF-BB was 3.75 ± 0.59, Se – 50%, Sp – 92%. The highest diagnostic efficacy for the heart transplant rejection was reached by a panel of biomarkers that included ST2 and PDGF-BB (RR = 5.0 ± 0.56 [95% CI 1.68–14.92], Se – 63%, Sp – 94%). Conclusion. ST2 had the biggest diagnostic value for heart transplant rejection in the long term period after heart transplantation. Its usage as a part of complex tests with other biomarkers improves the sensitivity of noninvasive diagnosis of the cardiac rejection. The highest diagnostic significance for cardiac transplant rejection in the long term period was shown by a panel of ST2 and PDGF-BB.

Aim. Single-center analysis of everolimus treatment after liver transplantation. Materials and methods. 23 patients having received Certican after OLT in RSCRST were observed in period from 6 months to 5 years; comparison group consisted of 50 patients who received immunosuppressive scheme with tacrolimus. Conversion to everolimus was performed in the period from 1 month after OLT after discharge and at later time according to the indications: hepatocellular cancer, cumulative CNI nephrotoxicity, the development of malignancies, and intolerance to CNI. The concentrations of CNI and everolimus in the blood (target concentration of tacrolimus 1.5–2 ng/ml, everolimus 3–8 ng/ml) were monitored. Glomerular filtration rate (GFR) was determined using the CKD-EPI equation. Adverse events of everolimus were evaluated. Results. The immunosuppressive scheme with everolimus is presented; adverse events with dose-dependent hypercholesterolemia (34.7%) as the main; the average level of blood cholesterol was not significantly different from that in the control group, 5.6 ± 0.9 vs 5.1 ± 1.4 mmol/l (Z = 1.3, p = 0.17). Renal function was stable throughout the observation period (35 ± 16 months). GFR (CKD-EPI) before conversion was 75.8 ± 17.5 ml/min. 6 patients treated with Certican for 5 years had final GFR 96.6 ± 5.1 ml/min. GFR in the group of Certican at 12 months post conversion was 87.5 ± 16.3 ml/min vs 94.2 ± 16.8 ml/min (p = 0.08) in the control group. We revealed metastases to the liver and lungs in 5 patients from 13 patients with HCC, survival rate in this group depended on the compliance with the Milan criteria (Z = 2.4, p = 0.02). Conclusion. Everolimus allows maintaining of a stable renal function to prevent progression of renal failure; conversion should be initiated as early as possible. Combination of everolimus with reduced dose of CNI is optimal. Despite the fact that side effects are developing in most patients, adequate monitoring of immunosuppressive drug concentration and timely dose adjustments are able to reduce their severity, discontinuation of Certican is not required.

Wilson’s disease is a rare congenital disease caused by deficiency of the copper-transporting P-type ATPase-B enzyme. The course of disease varies widely from the latent form to the acute liver failure which is observed in 5% of Wilson’s disease cases. This clinical case represents experience of liver transplantation as the only curative treatment for patients with fulminant form of Wilson’s disease demonstrating excellent postoperative results. Living donor liver transplantation allows performing the operation in the shortest possible time which is necessary in acute liver failure. The plasmapheresis with plasma exchange AB (IV) allows preparing the patient for transplantation with incompatible blood group.

Orthotopic liver transplantation is the only way to cure chronic liver failure and certain liver tumors. Deceased donor organs are the prevailing source in most transplantation centers. However, there is an organ shortage because of the increasing number of patients in need of transplantation. Using expanded criteria deceased donors is a routine way to overcome organ shortage. The majority of transplantation centers take older donors depending on the local rules. Successful liver transplantation from 73-year-old deceased donor. Recipient suffered from liver neuroendocrine tumor without signs of extrahepatic spread. Liver function is adequate during 90-day follow-up. Liver transplantation from older deceased donors has good outcome according to world experience. Careful donor-recipient selection is the key to success. The first positive trial in our center enlightens the way for further practice.

The article is dedicated to the problem of pregnancy management and delivery after simultaneous liver-kidney transplantation (SLKT). The article contains general historic and statistic information, and presents the first real world clinical case of favorable pregnancy outcome in patient after simultaneous liver-kidney transplantation with reno-portal transposition.

Aim. To optimize implantable axial pump to increase hydraulic efficiency and reduce blood hemolysis. Materials and methods. In this article the basic geometric parameters of impeller’s geometry (the blade’s angle, the blade’s length and the twist angle’s ratio) were investigated and optimized using methods of computer hydrodynamics. The calculations were carried out for the optimum operation of the pump at the speed of 8000 rpm. Results. The main parameters of impeller’s geometric were determined which made it possible to increase efficiency of the pump by an average of 7.5% (depending on the pump operation mode) and pressure drop of 8% on average. The value of shear stress in the flow region obtained as a result of the calculations did not exceed 147 Pa admissible from the point of view of blood hemolysis.

The aim of the study was to perform a series of in vitro tests of a prototype of the developing heart valve prosthesis to evaluate its functional characteristics. Materials and methods. In this work we have used the frames and full prototypes of the prosthesis, consisting of a stent-like stainless steel support frame with mounted biological leaflets and cover. The authors evaluated the calculated and experimental forces necessary for the displacement of the sutureless implanted prosthesis using the test machine under uniaxial tension. The risk of defects and damages to the supporting framework as a result of implantation was evaluated by scanning electron microscopy. The hydrodynamic characteristics of the prosthesis were investigated under physiological conditions and «valvein-valve» implantation. Evaluation of the ergonomics and applicability of the proposed construction on the cadaver heart model of cattle was carried out. Results. As a result of the forces assessment, it was found that the force required to shear the prosthesis was 3.12 ± 0.37 N, while the calculated value was 1.7 N, which is significantly lower than the obtained value. The comparison of the images obtained with small and large magnifications demonstrated the absence of critical surface defects. Additional analysis under the super-large magnifications also did not reveal problem areas. During the hydrodynamic study, it was shown that the average transplant gradient increased slightly from 2.8–3.4 to 3.2–4.5 mm Hg for the initial prosthesis and the «valve-in-valve» complex, respectively. The decrease of the effective orifice area was 6–9% relative to the initial one. Evaluation of the implantation technique demonstrated the consistency of the approach: the use of the developed holder in combination with the balloon implantation system made it possible to position the prosthesis throughout the procedure. Conclusion. The series of tests demonstrates the consistency of the developed design, intended for the replacement of a failed prosthetic valve of the heart with the «valve-in-valve» implantation.

Aim. A comparative analysis of the functional efficacy of biomedical cell products (BMCP) for the regeneration of damaged liver based on biopolymer scaffolded porous and hydrogel matrices was performed on the experimental model of acute liver failure. Materials and methods. Matrices allowed for clinical use were employed for BMCP in the form of a sponge made from biopolymer nanostructured composite material (BNCM) based on a highly purified bacterial copolymers of poly (β-hydroxybutyrate-co-β-oxyvalerate) and polyethylene glycol and a hydrogel matrix from biopolymer microheterogeneous collagen-containing hydrogel (BMCH). Cellular component of BMCP was represented by liver cells and multipotent mesenchymal bone marrow stem cells. The functional efficacy of BMCP for the regeneration of damaged liver was evaluated on the experimental model of acute liver failure in Wistar rats (n = 40) via biochemical, morphological, and immunohistochemical methods. Results. When BMCP was implanted to regenerate the damaged liver on the basis of the scaffolded BNCM or hydrogel BMCH matrices, the lethality in rats with acute liver failure was absent; while in control it was 66.6%. Restoration of the activity of cytolytic enzyme levels and protein-synthetic liver function began on day 9 after modeling acute liver failure, in contrast to the control group, where recovery occurred only by days 18–21. Both matrices maintained the viability and functional activity of liver cells up to 90 days with the formation of blood vessels in BMCP. The obtained data confirm that scaffolded BNCM matrix and hydrogel BMCH matrix retain for a long time (up to 90 days) the vital activity of the adherent cells in the BMCP composition, which allows using them to correct acute liver failure. At the same time, hydrogel matrix due to the presence of bioactive components contributes to the creation of the best conditions for adhesion and cell activity which accelerate the regeneration processes in the damaged liver compared to BMCP on scaffolded matrix. Conclusion. A statistically significant difference was found between the functional efficacy of the BMCP studied based on BNCM and BMCH matrices. BMCP based on hydrogel BMCH matrix was more effective for the regeneration of damaged liver.

Introduction. Extracellular matrix play an essential role in providing structural integrity and physiological support to Langerhans islets in pancreas. Imitation of the native microenvironment can be useful for viability of isolated pancreatic islets in vitro and in vivo. Aim. The purpose of this study was to characterize and compare the effect of biopolymer microstructured collagen-containing hydrogel (BMCH) on isolated rat islets survival. Materials and methods. Islets were isolated by classic collagenase techniques with some modifications. There were used hystological, immunofluorescence and immunohystochemistry methods. Results. Rat islets cultured with collagen-based gel don’t revealed destructive changes of structure and remained viabile 7 days incubation. Conclusion. Positive effect of BMCH to rat islet survival was revealed.

The main aim of our investigation was analysis and optimization of the existing protocols of esophagus decellularization in rats, identification of parameters affecting the quality of decellularization and intactness of the native properties of esophageal extracellular matrix (ECM). Materials and methods. We developed a modified decellularization protocol based on detergent-enzymatic method using sodium deoxycholate and DNAse. Results. Morphological evaluation of the obtained decellularized matrices demonstrated the absence of cells and cell elements while mechanical properties of ECM were preserved. Conclusion. The developed protocol of esophagus decellularization is a potential basis for obtaining of tissue-engineered esophagus scaffold constructions.

Aim. To carry out monitoring of the organization and tendencies in the development of organ donation and transplantation in the Russian Federation in 2016. Materials and methods. Questioning of the heads of all the centers of transplantation is carried out. The comparative analysis of the obtained data in dynamics of the years, between certain regions of the Russian Federation and transplantation centers is done. Results. According to the register 35 centers of kidney transplantation, 22 centers of liver transplantation and 11 centers of heart transplantation were functioning in the Russian Federation in 2016. The waiting list of kidney transplantation in 2016 included 4818 potential recipients that make 14% of total number of the patients (35 000) receiving dialysis. The rate of donor activity in 2016 made 3.3 p. m. p. Efficiency of donor programs in 2016 continued to increase: the share of multiorgan retrieval made 64.1%, average number of organs received from one effective donor made 2.7. In 2016 the rate of kidney transplantation made 7.4 p. m. p., the rate of liver transplantation made 2.6 p. m. p.; the rate of heart transplantation made 1.5 p. m. p. In 2016 the number of transplantations in the Russian Federation increased by 14.8% in comparison with 2015 having overcome the level of 1700 organs transplantation. The Moscow region still remains to be the core of stability and development of the organ donation and transplantation in the country where 10 centers of transplantation function and half of all kidney transplantations and more than 70% of all liver and heart transplantations are carried out. Conclusion. The results of 2016 were positively affected by the introduction of targeted financial support of medical activity, related to organ donation, from federal budget resources. Among unresolved problems which constrain the development there are collision of legal regulation of licensing of medical activities for organ donation and transplantation, lack of the state order for the organization of transplantological medical care in each region, lack of responsibility of the heads of the regions and medical organizations for the organization of organ donation. Positive tendencies of the development of organ donation and transplantation in Russia call for further monitoring, strengthening and building.

Analysis of intracardiac space-occupying lesions, surgically removed at V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs over 25 years (in the period from 1992 until 2016) was carried out. During that period 134 patients underwent surgery. Preoperative clinical diagnosis before surgery was heart myxoma. From 134 patients, only in 115 (85.8%) patients the removed intracardiac lesions were myxomas: left atrium – 103 (89.7%) patients, right atrium – 10 (8.7%), right ventricle – 2 (1.8%) and mitral valve – 1 (0.8%) patient. 9 patients had thrombi in the heart, 10 patients had not myxomas, but other benign and malignant heart tumors. This article presents macroscopic, histolological and ultrastructural characteristic of cardiac myxomas. Recurrence of the left atrium myxoma occurred in 2 patients. They were re-operated in four and six years after the first removal of myxoma. 2 patients died during hospital period. One patient with atherosclerosis of the coronary arteries as a concurrent disease died of embolization of the stent coronary artery with myxoma particles with the development of acute heart failure. Death of the 2nd patient was not directly related to the surgery, and was due to the acute heart failure as well in connection with the presence of concurrent disease, coronary heart disease.

Hypertension is a common syndrome in adult and pediatric cardiac transplant recipients affecting the great majority of patients. Elevated blood pressure is a major potentially modifiable risk factor associated with cardiac graft failure, vasculopathy, arrhythmias, stroke, renal failure and premature death. This review discusses the magnitude of the problem, its distinct mechanisms, and certain issues of prevention and treatment of post-transplant hypertension.

This review summarizes the current literature dedicated to the analysis of prognostic role of microRNAs in rejection of the transplanted heart. MicroRNAs are a class of small non-coding RNAs that regulate gene expression and affect various cellular functions. Variations of their profiles are noted at various pathological processes and rejection of solid organs. Presumably, measuring the level of microRNAs in heart transplant may have diagnostic and prognostic value in the assessment of risk of rejection and possibility of minimizing immunosuppressive therapy. Currently, accumulated clinical data on the role of the given biomarkers in heart transplantation are not enough, and further research on the relation of microRNAs levels and different clinical and laboratory parameters in heart recipients is necessary.

Heart transplantation is the «gold standard» of severe heart failure treatment. Sudden arrhythmic death is the leading cause of death among these patients. Amiodarone is the only antiarrhythmic drug with beneficial effect on survival of patients with end-stage heart failure. Given its long half-life, pre-transplant use of amiodarone has been extensively discussed focusing on divergent results regarding morbidity and mortality after heart transplantation. Its adverse clinical events after transplantation remain debatable. This review is aimed at evaluation of the impact of amiodarone pretransplant use on mortality and complications after heart transplantation.

The problem of antibody-mediated rejection of donor organ remains extremely relevant. The main targets of the antibodies are mainly donor HLA-antigens (Human Leucocyte Antigens), expressed, in particular, by the cells of graft vascular endothelium. This review describes the mechanisms of the development of humoral alloimmunity which are based on B-cell recognition of epitopes of donor HLA-molecules and affinity maturation of B-cell receptors in the germinal centers of peripheral lymphatic system. Monitoring of epitope load and cross-reactivity indicators to evaluate HLA-compatibility of donor and recipient plays an important role in the prevention of allograft humoral rejection.