Lung transplantation is not a routine treatment option of the pediatric lung diseases. Nowadays, there are performed not more than 100 of these operations per year worldwide due to the obvious diffi culty of obtaining the pediatric donor organs. One of the ways to solve this problem is using the adult donor lungs which have been previously reduced or anatomically partitioned. This is not a standard method of pediatric lung transplantation, but in case of the donor organs defi ciency it takes its place in the world medical practice. In this case we report the fi rst successful pediatric lung transplantation from adult donor in Russian Federation.

Malignancy is one of the leading causes of death in recipients with a kidney grafts. The use of proliferative signal inhibitors (PSI) is one of the approaches to solve this problem.

Aim: to evaluate the effi cacy and safety of everolimus in combination with reduced dose of calcineurin inhibitors (CNI) in patients with posttransplant malignancy.

Materials and methods. 62 kidney graft recipients (KGR) with neoplasia were converted from mycophenolate mofetil to everolimus in combination with reduced dose of CNI at 83.5 ± 69.3 months after transplantation. The duration follow-up was 35.5 ± 26.9 month. The effectiveness of management was assessed by patient survival, type of immunosuppression therapy, renal function and proteinuria. The patient survival in PSI group was compared with the survival in the patients in control group (n = 145), who did not receive everolimus.

Results. 10-year and 15-year patient survival was 92% and 85,7% in patients treated with PSi versus 61.1% and 52.8% in control group (p < 0.0003). Patients survival with everolimus-therapy after 1 year was 86.5%, after 3 year it was 64.2%, and by the end of 5 years the possibility of treatment with everolimus decreased to 50.8%, mainly due to the proteinuria and other adverse events. The recurrence rate of tumors among patients, who was treated with everolimus for 35 (26; 60) months was 13.2%. Creatinine level in serum increased from 0.13 ± 0.04 to 0.15 ± 0.09 mmol during the treatment (p < 0.031), and the daily proteinuria increased from 0.18 ± 0.25 g/day to 0.75 ± 1.63 g/day, p < 0.011.

Conclusion. The usage of PSi improves long-term survival of KTR with posttransplant malignancy and demonstrates a relatively low tumors recurrence rate (13.2%) over a period of 35 months. However this treatment is not suitable for many patients and it was stopped in almost half of them due to increasing proteinuria or serious adverse events. 

Aim. To analyse the dynamics of the need and availability of donor kidneys for transplantation. To construct the predictions for the number of waiting lists. To analyse the annual number of kidney transplants and the availability ofdonor kidney.

Materials and methods. Data base of Eurotransplant International Foundation 1969–2015 has been analyzed. We built a forecast of the kidney waiting list, kidney transplants quantity and availability of kidney grafts up to 2030.

Results. Random process analysis of kidney transplant recipients number has shown an increasing linear trend. Growing linear trend is due to the inability to fully meet the increasing need for a kidney transplant. Presence of a regular stochastic component is revealed that provides random fl uctuations in the number of patients waiting for kidney transplantation with a period of 35–40 years. Random process of the number of kidney transplants showed an exponential asymptotic trend growing to a certain saturation value. Estimation of its autocorrelation function showed the absence of regular stochastic components in it. Preservation of 1969–2015 dynamics for the period 2015–2030 allows to suggest a signifi cant increase in the number of people waiting for transplant and a decrease in the availability of donor kidneys.

Conclusion. The number of donor kidney transplantations tends to saturation limit, and limit is already lower than the current need for donor kidneys. The increase in the number of kidney transplantation programs and the improvement of organ donation system may lead to a limited increase in annual number of transplants and, possibly, the saturation limit, but not to a qualitative change in the dynamics of reduced availability of donor kidneys. A qualitative change in this dynamics towards increasing accessibility, is possible perhaps through activities that affect factors causing a constant increase in the number of people who need a transplant.

Biliary atresia is a congenital disease characterized by a progressive course with the lesion of primarily extrahepatic bile ducts leading to the development of cholestasis. Treatment consists in performing an operative intervention such as, Kasai portoenterostomy, or liver transplantation. This clinical case shows the experience of left lobe living donor liver transplantation in child, who underwent complicated portoenterstomy in young years. In case of AB0-compatible donors is absence, the AB0-incompatible living donor can become useful opportunity for urgent recipient. Endovascular embolization of the branches of the splenic artery can become a «bridge» to AB0-incompatible liver transplantation.

The effi ciency of lung transplantation is considerably limited by the complications associated with the bronchial pathologies. Despite the progress of the treatment methods, bronchial complications are still remaining as an actual problem in the postoperative period with frequency of occurrence from 7 to 29%. However, the bronchial stenosis are the most common bronchial complications after lung transplantation with mortality from 2 to 4%.

Aim. To study an experience of our center of bronchial stenosis treatment in lung recipients. Materials and methods. 34 patients underwent lung transplantation from September 2014 to January 2017. 6 (16%) of them had a stenosis of lobar or segmental bronchi from 84 to 494 postoperative day. 5 (83%) of them have demonstrated multifocal lesions. In all of the cases there was performed an endoscopic bougienage, which involved a balloon dilatation and electrocoagulated incision of granular tissue under X-ray control. After that the patients were administrated by everolimus.

Results. Restenosis was formed in 132,0 ± 94,2 postoperative day after primary treatment in all patients. In four cases (67%) we used nitinol stent placement under X-ray control. There were no complications. In 3 cases stents were dislocated distally, so we needed to use repeated endoscopic bougienage to replace the stent. Using of everolimus has allowed to decrease the rate of restenosis, but it need future research.

Conclusion. Distal bronchial stenosis after lung transplantation can be managed with endoscopic bougienage and stent placement. Adding everolimus has not signifi cantly affected the risk of frequency of restenosis.

Aim: to conduct a one-center retrospective research of heart myxoma relapses in a large group of patients.

Materials and methods. Since 1992 to 2016 115 surgical removal of sporadic cardiac myxoma was performed (44 male, 71 female).

Results. Two (1.7%) patients had recurrence of sporadic myxoma of the left atrium. One patient had the tumor returned due to inadequate removal of the tumor. Myxoma was removed without excising the place of fi xation to the interatrial septum. The second patient possibly had recurrence of myxoma due to the conservation of a small tumor fragment in another part of the interatrial septum that was not diagnosed during the removal of the primary tumor.

Conclusion. Recurrence of sporadic myxoma of the left atrium is rare. The reasons for the recurrence may be different but usually it is due to non-radical removal of the tumor. The results of our research show that even removal of the myxoma together with the interatrial septum does not fully guarantee the prevention of recurrence. The recurrence of sporadic cardiac myxoma is possibly associated with minor formations that are not diagnosed during surgery. We cannot exclude the possibility of forming myxoma denovo also. 

Introduction Peripheral veno-arterial extracorporeal membrane oxygenation (VA ECMO) is one of the most frequently used methods of temporary mechanical circulatory support (MCS) at patients with life-threatening circulatory derangement.

Aim: to evaluate the effectiveness and risk factors of peripheral VA ECMO in patients waiting of urgent heart transplantation (HT).

Materials and methods. The study included 149 (129 (86.6%) men and 20 (13.4%) women, age 12 to 72 (43.0 ± 1.2) years) heart transplant candidates who in the period 01.01.2011–31.12.2016 were supported by peripheral VA ECMO. These patients were 21.1% of the total waiting list (n = 706) of our institute at the same period. Indication for MCS by VA ECMO was advanced heart failure corresponding to I or II level of INTERMACS classifi cation.

Results. 135 (90.6%) from 149 patients were successfully supported to HT. 14 (9.4%) deed following MCS. Before of VA ECMO these patients (n = 14) had more severe (p < 0.05) hemodynamic disorders, organ dysfunction, electrolyte and metabolic disorders compared to patients TC successfully supported to HT. Left atrium (n = 24)/left ventricle drainage (n = 8) was performed for volume decompression of left heart (n = 32 (21.5%)). In a single-factor analysis, statistically signifi cant pre VA ECMO risk factors for the lethal outcome were: creatinine ≥ 140 mmol/l, urea ≥ 15 mmol/l, total bilirubin ≥ 80 μmol/l, ALT ≥ 300 U/l, AST ≥ 300 U/l, INR ≥ 3.0, procalcitonin ≥ 3.0 ng/ml, preexisting left ventricular thrombosis complicated thromboembolic stroke with brain death following VA ECMO (n = 3). Statistically signifi cant factors for the lethal outcome following MCS were: transthoracic left ventricle drainage (n = 8) compared to transcutaneous transfemoral transseptal left atrium drainage (n = 24) for volume decompression of left heart; hemolysis ≥ 300 mg%.

Conclusion. VA ECMO is high effi ciency method of temporary MCS in 90.6% heart transplant candidates needed at urgent HT. VA ECMO must be begin before development of potential lethal multiorgan and septic complications. Preexisting left ventricular thrombosis increase risk of lethal thromboembolic brain injury following VA ECMO. Patients with transcutaneous transfemoral transseptal left atrium drainage for left heart volume decompression had better outcome following MCS by VA ECMO. 

Aim: to evaluate the manipulative properties of the system being developed for cardiac valve re-operation on an in vitro bovine heart model.

Material and methods. The prototype of the prosthesis being developed, mounted on the implant holder, as well as the dilatation balloon of its own design, were used as the objects of the study. The bioprosthesis «UniLine» of 21 mm size for the aortic position was chosen as the target site of implantation, which was established by the «classical» suture method. After that, the implantation of the tested device was carried out as a «valve in valve» and the quality of the installation and the combined operation of all the components of the re-prosthesis system were evaluated.

Results. The test implantation demonstrated the consistency of the proposed method on the basis of balloon seamless fi xation, as well as high ergonomic characteristics: the average time of seamless implantation of the developed prototype on an in vitro animal heart model was 3 minutes versus the implantation of the «UniLine» bioprosthesis – 11 min, Implantation provided a reliable prosthesis The breaking force was 12.9 N, which is equivalent to a pressure of 279 mm Hg. 

One of the problems when you create a bioengineered liver, as an alternative to transplantation of the donor liver in the treatment of end-stage liver failure, is the matrix, able to temporarily perform the functions of the natural extracellular matrix (ECM) and provide the necessary conditions to maintain the viability of the liver cells. The main disadvantage of resorbable biopolymer matrices is the absence of tissue specifi c properties and the impossibility of reproducing the unique structure of the ECM of the liver.

Aim: to develop technology for decellularization of liver tissue fragments, saving the structural properties of native ECM of the liver.

Materials and methods. The decellularization of mechanically grinded human liver fragments was carried out in three changes of buffer solution (pH = 7.4) containing 0.1% sodium dodecyl sulfate and increasing the concentration of Triton X100 (1%, 2% and 3%, respectively). During technology development were investigated the effects of duration, conditions (static, dynamic, rotary system, magnetic stirrer) washing and methods of liver tissue grinding on the completeness of removal of cellular elements and detritus preserving the the liver ECM structure. Slices of decellularized liver tissue samples were stained by hematoxylin and eosin, and Masson method for the detection of connective-tissue elements.

Results. Histological analysis methods showed that the best from the point of view of effi ciency of decellularization and the safety of the structure of own human liver ECM, is a mode of washing of liver fragments for three days at room temperature in static conditions, accompanied by stirring by a magnetic stirrer for 2–3 times a day for one hour. Longer time or a large multiplicity of mixing mode is accompanied by increased risk of liver tissue damage. On the basis of the experimental results obtained the algorithm of preliminary study of donor human liver designed to optimize the process of obtaining decellularization fragments of liver tissue was elaborated.

Conclusion. It was elaborated the algorithm and technology of obtaining of decellularized liver tissue fragments from the human donor liver which saved the structural properties of native ECM of the liver and complete removal of cellular elements and detritus. 

Aim: to perform a three-dimensional analysis of micro- and nanosctucture and quantitative morphological parameters of alginate spherical microcarriers and porous regenerated silk macrocarriers modifi ed by microparticles of decellularized rat liver matrix and human hepatoma HepG2 cells adhered to micro- and macro carriers.

Materials and methods. Three-dimensional porous matrices made from regenerated silk by salt leaching technique and alginate spherical microcarriers fabricated by encapsulation were vitalized by human hepatome HepG2 cells. Study of three-dimensional structure of cells and micro- and macro carriers was carried out at –120 °С by scanning probe cryonanotomography technique with use of experimental setup combining cryoultramicrotome and scanning probe microscope.

Results. Three-dimensional nanotomographical reconstructions of HepG2 cells adhered to macropore wall of regenerated silk macrocarrier and to spherical alginate microcarrier are obtained. Morphological parameters (mean roughness, effective surface area and autocorrelation length) are determined for surfaces of macro and microcarriers and adhered cells. The determined mean roughness of alginate microcarrier surface is 76.4 ± 7.5 nm, while that of surface of macropore wall of regenerated silk macrocarrier is 133.8 ± 16.2 nm. At the same time mean roughness of cells adhered to micro- and macrocarriers are 118.5 ± 9.0 и 158.8 ± 21.6 nm correspondingly. Three-dimensional reconstructions of intracellular compartments with dimensions from 140 to 500 nm are also obtained.

Conclusion. Obtained as a result of study quantitative morphology characteristics of surfaces of cell carriers and adhered cells show signifi cant degree of correlation of morphological parameters of cells and their carriers. Use of scanning probe cryonanotomography technique for three-dimensional analysis of structure and characteristics of biomaterials, cells and bio-artifi cial cellular systems enables to improve effi ciency of development of novel cell-engineered constructions with predicted morphological, physical, chemical and biological characteristics for tasks of tissue engineering and regenerative medicine. 

Aim: to perform a comparative analysis of the effi cacy of the inhaled and intravenous delivery of equivalent doses of bone marrow mesenchymal stem cells (BMMSCs) in rabbits according to the standard model of bleomycin pulmonary fi brosis.

Materials and methods. After bronchoscopic instillation of bleomycin, 5 rabbits received intravenous transplantation of 2 × 106 allogeneic BMMSCs, other 5 rabbits – 2 × 107 MSCs inhaled via compressor nebulizer; control healthy and bleomycin group included 5 animals each.

Results. Both groups treated with BMMSCs had a signifi cantly lower Ashcroft fi brosis index than the bleomycin control group. Expression of collagen in lung tissue in all groups with bleomycin injury was superior to healthy controls, but in animals underwent intravenous BMMSC transplantation collagen score was 0.74 points, and in inhaled treated group – 0.51 points, while in bleomycin controls – 2.1 point. Levels of TNF-α and TGF-β1 in BAL fl uids tended to decrease in treatment groups, but did not differ signifi cantly from control. A similar picture was observed in the cytological analysis of BAL.

Conclusion. In general, both methods of delivering of BMMSCs to the lungs demonstrated similar therapeutic effects in inhibiting the development of experimental fi brosis, indicating that both intravenous and inhalational way of introduction can be used for subsequent clinical studies. 

Aim: to develop a three-dimensional composite cell-engineered constructs (CEC) for restoration of limited defects of the cartilage in experiment.

Materials and methods. To create a cell-engineered constructs (CEC), were used collagenic carriers: «Chondro Gide» impermeable bilayer membrane and «Osteoplast» permeable matrix. A comparative study of their cytotoxic and adhesion properties was made in vitro. Chondroplastic potential of prepared CECs based on collagenous matrices with allogeneic mesenchymal stem cells (MSC) of the rabbit bone marrow grown on their surface was assessed in vivo. A cylindrical defect of the cartilage of the medial femoral condyle 3.3 mm in diameter at a depth of 1.5 mm was formed on both rabbit feet. Laboratory animals were divided into 3 groups: control group; Experiment 1 group with Chondro Gide used as the MSC carrier within CEC; Experiment 2 group using Osteoplast matrix. Upon experiment completion, a morphometric and histomorphologic research of tissue specimens was made. For statistical evaluation of the results a defect region recovery factor (RF) was offered and used.

Results. After a 6-month observation period the control group showed partial recovery of the defect region with the recovery factor (RF) of 0.62 ± 0.06. The RF in Experiment 1 group equalled to 0.79 ± 0.07, Experiment 2 group revealed RF at the level of 0.88 ± 0.02. Statistical analysis of the research results shows that the use of CEC used in Experiment 2 group reduces a relative risk of therapeutic failures by 92.9%, and absolute risk – by 43.3% as compared to Experiment 1 group. Histomorphologic research data are indicative of a hyaline cartilage formation in the central defect zone, which is partially close to the intact cartilage to the maximum with zonality marked.

Conclusion. Results of the research of the developed three-dimension cell-engineered constructs consisting of mesenchymal stem cells of the bone marrow grown on the Osteoplast permeable collagenic matrix show the formation of a cartilaginous hyaline tissue with a high level of structural organization in the area of its implantation. The thickness of a newly formed cartilage is insignifi cantly less than that of the preceding cartilaginous tissue, thus facilitating a dynamic distribution of the axial load on the articular surface, and as a whole this holds out hope for good long-term results. Therefore, based on the data obtained, we consider it reasonable to perform next investigation phases of the offered cell-engineered constructs for chondroplasty of limited cartilage defects. 

This review briefl y discusses the experience of organizing and carrying out experimental studies in our center in order to increase the validity of the researches. The rules of organizational and methodological approaches aimed at increasing the suitability of the results of experimental studies are also given. Each research work in which experiments on laboratory animals are supposed to be carried out should be organized, planned and carried out in accordance with national and international ethical standards. Discussion and publication of both planned and conducted experimental work makes it possible to make the research process more open and objective. The experimental investigation is carried out in the following algorithm: the formulation of the problem and the hypothesis on the basis of the literature data; development of the purpose and objectives of the study with adequate methods and selection of equipment; distribution of material to control and trial groups; creation of a plan for monitoring the indicators during the experiment; processing and interpretation of results; preparation of a scientifi c report. 

Implantable left ventricular assist devices (LVAD) have become the leading method of mechanical circulatory support (MCS) in heart transplant candidates. But the temporary MCS as a mechanical bridge to heart transplantation (HT) continues to use. The temporary MCS remains an effi ciency method of treatment of life-threatening heart failure (HF), when implantation of permanent LVAD or BiVAD is associated with high risk. The temporary MCS creates clinical and organizational conditions for the urgent HT. This approach allows not only to save life of heart transplant candidates, but also to improve the availability of the HT. The choice of the temporary MCS is determined by the type and severity of HF and the expected duration of its application. The review presents a characteristic, and discusses the effectiveness of various methods of temporary MCS at heart transplant candidates needed in urgent HT.

Durable protection from hepatitis B virus (HBV) and other vaccine-preventable diseases assumes great importance due to improved long-term patient and graft survival rates in pediatric liver transplantation (PLT). Vaccine immunogenicity data in transplanted children is limited. The review presents aspects of current approach for childhood HBV immunization schedule prior to transplant, duration of time since transplant for receive booster dose, target median HBsAb levels before and after PLT. The latest data about types of vaccine against HBV and vaccine effectiveness in PLT centers in the world are also presented.

The syndrome of mineral and bone disorders in patients with chronic kidney disease after kidney transplantation include hypophosphatemia, hypercalcemia, hypovitaminosis D, and decreased bone mineralization (secondary osteoporosis). The modern strategy of prevention and treatment of post-transplantation mineral and bone disorders is based on the principles of individual approach, taking into account the assessment of risk factors and minimizing the factors that caused these disorders. An attempt to compensate for phosphorus defi ciency is usually ineffective and even dangerous due to complications. This review analyzes different correction´s methods of symptomatic hypercalcemia and hypercalcemia after kidney transplantation secondary to hyperparathyroidism. Also in this review presented modern approaches to the prevention and treatment of posttransplant osteoporosis. Also it shows the effects and indications for use steroid sparing/withdrawal, vitamin D and vitamin D receptor activator, drug and surgical correction of hyperparathyroidism, bisphosphonates and other medications.

There is a number of problems regarding bioengineered structures creation that require further study in the fi eld of regenerative medicine. One of the critical tasks that require solution is the fact that tissue engineered constructions, as a rule, are large, which signifi cantly limits the possibility of diffusion of nutrients and oxygen in them. Thus, the key task of fundamental medicine is to fi nd a technology for restoring the perfusion of the structures created. The article presents a modern overview of the mechanisms of angiogenesis and possible ways of its stimulation during transplantation of tissue engineered constructions.

Modern medical technologies raise the problems of the relationship between man and society, medical workers and patients. The ethical problems of medical technologies are nowhere so clearly defi ned as in the established practices of organ donation and transplantation. The project of a head transplant, widely represented in the media recently, raises a number of critical questions to the medical community. The article explores the ethical issues raised by the presentation in the media sphere the project of human head transplantation and risks for current transplant practice.

The article is devoted to the outstanding Soviet scientist, the head of the department of pharmacology of the Gorky Medical Institute (now the Nizhny Novgorod Medical Academy), the honored worker of science, professor N.P. Sinitsyn (1900–1972). His achievements in surgery, physiology, experimental transplantology and experimental cardiac surgery have studied. It is shown that in 1937–1943. N.P. Sinitsyn was fi rst man in the world carried out successful transplantations of an additional and isolated heart to frogs in the thoracic cavity and for the fi rst time in Russia transplanted the dog’s head; in 1940–1955 (with interruptions) he conducted experiments on transplantation of the additional heart in the chest to dogs; in 1955–1956 he invented a way of visual control of cardiac activity of the biological and donor heart per se; in 1956 a model of a «two-headed» frog was created, and in 1959–1979 he conducted experiments on modeling and resection of heart aneurysms, plastic of the ventricles of the heart, stimulation of myocardial regeneration by electric current, studied regeneration of cardiac and papillary muscles. The reasons for not allowing the results of these experiments to go beyond the physiological laboratory are discussed in this article.