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Aim. To carry out the analysis of enforcement of regulatory legal acts in transplantological practice, to specify the existing gaps and collisions in them, and to offer approaches for its elimination. Materials and methods. The legislation of the Russian Federation in the fi eld of donation and organ transplantation and(or) tissues (an information law system «Garant»). Archive of addresses to the chief transplantologist of the Russian Ministry of Healthcare concerning application of certain precepts of law in transplantology since 2009 till present. Results. Legislative and subordinate acts relating to the area of donation and organ transplantation and(or) tissues are studied; addresses to transplantologies regarding application of certain law precepts are analyzed. Conclusion. Legislative and subordinate acts in force in the fi eld of donation and organ transplantation and(or) tissues contain gaps and collisions which interfere with the work and development of the industry. With respect thereto, it is reasonable to make amendments eliminating legal defects to a number of regulatory legal acts: to the Federal law No. 323-FZ, to the Act of the Russian Federation No. 4180-I, to the Resolutions of the Government of the Russian Federation No. 291 and No. 294, to the Orders of the Ministry of Healthcare of the Russian Federation No. 567n, No. 307n/4, No. 355n. 

Aim. Analysis of relationship between transforming growth factor beta-1 (TGF-β1) level in blood and liver disease severity before and after liver transplantation in early age children with congenital liver diseases. Materials and methods. The study included 135 pediatric patients aged from 2 to 73 months with end-stage liver disease. Results. The level of TGF-β1 in the blood of children with liver failure on average was lower than in healthy children of the same age. The cytokine level depended on the liver disease etiology: in patients with biliary atresia, biliary hypoplasia, Alagille syndrome, Byler disease and other diseases it was lower than that at Caroli disease when it did not differ from the level in healthy children. The level of cytokine in the blood plasma of patients was associated with the severity of hepatic fi brosis: in fi brosis of grade 1 and 4 it was lower than in fi brosis of grade 2 and 3. The liver transplantation from related living donor resulted in increase of TGF-β1 level in the blood plasma of patients regardless of the initial etiology and severity of the liver disease. Conclusion. The blood level of TGF-β1 refl ects liver disease severity in children with congenital liver diseases and may be used as a marker of liver function state before and after liver transplantation. 

Aim. To evaluate the associations of genotypes of clinically relevant nucleotides rs11536865, rs913930 and rs5030717 of the TLR-4 gene with the risk of development and severity of early allograft dysfunction after liver transplantation. Materials and methods. A case-control study enrolling 71 patients was organized. Inclusion criteria: DBD liver transplantation. Exclusion criteria: living related liver transplantation, reduced graft transplantation, recipient’s age fewer than 18. Results. Within rs5030717 there were identifi ed three genotypes: AA (81.6%) and two genotypes with the minor G-allele: AG (12.6%) and GG (5.6%). Within rs913930 there identi- fi ed three genotypes: TT (59.1%) and two genotypes with the minor C-allele: C/T (29.5%) and CC (11.2%). The rs11536865 studying revealed no polymorphism (GG genotype). The early allograft liver dysfunction (EAD) developed in 19.7% of patients, the severe EAD in 11.2% of patients, septic complications in 14%, acute cellular rejection in 23.9% of cases. The C/T genotype of the TLR-4 gene in the SNP rs913930 sequence was closely associated with the EAD development (OR 4.8 to 1; p = 0.047; 95% CI 1–23.4). Рatients with the donor’s liver C/T genotype had a reliably higher proportion (%) of the HMGB1 positive hepatocytes in the donor’s bioptate, 21 (17–29%) vs the СС+TT genotypes, 16 (10–19%) (Mann–Whitney test, p = 0.01). The CD68 expression in the liver bioptate at the donor’s stage was reliably higher in the carriers of heterozygotes in the SNP rs913930 (C/T genotype) and in the SNP rs5030717 (AG genotype), (Mann–Whitney test, p = 0.03). Signifi cant positive correlation between the CD68 expression in the donor’s liver bioptates and the IL-23 level in the hepatic vein has been determined in an hour after the portal reperfusion (ρ = 0.62; p = 0.04) as well as between the HMGB1 expression in the donor’s liver bioptates and the АSТ level in 24 hours after the reperfusion (r = 0.4; p = 0.02). The HMGB1 staining in the donor’s liver bioptates was higher in the EAD patients, 21 (20; 29) cells/mm2 in comparison with the patients without EAD, 16 (12; 18) (Mann–Whitney test, p = 0.0036). Conclusion. The early allograft liver dysfunction is associated with the genetic predisposition caused by the TLR-4 gene polymorphism and is implemented via the HMGB1, Kupffer cells and IL-23 activation. 

Aim: to analyze the relationship between circulating anti-HLA antibodies (class-I and class-II), renal pathology and C4d deposition in cases of late acute and chronic antibody-mediated renal allograft rejection according to the method of antibodies detection (ELISA and LUMINEX). Materials and methods. Th e study included 192 patients with indicative graft biopsies (with C4d-staining) and screening detection of anti-HLA antibodies (109 patients by ELISA, 58 patients by LUMINEX, 25 patients – both methods). Patients were divided into 3 groups based on pathology fi ndings: 85 patients with chronic graft rejection, 39 patients with acute antibodymediated rejection (AMR), 68 patients of control group had no signs of AMR. Results. Anti-HLA antibodies (predominantly class-II anti-HLA) were identifi ed in 84.7% of patients with chronic graft rejection, in 84.6% of patients with acute AMR and 33.8% of control group (р < 0.001). Close correlation between the levels of antiHLA antibodies detected by different methods was revealed for both classes of antibodies (r² class-I anti-HLA = 0.773, r² class-II anti-HLA = 0.379, р < 0.01). LUMINEX proved to be more sensitive in anti-HLA antibodies detection in all groups. It was especially signifi cant for the diagnosis of C4d-negative acute AMR whose frequencies were 22.2% and 4.8% in detection by LUMINEX and ELISA, respectively (р < 0.01). On the other hand, anti-HLA antibodies being detected by LUMINEX in 55% of patients of the control group more often required determination of donor specifi city. Conclusion. Screening of anti-HLA antibodies (by ELISA and LUMINEX) along with specifi c renal pathology and C4d deposition is suffi cient for the diagnosis of acute and chronic AMR in most cases. Being more sensitive LUMINEX method is preferable for the revealing of C4d-negative AMR, but it requires specifi c DSA detection in many cases. 

Aim. To assess the possibilities of the use of laparoscopic transabdominal nephrectomy (LNE) for surgical treatment and preparation of the patients with autosomal dominant polycystic kidney disease (ADPKD) for kidney transplantation. Materials and тethods. In the course of the study 28 patients who underwent nephrectomy of a polycystic-modifi ed kidney were analyzed and divided into two groups. The fi rst group (15 patients) underwent open surgical intervention with the use of midline laparotomy and lumbotomy (16 operations), of which: bilateral nephrectomy – 11 (68.7%), monolateral nephrectomy – 5 (31.3%). In the second group (13 patients), laparoscopic transabdominal monolateral nephrectomy (17 operations) was done. Surgical interventions were performed for emergency indications and to prepare for kidney transplantation. Results. The average duration of laparoscopic and open surgical interventions was not signifi cantly different and amounted in the fi rst and second group to 146 ± 14 and 124 ± 11 minutes (p > 0.05), respectively. The frequency of postoperative complications after open surgical interventions made up 43.75%, the mortality rate was 6.25% (1 case). In patients operated on laparoscopically postoperative complications occurred in 11.8% of cases. Patients after laparoscopic procedures were activated in 2–3 days (2.63 ± 0.23), after open operations on 4–5 (4.13 ± 0.39, p < 0.05). The average length of postoperative hospital stay was in the fi rst group – 13–14 (13.7 ± 1.3), in the second group – 7–8 (7.7 ± 0.5, p < 0.05). Conclusion. Atraumatic laparoscopic technology leads to a more favorable course of the postoperative period after nephrectomy. It can reduce the duration of inpatient treatment and help activate patients at an earlier date. The method of LNE can signifi cantly reduce the frequency of postoperative complications and expand the possibilities of using nephrectomy in the treatment and management of patients with autosomal dominant polycystic kidney disease waiting for renal transplantation.

Aim. The global shortage of deceased organ donors caused increasing interest to the transplant program based on the use of organs from the donors with sudden irreversible cardiac arrest, or asystolic donors (DCD). Ischemia-reperfusion injury as a result of cardiac arrest remains a key problem that limits the use of organs from DCD. Our clinical study was intended to determine the acceptability of renal transplants derived from the DCD using extracorporeal perfusion in situ after 60 minutes of asystole. Materials and methods. In 2009–2014, St. Petersburg Organ Procurement Organization (OPO) obtained kidneys from 29 DCD with critically expanded warm ischemic time (WIT). The design of this study was approved by the Scientifi c Board and Ethics Committee of the State Research Institute for Emergency Medicine (Decision 7/0615/09). Initially, no one of died patients was considered as potential organ donors. In case of failed advanced CPR the death of a patient was declared initiating the protocol of subnormothermic extracorporeal abdominal perfusion with ECMO, thrombolytics (strepokinase 1.5 mln U), and LD. The procedures were established by the authorized OPO team which arrived with perfusion equipment in 30–40 minutes after declaration of donors’ death. Mean WIT was 58.1 (19.39) minutes (Mean (SD). Resuscitated grafts were transplanted into 58 recipients. The outcomes of transplantation of resuscitated kidneys were compared to those of 112 KTx from 115 brain death donors (BDDs). Results. Immediate functioning of kidney grafts was observed in 28 (48.3%) of 58 recipients. There were 4 cases of primary graft non-function. By the end of the fi rst post-transplant year there was an acute rejection rate of 12.1% (9 episodes of rejection) in the DCD group vs. 23.2% (26 episodes of rejection) in the BDD group (p < 0.05). The actuarial 5-year graft survival rate was 82.8% (n = 48) in DCD group, and 87.5% (n = 98) in BDD group (p > 0.05). Creatinine levels at the end of the fi fth year were 0.094 (0.06) and 0.103 (0.07) mmol/l in DCD and BDD groups, respectively (p > 0.05). Conclusions. Kidneys from DCDs with critically expanded WIT could be successfully used for transplantation if in situ organ “resuscitation” perfusion procedures are included into procurement protocol. The 5-year outcomes meet the generally accepted criteria for grafts’ and recipients’ rates of survival and functioning. This approach could substantially expand the organ donors’ pool. 

The need of circulatory support systems in the treatment of chronic heart failure is increasing constantly, as 20% of the patients on the waiting list die every year. Despite the great need for mechanical heart support systems, the use of available systems is limited by its expensiveness. In addition, there is no one system that is 100% responsible to all medical and technical requirements and that would be completely safe for patient. Therefore, further research in the field of circulatory support systems considering health and technical requirements is relevant. One of the new directions in the study are disc pumps of viscous friction for liquid transporting, based on the Tesla pump principle. The operation principle of such pumps is based on the phenomenon of the boundary layer which is formed on the disk rotating in a fluid. There are experimental studies of models with different variants of the rotor suspension, various forms and numbers of the disks, forms of the pump housing. However, none of the above samples was brought to clinical trials. Furthermore, despite the potential of that model there have been no pumps of similar type used so far in circulatory support systems. Published data provide a basis for further development and testing of the pump model and allow hoping for leveling a number of significant shortcomings of modern left ventricular bypass systems. 

Aim of this study is to research an effect of silk fi broin fi lms fabricated by casting method upon Wistar rat’s full-thickness skin wound regeneration. Materials and methods. 4 different kinds of fi lms with protein concentration equal to 20 mg/ml were fabricated: fi lms from silk fi broin aqueous solution, fi lms from silk fi broin formic acid solution, fi lms from silk fi broin aqueous solution containing 30% collagen by weight, fi lms from silk fi broin formic acid solution containing 30% collagen by weight. All kinds of fi lms were fabricated by casting method on polished Tefl on surface. Scanning electron microscopy was applied to research fi lms’ surface structure. Cytotoxicity test of the fi lms was realized on mouse 3T3 fi broblasts model by MTT assay. Manufactured fi lms were utilized to regenerate full-thickness skin wounds in Wistar rats. Results. It was shown that fi lms’ surface was characterized by micro- and nanorelief in the form of roughness. The proliferative activity of mouse 3T3 fi broblasts increased during 7 days of cytotoxicity test. Fabricated fi lms enlarge the regeneration rate of full-thickness Wistar rat skin wounds an average of 25%. Histological analysis indicated structural skin restoration without any infl ammatory tissue. Conclusion. All fabricated fi lms are non-cytotoxic and characterized by appropriate structure for the adhesion and proliferation of fi broblasts. The application of fi lms for full-thickness skin wound regeneration increases its restoration rate which is confi rmed by histological examination. 

Aim. Controlled treatment of the physico-chemical and mechanical properties of a three-dimensional crosslinked matrix based on reactive chitosan. Materials and methods. The three-dimensional matrices were obtained using photosensitive composition based on allyl chitosan (5 wt%), poly(ethylene glycol) diacrylate (8 wt%) and the photoinitiator Irgacure 2959 (1 wt%) by laser stereolithography setting. The kinetic swelling curves were constructed for structures in the base and salt forms of chitosan using gravimetric method and the contact angles were measured using droplet spreading. The supercritical fl uid setting (40 °C, 12 MPa) was used to process matrices during 1.5 hours. Using nanohardness Piuma Nanoindenter we calculated values of Young’s modulus. The study of cytotoxicity was performed by direct contact with the culture of the NIH 3T3 mouse fi broblast cell line. Results. Architectonics of matrices fully repeats the program model. Matrices are uniform throughout and retain their shape after being transferred to the base form. Matrices compressed by 5% after treatment in supercritical carbon dioxide (scCO2 ). The elastic modulus of matrices after scCO2 treatment is 4 times higher than the original matrix. The kinetic swelling curves have similar form. In this case the maximum degree of swelling for matrices in base form is 2–2.5 times greater than that of matrices in salt form. There was a surface hydrophobization after the material was transferred to the base form: the contact angle is 94°, and for the salt form it is 66°. The basic form absorbs liquid approximately 1.6 times faster. The fi lm thickness was increased in the area of contact with the liquid droplets after absorption by 133 and 87% for the base and the salt forms, respectively. Treatment of samples in scCO2 reduces their cytotoxicity from 2 degree of reaction (initial samples) down to 1 degree of reaction. Conclusion. The use of supercritical carbon dioxide for scaffolds allows improving biocompatibility of the applied material for 1 degree and increasing the elastic modulus of the material more than 3 times. Allyl chitosan forms stable three-dimensional networks during laser photopolymerization. This enables desorbing toxic low molecular weight component without destruction of the matrix structure. 

At present, vascular surgery using small diameter synthetic grafts is associated with a higher incidence of complications (thrombosis, restenosis, intimal hyperplasia) than in operations using autologous vessels. However, the occurrence of concomitant pathology, reoperations and multifocal vascular disease limit the use of autologous vein and arteries. The important factor providing a long-term patency is the presence of vascular cells, which produce biologically active substance and provide mechanical properties. Aim. Selection of the optimal scaffold for creating cell-seeded tissue-engineering vessels. Materials and methods. Endothelial (EC) and smooth muscle cells (SMC) derived from human myocardium were seeded on different surfaces: decellularized homoarteriа, хenopericardium, polytetrafl uoroethylene (PTFE), polyethylene terephthalate (PET), polycaprolactone (PCL) and polylactide-co-glycolide (PLGA). Results. Synthetic biodegradable materials polycaprolactone and polylactide-co-glycolide provide cell adhesion. The cells cultured on the polycaprolactone and polylactide-coglycolide scaffolds retain their functional properties: viability and proliferative properties, maintain specifi c endothelial antigens and synthesis of extracellular matrix. Conclusion. Synthetic biodegradable polycaprolactone and polylactide-co-glycolide electrospun scaffolds can be used for creation of cell-fi lled vascular prostheses. 

The shortage of donor organs leads to a gradual extension of the selection criteria for living donors including age and presence of comorbidities. Performing simultaneous operations with donor nephrectomy would further increase the number of living donors and increase the attractiveness of operations. In this observation, the examination of a 60-year-old potential donor revealed a concomitant disease: chronic calculous cholecystitis, which had existed for over 20 years. Ultrasound examination of the abdomen showed a strong adhesion of the bowel to the anterior abdominal wall. To prevent the risk of damage to the abdominal organs, it was decided to perform the nephrectomy retroperitoneoscopically and a simultaneous cholecystectomy from the same access. This procedure has three major advantages: no contact with the abdominal cavity when performing the access, the easiest access to the renal arteries, and the absence of a systematic increase in intraperitoneal pressure. Such access is of particular importance for the patients who have had previous interventions on the abdominal organs. 

Aim. Clinical use of implants based on patient’s individual topographic anatomical features. Materials and methods. The paper describes two case reports involving the correction of nasal anatomical structure affected during the surgery for facial cancer. Using selective laser sintering technology we manufactured 2 intricate 3D-deformed individual implants from Ti70V30 alloy powders. Implant design was based on CAT/MRT data. Clinical use was conducted on the premises of the department of head and neck surgery in Chelyabinsk Regional Oncological Dispensary. Results. In the fi rst case we obtained an impressive functional result – huge and wide nasal cavity, nose skeleton, and easy nasal breathing. In 30 days we performed endoscopic video-analysis (via nasal passages) which showed that 65% of implant surface was covered with mucosa. In the second case, the designed implant allowed the combined surgery including excision of soft tissues, atypical resection of the upper jaw (left part) and the left cheek, left maxillary sinusotomy and reconstruction of the left part of the nose and the left cheek with implant and skin fl ap. Conclusion. Clinical use revealed pros and contras of the applied technology. Among contras there are relatively high cost of technology, high standards of competency of a surgeon, a programmer and engineers. Pros include free modeling and setting the implant parameters before operation, exact match between implant size/shape and topographic anatomical data of a certain patient. 

Heart Transplantation (HTx) to date remains the most effective and radical method of treatment of patients with end-stage heart failure. The defi cit of donor hearts is forcing to resort increasingly to the use of different longterm mechanical circulatory support systems, including as a «bridge» to the follow-up HTx. According to the ISHLT Registry the number of recipients underwent cardiopulmonary bypass surgery increased from 40% in the period from 2004 to 2008 to 49.6% for the period from 2009 to 2015. HTx performed in repeated patients, on the one hand, involves considerable technical diffi culties and high risks; on the other hand, there is often no alternative medical intervention to HTx, and if not dictated by absolute contradictions the denial of the surgery is equivalent to 100% mortality. This review summarizes the results of a number of published studies aimed at understanding the immediate and late results of HTx in patients, previously underwent open heart surgery. The effect of resternotomy during HTx and that of the specifi c features associated with its implementation in recipients previously operated on open heart, and its effects on the immediate and long-term survival were considered in this review. Results of studies analyzing the risk factors for perioperative complications in repeated recipients were also demonstrated. Separately, HTx risks after implantation of prolonged mechanical circulatory support systems were examined. The literature does not allow to clearly defi ning the impact factor of earlier performed open heart surgery on the course of perioperative period and on the prognosis of survival in recipients who underwent HTx. On the other hand, subject to the regular fl ow of HTx and the perioperative period the risks in this clinical situation are justifi ed as a long-term prognosis of recipients previously conducted open heart surgery and are comparable to those of patients who underwent primary HTx. Studies cited in the review may have important clinical applications, because they outline the range of problems and possible solutions in the performance of the HTx in recipients previously operated on open heart. This knowledge can facilitate the decision making process with regard to the opportunities and risks of the implementation of HTx. Given the uniqueness of each of the recipient and the donor, it is required to make a personalized approach to the question of the possible risks and to the preventive measures to reduce those risks in any given clinical situation. 

In the review a comparative analysis of the treatment of end-stage chronic heart failure using heart transplantation and durable mechanical circulatory is conducted. It shows the main advantages and limitations of heart transplantation and the prospects of application of durable mechanical circulatory support technology. The main directions of this technology, including two-stage heart transplant (bridge to transplant – BTT), assisted circulation for myocardial recovery (bridge to recovery – BTR) and implantation of an auxiliary pump on a regular basis (destination therapy, DT). 

This review of literature is dedicated to the analysis of the current studies of biomarkers, which could help predict immune tolerance development and identify the patients, who can safely minimize immunosuppression after liver transplantation. The review analyzed 46 sources of literature, more than half of those were published in the last fi ve years. Up to date advanced technologies are intensively developed, which help understand molecular mechanisms of normal, pathological and pharmacological processes involved in organ transplantations. However, there are no biomarkers yet validated for the identifi cation of immune tolerance development or individual prescription of immunosuppressants. Further data collection on patients along with the progress in bioinformatics could accelerate development of approaches for patient stratifi cation. 

Development of new methods of visualization of the lymphatic system and in the treatment of several pathologies associated with impaired lymph fl ow. The lymphatic system is an integral part of the circulation. One of the main functions of the lymphatic system is to transport residual interstitial fl uid from the tissue back to the venous system. Despite growing recognition of the role of the lymphatic system in many disease processes, the techniques for imaging and interventions on the lymphatic system have lagged behind the well-developed methods for imaging and interventions on the cardiovascular systems. This is primarily due to small size and variability in anatomy of the lymphatic vessels, and diffi culty of introducing contrast into lymphatic ducts. Due to lack of imaging and intervention options, the fl ow function of the lymphatic system was relatively ignored over the last few decades. Recently, there has been resurgence in the interest in the fl ow function of the interventions on the lymphatic system with the development of percutaneous minimally invasive techniques, such as thoracic duct embolization, to treat life threatening lymphatic leaks. Our group recently introduced two new methods of lymphatic imaging: intranodal lymphangiography and dynamic contrast MR lymphangiography. These methods have allowed further understanding of lymphatic anatomy, pathophysiology, lymphodynamics, as well as provided guidance for novel minimally invasive lymphatic interventions. Using new techniques, the group discovered the causes and then developed treatments for several fatal conditions effecting single ventricle patients including plastic bronchitis and protein loosing enteropathy. Treatment for other conditions has evolved as well including congenital lymphodysplasia, chylothorax, and chylous ascites. The study of the liver lymphatic system has been little explored despite its signifi cant relevance as exampled in ascites formation in association with cirrhosis, one of the most recognized clinical manifestations of lymphatic vascular system disorders. Liver lymphangiogram is an additional minimally invasive technique that allows visualization of the liver lymphatics. Embolization of the liver lymphatic system has been proven to be curative for liver lymphorrea. Due to the lack of the imaging ability of the lymphatic system the understanding of these relationships lacked. Intranodal lymphangiogram, and liver lymphangiograms are one of the fi rst steps in attempt to understand these relationships. Embolization of the lymphatic system provides the opportunity to treat the abnormal lymphatic fl ows in conditions such as pulmonary lymphatic perfusion syndrome, liver cirrhosis, cardiac failure. 

State accreditation of the educational programs in the V.I. Shumakov Federal Research Center of Transplantology and Artifi cial Organs.

By the 85th anniversary of academician Valeriy Ivanovich Shumakov.

On scientifi c and medical personnel training at V.I. Shumakov Federal Research Center of Transplantology and Artifi cial Organs of the Ministry of Healthcare of the Russian Federation