This paper reviews modern literature and presents a brief analysis of our own data on one of the most pressing issues in modern transplantology and, in particular, transplant hepatology – the role and place of gut-liver axis (GLA) in the early post-transplant period. Objective: to compare the correlation between gut microbiome palette and incidence of certain early postoperative complications in liver transplantation. Materials and methods. The study design is presented as a pilot, prospective, observational, double-blind study based on investigation of the composition of the microbiome residing in the large intestinal in patients that underwent orthotopic liver transplantation (OLTx). The primary cohort of patients consisted of 12 patients who underwent OLTx from a postmortem donor. To assess the gut microbiome palette, biomaterial was collected from all patients in the preand post-transplant period followed by next-generation sequencing. The study was conducted as primary study results registered under number NCT04281797. Results. In the preoperative period, differences close to statistically reliable in relation to Actinobacteria were observed in patients included in the liver transplant waiting list for cirrhosis (LC) and hepatocellular carcinoma (HCC) in cirrhosis. However, due to the pilot nature of the study, this study cohort was limited to an extremely small sample. In turn, in the post-transplant period, there was a statistically significant difference in the taxonomic range of Actinobacteria (p < 0.05) between the above groups, indicating a possible effect of liver transplantation on the gut microbiome. In addition, in the early post-transplant period, there was a marked difference in the microbiome palette between patients with and without acute cellular rejection. Conclusion. GLA and the gut microbiome play a critical role in many liver diseases, and may also have a significant impact on the post-transplant period. In this regard, further research in this direction will not only characterize the predictors and risk factors of bacterial infection and rejection episodes, but will also allow us to form a completely new approach to the treatment tactics for certain complications, including through formation of a microbiota-oriented pharmacotherapy.

Objective: to present an analysis of the results of 100 cadaveric liver transplants performed at Botkin Hospital from July 2018 to October 2021. Materials and methods. From July 2018 to October 2021, 100 orthotopic liver transplantation (LTx) from a deceased donor were performed at the surgical clinic of Botkin Hospital. The recipients were 58 males (58%) and 42 females (42%). The mean age of the recipients was 48.73 ± 8.56 (24–66) years, while their mean MELD was 19.54 ± 4.35 (15–33). The main indications for LTx were cirrhosis resulting from chronic viral hepatitis (CVH) C (52%), nutritional-toxic cirrhosis (20%), autoimmune liver and bile duct disease (18%), CVH B (7%), and hepatocellular carcinoma (HCC) (3%). During the period under study, 119 potential liver transplant donors were evaluated. The mean age of the donors was 44.2 ± 11.12 (21–63) years. Median levels of sodium, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin were 141 (138–146) mmol/L, 27 (20.7–47.4) units/L, 25 (17–41.5) units/L, and 9.65 (6.42–13.7) μmol/L, respectively. The median graft hepatic steatosis was 10% (5–15). LTx was performed using the piggyback technique (99/100 cases) and classic technique with inferior vena cava resection (1/100). End-to-end porto-portal vein anastomosis was performed (99/100 cases). Anastomosis of the donor organ’s portal vein with the recipient’s left gastric vein due to occlusive thrombosis of the recipient’s portal vein was carried out (1/100). In all cases, a continuous end-to-end arterial anastomosis was formed. End-to-end choledochocholedochal anastomotic strictures (95/100) and end-to-side hepaticojejunostomy (5/100) were formed. Results. Median cold ischemia time was 312.5 minutes (280–380). Mean operative time was 488.91 ± 65.34 (95% CI: 475.9–501.9) minutes, median intraoperative blood loss was 1000 (600–1500) mL. Thirty-day mortality was 2% (Clavien–Dindo class V). Early postoperative complications (Clavien–Dindo class IIIa–IVa) developed in 12/100 patients (12%). Graft arterial thrombosis occurred in 3 cases (3%), biliary anastomotic strictures in 6 (6%), and subhepatic hematoma in 2 (2%). The average intensive care unit (ICU) bed day was 2.34 ± 1.67 (1–8). Total postoperative bed-day was 14.63 ± 5.35 (10–39). During case follow-up, a prolonged form of calcineurin inhibitor (CNI) was administered as immunosuppressive therapy in mono regimen (85 patients), in combination with mycophenolic acid derivatives (7), and in combination with everolimus (6). Of the 93 patients, 46 patients (49.46%) had the new coronavirus infection (COVID-19) before or after transplantation; in no case did COVID-19 lead to death. Six patients (13.04%) were hospitalized due to COVID-19. To date, 33/93 (25.48%) patients have been vaccinated, resulting in 75 (75%) liver transplant recipients immune to COVID-19. The overall 1-year survival rate was 95% and the 3-year survival rate was 91%. Conclusion. Introduction of LTx in multidisciplinary hospitals allows to, already at the start of the program, achieve immediate and long-term treatment outcomes (in decompensated diffuse liver disease) that are comparable to those of leading transplantation centers.

Chronic hepatitis B virus (HBV) infection is common throughout the world. According to the World Health Organization, about 300 million people around the world are living with the HBV infection markers, with prevalence ranging from 0.4% to 8.5%, depending on the region. Untreated HBV infection results in severe liver disease, including cirrhosis and hepatocellular carcinoma (HCC), in at least one third of patients. While vaccination and new antiviral drugs are effective in preventing the severe consequences of HBV infection, liver transplantation remains the ultimate therapy for patients with HBV in cirrhosis. In patients with HBV replication, recurrence in the graft occurs in 100% of cases, which requires antiviral therapy combined with immunosuppressive therapy. According to the literature, de novo HBV infection after orthotopic liver transplantation (OLTx) in patients without replication and even in patients negative for hepatitis B surface antigen is between 1.7% and 5% [Castells L. et al., 2002]. After OLTx, liver recipients with baseline chronic HBV infection and patients with de novo HBV infection occurring after transplantation are indicated for long-term antiviral therapy.

Autoimmune hepatitis (AIH) can occur at any age and is more common in women. The disease is a manifestation of autoimmune predisposition caused in genetically susceptible people exposed to certain environmental factors. The pathogenetic mechanism of AIH is not yet fully understood, but it involves an aggressive cellular immune response. The pathogenesis and severity of AIH also depend on various cytokines. This disease is characterized by elevated levels of transaminases – aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Liver histology plays a crucial role in confirming or supporting the clinical diagnosis of AIH. Diagnosis of AIH remains a challenge in clinical practice. AIH is one of the few liver diseases for which pharmacologic treatment has been shown to improve survival. Standard treatment is based on high-dose prednisone alone or prednisolone plus azathioprine. It leads to disease remission in 80%-90% of patients. Approximately 20% of patients do not respond to the standard steroid treatment and are treated with second-line immunosuppressive drugs: mycophenolate mofetil, budesonide, cyclosporine, tacrolimus, everolimus, and sirolimus. There have been reports on the use of infliximab and rituximab. In the natural course of AIH and resistance to therapy, there is a tendency for cirrhosis to develop and for the disease to progress to an end stage. These patients, as well as those diagnosed with fulminant liver failure, require liver transplantation.

The role of frailty in cardiovascular disease is becoming increasingly recognized. Up to 79% of patients with heart failure are frail. Frailty is associated with reduced quality of life and poor prognosis. This review summarizes the available literature on frailty and its key role in waitlisting patients for heart transplantation.

Hypertrophic cardiomyopathy (HCM) is a disease that is usually unresponsive to conservative pathogenetic therapy. It does not have clearly developed surgical correction algorithms. Heart transplantation (HTx) is the sole therapeutic option when drug therapy is ineffective and surgical reduction of hypertrophic myocardium is not feasible. There are only sporadic reports in the literature about HTx for HCM. The novel coronavirus disease 2019 (COVID-19) pandemic has significantly affected the work of cardiac surgical units and, in particular, organ transplantation activities. This paper presents a clinical case of an HCM patient who underwent HTx, complicated by COVID-19 infection in the early postoperative period.

Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) are the most important regulators of growth, regeneration and metabolism. The influence of GH and IGF-1 on pediatric liver transplant outcomes is mediated through growth and body weight regulation, specific effects on hepatocyte function and immune system activity. In recent years, the blood levels of these factors and life expectancy, both in healthy individuals and liver recipients, have been shown to be correlated. In pediatric liver recipients, neurohumoral regulation of graft function and other functions of the growing organism, has not been studied enough. The results of studies on the levels and dynamics of GH and IGF-1 in the blood of liver recipients can serve as a basis for assessing the state of graft using new minimally invasive methods and identifying therapeutic targets for personalized therapy. This review summarizes the current understanding of the significance of GH/IGF-1 hormones in hepatobiliary diseases and pediatric liver transplantation (LTx).

Objective: to evaluate the features of reparative chondrogenesis and osteogenesis in animal experiments with the implantation of porous poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogel into osteochondral defects. Materials and methods. Cylindrical pHEMA implants (5 mm in diameter) were synthesized by radical polymerization. The implants were subjected to light microscopy and mechanical tests to characterize the structure and viscoelastic properties of the material. In experimental group #1, four pHEMA specimens were implanted into formed defects in the distal femoral epiphysis of rabbits. In experimental group #2, allogeneic chondrocytes were applied to the surface of four specimens before implantation. In the control series, four defects were not replaced with implants. Tissue regeneration was investigated by morphological and morphometric methods 30 days after operation. Results. The pHEMA implants were heterogeneous specimens with irregularly shaped pores – up to 30 × 10 μm at the surface and 300 × 120 μm inside. With >10% static compressive stress, the Young’s modulus was 54.7 kPa. For dynamic stress, increased frequency of compression-relaxation cycles from 0.01 Hz to 20.0 Hz led to increased storage modulus from 20 kPa to 38 kPa on average, and increased loss modulus from 2 kPa to 10 kPa. Indicators of semi-quantitative assessment of local inflammatory response to pHEMA implantation had the following values in points: pHEMA, 4.7 ± 0.3; pHEMA with allogeneic chondrocytes, 6.0 ± 1.0; control, 4.3 ± 0.3. The ratio of connective, bone, and cartilage tissues proper in the regenerates had the following respective values: pHEMA, 79%, 20%, 1%; pHEMA with chondrocytes, 82%, 16%, 2%; control, 9%, 74%, 17%. Conclusion. In a short-term experiment, pHEMA implants did not trigger a pronounced inflammatory response in the surrounding tissues and can be classified as biocompatible materials. However, the tested implants had low conductivity with respect to bone and cartilage cells, which can be improved by stabilizing the pore size and increasing the rigidity when synthesizing the material.

Objective: to investigate the biological properties of a matrix made of cryogenically structured hydrogel in the form of a macroporous gelatin sponge, as well as the possibility of creating cell-engineered constructs (CECs) on its basis. Materials and methods. The main components of the cryogenically structured hydrogel were gelatin (type A) obtained from porcine skin collagen, N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide, (EDC) and urea (all from Sigma-Aldrich, USA). Surface morphology was examined using scanning electron microscopy (SEM). The degree of swelling in water of the samples was determined by gravimetric method. Cytotoxicity was studied on NIH3T3, a fibroblast cell line isolated from a mouse, and on human adipose-derived mesenchymal stem/stromal cells (hAMSCs) using IncuCyte ZOOM (EssenBioscience, USA). The metabolic activity of hAMSCs was assessed using PrestoBlue™ reagents (Invitrogen™, USA). To create CECs, we used hAMSCs, human hepatocellular carcinoma cell line HepG2 or human umbilical vein endothelial cell lines EA.hy926. Albumin content in the culture medium was determined by enzyme immunoassay. Ammonia metabolism rate was assessed after 90 minutes of incubation with 1 mM ammonium chloride (Sigma-Aldrich, USA) diluted in a culture medium on day 15 of the experiment. Results. Obtaining a cryogenically structured hydrogel scaffold in the form of macroporous gelatin sponge included freezing an aqueous solution of a gelatin+urea mixture, removal of polycrystals of frozen solvent by lyophilization, extraction of urea with ethanol and treatment of the cryostructurate with an ethanol solution of EDC. Scanning electron microscopy identified three types of pores on the carrier surface: large (109 ± 17 μm), medium (39 ± 10 μm), and small (16 ± 6 μm). The degree of swelling in water of the matrix samples was 3.8 ± 0.2 g H₂O per 1 g of dry polymer. The macroporous gelatin sponge as a part of CEC was found to have the ability to support adhesion and proliferation of hAMSCs, EA.hy926 and HepG2 for 28, 15 and 9 days, respectively. Albumin secretion and ammonia metabolism when HepG2 cells were cultured on the gelatin sponge were detected. Conclusion. The use of a matrix made from macroporous cryogenically structured gelatin-based hydrogel for tissue engineering products is shown to be promising using a cell-engineered liver construct as a case.

According to global health statistics, respiratory diseases, together with infectious complications and hereditary lung diseases, rank as the third leading cause of death. Today, lung transplantation (LTx) is a well-recognized modality of treatment for end-stage chronic lung disease. However, the number of LTx surgeries performed is much lower than other solid organs. This is due to the high requirements for the potential donor and characteristics of the lung graft, reflecting the efficiency of gas exchange function. Non-compliance with the selection criteria leads to deselection of donors, which, according to various estimates, occurs in 80–85% of cases. One of the ways to increase the number of lung transplant surgeries is to restore them to the level of optimal gas exchange parameters, which can be achieved and objectively assessed during normothermic ex vivo lung perfusion (EVLP). EVLP is becoming increasingly common at leading transplantation centers in Europe and North America. This has significantly increased the number of transplant surgeries as a result of using lungs procured from suboptimal donors and rehabilitated via EVLP. In our pilot study, the developed Russian-made mechanical circulatory support system showed that performing normothermic EVLP for isolated lungs under experimental conditions is feasible. Basic and optimized perfusion protocols have fully shown that they are reliable and efficient.

Objective: to demonstrate, using a clinical case, the first successful experience in a combined use of an automated chest compression device (ACCD) and hypothermic oxygenated machine perfusion (HOPE) for kidney transplantation from a donor with irreversible cardiopulmonary arrest. Materials and methods. In the presented clinical case, ACCD was successfully used in a donor who was pronounced dead following an irreversible cardiopulmonary arrest. This allowed to minimize the primary warm ischemia time. Kidney graft HOPE for 585 minutes reduced the static cold storage time to 165 minutes. Results. In the uneventful postoperative period, there was immediate kidney graft function. This allowed for rapid rehabilitation and discharge from hospital. Conclusion. Introduction of ACCD and HOPE will increase the number of donor organs, mainly kidneys intended for transplantation.

Over the past 10 years, significant breakthroughs have been achieved in Russian transplantology in the field of regulatory legal framework. During this period, the powers of government authorities in the field of healthcare on organization of transplant care and organ donation have been defined, and sources and mechanisms for target financing of medical activities related to organ donation for transplantation purposes have been identified. The procedure for providing medical care under surgery (human organ and/or tissue transplantation) has been adopted, and a state registry system for donor organs, donors and recipients has been created. Measures on organ donation and transplantation in the Russian Federation have been approved within the «Healthcare Development», a framework of the state program of the Russian Federation. The Shumakov National Medical Research Center of Transplantology and Artificial Organs (Shumakov Center) has also been identified as the core institution that coordinates the activities of the entire transplant industry in the Russian Federation. Transplant medical care is currently being provided by specialist physicians trained in human organ and tissue transplantation, in collaboration with other specialist physicians. The Nomenclature of Specialties of Specialists with Higher Medical and Pharmaceutical Education, approved by the Russian Ministry of Health via Order No. 700n of October 7, 2015, does not contain a separate specialty related to human organ and tissue transplantation activities, and this is quite justified. However, in order to improve the legal regulation of transplantation activities, it is necessary to unify the requirements for specialists providing medical care in human organ/tissue transplantation. This can be achieved by developing uniform approaches to the definition of labor functions in the professional standards of specialist doctors involved in transplantation.

Background. As scientific knowledge about the peculiarities of the structure and functional properties of the skin increased, it became clearer that during transdermal administration, drug may accumulate in the deep layers of the dermis and subsequently get diffused into the bloodstream even after the transdermal therapeutic system (TTS), also called transdermal patch, had been removed. Objective: to quantify active drug substances remaining in an animal skin after TTS application. Materials and methods. Two previously developed transdermal patches containing Russian-made drug substances were chosen for the study: aminodihydrophthalazinedione sodium (immunomodulator) and bis(1-vinylimidazole-N) zinc diacetate (antidote for carbon monoxide). The study was performed on male Chinchilla rabbits weighing 2.5–3 kg. Five series of experiments were performed for each substance: immediately after removal of the patch, 4 hours later, at week 1, 2 and 3 after removal. High-performance liquid chromatography and atomic absorption spectroscopy methods were used to quantify residual drug substances left in the skin. Results. In the skin flap that was in contact with the aminodihydrophthalazinedione sodium TTS for 24 hours, 0.516 mg of the drug was detected immediately after removal of the patch. Over the next two weeks, the drug substance in the skin decreased with the immunomodulator significantly reducing to 0.41 mg in the first 4 hours. In the skin flap that had been in contact with zinc bis(1-vinylimidazole-N) diacetate for 24 hours, about 1 mg of the drug was present immediately after patch removal. Four hours after removal of the transdermal patch, the quantity of active substance in the skin remained practically unchanged. At week 1 and 2, the quantity of the antidote decreased slightly to ~0.7 mg and ~0.25 mg, respectively. Conclusion. For transdermal application of aminodihydrophthalazinedione sodium, the skin can act as a drug depot and prolong the effect of this drug even after the transdermal patch had been removed. No such effect was found in the case of bis(1-vinylimidazole-N) zinc diacetate, which is apparently due to the different solubility of the drugs in the biotissue.

Obesity is a modern «epidemic» not only in the general population but also among patients with end-stage renal disease (ESRD) who require kidney transplantation (KTx). The objective of this literature review is to analyze global studies on surgical methods of treating morbid obesity and their potentials in ESRD patients in preparation for KTx.

Cardiovascular disease is the leading cause of death in patients with a transplanted kidney and in graft loss. We present the first clinical case of successful surgical correction of ascending aortic dissection (DeBakey type I) in a young patient with a functioning kidney graft. The patient underwent the first cadaveric kidney transplantation (KTx), which was complicated by acute humoral rejection and suboptimal graft function. High blood pressure, anemia, elevated blood levels of triglycerides, phosphorus, parathyroid hormone, and uric acid were recorded. A repeat KTx was performed five years later; the patient’s condition and kidney function were satisfactory. Three years later,the patient started experiencing severe pain along the thoracic and lumbar spine; his blood creatinine level was 408 μmol/L. Computed tomography and echocardiography diagnosed DeBakey type I aortic dissection (AD) with critical narrowing of the true aortic lumen at certain levels, dissection of aortic branches. Aortic resection surgery with prosthetic replacement of the ascending aorta according to David procedure with reimplantation of coronary artery orifices according to Kouchoukos technique, prosthetic replacement of the aortic arch with debranching of brachiocephalic artery and left common carotid artery were successfully performed as planned under endotracheal anesthesia, cardiopulmonary bypass and selective pharmacological cold cardioplegia. The peculiarities of the course, possible causes and outcomes of surgical correction of thoracic AD in the patient are discussed.