Background. High long-term survival rates have been achieved in liver transplant recipients. However, personalised approaches are still needed for selecting and managing the initial immunosuppressive therapy regimen throughout the entire period of graft function.

Objective. To evaluate the outcomes of various immunosuppressive therapy regimens in liver recipients over a period of up to 20 years.

Material and methods. A retrospective cohort study was conducted using data from 173 patients who underwent 176 liver transplants between December 2004 and December 2021. The following immunosuppressive drugs were used: tacrolimus, steroids, mycophenolates, and everolimus, as monotherapy and in various combinations. Modifications to the initial regimen were studied in each patient over time, and the frequency with which various regimens were used at 1, 3, 5 and 10 years after transplantation was analyzed. Clinical observations were divided into two groups depending on whether steroids and/or mycophenolates were present (group 2, n=95) or absent (group 1, n=81) in the initial immunosuppression regimen.

Results. The median follow-up duration was 79.5 (58;120) (6–220) months, the total duration was 1355 patient-years. The initial immunosuppression regimen included: tacrolimus (100% of patients), mycophenolates (48% of patients), steroids (39% of patients), everolimus (8% of patients). Tacrolimus monotherapy was initially prescribed to 38% of patients. The regimens prescribed at discharge were modified at various times in 77 (44%) patients, in the 1st group in 14 (17.3%), in the 2nd group in 63 (66.3%), (p<0.05). The 10-year survival rate of the initial immunosuppression regimen was 89% in the 1st group, 33% in the 2nd group (p<0.05). Rejection was observed in 21.1% of cases in group 2 and 6.2% (n=5) in group 1 (p=0.004). Immune or unspecified graft dysfunction as a cause of death or retransplantation was significantly less common in group 1 than in group 2: 1 (1.2%) and 7 (7.4%), respectively (p=0.039). The average /CF level after 5 years in patients receiving tacrolimus monotherapy was 69.7±14.1 ml/min/1.73m², while in the combination therapy group it was 62.4±20.7 ml/min/1.73m² (p>0.05). SCF ≥ 60 ml/min/1.73m² was recorded in 76.9% and 48.3% of patients, respectively (p<0.01).

Conclusion. Tacrolimus monotherapy or its combination with everolimus are considered optimal for a selective group of adult liver transplant recipients. With careful selection, strict clinical and drug monitoring, these regimens are characterized by the best survival of therapy, minimal risk of rejection, rare development of late graft dysfunction, favorable safety profile in terms of side effects, in particular, nephrotoxicity.

Introduction. The ability of cells to adhere on bone graft increases its reparative and regenerative properties. The native cortical bone has a very low biological conductivity, which greatly impedes cell migration and adhesion. Various methods of bone surface modification can be used to enhance the bioconductive properties of bone grafts.

Objective. To evaluate the adhesion and proliferative activity of human cells on the surface of cortical bone grafts modified by various methods.

Material and methods. Fragments of cortical bone grafts (CBGs) were used in the study. For physical modification the outer surface of the bone fragments was processed with a flat file with high or low density of grinding teeth. A 2N hydrochloric acid (HCl) solution, 0.005% collagenase I solution, and the collagenolytic enzyme preparation Fermenkol (0.05 mg/mL) were used for chemical modification. In vitro studies of the CBG adhesion were performed in culture of human fibroblasts M-22 line. Untreated CBGs (control) and modified CBGs were placed in the wells of culture vials; a cell suspension containing 10,000 cells was added to each well. Cells were cultured for 7 days.

Results. After 3 days of cultivation, the cells were completely absent or detected in very small numbers on the control CBG samples and CBG samples subjected to mechanical processing. On CBGs treated with 2N hydrochloric acid solution for 3 and 6 hours, the average cell density on the CBG surface estimated 1.0–1.2 thousand/cm²; on CBGs treated with 2N hydrochloric acid solution for 12 hours, the CBG adhesiveness acutely decreased. The highest cell density was observed on CBGs, treated with 0.005% collagenase 1 or Fermencol for 24 hours and amounted to 2.0–2.5 thousand/cm². After 7 days of cultivation, the cell growth was completely absent on the control CBGs, on CBGs processed with a file with a high grinding tooth density, and CBGs treated with 2N hydrochloric acid solution for 12 hours. In experiments with collagenase 1 and Fermencol, as well as in experiments with the treatment with a 2N hydrochloric acid solution for 3 hours, an intensive cell growth was observed on the CBG surface, density of human fibroblasts of the M-22 line and their total number on CBGs increased 3–5-fold without affecting their viability.

Conclusion. Physical modification did not effectively increase the adhesiveness of cortical bone grafts. Effectiveness of chemical modification depends on the duration of exposure to the chemical agent. To increase the adhesion, the cortical bone graft should be optimally treated either with 2N hydrochloric acid solution for 3 hours, or 0.005% collagenase 1 solution for 24 hours, or with Fermencol (0.05 mg/mL) for 24 hours.

Background. Among the numerous developed models of experimental pancreatitis, models of acute traumatic pancreatitis are extremely poorly presented in the literature.

Objective. To create a model of experimental acute traumatic pancreatitis caused by crushing a section of pancreatic tissue.

Material and methods. The study material consisted of 80 male Wistar rats weighing 450-500 g. After induction of anesthesia and median laparotomy, acute pancreatitis was induced by crushing a section of the parenchyma with an L-shaped clamp. Two experimental groups were formed: experimental (n=70) and control (intact animals, n=10). In the experimental group, animals of 10 rats were withdrawn from the experiment after 1, 3, 6, 24, 72 hours, 7 days and 14 days from the beginning of the modeling. During these periods, blood was collected for biochemical analysis and pancreatic tissue was collected for morphological examination.

Results. We have demonstrated for the first time the dynamics of laboratory markers of acute pancreatitis and morphological changes in pancreatic tissue both in the daily terms after injury (1, 3, 6, 24 hours) and the first two weeks (72 hours, 7 days and 14 days) from the start of modeling. We have convincingly shown the stages of the pathological process: from early morphological manifestations of the alterative-exudative phase of inflammation on days 1-3, accompanied by daily peak amylase values, up to complete scarring by day 14 against the background of increased lipase activity at the end of the infiltrative-proliferative phase.

Conclusion. The model of experimental acute traumatic pancreatitis allows us to trace all the characteristic stages of the evolution of the pancreatogenic destruction zone with all the typical laboratory and morphological manifestations.

Background. Patients following radical corrections of conotruncal congenital heart defects often develop right ventricular outflow tract dysfunctions as the child grows. It is well known that repeat surgical interventions, in addition to technical challenges, are associated with high risks and mortality. With advancements in endovascular surgery, transcatheter prosthetic right ventricular outflow tract (RVOT) replacement has become a viable alternative to thoracotomy surgery for a specific patient group. However, the choice of the "ideal" valve for transcatheter interventions remains a subject of debate.

Objective. The aim of this study was to develop a valve for transcatheter implantation into the pulmonary artery position, considering anatomical variations of the RVOT, and to evaluate the hydrodynamic properties of the valve in vitro using bench testing.

Material and methods. Based on the data obtained from a retrospective analysis of patients after radical correction of conotruncal congenital heart defects, a team of researchers from the Bioprosthetics Laboratory at the Center for New Surgical Technologies of National Medical Research Center n.a. Academician E.N. Meshalkin developed a prototype of a self-expanding nitinol frame for transcatheter pulmonary artery replacement.

Conclusions. The prototype of the first domestically produced self-expanding pulmonary bioprosthesis for transcatheter implantation with an anatomically shaped nitinol frame demonstrated optimal hydrodynamic properties during the initial stages of preclinical testing. The anatomical design of the frame allows for valve implantation into the native right ventricular outflow tract without prior stenting.

Introduction. Acute aortic dissection is a current and urgent problem in modern cardiac surgery. In the early stages of the dissection, the surgeon is faced with the dilemma of choosing the volume of intervention from the ascending part reconstruction only or radically ascending and aortic arch replacement. Hybrid systems for one-stage reconstruction of the thoracic aorta are currently being actively developed. The Frozen Elephant Trunk (FET) technique allow us to replacement ascending and arch of the aortae combined with antegrade stent grafting into the descending aorta from the classical sternotomy access. This type of operation doesn’t increase the time of the intervention, there isn’t stage-by-stage reconstruction of the aorta, adequate blood flow in the descending aorta and aortic vessels is restored, and the risks of an adverse outcome are reduced.

Objective. To analyze the results of surgical treatment of acute aortic dissection type A, performed using the FET technique in a multidisciplinary surgical hospital – N.V. Sklifosovsky Research Institute for Emergency Medicine.

Material and methods. The research included 18 patients which were operated from 2022 to 2024 in acute stage of aortic dissection. All patients were operated using a hybrid technique FET.

Results. Multisystem organ failure developed in 5 patients (27.8%). Four patients (22.2%) required renal replacement therapy due to acute renal failure. In 38.9% of the subjects, prolonged artificial ventilation was complicated by pneumonia. Cerebral complications were observed in 6 patients (33.3%). Sepsis accompanied the course of the disease in 16.7% of cases. The 30-day mortality was 22.2%, in the study group.

Conclusion. Using the hybrid prosthesis allowed us to obtain relatively satisfactory results of reconstruction thoracic aortae in case of the acute dissection in the early postoperative period.

Background. Surgical treatment of acute thoracic aortic dissection is often associated with the need for selective cerebral perfusion at the stage of total hypothermic circulatory arrest.

Objective. To establish the preferred method and mode of selective cerebral perfusion (SCP) during complete hypothermic circulatory arrest in surgical treatment of acute thoracic aortic dissection.

Material and methods. Study design: prospective, cohort, single-center. Inclusion criteria: surgical intervention using cardiopulmonary bypass, confirmed diagnosis of acute aortic dissection type A according to Stanford, age > 18 years. The study included 112 patients: 77 men and 32 women aged 31 to 75 years, M±SD=54.79±11.33. All patients (n=112) were treated between 2019 and 2023 and were divided into 3 groups depending on the method of selective cerebral perfusion: antegrade unilateral perfusion (n=51), antegrade bilateral perfusion (n=49), and retrograde perfusion (n=12). The endpoints of the study were cerebrovascular accident (CVA) in the early postoperative period and 30-day in-hospital mortality.

Results. In the bilateral antegrade cerebral perfusion group (biACP), the incidence of CVA in the early postoperative period (p=0.002) and 30-day in-hospital mortality (p=0.006) were statistically significantly lower. Acute cerebral circulatory failure in the postoperative period increases the risk of death by 7.977 times. The volumetric rate of selective perfusion in biACP is a statistically significant predictor of death, and biACP > 12.5 ml/kg/min when calculated for the true body weight according to Broc is associated with an increased risk of hospital mortality.

Conclusions. Bilateral antegrade cerebral perfusion is the preferred technique for selective cerebral perfusion as part of the cardiopulmonary bypass procedure in the surgical treatment of acute thoracic aortic dissection. Restrictive biACP tactics can reduce the risk of 30-day hospital mortality.

Objective. To evaluate the efficacy and safety of the new drug inclisiran (Novartis Overseas investments, AG (/witzerland)) in patients with chronic kidney disease (CKD) and transplanted kidney with impaired lipid metabolism.

Material and methods. The first results of a prospective case series study in three patients with combined diseases: cardiovascular diseases (CVD), lipid metabolism disorder and CKD with transplanted kidney, who have a very high risk of cardiovascular complications are presented. All patients received maximum combined lipid-lowering therapy (statins and ezetimibe) and immunosuppressive therapy. With this therapy, the target level of low-density lipoproteins was not achieved.

Results. The patients underwent general clinical examination. Biochemical parameters, renal excretory function, immunosuppressive therapy, lipid metabolism parameters (total cholesterol, low-density lipoproteins, high-density lipoproteins, triglycerides) were evaluated. The evaluation was carried out before the administration of inclisiran, 3 months after the first administration, six months after the second administration and before the third administration of inclisiran. At the study stages, a stable decrease by 18.4-19.1% in total cholesterol and 51-59.6% in low-density lipoproteins from baseline was found. The level of high-density lipoproteins and triglycerides did not change significantly. Correction of immunosuppressive therapy was not performed. No adverse events and complications were detected during the study. The target level of low-density lipoproteins was achieved.

Conclusion. The first data of the study on the use of inclisiran in patients with CVD, CKD with transplanted kidney and lipid metabolism disorders testify to its efficacy and safety.

Background. Infectious complications in kidney recipients contribute to a significant decrease in the survival rates of transplants and recipients. If it is difficult to determine the source and localization of inflammation in immunocompromised patients using standard research methods, it is possible to use a radionuclide method using labeled autoleukocytes.

Objective. To demonstrate the possibilities of using an autoleukocyte tag in a kidney recipient to search for a focus of inflammatory infiltration.

Material and methods. A 33-year-old patient underwent primary kidney transplantation from a postmortem donor. The early postoperative period was complicated by the development of an infection site, the localization of which could not be identified using standard diagnostic methods. The search for the inflammatory focus was carried out using the radionuclide label of autoleukocytes.

Results. The study of radionuclide labelling of autologous leukocyte made it possible to identify the focus of inflammation, which was represented by infiltrate in the projection of the lower third of the sigmoid colon due to its microperforation. The treatment performed made it possible to cure this infectious complication.

Conclusions. The use of clarifying and non-routine diagnostic methods helps to promptly and accurately determine the location and size of the leukocyte infiltration.

Introduction. The problem of treating chronic heart failure (CHF) remains one of the most important challenges in cardiology. Despite advances in pharmacotherapy of cardiovascular diseases and the use of the entire arsenal of existing treatment methods, heart transplantation remains the only radical treatment for patients with end-stage heart failure that can significantly improve their prognosis and quality of life.

Objective. To investigate the morbidity, the structural-functional state of the myocardium, and mortality of recipients after orthotopic heart transplantation (OHT) in the long term.

Material and methods. The study included 50 recipients (44 males and 6 females) who underwent OHT at the N.V. Sklifosovsky Research Institute for Emergency Medicine. The mean age of the patients was 51.2±10.5 years. The mean follow-up period after OHT was 6.5±1.5 years.

Results. In the long term after OHT, 16% of recipients were considered healthy; the others were diagnosed with chronic heart failure (CHF) with preserved left ventricular (LV) ejection fraction of functional classes I and II (86%); arterial hypertension (50%); and ischemic heart disease (IHD) without hemodynamic stenosis of the coronary arteries (98%). Normal values of LV global longitudinal and circumferential myocardial strain suggested that after 6 years, the adaptive functions of the heart in transplant recipients was restored, indicating a favorable outcome, confirmed by the absence of remodeling of the right heart chambers and restoration of work capacity (77%). In the long term, side effects of immunosuppressive therapy (oncopathology, post-transplant hypertension, nephropathy, and infections) were observed, which did not differ in frequency from the results of other studies. The mortality rate was 42%. After 1 year, 11.3% had died, and thereafter the mortality rate was 4–6% per year. The highest mortality rate was observed in the first 3 years post-OHT. The main causes of death in the long term were oncological diseases, chronic graft rejection and sudden cardiac death.

Conclusion. In the long term after OHT, 16% of recipients were considered healthy; 77% were capable of work. After 6 years of follow-up, the adaptive functions of the heart in recipients were restored. The long-term mortality rate was 4–6% per year.

Background. Liver transplantation is the only radical treatment for end-stage liver diseases; however, postoperative infectious complications, particularly sepsis, significantly worsen prognosis and increase mortality. Sepsis after liver transplantation develops in 20–40% of recipients and is associated with high mortality (up to 50%), which is caused by immunosuppressive therapy, surgical trauma, and the baseline severity of the patient's condition.

Objective. To provide a literature review on sepsis biomarkers after liver transplantation.

Material and methods. Analysis of scientific publications in PubMed, Google Scholar, and Medline databases for the period 2015–2025 on the topic of sepsis biomarkers after liver transplantation.

Results. The main groups of sepsis biomarkers after liver transplantation were identified and systematized: immunological (T-cell clonality, sTREM-1, presepsin, cytokines), biochemical (procalcitonin, hyaluronic acid, bilirubin, INR), hematological (neutrophil-lymphocyte ratio, platelets), genetic and epigenetic (microRNA, long non-coding RNA). Combined prediction algorithms using clinical scales (SOFA, MELD) and machine learning methods were analyzed.

Conclusion. Current data indicates significant prognostic potential of sepsis biomarkers after liver transplantation. The most promising direction is the combination of immunological (T-cell clonality, sTREM-1) and biochemical (PCT, HA) markers, integration of traditional scales (SOFA, MELD) with machine learning algorithms, and the use of genetic and epigenetic markers for a personalized approach. Implementation of these approaches in clinical practice will significantly improve outcomes in liver recipients through early diagnosis of sepsis, timely initiation of therapy, and personalized immunosuppressive treatment.

Introduction. Articular hyaline cartilage has special structural and functional characteristics, which are critically important for preserving tissue grafts, containing cartilage elements. Allogeneic bone-cartilage grafts (BCG) could be very perspective in the treatment of joint defects. However, the widespread clinical use of BCG shows significant difficulties, associated with effective choice of preservation and sterilization methods.

The aim of the study was to analyze modern methods of allogeneic BCG-preserving, according to their effect on the structural integrity of tissue, biomechanical properties and cellular viability.

Material and methods. We systematized data from scientific publications selected in the Scopus, PubMed, eLibrary, and CyberLeninka databases for the period from 1980 to 2024, with a focus on research published over the past 15 years.

Results. Cryopreservation is considered as the most convenient method for long-term storage of BCG, however, its effectiveness significantly depends on the optimization of protocols, including the selection of adequate cryoprotectors, freezing and thawing modes. Lyophilization successfully allows to preserve bone part of BCG, but it causes significant deformation of cartilaginous part, loss of its structural organization and mechanical properties. BCG-storage in liquid culture media and solutions ensures short-term preservation of the graft (about 2–3 weeks), longer storage is accompanied with progressive decrease of biomechanical characteristics and the development of matrix edema. The use of chemical agents (aldehydes, alcohols, glycerol) for BCG-preservation seems impractical due to their pronounced cytotoxic effect and negative effect on tissue architecture. Supercritical CO₂ treatment is considered as potentially promising method, targeted on combining tissue sterilization and preservation of structural properties.

Conclusion. The development of effective methods for preserving allogeneic BCG, ensuring the maintenance of their structural and functional characteristics, remains an urgent interdisciplinary task, requiring integration of advances in cell biology, cryobiology and tissue engineering. At the current stage, cryopreservation is the most reasonable approach, while other methods require further experimental and clinical verification.

Introduction. In diseases of the esophagus, operations are often performed to resect or completely remove it with plastic restoration with the stomach or intestine, which is associated with various complications immediately after surgery and in the late period (graft necrosis, stenosis, anastomositis, recurrence of the diseases, etc.). Replacing one's own esophagus with an implant is a promising method for solving the urgent problem of esophageal surgery.

The purpose of this review is to summarize knowledge and describe the current state of research on the creation of an artificial esophagus.

Material and methods. The review includes foreign and domestic publications on this topic. /cientific papers found in the electronic libraries eLIBRARY, Elektronische Zeitschriftenbibliothek, the Cochrane Library and PubMed in three languages: Russian, English and German were analyzed.

Conclusion. The analyzed publications reflect two main ways to solve the problem: the development of prostheses based on artificial tissues and bioengineering restoration of the esophagus. The creation of a bioengineered esophageal transplant is possible due to the combination of a framework and a cellular component. In order for the use of a bioengineered neoesophagus to become an effective method for treating esophageal diseases, it is necessary to solve issues related to its mobility, vascularization, intercellular interaction and interaction of cells with the framework. In this regard, the creation of a bionic esophageal prosthesis with controlled motor function is a possible solution to the problem. Modern synthetic materials and technologies make it possible to create all components of the esophageal wall. At present, the indicated problem is still at the stage of development and experiments.