Objective: to demonstrate the first long-term outcomes of treatment of unresectable hilar cholangiocarcinoma (HCCA) after combined neoadjuvant therapy followed by liver transplantation (LT). Materials and methods. From 2017 to 2023, at the Russian Research Center of Radiology and Surgical Technologies, 10 patients were included in the treatment protocol for unresectable HCCA. Combined neoadjuvant therapy included endobiliary photodynamic therapy (EPDT), regional chemotherapy (RCT) and systemic polychemotherapy (SPCT). Each modality was applied at least three times over a period of four to six months. Patients were placed on the LT waitlist when tumor marker CA19-9 reduced, there was no radiological evidence of disease progression, and there was no evidence of acute cholangitis. Before LT, the recipients underwent diagnostic laparoscopy to exclude carcinomatosis and also evaluation of regional lymph nodes with urgent morphologic examination. In the absence of extrahepatic tumor spread, LT from a deceased donor was performed according to the classical technique with paracaval and hepatoduodenal lymph node dissection, biliodigestive anastomosis using the Roux-en-Y procedure. The operation was performed in six patients. Patient age ranged from 40 to 55 years (mean, 46.3). The mean time from start of treatment to LT was 9.1 months (range 6 to 14). The mean CA19-9 level at the time of LT was 66.5 IU/mL (8 to 212). Results. After combined neoadjuvant treatment, the CA19-9 marker normalized in four patients and there was a 3–4-fold decrease in two patients. Radiological evaluation indicated stable disease in five patients, and a partial response in one. Disease progression was noted in four out of 10 patients. Currently, one of the 6 patients is alive with a follow-up of 34 months. Median (Me) overall survival is 28 months; Me overall survival after LT is 22.2 months; Me survival before progression is 27 months. During long-term follow-up of patients after LT, three patients out of six had disease progression: implantation metastasis (n = 2) at 25 and 27 months follow-up (metastasectomy was performed), carcinomatosis (n = 1) at 20 months follow-up. Conclusion. LT for unresectable Klatskin tumor is effective when combined neoadjuvant treatment is used and there is no acute cholangitis. However, the use of endobiliary manipulations (drainage change, EPDT) are risk factors for the development of implantation metastasis.

Objective: to analyze the immediate and long-term outcomes of kidney transplantation (KT) depending on the duration of delayed graft function (DGF). Materials and methods. The study conducted a retrospective analysis of KT outcomes in 312 patients operated on at Botkin Hospital from June 2018 to December 2022. Exclusion criteria were primary non-function, severe surgical complications that required emergency transplantectomy in the first week after KT and cases where a comprehensive approach to DGF prevention was applied. DGF was defined as the need for dialysis within the first 7 days of KT. The severity of this complication was assessed by the time it took the transplanted kidney function to normalize from mild DGF to severe. We analyzed the immediate and long-term outcomes of KT depending on the presence of initial function and the severity of DGF. Results. DGF developed in 25.3% of cases. The mean time for graft function normalization was 16.5 ± 6.8 days. Mild DGF occurred in 68% of cases, severe DGF was determined in the remaining cases (32%). The incidence of complications was statistically significantly higher in the severe DGF group: 14/25 (56%) vs. 15/54 (27.8%) (p = 0.047). There were also no significant differences in the rate of complications between recipients with immediate and mild DGF: 43/233 (18.4%) vs. 15/54 (27.8%) (p > 0.05). Severe DGF lasting for more than 2 weeks had a statistically significant association with postoperative complications (p = 0.047) and with decreased long-term graft survival (log-rank p = 0.021). Conclusion. Development of severe DGF mainly depends on donor characteristics, timing and peculiarities of graft preservation. Nevertheless, other factors, such as acute calcineurin inhibitor nephrotoxicity, should not be ignored. Therefore, prevention of all potentially modifiable risk factors for DGF should go hand in hand with the expansion of the indications for donation.

This review paper aims to analyze the problem of diagnosis and treatment of coronary heart disease (CHD), also called ischemic heart disease (IHD), in patients with end-stage renal disease (ESRD). The analysis is based on current literature data. The issues of CHD risk stratification before patient listing for kidney transplantation (KT) and possible difficulties of diagnosing CHD using non-invasive examination methods in ESRD patients are considered. The effectiveness of myocardial revascularization and drug therapy, endovascular and surgical myocardial revascularization, is compared. The paper also discusses the peculiarities of drug therapy, particularly antiplatelet and antihyperlipidemic therapy in the treatment of CHD in dialysis-dependent patients and kidney recipients.

Objective: to compare the effects of nonselective beta-blockers (NSBB) and endoscopic variceal ligation (EVL) on patient survival, ascites dynamics, and development of acute kidney injury (AKI) during primary prevention of bleeding from the esophageal varices and cardia in patients with decompensated cirrhosis on the liver transplant waiting list (LTWL). Materials and methods. A retrospective comparative study of the clinical data of patients with severe ascites and esophageal varices without a bleeding history at the time of their inclusion in the LTWL was performed. Group 1 patients (n = 84) were prescribed NSBB, alpha and beta-adrenoblockers in order to prevent bleeding and reduce progression of decompensated cirrhosis. Group 2 patients underwent EVL. Results. Demographic, laboratory and instrumental parameters of patients in the compared groups had no significant differences. In both groups, there were no significant differences between the indicators of severity of liver lesions (MELD-Na, Child–Turcotte–Pugh), frequency of severe ascites, frequency of varicose nodes grades 2–3. At follow-up, bleeding developed in 22 patients (13.25%) – 13 patients in the NSBB group and 9 patients in the EVL group (15.47% and 10.97%, respectively, p > 0.05). Patient survival was significantly higher in the EVL group than in the NSBB group. Incidence of refractory ascites, number of patients with grade 3 ascites, and AKI stages 2–3 in the NSBB group, were significantly higher (p < 0.05) than in the EVL group. MELD-Na was the independent predictor of mortality in the EVL group, while low mean arterial pressure (mAP) and presence of AKI were those for patients receiving NSBB. Conclusion. NSBB and EVL are effective methods of primary prevention of bleeding. Mortality rate, number of patients with refractory ascites and severe ascites, and number of patients with AKI stages 2–3 were higher in the NSBB group than in the EVL cohort. In EVL patients, the independent predictor of death was MELD-Na, while in NSBB patients, the independent predictors of mortality were low mAP and presence of AKI.

Bronchial stenoses are one of the most common airways complications after lung transplantation. One of the main methods to restore airway patency is bronchial stenting. However, bronchial stenting is associated with a number of complications, such as stent migration, granulation tissue formation along the proximal and distal edges, and mucus obstruction of the lumen. This article demonstrates the possibility of manufacturing an everolimus-eluting stent from thermoplastic polyurethane and polylactide using 3D printing.

Heart transplantation (HT) with extremely prolonged (>6 hours) graft ischemia is associated with severe cardiac graft dysfunction. The high efficiency of prophylactic (preoperative initiation) veno-arterial extracorporeal membrane oxygenation (VA-ECMO) to prevent severe hemodynamic disorders during cardiac surgery has been demonstrated. Objective: to determine the effect of prophylactic VA-ECMO on the perioperative period in HT with an expected graft ischemia >6 hours. Materials and methods. Thirty-eight recipients (33 (86.8%) males and 5 (13.2%) females), age 11–66 (44.7 ± 12.0) years (median 48.0 years) were examined. Pre-transplant mechanical circulatory support (MCS) using peripheral VA-ECMO was applied in 15 (39.5%) recipients, in 6 of whom by prophylactic technique. The recipients (n = 38) were divided into 3 groups: 1) «no pre-HT VA-ECMO» (n = 23); 2) «pre-HT VA-ECMO» (n = 9) – pre-transplant VA-ECMO as a bridge to HT; 3) «prophylactic VA-ECMO» (n = 6). Results. In «prophylactic VA-ECMO» group, extracorporeal circulation (ECC) (94.0 [85.5; 102.8] min) and reperfusion time (20.0 [18.3; 27.6] min) were shorter (p < 0.05) compared to «no pre-HT VA-ECMO» (161.0 [122; 191.5] and 60.0 [55.3; 70.5] min) and «pre-HT VA-ECMO» (127.0 [117; 150.3] and 35.0 [27.8; 48.8] min) groups. The vasoactive-inotropic score was lower (p < 0.05) in «pre-HT VA-ECMO» and «prophylactic VAECMO» groups compared to recipients in «no pre-HT VA-ECMO» group, 12.1 [11.2; 14.0] and 12.5 [11.7; 14.8] vs. 16.0 [15.0; 18.5], respectively. The groups did not differ in terms of incidence of severe primary dysfunction. The «pre-HT VA-ECMO» and «prophylactic VA-ECMO» groups were characterized by shorter duration of mechanical ventilation (MV) compared with «no pre-HT VA-ECMO» group (11.7 [10.0; 16.5] and 12.7 [11.3; 18.4], respectively, vs. 14.5 [13.0; 19.3]). The «no pre-HT VA-ECMO» and «prophylactic VA-ECMO» groups did not differ in the need for postoperative MST, 21.7% and 16.7%, respectively. The groups did not differ in terms of length of stay in the intensive care unit (ICU) and in-hospital mortality – 0% («prophylactic VA-ECMO») and 8.7% («no pre-HT VA-ECMO») and 11.1% («pre-HT VA-ECMO»), respectively. Conclusion. Prophylactic VA-ECMO in HT with extremely prolonged cardiac graft ischemia reduces ECC duration, reperfusion period, postoperative mechanical ventilation period, and the need for inotropic therapy.

Background. There is quite a high number of patients with advanced heart failure (HF) who have undergone surgical treatment for complex congenital heart defects. Implantation of mechanical circulatory support systems is the only treatment option for patients with refractory end-stage heart failure. Only a few centers have experience in implantation of ventricular assist devices (VAD) in children, which is a major challenge for modern pediatric cardiac surgery. Objective: to present our first experience of implantation of HeartMate III VADs in patients after surgical correction of complex congenital heart defects. Materials and methods. From 2021 to 2022, at Bakulev Center for Cardiovascular Surgery, four HeartMate III systems were implanted in children with advanced HF, who had previously undergone surgery for a complex congenital heart defect. In one case, aortic valve implantation was carried out simultaneously with VAD implantation. Results. All patients were discharged from the center. One patient developed right-sided heart failure intraoperatively, which required the use of a right ventricular assist device (RVAD) for 8 days. There were no complications from the central nervous system, bleeding, pump thrombosis, or infection. Conclusion. HeartMate III can be implanted in patients with body weight ≥21 kg and BSA ≥0.88 m2 . Children’s tolerance to physical activity increases, they are fully adapted socially, and can attend school.

Mechanical circulatory support (MCS) devices, designed specifically for patients with small anthropometric parameters, are now emerging. A detailed systematic literature review of existing systems for long-term circulatory support in this patient cohort was conducted. Circulatory support devices and their main technical and biological characteristics were studied in detail. Despite significant scientific and technological progress, there is still no technology for creating an assist pump to support patients with small body surface area (BSA), given the wide range of patient sizes, increased cardiovascular demand due to growth, as well as anatomical and physiological heterogeneity of congenital heart disease.

The emergence of new groups of medications used in the treatment of chronic heart failure (CHF) has made it possible to optimize treatment regimens, changing the clinical status and prognosis in this patient cohort. In this regard, the relevance of individual prognostic markers and risk assessment scales for heart failure (HF) is losing its value. The aim of our review is to summarize the currently available evidence on modern methods of evaluating the functional capabilities of the body and exercise tolerance in CHF patients on the background of systolic dysfunction before heart transplantation.

Cardiac allograft vasculopathy (CAV) is a coronary heart disease (CHD), arising after an orthotopic heart transplant (OHT), and it is one of the leading causes of death in heart recipients. The probability of death is 10%. CAV can manifest as early as 1 year after OHT. Patients do not have pain syndrome that is typical for CHD due to cardiac denervation. The first clinical manifestations may be congestive heart failure, ventricular arrhythmias or even sudden cardiac death. Coronary angiography is the routine technique for CAV detection. However, it is not sensitive enough (about 44%) for CAV detection at an early stage of the disease. Today, intravascular imaging methods (intravascular ultrasound, optical coherence tomography), which allow the evaluation of the morphology of coronary artery lesions, including CAV, have become widespread. This article is devoted to the modern capabilities of intravascular imaging methods in the diagnosis of CAV. CAV is the main cause of myocardial infarction and chronic heart failure in patients after OHT. Intravascular imaging techniques allow early detection of this condition and prevention of unfavorable outcomes in a complex category of heart recipients. Given the advantages of optical coherence tomography (OCT) and disadvantages of intravascular ultrasound (IVUS), OCT appears to be a more informative method of CAV detection.

Background. According to the World Health Organization, corneal diseases are one of the major causes of blindness globally. Endothelial dystrophy is one of the etiological factors leading to corneal diseases. The corneal endothelium is a monolayer of cells with virtually no mitotic activity. When the density of corneal endothelial cells falls below a critical threshold, the endothelium loses its ability to regulate corneal stromal hydration. This leads to corneal clouding and, consequently, to reduced visual acuity and quality of life of the patient. In this regard, various keratoplasty methods are widely used in clinical practice. Today, it is technically possible to transplant all corneal layers via penetrating keratoplasty, and to transplant the posterior epithelium via layer-bylayer keratoplasty. These surgical approaches are now widely used in everyday practice, but they require the use of scarce material – cadaveric donor corneas, from which grafts for the above-mentioned operations are formed in the conditions of an eye bank. In this regard, protocols for obtaining human corneal endothelial cell (HCEC) culture for subsequent transplantation have been proposed in recent years. However, the use of such approaches in Russia is limited by the law. The aim of this study was to experimentally justify the possibility of transplanting uncultured endothelial cells, isolated from cadaveric human corneas. Materials and methods. The first stage of the work consisted of obtaining a suspension of endothelial cells from cadaveric donor corneas and studying it; at the second stage, the transplantation effectiveness of the resulting cell suspension was assessed in an ex vivo experiment. Results. The cell phenotype after transplantation by the proposed method had high viability and preservation. Conclusions. The presented results suggest that phenotype and adhesion ability are preserved, and that the cell suspension has a high level of viability under adequate loss of endothelial cells during transplantation in the ex vivo experiment.

Objective: to analyze data on the synthesis and properties of cerium oxide nanoparticles, as well as the prospects of its application in regenerative medicine for wound healing. Methodology. World literature was reviewed using PubMed, SCOPUS, ResearchGate, CyberLeninck, and Elibrary databases, as well as manual searches for authors and reference lists. Key search terms were «cerium oxide» AND nano* AND (healing OR regeneration OR repair) AND wound». The timeline was from the date of publication through August 2023. Results. The final analysis included 59 sources containing information on the synthesis and size of nanoparticles (and/or other physicochemical characteristics), methodology and results of in vivo and in vitro studies on the efficacy and/or safety of nanoceria for wound regeneration. It is shown that despite the progressive growth of research interest over the last 15 years, the actual use of nanoceria in practical medicine is still not widespread. This is due to a wide variety of non-standardized synthesis methods and conditions, resulting in the variability of physicochemical parameters of nanoparticles (size, form), thereby affecting the safety and biomedical efficacy of nanoceria. Regeneration mechanisms, including the antioxidant-prooxidant, anti-inflammatory and antimicrobial effects of nanoceria, which contribute to accelerated wound healing, are discussed. The severity of the regenerative effects depends on the method and conditions of synthesis, hence the resulting physicochemical characteristics of the nanoparticles. Therefore, after each batch, newly synthesized nanoceria needs physicochemical and biomedical experimental tests. Conclusion. Nanoceria has great potential in tissue engineering for regenerative medicine, particularly for healing of various kinds of wounds. Having developed a technology for standardized synthesis for effective and safe nanoceria (of the right form and size) on a production scale, it can be introduced in medicine, possibly improving the outcomes of treatment of many diseases and pathologies. The authors present conclusions on the results of the study of nanoceria for accelerating qualitative regeneration and the requirements for nanoparticles obtained during synthesis.

Introduction. Intradialytic hypotension (IDH) is a common complication of renal replacement therapy (RRT) sessions and may be a particularly detrimental factor in heart recipients. Objective: to investigate the incidence of IDH in heart recipients with acute kidney injury (AKI). Patients and Methods: Two groups of recipients were compared – the study group (SG), n = 313, in which 49 patients required intermittent RRT (IRRT) and in which online hemodiafiltration (OL-HDF) sessions were performed using acetate-free hydrochloric acid-based dialysate fluid; and control group (CG) n = 387, in which 88 patients required IRRT, where standard dialysate with an acetate ion content of 3 mmol/L was used for OL-HDF. Results. There was a significantly lower incidence of IDH in the SG compared to the CG: 10.46% vs 20.47% (p < 0.05). Conclusions. In heart recipients for whom IDH can be considered as a significant adverse factor, the use of acetate-free dialysis fluid can significantly reduce the incidence of this complication.

Organ transplantation is the best therapy for terminal and irreversible organ failure. The global development of organ transplantation as a type of medical care is inextricably linked to the establishment of neurological criteria for declaring human death (brain death). In the early evolutionary period of transplantation, organs were used, mainly kidneys, obtained from donors whose death was ascertained in accordance with the generally accepted criteria of cessation of blood circulation and respiration. As this type of organ donation developed, numerous terms were used in the world literature to designate it, such as ‘asystolic donors’, ‘non-heart beating donors’, ‘donors after cardiac death’, etc. In Russia, there is an established practice of dealing with donors after cardiac death (DCD), but the active development of Russian transplantology in the last 20 years is primarily associated with brain-dead organ donation. However, countries with the most active and advanced organ donation practices have in recent years been successfully dealing with donors who have suffered sudden out-of-hospital cardiac arrest (OHCA). Previously, this type of donation was considered inaccessible due to the unacceptable warm ischemia time and consequently severe damage to donor organs. Due to the development of new technologies in emergency medical care, it became possible to transport a patient with clinical death that occurred in an outof-hospital setting, to the hospital, while providing cardiopulmonary resuscitation by means of automatic chest compression and artificial ventilation. The article presents historical aspects of donation after cardiac death, and the most actualized definitions and practices of dealing with such donors.

Objective: to develop, master and evaluate the efficiency of an isolated lung transplantation (LT) technique on a rabbit animal model using Perfadex Plus® solution for cold static storage. Materials and methods. Scottish Giant rabbits (n = 20) were used in this study and divided into two groups: donors and recipients. Donor lungs were preserved with Perfadex Plus® solution and stored for 6 hours at 4 °C. Recipient animals underwent unilateral orthotopic left LT. The postoperative follow-up period was 24 hours. Laboratory and instrumental control with assessment of blood gas composition, lactate level, ventilation parameters, and central hemodynamic parameters, was performed during the follow-up. Chest X-ray in direct projection was performed twice, and at the end of follow-up, material was taken for histologic examination. Results. We obtained a high oxygenation index in the post-transplant period (>350 at p < 0.023), as well as physiological indicators of lactate (3 ± 0.3 mmol/L at p < 0.002) and peak inspiratory pressure (15 ± 1 cmH2O, p < 0.001). Radiological examination showed no radiological signs of severe primary graft dysfunction in all cases (mean RALE score 1), which was confirmed by histological studies. Conclusion. Left LT in rabbits is possible, the LT technique on a biological rabbit model using Perfadex Plus® solution is valid and efficient with the achievement of satisfactory gas exchange, ventilation and metabolism parameters.

This paper analyzes the problem of euthanasia, gives the history of this phenomenon, presents traditional ethical arguments for and against this practice, critically evaluates the practice of organ donation after euthanasia or euthanasia as a consequence of organ donation as established in some countries of the European Union, the US and Canada. The current status of this controversial practice is assessed.

Autologous bone grafts are considered the gold standard for bone grafting, but in cases where their use is limited or impossible, allogeneic bone tissues become the first alternative. To date, the legal status of the activity on manufacturing bone grafts from femoral heads after total hip replacement surgery has not been defined. This somewhat hampers the development of this technology in Russia. Specialized institutions typically use internal instructions developed and approved taking into account existing legal norms in various fields. The creation of uniform operating rules, standards, instructions, clinical guidelines for working with donor tissues, as well as relevant sufficient regulatory and legal support would promote the development of tissue transplantology, bioimplantology and tissue engineering. This, in turn, would open up wide opportunities for the development of new methods of treatment of diseases, injuries, traumas and their consequences.

The global development of transplantology faces several objective obstacles. One of the major ones is widespread organ shortage. This is most pronounced in clinical lung transplantation (LT). The development of this area is directly connected with more intensive development of available donor resources and search for new sources of donor organs that are suitable for transplantation. Along with the existing methods of increasing the number of lungs suitable for transplantation, LT with donation after cardiac death (DCD) is attracting increasing attention. The effectiveness of this approach has been confirmed by the International Society for Heart and Lung Transplantation and deserves more attention from Russian specialists.

Prosthetic heart valves are widely used biomedical devices. The need for these prostheses is increasing due to the increasing life expectancy of the general population and the consequent incidence of age-related degenerative valvular defects. However, even though mechanical prosthetic valves have been significantly modernized over the last decades, they are still associated with several life-threatening complications, the main one being thrombosis. Addressing this problem is challenging and requires collaboration between bioengineering and cardiothoracic surgery. Thus, the problem of creating the most adapted model of prosthetic heart valve (PHV) turns out to be at the confluence of sciences – medicine, biology, applied mechanics, mathematical modeling, etc. Today, it seems clear that the engineering ideas for hemodynamic adaptation of PHV models have been fully developed. However, research in the field of materials science, as well as a search for surface modification methods, remain a pressing bioengineering challenge.