Deceased brain-dead donor liver transplantation (LT) is a high-risk intervention. The outcome depends on a large number of modifiable and non-modifiable factors. Objective: to analyze our own experience and identify preoperative and perioperative prognostic factors for poor outcomes in LT. Materials and methods. The study included 301 liver transplants performed between January 2016 and December 2021. Donor and recipient characteristics, intraoperative data, perioperative characteristics including laboratory test data, and the nature and frequency of complications were used for the analysis. Results. The 1-, 3- and 5-year recipient survival rates were 91.8%, 85.1%, and 77.9%, respectively; graft survival rates were 90.4%, 83.7%, and 76.7%, respectively. The most significant predictors of poor outcome of LT on the recipient side were biliary stents (HR 7.203, p < 0.01), acutely decompensated cirrhosis (HR 2.52, p = 0.02); in the postoperative period, non-surgical infectious complications (HR 4.592, p < 0.01) and number of reoperations (HR 4.063, p < 0.01). Donor creatinine level (HR 1.004, p = 0.01, one factor analysis; HR 1.004, p = 0.016, multivariate analysis) was the only reliable prognostic negative factor. Conclusion. LT taking into account established risk factors will improve surgery outcomes and help personalize the therapy for each patient.

Kidney transplantation (KT), the optimal treatment for stage 5 chronic kidney disease (CKD), restores impaired fertility in most women of reproductive age. However, infertility occurs in some patients after successful KT. We present our own experience of overcoming secondary tubal infertility by in vitro fertilization (IVF). The patient was a 36-year-old with a transplanted kidney, who had lost two pregnancies in the past due to severe preeclampsia (PE). After the second attempt on cryo-thawed embryo transfer against the background of hormone replacement therapy, one embryo was transferred into the uterus, resulting in pregnancy. Gestational diabetes mellitus (GDM) was diagnosed in the first trimester, and a diet was prescribed. Immunosuppression with tacrolimus, azathioprine and methylprednisolone, prophylaxis of PE with low molecular weight heparin and antiplatelet drugs were administered during pregnancy. Elective cesarean section was performed at 37–38 weeks and a healthy boy was born, weighing 2760 g (25th percentile), 48 cm tall (36th percentile). A stay in the neonatal intensive care unit was not required. The baby is growing and developing normally, the mother’s renal graft function is satisfactory. So, IVF can be successfully used in post-KT patients with infertility issues, provided that the IVF program is carefully controlled, and the pregnancy is managed in a multidisciplinary manner.

Immunosuppressive therapy (IMT) is the cornerstone of treatment after transplantation. The goal of immunosuppression is to prevent acute and chronic rejection while maximizing patient survival and long-term graft function. However, the expected effects of IMT must be balanced against the major adverse effects of these drugs and their toxicity. The purpose of this review is to summarize world experience on current immunosuppressive strategies and to assess their effects on renal function.

In recent years, cardiologists and cardiovascular surgeons are increasingly encountering radiation-induced heart disease (RIHD) in their practice. This complication is described in literature but is poorly understood and clinically challenging. Radiation therapy (RT) is widely used in the treatment of many cancers. Despite the considerable risk of RT complications, it is used in 20–55% of cancer patients. Radiation-associated cardiotoxicity appears to be delayed, typically 10 to 30 years following treatment. Mediastinal irradiation significantly increases the risk of non-ischemic cardiomyopathy. Recent reviews estimate the prevalence of radiation-induced cardiomyopathy at more than 10%. Therefore, it is important to understand the pathophysiology of RIHD, consider risk factors associated with radiation injury, and detect the condition early.

The development of low-traumatic surgical drains aimed at maximum possible separation of blood and air, is an important trend in modern medicine. The objective of this work is to create an inexpensive, user-friendly and low-traumatic dynamic blood aspiration system (DBAS). The system allows effective separation of blood and air when drawing blood from a wound under vacuum conditions required for blood aspiration. The operating principle of the system is to separate liquid and gas fractions of the blood-air mixture by modifying the blood intake cannula. The effect is achieved by applying the principles of centrifugal forces of a rotating blood-air flow combined with Archimedes lift forces.

Objective: to investigate the effectiveness of a new mechanized lymphatic drainage method in acute decompensated heart failure (ADHF) modeling through local reduction in venous pressure in the site of lymphatic drainage from the thoracic duct.

Materials and methods. Main components of the device are a catheter with built-in inlet and outlet mechanical valves designed for insertion into the left brachiocephalic vein through the left internal jugular vein. It comes with an extracorporeal drive system made as a valveless pulsator pump with a 10 ml shock discharge and a controller ensuring preset frequency and pressure/rarefaction duty cycle. The operating principle of the device is based on local reduction of venous pressure in the site of lymphatic drainage from the thoracic duct (in the junction of the left internal jugular and subclavian veins).

Results. When modeling hydrodynamics under ADHF conditions on a hydrodynamic test bench, the upper venous flow through the left brachiocephalic vein was 0.4 l/min, the pressure in the site of lymphatic drainage from the thoracic duct, was decreased from 20–25 mmHg to 0–5 mmHg due to operation of the mechanized drainage device with suction/injection phase duration ratio 0.2/0.8 and pulsator pump operating frequency from 30 to 60 beats/min.

Objective: to study the effectiveness of correcting the morphofunctional characteristics of the liver in an experimental model of chronic liver disease (CLD), using implanted cell-engineered constructs (CECs).

Materials and methods. Experiments were carried out on male Wistar rats (n = 80) aged 6–8 months with an initial weight of 230–250 g. CLD was modeled by inoculating the rats with 60% CCl4 oil solution for 42 days based on a modified scheme. Microgel based on recombinant spidroin rS1/9 was used as a matrix for CECs fabrication. Allogeneic liver cells (LCs) and multipotent bone marrow-derived mesenchymal stem cells (BM-MSCs) from a healthy donor were used as the cellular component of the CECs. The effectiveness of the corrective effect of the implanted CECs was assessed in an experimental CLD model (n = 60) in two groups of rats: Group 1 (control, n = 20, 1 mL of saline solution was injected into the damaged liver parenchyma) and Group 2 (experimental, n = 40, CECs containing allogenic LCs and BM-MSCs in a 5 : 1 ratio in a volume of 1 mL were implanted into the damaged liver parenchyma). For long-term monitoring of the CEC state, the CECs were labeled by additional inclusion in Cytodex-3. The effectiveness of the regulatory effect of CECs on regenerative processes in the liver was evaluated using biochemical, morphological and morphometric techniques, as well as by flow cytometry at 90 days after implantation.

Results. In the control group, the mortality rate in CLD was 25%. There was no death in the experimental group with CLD after CEC implantation. The CECs were found to have a corrective effect on the biochemical and morphological parameters of the liver in CLD during 90 days of follow-up, with concomitant preservation of structural cellular homeostasis in the implanted CECs. Conclusion. Implantation of CECs in the liver facilitates effective correction of CLD by activating regenerative processes in the damaged liver, which is due to long-term preservation of structural cellular homeostasis in the CECs.

In contrast to decellularization of soft tissues for use as tissue-specific matrices in the creation of tissue-engineered constructs, decellularization of cartilage tissue requires several processing techniques, which can negatively affect the biocompatibility and functional properties of the native extracellular matrix (ECM).

Objective: to study the biocompatible and functional properties of microdispersed tissue-specific 3D matrix from a porcine cartilage that is decellularized by sequential use of chemical, physical and enzymatic techniques.

Materials and methods. For decellularization, microdispersed cartilage particles (MCPs), obtained by cryomilling, were incubated in detergent solutions (sodium dodecyl sulfate and Triton X-100), then treated with supercritical carbon dioxide (scCO2) with 10% ethanol and DNase I. The Ames test (Salmonella typhimurium reverse mutation assay) was used to determine the genotoxicity of decellularized microdispersed cartilage particles (dMCPs). Local and general toxic effects, as well as resorption of dMCPs were studied in vivo on sexually mature outbred rats. Decellularized MCP specimens (10 mg) were implanted into the thigh muscle tissue. Viability of human adipose-derived mesenchymal stem/stromal cells (hAdMSCs), when cultured on dMCPs, was analyzed by in vivo microscopy, stained with fluorescent Calcein AM dye. Cell metabolic activity was assessed using PrestoBlue™ Cell Viability Reagent.

Results. It has been proven that porcine dMCPs implanted in rat muscle after treatment with scCO2 do not exhibit local and general toxic effects, and do not show genotoxicity and negative effects on the reproductive system of animals. After 6 months of in vivo experiment, most (87%) of the implanted decellularized cartilage was resorbed. It was shown that the resulting matrices are able to support adhesion and proliferation of hAdMSCs. Conclusion. Porcine dMCP specimens are suitable for biocompatible medical products in terms of local and general toxic effects, genotoxicity and reproductive toxicity, and can be used as a matrix for creating cell- and tissue-engineered cartilage constructs.

Objective: to compare the efficiency of regenerative processes in the liver using apoptotic bone marrow-derived mononuclear cells (BMMCs) and intact BMMCs from healthy animals on an extended liver resection (ELR) model.

Materials and methods. Male Wistar rats (n = 77) with an ELR model (70–75%) were divided into 3 groups: group 1 (control with a single intraperitoneal injection of saline), group 2 (single intraperitoneal injection of unsorted intact BMMCs at a dose of 30–35 × 106, and group 3 (single intraperitoneal injection of apoptotic BMMCs at the same dose). Restoration of biochemical parameters of liver function and mass, as well as the emerging microstructural changes in hepatocytes in histological preparations, were monitored by assessing hepatocyte mitotic activity (MA) during the first 7–10 days after ELR.

Results. It was found that in groups 2 and 3, as compared with group 1, there was no death after ELR modeling, and that the biochemical parameters of liver function normalized more rapidly (at days 10–14). Hepatocyte MA in group 3 sharply increased as early as on day 1, and mitotic index (MI) averaged 14‰, reaching 20.9‰ in some experiments; MI in the control group remained at the baseline by this time, while in group 2, MI was only 3.2‰. In group 3, liver mass recovered more rapidly after ELR to baseline values already at days 8–10, whereas the recovery was at day 12–14 and day 17–20 in group 2 and group 1, respectively. It was suggested that the more pronounced increase in the efficiency of regenerative processes in the liver after ELR in group 3 after using apoptotic BMMCs was due to the release from these cells of a large spectrum of formed paracrine factors, including various classes of RNA molecules involved in the regeneration process.

Conclusion. Apoptotic BMMNCs have a more effective adaptive and regulatory potential than intact BMMCs because reorganizations are rapidly formed in the damaged liver cells, providing an early and more powerful activation of the targeted regenerative program.

Carotid endarterectomy (CEA) with patch angioplasty is the most effective treatment for carotid artery stenosis. However, the use of existing vascular patches is often associated with thrombosis, restenosis, calcification and other complications.

Objective: to develop biodegradable patches for arterial reconstruction, containing vascular endothelial growth factor (VEGF) or arginyl-glycyl-aspartic acid (RGD), and comparatively evaluate their biocompatibility and efficacy in in vitro experiments and during preclinical trials in large laboratory animal models.

Materials and methods. Biodegradable patches, made from a mixture of poly(3-hydroxybutyrate-co-3- hydroxyvalerate (PHBV) and poly(ε-caprolactone) (PCL), were fabricated by electrospinning and modified with VEGF or the peptide sequence RGD in different configurations. In in vitro experiments, the surface structure, physicomechanical and hemocompatibility properties were evaluated. In in vivo experiments, we evaluated the effectiveness of the developed vascular patches for 6 months after implantation into the carotid artery of 12 sheep. The quality of remodeling was assessed using histological and immunofluorescence studies of explanted specimens.

Results. The PHBV/PCL/VEGF patches had physicomechanical characteristics closer to those of native vessels and their biofunctionalization method resulted in the smallest drop in strength characteristics compared with their unmodified PHBV/PCL counterparts. Modification with RGD peptides reduced the strength of the polymer patches by a factor of 2 without affecting their stress-strain behavior. Incorporation of VEGF into polymer fibers reduced platelet aggregation upon contact with the surface of the PHBV/PCL/VEGF patches and did not increase erythrocyte hemolysis. At month 6 of implantation into the carotid artery of sheep, the PHBV/PCL/ VEGF patches formed a complete newly formed vascular tissue without signs of associated inflammation and calcification. This indicates the high efficiency of the VEGF incorporated into the patch. In contrast, the patches modified with different configurations of RGD peptides combined the presence of neointimal hyperplasia and chronic granulomatous inflammation present in the patch wall and developed during bioresorption of the polymer scaffold.

Conclusion. PHBV/PCL/VEGF patches have better biocompatibility and are more suitable for vascular wall reconstruction than PHBV/PCL/RGD patches.

The culture of islets of Langerhans with bioscaffolds – extracellular matrix (ECM) mimetics – can provide a native microenvironment suitable for islets. This is one of the main conditions for creating a pancreatic tissue equivalent.

Objective: to compare the secretory capacity of viable human pancreatic islets in monoculture (control group) and cultured in the presence of two bioscaffolds: biopolymer collagen-based hydrogel scaffold (experimental group 1) and tissue-specific scaffold from decellularized deceased donor pancreas (experimental group 2).

Materials and methods. Islets of Langerhans were isolated from the caudal pancreas using a collagenase technique. The viability of cultured islets was accessed by vital fluorescence staining, while secretory capacity was evaluated by enzyme-linked immunosorbent assay (ELISA).

Results. Pancreatic islets cultured with bioscaffolds showed no signs of degradation and fragmentation, they remained viable throughout the entire period of observation (7 days). The monoculture of islets showed significant destructive changes during this period. Basal insulin levels in experimental groups 1 and 2 increased by 18.8% and 39.5% on day 1 of culture compared to the control group, by 72.8% and 102.7% on day 4 of incubation, and by 146.4% and 174.6% on day 7, respectively. The insulin secretion level of islets with tissue-specific scaffolds was 17.4% higher than that when cultured with biopolymer collagen-based scaffolds.

Conclusion. Biopolymer and tissue-specific ECM mimetics contribute not only to preservation of the viability of isolated islets of Langerhans but also maintain their insulin secretion capacity for 7 days at a higher level in comparison with monoculture. The experiments revealed that the use of a tissue-specific scaffold for the creation of a pancreatic tissue equivalent has slight potential advantage over biopolymer scaffold.

Fatty liver disease (steatosis) is considered a risk factor in donor liver transplantation (LT). Macrosteatosis (>50%) is associated with primary graft dysfunction and may reduce long-term recipient survival.

Objective: to identify predictors of macrovesicular steatosis (>50%) by analyzing donor characteristics.

Materials and methods. The retrospective study included 525 potential liver donors between January 1, 2019 and December 31, 2020. Clinical and morphological characteristics of donors were studied using logistic regression and receiver operating characteristic (ROC) analysis. Threshold values of parameters demonstrating statistical significance in multivariate analysis as predictors of >50% hepatic steatosis were obtained by ROC analysis based on calculation of the optimal cutoff point.

Results. Diabetes mellitus (DM), cause of donor’s death (traumatic brain injury), alanine transaminase (ALT) >90 units/L and aspartate transaminase (AST) >110 units/L were predictors of >50% steatosis, revealed by time-zero biopsy in the donor. Almost identical sensitivity and specificity indicators were determined in ROC analysis for liver enzymes – ALT and AST – which were 69.1 and 80.6; 72.2 and 81.1, respectively. Given the obtained values, we can say that with elevated levels of liver enzymes in the donor’s blood, there is a high degree of probability of liver parenchymal damage, but low sensitivity indicates possible multifactoriality of liver damage, and fatty liver disease may be one of the factors, but there may also be no damage to the liver parenchyma. At the same time, the rather high specificity revealed in ROC analysis for liver enzymes is a reliable sign of the absence of fatty liver disease at enzyme values less than the threshold.

Conclusion. The thresholds established for ALT and AST and their corresponding levels of sensitivity and specificity indicate that these parameters have a relatively low predictive level in the context of the presence of severe fatty liver disease in a donor. This allows, nevertheless, to use models built on their basis as screening models in the primary evaluation of liver donors.

Objective. The objective of this study is to develop a therapeutic strategy for protecting grafts in order to improve the efficiency of kidney transplantation (KT) using polyclonal antibodies (pAbs) through elimination of activated forms of neutrophils, chemo- and cytokines from the donor’s bloodstream, and a decrease in the level of expression of adhesion molecules on the renal vascular endothelium at the pre-transplant stage.

Materials and methods. In 2017, we developed and for the first time applied a therapeutic strategy for ischemia-reperfusion injury (IRI) in a brain-dead donor (BDD). Given the limited time interval after brain death has been diagnosed, Timoglobulin (Sanofi Genzyme, France) was administered to the donor at a dose of 8 mg/kg intravenously for 6 hours. Before drug administration and immediately before the start of cold perfusion, a complete blood count and renal transplant biopsy were performed. The study group included 10 BDDs (mean age 39.3 ± 4.4 years) who received anti-thymocyte globulin (ATG). The comparison group included 10 BDDs (mean age 38.5 ± 4.3 years) who did not undergo the new strategy. Donor kidneys were transplanted to 40 recipients (average age 47.5 ± 4.3 years), who were also divided into 2 groups, depending on the graft received (with and without ATG). At the organ donation center, a biobank of specimens from donors of various categories, including those using the IRI therapeutic strategy and recipients for retrospective assessment of the effectiveness of pAbs, was formed.

Results. Clinical blood test results show that in the ATG group, there was stable leukopenia (neutropenia and lymphopenia) of 1.46 ± 0.18x109/l. Fifteen (75%) recipients of kidneys obtained from donors with ATG had immediate graft function; in the control group – 10 (50%) recipients.

Conclusion. Data obtained testify to the prospects of implementing the proposed strategy in clinical practice, which will improve the quality of the resulting grafts and their suitability for subsequent transplantation, prolong graft functioning due to elimination of leukocytes as a factor of IRI, prevention of early allograft nephropathy, increase in the donor pool by using expanded criteria donors (ECDs).

After removal of metastatic malignant tumors of the hypopharynx and larynx, hypopharyngeal defects are formed. To restore the hypopharynx, a mucosa and a muscular component are needed.

The objective of this study is to develop a hypopharyngeal reconstruction technique using prelaminated pectoralis major flap with mucosal epithelium analogue from autologous epithelial layers.

Materials and methods. Nine patients underwent reconstruction of the hypopharynx using bioengineered prelaminated pectoralis major flaps. The mucosa was restored by tissue-engineered autologous epithelial cell layers that were obtained by culturing in vitro cells isolated from skin biopsies that were previously obtained from patients.

Results. Oral nutrition was restored in all cases. Pharyngeal stenosis was detected in one (11%) patient. A stratified squamous epithelium on the pectoral fascia was revealed in 67% of cases at week 2 after prelamination, in 89% of cases at week 4 after reconstruction and in 100% of cases at month 3, 6, 12 and 24 after reconstruction.

Conclusion. Reconstruction using prelaminated bioengineered flaps allows recreating the anatomical integrity and function of the hypopharynx.

This work is a scientific and educational analytical review intended for practicing cardiologists. The purpose of the review is to draw physicians’ attention to the role of myocardial contractility in the regulation of coronary circulation. We consider the fundamental phenomenon of arterial compression (squeezing) in the left ventricular (LV) wall, creating an obstruction to blood flow during cardiac systole. This phenomenon formally resembles functional coronary artery stenosis. Based on a review of the literature, the positive role of arterial compression in coronary hemodynamics is interpreted. Understanding the mechanical relationship between the contractile and coronary systems in the cardiac wall may be useful for practicing physicians when choosing treatment tactics for patients, optimizing LV bypass during heart surgeries, and improving the efficiency of adaptation of the transplanted heart.