Objective: to determine the efficacy and safety of an integrated strategy aimed at preventing delayed renal graft function (DGF).

Materials and methods. From June 2018 to December 2022, 478 deceased-donor kidney transplants were performed at Botkin Hospital, Moscow. The patients were divided into two groups: Group I consisted of 128 patients who did not use the integrated strategy; Group II included 67 patients in whom the DGF prevention strategy was used at the perioperative stage. The integrated strategy involved the use of hypothermic oxygenated machine perfusion (HOPE) using expanded criteria donors, the use of a second warm ischemia (SWI) elimination device, personalized initial calcineurin inhibitor (CI) dosing, and use of alprostadil for high vascular resistance in renal graft arteries.

Results. DGF occurred in 5 of 44 patients (11.4%) that used the integrated strategy, and in 13 of 44 patients (29.5%) in the control group. The differences were statistically significant (p = 0.034), there was a medium strength relationship between the traits (V = 0.225). The use of the integrated DGF prevention approach reduced the chances of developing DGF by a factor of 0.3 (95% CI: 0.1–0.95). The risk of DGF in the integrated strategy group was 61.3% of the risk of DGF in the non-strategy group, thus the relative risk (RR) is 1.63 (95% CI: 1.1–2.4). Median duration of graft function normalization was statistically significantly lower in group II: 5 (IQR: 3–9) versus 15 (IQR: 7–19) days (p = 0.012). Mean length of hospital stay was 19.1 ± 4.2 (95% CI: 14.5–26.1) bed-days in group I and 13.9 ± 3.4 (95% CI: 9.3–17.2) bed-days in group II. Differences in this indicator were also statistically significant (p = 0.043).

Conclusion. The set of DGF prevention measures, developed at Botkin Hospital, evidence-based and implemented in clinical practice, can reduce the burden of modifiable risk factors of this complication significantly, thereby improving treatment outcomes for kidney transplant recipients considerably.

St. Petersburg, Russian Federation The paper presents a comparative assessment of different methods of treating symptomatic bladder outlet obstruction (BOO) in patients with benign prostatic hyperplasia (BPH) who underwent kidney transplantation (KT).

Objective: to evaluate the effectiveness of a new device for second warm ischemia (SWI) elimination in kidney transplantation (KT).

Materials and methods. The study included clinical and experimental stages. The clinical stage included 63 patients out of 219 who underwent KT at Botkin Moscow City Clinical Hospital between July 2018 and August 2022. The inclusion criteria were kidneys from donation after brain death (DBD) donors with expanded criteria or kidneys from donation after circulatory death (DCD) donors, and an SWI time greater than 45 minutes. The first group consisted of 24 recipients operated on using the new SWI elimination device. The second retrospective control group consisted of 39 patients where sterile ice bags were used at the implantation stage. The groups had no statistically significant differences in the main recipient and donor characteristics, as well as in perioperative parameters. Also, from November 2021 to April 2022, 23 kidney autotransplantation experiments in female Landrace pigs were performed. The animals were cared for in accordance with the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes (Strasbourg, 18 March 1986). Efficiency of different SWI elimination techniques was compared on two experimental models: standard donor (group 1, n = 12) and asystolic donor (group 2, n = 11).

Results. In the clinical trial group, mean graft temperature (t_m) before reperfusion was statistically significantly lower in group 1 using the special SWI elimination device: 6.4 ± 1.7 °C (95% CI 3.2–8.5) versus 22.1 ± 2.3 °C (18.1–24.6), р < 0.001. The risk of delayed graft function (DGF) was 3.86 times higher (95% CI 1.11–13.43) with the standard SWI elimination technique. In the experimental group, in the subgroups using the new device (n = 12), graft t_m before reperfusion was 5.1 ± 0.4 °C (95% CI 4.5–5.8), whereas in the ice bag subgroups (n = 11), t_m was 29.3 ± 1.3 °C (95% CI 27.7–30.8), which was significantly higher (p < 0.001). The overall 1-week survival of the experimental animals was significantly higher in the SWI elimination device subgroup (logrank p = 0.036).

Conclusion. The developed device is effective in eliminating SWI of renal graft.

Federation In certain categories of patients with end-stage heart failure (HF), short-term mechanical circulatory support (MSC) is successfully used as a mechanical «bridge» to heart transplantation (HTx). In predominantly left-ventricular (LV) dysfunction, the use of isolated coronary artery bypass, especially amidst high pulmonary hypertension (PH), seems to be a more physiological method of short-term MSC.

Objective: to present the results of a series of clinical cases of the use of percutaneous left ventricular assist device (pLVAD) before HTx in potential recipients with predominantly LV dysfunction and concomitant high PH.

Materials and methods. Three potential heart recipients with predominantly left-sided HF and high pre-transplant PH (pulmonary vascular resistance, PVR, 4.7–6.6 Wood units) who required MSC due to progression of hemodynamic disorders were included in the study. A standard venous extracorporeal membrane oxygenation (ECMO) cannula (26 F) was used for percutaneous left atrial-femoral artery (LA–FA) bypass. The cannula was passed from the transfemoral route through the interatrial septum into the left atrial cavity. A paracorporeal centrifugal pump provided blood injection through a standard arterial ECMO cannula (15 F).

Results. pLVAD unloaded the left ventricle effectively (PCWP reduced from 27–32 to 15–20 mmHg), reduced pre-transplant PH (mean pulmonary artery pressure (mPAP) reduced from 45–53 to 28–33 mmHg) and improved systemic hemodynamics (cardiac index (CI) increased from 1.8–1.9 to 2.1–2.6 l/min/m² and mean arterial pressure (mAP) from 56–59 to 70–75 mmHg). All these created the prerequisites for subsequent successful HTx. Against the background of pLVAD, transpulmonary pressure gradient (TPG) decreased from 15–25 to 13–15 mmHg, and PVR decreased from 4.7–6.6 to 2.7–3.4 Wood units. pLVAD flow rate was 2.9–3.8 L/min or 1.38–1.83 L/min/m² at 4700–7100 rpm. pLVAD duration ranged from 4 (n = 1) to 7 (n = 2) days. All patients underwent successful HTx.

Conclusion. pLVAD is a highly effective method of short-term MSC in potential recipients with predominantly LV dysfunction and concomitant high PH, leading to rapid regression of the dysfunction against the background of left ventricular unloading. This short-term MSC technique can be successfully realized using standard ECMO cannulas and centrifugal pumps of any modification, without requiring additional special equipment.

Medical management of end-stage chronic heart failure (HF) has evolved significantly over the past few decades. With a better understanding of the pathophysiology of HF, new pharmacological agents have been synthesized. However, survival in this cohort of patients with medical treatment remains extremely low. This has stimulated the development of surgical methods of treatment. Recent technological advances in the development of mechanical circulatory assist devices have made possible a single-stage implantation of two centrifugal pumps as an alternative to a total artificial heart. Today ventricular assist devices can be implanted to provide both univentricular and biventricular support depending on the severity of hemodynamic disorders, target organ damage, likelihood of recovery and heart transplantation.

Postoperative pericardial effusion (PPE) represents a very common complication in cardiac surgery. Accumulation of a significant amount of free fluid in the pericardial cavity is a multifactorial process. Identifying the cause is not always possible. This complication occurs more frequently in patients after heart transplantation than in patients who underwent reconstructive cardiac surgery. Having hemodynamically significant effusion requires surgical evacuation of fluid from the pericardial cavity. This can affect the postoperative period and increase the length of stay at the hospital. For this reason, developing and ensuring widespread use of methods for prevention of this complication are urgent and relevant tasks.

Three-dimensional (3D) printing is a method of creating a material object layer-by-layer in space from a virtual, mathematical model. 3D printing is based on additive technologies – a step-by-step formation of a structure by adding material to the base. 3D bioprinting is the fabrication of functional biological structures that mimic human organs and tissues. Analysis of scientific publications showed that in the near future, viable and fully functional artificial copies of individual human organs and tissues can be obtained.

Despite great progress in the field of biomaterials for tissue engineering and regenerative medicine, the high requirements placed on artificial matrices (matrices, carriers, scaffolds) are the reason for the ongoing search for natural or synthetic extracellular matrix mimetics. Among such materials, decellularized umbilical cord (UC) stroma appears to be very attractive – it has a high content of hyaluronic acid, cytokines, and growth factors, and there are no ethical restrictions for its production. Decellularized UC stroma has been found to promote cartilage, liver tissue and nerve tissue repair, as well as wound healing. The review critically analyzes and summarizes published data on the ability of decellularized UC stroma to maintain the necessary conditions for adhesion, migration, differentiation and functional activity of adherent cells, thus stimulating the internal (physiological) regenerative potential of tissues. Literature was searched for in the following electronic databases: Medline/PubMed (www/ncbi. nlm.nih.gov/pubmed), Cochrane library (https://www.cochrane.org), and eLIBRARY/Russian Science Citation Index (https://www.elibrary.ru). Inclusion criteria were the presence of biomaterials obtained from decellularized human UC stroma. Exclusion criteria for papers included research objects as decellularized umbilical cord vessels (veins and arteries) and umbilical cord cell cultures. Twenty-five original articles in English and Russian were selected for analysis of the products obtained, their applications, decellularization methods and research results. The review also discusses the prospects for decellularized umbilical cord in medicine.

At present, the search for effective ways of restoring peripheral nerves with anatomical damage continues. Autoplasty still remains the gold standard, which, however, is not without its drawbacks. The use of nerve implants for promoting directional axon growth is essential and promising.

Objective: to study the biomechanical properties of laboratory samples of an artificial nerve conduit (NGC) made of hybrid biomaterials and to, on cadaveric material, assess the technical feasibility of using them in surgical practice to repair extended peripheral nerve defects.

Material and methods. The objects of the study were three electrospun NGC samples: from synthetic material (polycaprolactone, PCL) and hybrid biomaterials (PCL + gelatin or PCL + collagen). The work compared the physical and mechanical properties of NGC: stiffness, plasticity, elasticity, brittleness, resistance to chemical attack, their ability to be impregnated with liquid media, permeability, possibility of making an anastomosis between the implant and the nerve during surgical procedure. Cadaveric material was the object of the study: we used a dissected superficial sensory branch of the human right radial nerve, 2 mm in diameter, isolated on the forearm, about 12 cm in length, because it most corresponded to the diameter of the NGC samples tested. After surgery, the echogenic features of the implants and their anastomoses with the nerve were assessed by ultrasound imaging.

Results. It was found that hybrid NGC samples, based on their biomechanical properties, are fundamentally suitable for use in surgical practice, to ensure growth and replacement of a peripheral nerve defect. However, the best composition of a nerve guide can be established after comparative preclinical study of the biocompatible and functional properties of hybrid material samples.

Conclusion. The physical and mechanical properties of the investigated NGC samples made of hybrid biomaterials meet the technical requirements for implantable nerve conduits for surgical application.

Creation of a bioartificial pancreas, including a cell-engineered construct (CEC) formed from pancreatic islets (islets of Langerhans) and a biocompatible matrix mimicking the native microenvironment of pancreatic tissue, is one of the approaches to the treatment of type 1 diabetes mellitus (T1D).

Objective: to conduct preliminary in vivo studies of the functional efficacy of intraperitoneal injection of a cell-engineered pancreatic endocrine construct and a suspension of rat pancreatic islets in an experimental T1D model.

Materials and methods. Tissue-specific scaffold was obtained by decellularization of human pancreatic fragments. The viability and functional activity of rat islets isolated with collagenase were determined. Experimental T1D was modeled by intraperitoneal injection of low-dose streptozotocin and incomplete Freund’s adjuvant into rats. The rats were intraperitoneally injected twice with pancreatic CEC (n = 2) or islet suspension (n = 1). Glucose levels in the blood and urine of the rats were assessed. Histological examination of organs (pancreas and kidneys) of the experimental animals was carried out.

Results. After the first injection, blood glucose levels gradually decreased in all animals by more than 47% of the initial values; by follow-up day 24, the glucose level rose to the initial hyperglycemic values. After repeated administration, a 63.4% decrease in glycemic level was observed in the rats with pancreatic CEC and a 47.5% decrease in the one with islet suspension. At week 5 of the experiment, blood glucose levels gradually increased in all animals. At the same time, the glycemic index of the rat with injected pancreatic CEC was 62% lower than the glycemic index of the rat with injected islets.

Conclusion. Allogeneic pancreatic islets in pancreatic CEC increase the duration of stable glycemic level in T1D rats.

Delivering bioactive substances to certain spots in the human and animal body is a crucial task. To address this problem, we have developed a delayed-release bioactive substance carrier – an albumin-based cryogel obtained by cryostructuring. It was tested on an organotypic culture model of the posterior eye segment of a newt.

Objective: to study the effectiveness of porous albumin-based cryogel obtained by cryostructuring and loaded with a bioregulator isolated from bovine sclera in different quantities in maintaining eye tissue integrity and preserving Iberian ribbed newt fibroblasts on an organotypic culture model.

Materials and methods. Albumin sponges were obtained after being denatured at temperatures –15 °C, –17.5 °C, and –20 °C, with albumin levels 40 mg/mL, 50 mg/mL, and 60 mg/mL in a thermostatic cooler. Their modulus of elasticity was measured. Eye tissues were isolated from adult sexually mature Iberian ribbed newts of both sexes. The posterior segment of each eye was placed on a sponge sample of albumin cryogel in penicillin vials, sealed and placed in a thermostat. At the end of cultivation, the samples were fixed, washed, dehydrated, and embedded in paraffin. Paraffin sections were made, followed by staining. A Leica microscope (Germany) with an Olympus DP70 camera (Japan) was used to view histological sections. Fibroblast count in the histological sections was estimated using the ImageJ program.

Results. Cryogel with initial albumin solution levels of 50 mg/mL obtained at –20 °C with 4.50 kPa elastic modulus, was chosen for the organ culture experiment. Histological studies showed that eye tissue integrity was maintained in the experiment when albumin-based scaffold was loaded with the bioregulator at doses of 2.46 × 10^–5, 2.46 × 10^–7, 2.46 × 10^–9, 2.46 × 10^–13, 2.46 × 10^–15 μg. Moreover, the statistically significant difference for fibroblast count per unit area in the sclera partially correlates with the qualitative state of the posterior eye tissue itself. Groups where bioregulator isolated from the sclera had a dose of 2.46 × 10^–7, 2.46 × 10^–9 and 2.46 × 10^–15 μg, showed the best result as compared with the control group.

Conclusion. Albumin-based scaffold as a carrier with a bioregulator adsorbed on it (doses of 2.46 × 10^–5, 2.46 × 10^–7, 2.46 × 10^–9, 2.46 × 10^–13, 2.46 × 10^–15 μg) is effective in maintaining eye tissue integrity and preserving Iberian ribbed newt fibroblasts. Albumin cryogen is an effective carrier for delayed release of bioactive substances.

Galectin-3 (Gal-3) is an important regulator of cell adhesion, migration, proliferation, differentiation and apoptosis under pathophysiological conditions. It plays a crucial role in diseases associated with chronic inflammation and fibrosis. In recent years, there have been reports indicating changes in serum Gal-3 levels in solid organ transplant recipients in the verification of kidney, liver, heart and lung transplant pathologies. Studies on Gal-3 levels and dynamics in solid organ recipients may serve to assess graft conditions using new minimally invasive methods and to identify therapeutic targets for personalized therapy. The first clinical trial data on Gal-3 pharmacological inhibition are emerging. This review summarizes the current understanding of the role of Gal-3 in transplant pathology and the prospects for its use as a diagnostic marker and therapeutic target in solid organ recipients.

Growth hormone (GH) plays a leading role in the regulation of cell and tissue metabolism and growth. Its effects are mediated through the so-called somatomedins, among which the most important is the liver-produced insulinlike growth factor 1 (IGF-1). It has been reported that serum GH levels in liver recipients is related to the clinical transplant outcomes.

Objective: to evaluate the prognostic significance of GH in pediatric liver transplantation (LT).

Materials and methods. The study enrolled 148 children (61 boys) aged 2 to 60 months (median, 8) with end-stage liver disease resulting from biliary atresia (n = 86), biliary hypoplasia (n = 14), Byler disease (n = 15), Alagille syndrome (n = 12), Caroli syndrome (n = 5), and other liver diseases (n = 16, cryptogenic cirrhosis, fulminant and autoimmune hepatitis, Crigler–Najjar and Budd–Chiari syndromes, alpha-1 antitrypsin deficiency, glycogenosis and hepatoblastoma). All the patients were transplanted with the left lateral segment of the liver from a living related donor. GH concentrations were measured by enzyme immunoassay before, at one month and at one year after transplantation.

Results. Median plasma GH levels in children with liver disease were 4.3 [1.6–7.2] ng/mL, significantly higher than in healthy children of the same age at 1.2 [0.3–2.4] ng/mL, p = 0.001, while mean height and body weight were lower than in healthy controls. GH levels decreased significantly after transplantation. At one month and one year later, the levels did not differ from those of healthy children (p = 0.74, p = 0.67, respectively). One month after transplantation, GH concentrations were lower in 1-year survivors than in non-survivors (p = 0.02); the diagnostically significant threshold GH level was 1.8 ng/mL. Prior to LT, plasma GH levels did not differ between 1-year survivors and non-survivors. Children with GH levels below 1.8 ng/mL post-LT were 9 times more likely to survive one year post-transplant than patients with levels above the threshold.

Conclusion. GH concentrations in pediatric liver recipients is a positive prognostic indicator of pediatric LT outcomes.

Federation Clinical outcomes of solid organ transplantation depend on many factors. One of the main factors is the risk of post-transplant complications, which affect allograft and recipient survival. Multifactorial organ damage in post-transplant complications and the search for diagnostic and prognostic indicators of the condition have contributed to the study and selection of a wide range of proteomic and molecular genetic biomarkers, which have shown to be effective in solid organ transplantation. The use of biomarkers opens up additional possibilities for assessing the risk of complications and their early diagnosis. This potentially reduces the frequency of invasive diagnostic procedures. Transforming growth factor beta 1 (TGF-β1) regulates many biological processes, has anti-inflammatory and immunosuppressive effects, participates in immune response, and plays a key role in extracellular matrix (ECM) protein synthesis. ECM dysregulation leads to fibroblast hyperproliferation and increased collagen synthesis and, consequently, tissue fibrosis. The variability of the diagnostic and prognostic potential of TGF-β1 has been demonstrated in studies on recipients of various solid organs. The objective of this review is to analyze recent evidence on the role of TGF-β1 in the development of post-transplant complications and to assess its prospects as a marker of graft pathology or as a target for therapy.

The continued unavailability of adequate organs for transplantation to meet the existing demand has resulted in a major challenge in transplantology. This is especially felt in lung transplantation (LTx). LTx is the only effective method of treatment for patients with end-stage lung diseases. Normothermic ex vivo lung perfusion (EVLP) has been proposed to increase the number of donor organs suitable for transplant – EVLP has proven itself in a number of clinical trials. The ability to restore suboptimal donor lungs, previously considered unsuitable for transplantation, can improve organ functionality, and thus increase the number of lung transplants. However, widespread implementation of ex vivo perfusion is associated with high financial costs for consumables and perfusate.

Objective: to test the developed solution on an ex vivo lung perfusion model, followed by orthotopic LT under experimental conditions.

Materials and methods. The experiment included lung explantation stages, static hypothermic storage, EVLP and orthotopic left LTx. Perfusion was performed in a closed perfusion system. We used our own made human albumin-based perfusion solution as perfusate. Perfusion lasted for 2 hours, and evaluation was carried out every 30 minutes. In all cases, static hypothermic storage after perfusion lasted for 4 hours. The orthotopic single-lung transplantation procedure was performed using assisted circulation, supplemented by membrane oxygenation. Postoperative follow-up was 2 hours, after which the experimental animal was euthanized.

Results. Respiratory index before lung explantation was 310 ± 40 mmHg. The PaO2/FiO2 ratio had positive growth dynamics throughout the entire EVLP procedure. Oxygenation index was 437 ± 25 mm Hg after 120 minutes of perfusion. Throughout the entire EVLP procedure, there was a steady decrease in pulmonary vascular resistance (PVR). Initial PVR was 300 ± 100 dyn×s/cm5; throughout the EVLP, PVR tended to fall, reaching 38,5 ± 12 dyn×s/cm5 at the end of perfusion.

Conclusion. A safe and effective EVLP using our perfusate is possible. The developed orthotopic left lung transplantation protocol under circulatory support conditions, supplemented by membrane oxygenation, showed it is efficient and reliable.

Objective: to analyze the possibility of using the liver of a donor undergoing hemodialysis as a transplant.

Materials and methods. A case of successful liver transplantation (LT) from a 40-year-old deceased donor, who had been on hemodialysis for 10 years for chronic pyelonephritis and nephrosclerosis, is presented. Of the known hemodialysis complications of chronic kidney disease, the donor’s medical records showed anemia and grade 3 arterial hypertension.

Results. The recipient’s post-LT period had no significant differences from the postoperative period of those that received liver from donors with standard criteria.

Conclusion. Our first experience with the use of a liver transplant from a donor who was on hemodialysis, in the absence of other risk factors, suggests that the liver of this category of donors can be used for transplantation.

In recent years, oxidative stress, characterized by excess free radicals in the body, has been called the cause of many diseases. There is an active search for drugs with antioxidant properties that are suitable for long-term maintenance therapy. Nicotinamide (NAM), an antioxidant, is used to treat a variety of diseases, usually in oral or injectable form. Given the peculiarities of the drug regimen (dose, prolonged administration), a new dosage form of NAM, a microemulsion-based transdermal patch (TP), containing 20 mg/10 cm² of NAM, has been proposed.

The objective of this work is to compare the pharmacokinetic parameters of intramuscular and transdermal NAM administration in animal experiments for 24 hours.

Materials and methods. We used laboratory samples of nicotinamide TP based on a microemulsion-based transdermal delivery emulsion (TDS) with different content of sodium docusate transfer activator. The pharmacokinetics of transdermal and intramuscular injections were studied in male Chinchilla rabbits weighing 3.5–4.0 kg. Plasma NAM levels of the experimental animals were determined by high-performance liquid chromatography using a specially designed method on NUCLEODUR PFP columns (5 μm, 250 × 4.6 mm) using the mobile phase acetonitrile: deionized water. The samples were preliminarily purified by solid-phase extraction using Chromabond C18 Hydra cartridges.

Results. When administered intramuscularly, the maximum blood NAM level was 13.3±1 μg/mL; when NAM transdermal forms were applied in the same dosage with different contents of the transfer activator, the levels did not differ significantly – 3.1 and 3.2 μg/mL. It was shown that in transdermal administration of NAM, concentration of the active substance remained at a constant level for ~6 hours. The bioavailability of NAM with transdermal administration was calculated relative to intramuscular administration: 1.43 for TP with 9.8% docusate sodium and 1.84 with 3.3% docusate sodium.

Conclusion. NAM has a higher bioavailability when administered transdermally at 20 mg than when administered intramuscularly in the same dose. With transdermal administration, NAM concentration can be maintained at a constant level for a long time, without the jumps that are typical of intramuscular administration.