Pregnancy after kidney transplantation (KT) has become more common, but the risk of complications and adverse obstetric outcomes in this group of women remains high.

Objective: to study pregnancy complications and outcomes in kidney recipients and renal graft (RG) survival after childbirth.

Material and methods. The study included 22 pregnancies in 20 women with RG (transplants performed in 2006–2020). The comparison group consisted of 20 healthy women who had 20 pregnancies. Frequency and nature of pregnancy complications, neonatal health indicators, and pregnancy outcomes were evaluated. Graft survival was compared in the main group and in a group of 102 women after KT who did not have pregnancies.

Results. Compared with healthy women, RG recipients had a higher rate of preeclampsia (25% and 0%, p = 0.047), fetal growth restriction (30% and 0%, p = 0.020), gestational diabetes (40% and 5%, p = 0.020), asymptomatic bacteriuria (35% and 5%, p = 0.044), preterm birth (60% and 0%, p < 0.001), and cesarean section (70% and 10%, p < 0.001). Median gestational age and birth weight were significantly lower in women with RG: 36.0 [33.9; 37.4] vs. 38.9 [38.9; 39.6] weeks, p < 0.001, and 2405 [2023; 2958] vs. 3355 [3200; 3690] g, p < 0.001, respectively. The rate of favorable pregnancy outcomes after KT was 81.8%, or 90% when early pregnancy loss is excluded. Two children were found to have genetic diseases passed from the mother. Graft survival did not differ between RG recipients with and without pregnancy, p = 0.272.

Conclusions. Pregnancy outcomes in patients with RG are generally favorable, pregnancy and childbirth do not affect graft survival. When planning pregnancy after KT, it is necessary to consider the risk of complications and the possibility of transmitting genetic disorders to offspring.

Objective: to substantiate the choice of an optimal method of preventing and reducing the risk of variceal bleeding (VB) and cardia in patients with decompensated cirrhosis who have been enlisted for liver transplantation (LT).

Materials and methods. Patients with diuretic-resistant and diuretic-responsive ascites underwent prophylaxis for recurrent bleeding via transjugular intrahepatic portosystemic shunt (TIPS) or a combination of endoscopic variceal ligation (EVL) and nonselective beta-blockers (NSBB).

Results. Leukocyte counts, Na levels, and Child–Turcotte–Pugh (CTP) liver disease class in patients with diuretic-resistant ascites had significant differences when comparing individuals who received EVL + NSBB or underwent TIPS. In diuretic-responsive patients, there were significant differences for blood platelet count, albumin and Na levels, and CTP class when comparing EVL + NSBB and TIPS groups. In diuretic-resistant patients, incidence of grade 2 varices in EVL + NSBB group was significantly higher than in TIPS. Incidence of grade 3 varices was significantly higher in TIPS patients than in EVL + NSBB cohort. In diuretic-responsive patients, incidence of grade 2 and 3 varices had no significant differences when comparing these indicators in both groups. The proportion of patients with CTP class B was significantly higher both in diuretic-resistant and diuretic-responsive patients with various methods of rebleeding prophylaxis. The proportions of CTP class C patients with both forms of ascites were significantly higher in EVL + NSBB group than in TIPS. During the LT wait period within 2 years from the start of bleeding prophylaxis in diuretic-resistant patients, 78.4% of patients who underwent TIPS implantation developed recurrent bleeding, 100% of EVL + NSBB group within the same time frame, developed recurrent bleeding. Using the Kaplan–Meier estimate with the Log-Rank test, we were able to establish that there is a significant difference between the proportions of patients with recurrent VB in EVL + NSBB or TIPS groups with both forms of ascites.

Compared with the general population, solid organ transplant recipients have a higher cancer risk. This is mainly due to the use of immunosuppressive therapy. Colorectal cancer is one of the most common cancers in recipients. This paper presents the experience of endoscopic full-thickness resection (EFTR) of a sigmoid colon cancer in a liver recipient.

Objective: to compare the efficacy of azygoportal disconnection (APD) surgery and a combination between endoscopic variceal ligation (EVL) and non-selective beta-blockers (NSBBs) in the prevention of recurrent variceal bleeding (RVB). To compare the incidence of gastric variceal bleeding (GVB) after these manipulations in patients with decompensated cirrhosis waitlisted for liver transplantation (LTx).

Materials and methods. Patients with decompensated cirrhosis underwent RVB prophylaxis by APD surgery or by a combination of EVL and NSBBs.

Results. There were no significant differences in clinical, laboratory, demographic parameters, MELD-Na and Child–Turcotte–Pugh (CTP) scores, and frequencies of medium- and large-sized varicose veins among subgroups of patients with different RVB prophylaxis methods Patients with decompensated cirrhosis who underwent APD surgery did not experience any RVB episodes during the LTx waiting period, which lasted two years from the start of bleeding prophylaxis. In the same period, RVB occurred in 100% of cases in the EVL plus NSBBs group. Using the Kaplan–Meier method with the Log-Rank test, a significant difference (p = 0.0001) was found between the proportions of non-RVB patients in the APD and EVL + NSBBs groups. In the meantime, 48.1% of patients who had APD surgery developed GVB, while 100% of cases in EVL + NSBBs group did not. The Kaplan–Meier method with the Log-Rank test revealed a significant difference (p = 0.0001) between the proportion of non-GVB patients in EVL + NSBBs and APD groups.

Transplant coronary artery disease (TCAD) is one of the main causes of graft dysfunction and graft loss. Early diagnosis and treatment of cardiac allograft vasculopathy (CAV) can increase graft survival and improve the prognosis for heart transplant recipients. This review presents current data on the problem of CAV, its pathogenesis and the main factors influencing the course of this disease.

The co-occurrence of chronic heart failure (CHF) and cancer is becoming more and more common as people live longer. The lack of a structured approach to the treatment of cancer patients with severe cardiovascular conditions is an essential issue. Up to 25% of cancer patients cannot be operated on for their main disease profile due to the presence of cardiovascular disease. This article describes a clinical case of successful treatment of a patient with two competing (prognosis-determining) diseases: end-stage heart failure and stomach cancer within the framework of a bridge-to-cancer strategy.

The shortage of organs for transplant remains a major challenge in transplantology. Transporting donor organs over long distances increases cold ischemia time, which is a risk factor for ischemia-reperfusion injury (IRI). In the face of critical shortages, the method and timing of organ preservation are crucial in increasing the donor pool. This paper examines the approaches, benefits, and drawbacks of organ preservation techniques used around the world.

Introduction. The organ shortage has prompted transplant surgeons to accept grafts from deceased donors, which can lead to complex reconstructions. The presence of an aneurysm can complicate the arterial anastomosis of the liver transplant, leading to postoperative vascular complications such as hepatic artery thrombosis or stenosis.

Objective: review published cases of donor liver aneurysms and their management.

Materials and methods. After an exhaustive literature search, only 4 published cases of liver transplants from grafts with aneurysms in their vascular territory have been found.

Results. These vascular anomalies were corrected by vascular reconstructions and no postoperative arterial complications were observed.

Conclusion. Although no particular arterial configuration precludes the use of a donor liver for transplant, more arterial complications can be anticipated with complex arterial reconstructions. However, properly managed arterial anomalies do not necessarily compromise graft outcome. Therefore, our review of the literature shows the possibility of using these organs for liver transplantation, which would otherwise be discarded.

Objective: to improve the outcomes of liver transplantation (LTx) from expanded criteria donors (ECDs) through hypothermic oxygenated machine perfusion (HOPE).

Material and methods. The study included 63 cases of LTx from suboptimal brain-dead donors. Group I (control) consisted of 34 persons in which liver transplant was preserved only by static cold storage (SCS), while group II (main) comprised 29 cases where ex situ HOPE was used after static preservation. We evaluated the efficacy and safety of the latter in a comparative clinical study and by studying ultrastructural changes in the liver using electron microscopy.

Results. No statistically significant differences between the groups in terms of baseline characteristics of donors, recipients and several perioperative parameters (p > 0.05) were obtained. Peak aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in the first week after transplantation were 1,052 (IQR: 712–1,842) U/L and 1,213 (IQR: 613–2,032) U/L in the HOPE group, and 1,943 (IQR: 1,294–5,214) U/L and 2,318 (IQR: 1,032–6,219) U/L in the SCS group (control). The levels were statistically significantly lower (p = 0.002 and p < 0.001, respectively). Median comprehensive complication index (CCI) in the main and control groups was 0 (IQR: 0–22.6) and 27.6 (IQR: 0–100) respectively. The differences were statistically significant (p = 0.001). Similarly, statistically significant differences were noted in terms of recipient time in the intensive care unit (ICU) and overall length of hospital stay (p = 0.042 and p = 0.028) – they were less in the HOPE group. Electron microscopy evaluation of the morphology of liver grafts revealed that hepatocytes sustained less injury during HOPE.

Conclusion. Ex situ HOPE is a safe and effective way of preserving liver transplants. Its use in LTx from expanded criteria donors can lessen the severity of ischemia-reperfusion injury (IRI) in the organ and enable additional assessment of the suitability of an organ for transplantation.

Objective: to evaluate the efficacy of hypothermic machine perfusion (HMP) of a donor kidney obtained from a non-heartbeating (NHB) donor, using an experimental dextran-40-based preservation solution, in subsequent orthotopic transplantation in a rabbit model.

Materials and methods. Twenty grey giant rabbits weighing 2,500–3,100 g, divided into donors (n = 10) and recipients (n = 10), were used in the study. After obtaining kidney from an NHB donor, ex vivo HMP of the left donor kidney using a dextran-40-based preservation solution was performed and peripheral vascular resistance (PVR) parameters were measured. This was followed by bilateral nephrectomy and orthotopic transplantation. The follow-up period was 12 days. Creatinine levels, urea levels, and glomerular filtration rate (GFR) were measured during follow-up.

Results. During ex vivo HMP of donor kidneys from NHBs, PVR dropped progressively from 1.90 ± 0.27 mmHg/mL/min to 0.72 ± 0.09 mmHg/mL/min at p < 0.001. In the early post-transplant period (during the first 2 days after implantation), creatinine and urea levels were moderately elevated compared to normal. Creatinine and urea levels were 91.07 ± 11.49 μmol/L at p < 0.011 and 9.09 ± 1.06 mmol/L at p < 0.009 on day 2, respectively, but by day 12, they reverted to physiologic values, which were 77.17 ± 10.19 μmol/L at p < 0.019 and 4.88 ± 0.54 mmol/L at p < 0.022, respectively. These findings were correlated with GFR values, which ranged from 26.29 to 26.74 mL/min/1.72 m² in mean values over the course of a 12-day follow-up period.

Conclusion. Ex vivo HMP using dextran-40-based preservation solution has a positive effect on the kidney at 30 minutes of warm ischemia following asystole and achieves satisfactory graft function over 12 days of follow-up.

Objective: to evaluate the effects of secondary hyperparathyroidism (HPT) in kidney transplantation (KT) candidates on recipients’ parathyroid gland function in the first postoperative year.

Materials and methods. The retrospective cohort study included 210 patients (103 women, 107 men, age 45 ± 9 years) with stage 5 chronic kidney disease (stage 5 CKD, including dialysis-dependent patients), who had undergone cadaveric KT. Biochemical screening before kidney transplantation and in the postoperative period at 3 and 12 months determined serum levels of parathyroid hormone (PTH), calcium, phosphorus, alkaline phosphatase activity, albumin and creatinine using standard methods. PTH levels of 130–595 pg/mL and ≤130 pg/mL were taken as the target level in the pre- and post-transplant periods, respectively.

Results. Fifty-six KT candidates (group 1) had HPT and 154 (group 2) had the target PTH levels. PTH level was 897 (722; 1136) and 301 (229; 411) pg/mL, respectively, p < 0.001. PTH decreased in all recipients at 3 months after KT: by 595 (420; 812) in group 1 and 148 (77; 230) pg/ mL in group 2, p < 0.001, to 254 (180; 455) and 150 (118; 212) pg/mL, respectively, p < 0.001; the target level was detected in 10.7% and 42.2% of recipients, respectively, p < 0.001. At 12 months, blood PTH was 171 (94; 239) pg/mL in group 1 and 112 (90; 135) pg/mL in group 2, p = 0.004; target level was found in 48.2% and 73.4% of recipients, respectively, p < 0.001. Kidney graft function was identical in both recipient groups: acute tubular necrosis in 41.1% and 54.5%; at 3 months, median glomerular filtration rates (GFR) of 60 and 65 mL/min (n.d.); at 12 months, 56 and 54 mL/min (n.d.). Post-transplant PTH levels correlated directly with preoperative levels in both groups and inversely with renal graft function in group 2 recipients.

Conclusion. HPT in kidney transplant candidates is a major, graft function-independent predictor of excess PTH secretion in recipients, increasing the risk of persistent HPT 1.9-fold, one year after KT.

The creation of a cell-engineered pancreatic construct (CEPC) from islets of Langerhans and biocompatible matrix carrier (framework/scaffold), which imitates the native microenvironment of pancreatic tissue, is an approach to the treatment of type I diabetes mellitus (T1D).

The objective of this work is to conduct a comparative analysis of the functional efficacy of CEPC and isolated rat islets of Langerhans after intraperitoneal administration into rats with experimental T1D.

Materials and method. T1D was induced in rats by injecting low-dose (15 mg/ kg) streptozotocin (STZ) for 5 days. CEPC samples were created using viable and functional allogeneic isolated islets of Langerhans and tissue-specific scaffold obtained by decellularization of human pancreatic fragments. The rats received intraperitoneal injection of allogeneic islets of Langerhans (experimental group 1, n = 4) and CEPC (experimental group 2, n = 4). Control group rats received no treatment (n = 4). Blood glucose levels in the rats were measured, and the pancreas and kidneys of the experimental animals were examined histologically. The follow-up period for all animals continued for 10 weeks. Results. In experimental group 1, on day 7 after injection of Langerhans islets, glycemia decreased significantly from 28.2 ± 4.2 mmol/L to 13.4 ± 2.6 mmol/L. This fall persisted for 7 weeks, following which blood sugar increased to nearly their initial levels (prior to islets administration). In experimental group 2, on day 7 after CEPC administration, there was a more noticeable drop in blood sugar levels from 25.8 ± 5.1 mmol/L to 6.3 ± 2.7 mmol/L compared to experimental group 1. By the 10th week of the experiment, the average glucose level was two times lower than it was at the beginning. Blood glucose levels dropped more sharply in the CEPC group than in the islet group (by 75.6% and 52.5%, respectively).

Conclusion. In T1D rats, CEPC has a more potent antidiabetic effect than islets of Langerhans. Thus, it has been shown that a tissue-specific scaffold may be used to create bioartificial pancreas in order to increase the functional efficiency of islets.

Surface modification of polymeric scaffolds with drugs to avoid thrombus formation and infection is a promising area in tissue engineering, which also makes it possible to accelerate the remodeling of such scaffolds and improve long-term patency.

The objective of this paper is to study the histologic and genetic features of remodeling of tissue-engineered small-diameter vascular grafts (SDVGs) with antithrombogenic drug-coated and reinforced external scaffolds, implanted into a sheep carotid artery.

Materials and methods. Poly(ε-caprolactone) (PCL) matrices, ∅4 mm in diameter, were fabricated via electrospinning, followed by creation of a reinforcing spiral PCL scaffold on their outer surface by extrusion. To prevent thrombus formation and infection, the fabricated grafts were modified with iloprost and cationic amphiphile by complexation through polyvinylpyrrolidone (PVP). The work was carried out to evaluate, by infrared spectroscopy, the formation of PVP-based coating, to study the physical and mechanical properties of the grafts in longitudinal and transverse directions, and to implant the vascular grafts (VGs) into a sheep carotid artery. To assess and control the patency of the implanted grafts, Doppler ultrasound was performed at days 1 and 5, then at 1, 3 and 6 months. The explanted samples were studied via histological and immunofluorescent analyses; gene expression profile was evaluated.

Results. Ultrasound on days 1 and 5 after implantation showed the patency of vascular grafts to be 100%. At 1 month, the patency decreased to 83.3%; patency was 50% by the end of the implantation period (6 months), without aneurysm formation and detachment of the reinforcing scaffold. Histological and immunofluorescence studies of patent grafts showed the formation of a newly formed three-layer vascular tissue structure on their basis, without signs of inflammation and calcification. However, despite the structural similarity between the newly formed vascular tissue and the native tissue of a sheep carotid artery, analysis of the gene expression profile revealed some differences in terms of genetic profile: CNN and SNA12 expression levels in the neotissue decreased, and those of CTSB, TNFa, and TGFb increased.

Conclusion. Modified polymeric vascular scaffolds showed good remodeling of the prosthetic wall, without aneurysm formation. The identified genetic differences between newly formed tissue and native tissue are logical in view of formation on the basis of the artificial polymeric scaffold. Further research on reinforced polymeric scaffolds will be aimed at improving the inner surface in order to improve their thromboresistance.

Objective: to obtain a stable mouse model of type 1 diabetes mellitus (T1DM) using streptozotocin (STZ), which has a toxic effect on pancreatic beta cells.

Materials and methods. Experiments were performed on 30 white non-diabetic male mice of the SHK colony, which were injected intraperitoneally with STZ at a dose of 200 mg/ kg by two methods: 15 animals (group 1) once and 15 animals (group 2) intermittently – 5 consecutive days at 40 mg/kg per day.

Results. In group 1, one mouse died after 2 days due to hypoglycemic coma, 4 mice developed hyperosmolar hyperglycemia (>33.3 mmol/l), 3 mice had spontaneous remission of diabetes, and 7 mice had stabilized hyperglycemia at levels close to 20 mmol/l. In group 2, only one mouse showed spontaneous remission of diabetes, while the remaining 14 animals showed stable diabetes with average hyperglycemia levels moderately above 20 mmol/L until the end of the 4-week follow-up. A histological study of the pancreas of these animals confirmed the destructive effect of STZ on islets in the form of mass death of insulin-producing β-cells.

Conclusion. Split-dose intraperitoneal injection of STZ provides a stable experimental T1DM in 93% of laboratory mice.

Multipotent mesenchymal stem cells (MMSCs) are known to be excellent therapeutic agents. Apart from their ability to differentiate into various cell types, and thus participate in the repair of injured tissues and organs, they can influence the regeneration process through secretion of paracrine factors. Thus, MMSC therapy represents a special type of medical intervention that has both a systemic range of therapeutic efficacy and local activity on 

individual sites of an organ. Over the past decades, MMSC therapy has continuously been in a cautious transition from research development to clinically approved therapies. Clinical trial data has shown that this therapy is rarely associated with severe adverse events, is well tolerated and quite safe in the short-term period. However, it has a number of limitations for use, mainly due to the risk of malignant transformation. The success of stem cell transplantation in the treatment of various diseases has been confirmed both in preclinical studies and in clinical practice. The main issues that arise when assessing the therapeutic efficacy of MMSC-associated therapy are the type of cells (adipogenic, bone marrow, etc.), delivery route, number of cells injected, and the optimal number of injections. There is a growing body of experimental and clinical evidence suggesting that both an adequate delivery route and an adequate dose can increase the likelihood of success of MMSC-associated. Each cell delivery route has costs and benefits. However, there is generally contradictory evidence on the comparative efficacy of different cell delivery routes. The optimal dose of transplanted cells is also debated, as high MMSC doses may increase the risks of complications and may not have the proper effect both when administered systemically and locally. These aspects require further systematization of available data to maximize the effect of cell therapy by selecting the safest and most appropriate approaches.

Human posterior corneal epithelium (corneal endothelium) has limited proliferative activity both in vivo and in vitro. Disease or dysfunction in these cells leads to impaired corneal transparency of varying degrees of severity, up to blindness. Currently, the only effective standard treatment for corneal endothelial dysfunction is transplantation of donor cornea that contains a pool of healthy and functionally active cells. However, there is a global shortage of donor corneas, which has led to an unmet clinical need and the fact that only 1 patient out of 10 in need receives surgical treatment. Therefore, creation of cellular constructs and artificial human corneas containing healthy endothelium is a very urgent challenge facing modern ophthalmic transplantology. This review presents the current state of affairs, challenges and prospects for obtaining cultured corneal endothelial cells (CECs) in vitro for transplantation purposes.

Objective: To create 2-mm diameter multilayer porous tubular scaffolds (PTS) with characteristics that resemble small-diameter native blood vessels in terms of characteristics.

Materials and methods. PTS made of polycaprolactone (PCL, MM 80000) with a PCL-made sealing coat/layer with gelatin addition (PCL-gelatin) with a diameter of 2 mm were created by electrospinning (NANON-01A). Bioactive coating was applied to the PTS surface by sequential incubation in solutions of bovine serum albumin, heparin (Hp), and platelet lysate (PL). Cytotoxicity was investigated under conditions of direct contact of PTS with a monolayer of NIH/3T3 mouse fibroblasts. Viability of human umbilical vein endothelial cells (EA.hy926) was evaluated using Live/Dead^® Viability/Cytotoxicity Kit. Permeability and blood flow parameters of the PTS implanted in the infrarenal section of the rat aorta were recorded using Doppler imaging.

Results. A three-layer PTS construct with an inner diameter of 2 mm was developed. Its inner and outer layers were formed from 0.2 mL of PCL solution, and the middle sealing coat/layer was from 0.5 mL of PCL with addition of 30% (by weight of polymer) gelatin. Introduction of the sealing coat/layer reduced surgical porosity (SP) from 56.2 ± 8.7 mL/(cm²·min) for a single-layer PTS made of pure PCL to 8.9 ± 2.6 mL/(cm²·min) for a three-layer PTS. The resulting PTS demonstrated physicomechanical characteristics similar to those of native blood vessels; it also showed no cytotoxicity. Application of a bioactive coating of Hp and PL allowed for increased in vitro adhesion and proliferation of endothelial cells. The technique of implantation of 10 mm long fragments of three-layer PTS into the infrarenal section of a rat aorta was corrected, thus minimizing blood loss and narrowing the anastomosis site. In an acute experiment, it was proven that the prostheses were patent and that blood flow parameters (systolic and diastolic velocity, resistivity index) were close to the corresponding indicators of native rat aorta.

Conclusion. The developed three-layer PTS constructs have low SP and physicomechanical properties close to those of native blood vessels. Bioactive coating improves the in vitro matrix properties of PTS relative to human endothelial cells. At short-term implantation into the aorta of experimental animals, PTS showed no early thrombosis, while blood flow parameters were close to those of native rat aorta. Thus, three-layer PTS with bioactive coating can be used as a scaffold for creation of in situ tissue-engineered construct of a small-diameter blood vessel.