In the presented case, after liver transplantation (LT) for hepatocellular cancer (HCC), the disease progressed in the graft, left lung and bronchopulmonary lymph nodes after 16 months, according to the Milan criteria. Against the background of combined treatment – hepatic artery chemoembolization (HAC), systemic targeted therapy and 

stereotactic radiotherapy for metastatic node of the left lung – HCC in the extrahepatic foci was stabilized. In this situation, we considered resection of the liver transplant as the only therapeutic option that provides a chance for significant prolongation of the patient’s life. However, extensive resection of the right liver lobe seemed unsafe due to a number of limiting factors – borderline functional residual capacity of the remaining liver: future liver remnant (FLR), 599 cm³ (32%); plasma disappearance rate (PDR), 12.3%/min; tumor invasion of the middle hepatic vein basin. In this case, right portal vein branch (RPVB) embolization could promote vicarious hypertrophy of the remaining part of the liver, but the waiting period usually exceeds three to four weeks, and the RPVB was already partially blocked by the tumor at that time. The only option for surgical intervention was, in our opinion, two-stage hepatectomy according to the Associated Liver Partition and Portal Vein Ligation for Staged hepatectomy (ALPPS) procedure, despite the absence of literature data on the performance of such operations on a liver transplant. On postoperative day 5 from the first stage, a 799 cm³ FLR hypertrophy was achieved, which allowed to perform the second stage of intervention relatively safely. Competent tactics regarding medication in the intensive care unit (ICU) and renal replacement therapy allowed to cope with sepsis and acute renal failure – the prevailing postoperative complications.

Background. Cardiovascular diseases are very common among solid organ recipients. They are associated with worsening transplant outcomes. Arterial vascular wall elasticity is an important prognostic indicator and a risk marker for cardiovascular events. Noninvasive measurement of common carotid artery (CCA) elasticity may be useful in assessing cardiovascular risk in solid organ recipients.

Objective: To conduct a comparative analysis of indicators of CCA elasticity in solid organ recipients and to study their relationship with factors that potentially have a negative impact on the risk of adverse events.

Materials and methods. The study included 154 patients aged 10 to 75 years, including heart (n = 77), liver (n = 9), and kidney (n = 35) recipients, as well as 33 patients with end-stage heart failure waitlisted for heart transplantation (HT). In all participants, carotid artery ultrasound was performed, pulse wave velocity was measured, and CCA elasticity was calculated.

Results. CCA elasticity was found to be strongly inversely correlated with age, body mass index, systolic blood pressure, renal tubular filtration rate, CCA intima media thickness, and aortic pulse wave velocity. In heart recipients, CCA elasticity was significantly lower than in liver and kidney recipients (p = 0,002) and it inversely correlated with the length of time elapsed after transplantation, which is probably associated with cardiac denervation.

Conclusion. CCA elasticity calculated via noninvasive ultrasound reflects the degree of adverse effects of pathological factors on the main arteries in solid organ recipients.

Objective: vascular complications (VCs) following liver transplantation (LT) can pose a significant threat to the recipient’s life – as the risk of graft loss increases significantly when blood flow in the graft is impaired. Diagnosis and early treatment of VCs seems to be a pressing issue in transplantology. The aim of this study is to evaluate the incidence, treatment and outcome of VCs in patients after orthotopic LT at the Center for Surgery and Donor Coordination, Rostov Regional Clinical Hospital.

Materials and methods. Between July 2015 and April 2023, 100 orthotopic LTs were performed. VCs were retrospectively identified and analyzed.

Results. The overall incidence of VCs was 24% (n = 24): hepatic artery stenosis, 5% (n = 5); intra-abdominal bleeding, 6% (n = 6); hepatic artery dissection, 2% (n = 2); intrahepatic venous thrombosis Budd–Chiari syndrome), 2% (n = 2); portal vein thrombosis, 1% (n = 1); inferior vena cava thrombosis/iliofemoral deep vein thrombosis, 2% (n = 2); inferior vena cava stenosis, 1% (n = 1); hepatic vein stenosis, 1% (n = 1); recurrent hepatic artery stenosis/thrombosis, 2% (n = 2); mesenteric vein thrombosis, 2% (n = 2).

Conclusion. Most VCs following orthotopic LT occur in the early postoperative period and can lead to a high risk of graft dysfunction and patient death. Early recognition, diagnosis, and treatment of post-LT complications are critical to successful short- and long-term graft function and patient survival, even in patients with asymptomatic complications. Treatment options typically include surgical revascularization, percutaneous thrombolysis, percutaneous angioplasty, retransplantation, or, less commonly, a conservative approach.

Objective: to study the dynamics of hemostasis parameters in the early postoperative period and to identify the timing of restoration of the level of procoagulants and anticoagulants synthesized by the liver (received from a living related donor) in liver lobe recipients.

Materials and methods. Under observation were 31 recipients and 31 related donors of liver lobe. They were treated at the Republican Specialized Scientific and Practical Medical Center for Surgery in Tashkent, Uzbekistan, from August 2022 to August 2023. Hemostasis parameters were determined in recipients, whose postoperative period was uneventful.

Results. It was revealed that compensation in the hemostasis system occurs even at low levels of coagulation factors on day 10 after liver transplantation (LT). In recipients, a decrease in anticoagulants was more pronounced than that of procoagulants. In general, the hemostasis system was in an unstable equilibrium, which, under the influence of external and internal factors, can easily shift both towards hypercoagulable and hypocoagulable state. Activity of the fibrinolytic system and fibrinogen level are significant influencing factors. Gradual recovery of fibrinogen levels by the end of day 1 after surgery is the result of activation of the synthetic function of the liver. After LT, there were signs of endothelium activation, but not endothelial damage, which regress and normalize by postoperative day 10. At the same time, in the initial status, recipients had an increase in both the amount and activity of von Willebrand factor, which indicates endothelial damage and dysfunction. The low level of homocysteine in recipients is probably a protective factor against the development of thrombotic complications, and homocysteine dynamics reflects the gradual restoration of the functional activity of the liver, adaptation of the donor liver to functioning.

Conclusion. Monitoring of hemostasis system in recipients after liver transplantation allows to prevent thrombohemorrhagic complications in time but also to assess the dynamic equilibrium of procoagulants and anticoagulants, the timing of restoration of the activity of the main hemostasis factors and, according to this, to vary the administration regimes of anticoagulants, antiplatelet medications, and fibrinolysis inhibitors, to carry out replacement therapy and to realize the concept of hemostasis management.

Bronchial stenosis is a major cause of severe postoperative period in lung recipients. One of the methods to restore airway patency is recanalization using laser. This technique is popular due to the combination of cutting and coagulation effects. In this article, we demonstrate the possibility of intraluminal use of a thulium fiber laser (TFL) to recanalize bronchial stenosis in lung recipients.

Vascular complications (VCs) after liver transplantation (LT) are rare but are one of the most dreaded conditions that can potentially lead to graft loss and recipient death. This paper has analyzed the international experience in the early diagnosis of various VCs that can develop following LT, as well as the optimal timing and methods of treatment of these complications.

Background. The possibility of inducing immunological tolerance in allogeneic organ transplant recipients is a research goal of the transplantology community, as it will ensure the likelihood of complete engraftment of a foreign organ. However, such a task presently remains difficult to accomplish.

Objective: to demonstrate longterm kidney graft survival without signs of acute rejection and without immunosuppressive therapy in a patient who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) from a haploidentical donor for post-transplant lymphoproliferative disorder (PTLD).

Methods and materials. Recipient’s graft function was assessed using clinical, laboratory, instrumental and pathomorphological examination methods.

Results. With no immunosuppressive therapy for more than four years, the kidney recipient showed stable, satisfactory graft function.

Conclusion. The described clinical case demonstrates the development of immunological tolerance to a kidney graft in a recipient of allogeneic hematopoietic stem cells (HSCs).

Introduction. Atypical hemolytic uremic syndrome (aHUS) is a systemic orphan disease that reproduces as an uncontrolled activation of the alternative pathway of the complement system and is expressed as systemic thrombotic microangiopathy (TMA). The classical triad of aHUS symptoms are hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI). Currently, diagnosis of aHUS is a diagnosis of exclusion and has no pathognomonic features. It is established based on the clinical presentation of the disease after excluding other forms of TMA, 

Objective: to increase physicians’ awareness of this rare disease, the diagnosis and treatment of aHUS using a clinical case study.

Conclusion. Early diagnosis of aHUS is extremely important, as timely targeted therapy can significantly improve or completely restore the functions of the affected organ.

Background. Malignant tumors are one of the main causes of unfavorable outcomes in solid organ transplant recipients in the long term after transplantation. Localization of these tumors in a transplanted organ may cause loss of graft function. After chronic graft dysfunction and infections, malignant neoplasms come next as one of the leading causes of late kidney graft loss. The incidence of different types of malignancies varies according to the transplanted organ. Knowledge of etiology, pathogenesis, peculiarities of diagnosis and treatment of malignant tumors in solid organ transplant recipients is a significant part of screening at any stage of post-transplant period. Late diagnosis of malignancies in a transplanted kidney amidst disconnected stages of treatment and follow-up leads not only to graft loss, but also jeopardizes the life of recipients.

Clinical case description. The patient is a 29-year-old female. History: IgA nephropathy with nephrosclerosis. Renal replacement therapy (RRT) with long-term hemodialysis since March 2019. Kidney transplantation from a deceased donor to the right external iliac vessels on March 13, 2019. Graft function is immediate. In October 2020, a tumor in the transplanted kidney was detected for the first time. In November 2021, an emergency graft nephrectomy was performed for health reasons. Antibacterial, antifungal therapy was carried out. Results of morphological study of the removed renal graft with immunohistochemistry (IHC) were obtained. The structure and phenotype of the tumor are consistent with myeloid sarcoma. Trephine biopsy: normocellular bone marrow.

Conclusion. The 29-year-old patient was diagnosed with donor-derived myeloid sarcoma in her kidney transplant with the development of paraneoplastic syndrome and multi-organ failure. Currently, the patient is receiving RRT by long-term scheduled hemodialysis. Organ recipients need to be managed by a multidisciplinary team of specialized and highly specialized specialists, taking into account comorbid status and features of the course of the underlying disease.

Objective: to evaluate the outcomes of heart transplants performed at Rostov Regional Clinical Hospital within five years.

Materials and methods. Between 2017 and 2022, 29 orthotopic heart transplants (HT) were performed in our clinic. Heart failure was caused by postinfarction cardiosclerosis (21 cases, 72.4%) and dilated cardiomyopathy (8 cases, 27.6%). Among the recipients, 27 (93.1%) were men and 2 (6.9%) were women. Mean age was 53.14 ± 8.7 years (34 to 67 years). All patients received quadruple-drug immunosuppressive therapy, including induction with monoclonal antibodies; calcineurin inhibitor, mycophenolic acid, and corticosteroid were used after HT.

Results. In-hospital mortality was 10.34% (n = 3). The causes of death were multiple organ failure and infectious and septic complications. After discharge, 4 (13.8%) recipients died over 5 years. Rejection reaction with the development of graft dysfunction (3 recipients, 75%), infectious and septic complications (1 recipient, 25%) were the causes of death in the long-term period. The survival rate was analyzed according to the Kaplan–Meier estimate. One-year survival was 80.9%. Three-year survival rate corresponded to the 5-year survival rate – 70.56%. Five-year survival of patients surviving the first year after HT was 86.1%. Maximum follow-up period was 64 months.

Conclusion. HT continues to be the gold standard for patients with end-stage heart failure. Five-year HT experience in our center has shown a survival rate that is comparable to that of the International Society for Heart and Lung Transplantation (ISHLT).

Objective: to present a clinical case of an 11-year-old child who underwent repeat heart transplantation (HT) at Almazov National Medical Research Centre in St. Petersburg, Russia.

Materials and methods. A case of successful heart retransplantation in an 11-year-old child with cardiac allograft vasculopathy (CAV) is presented.

Results. The postoperative period after heart retransplantation had no significant differences with the postoperative period of primary heart recipients. The complexity of the intraoperative stage was determined by pronounced adhesions. As part of preoperative preparation, the patient underwent chest CT scan, which, in our experience, allows us to evaluate the heart syntopy and, in turn, is an important preparatory stage in planning repeat interventions.

Conclusion. Our first experience of cardiac retransplantation in pediatric patients suggests that repeat HT is the most optimal treatment for pediatric patients with CAV and requires more thorough preoperative preparation.

Objective: to study the biological properties of macroporous cryostructurate from multicomponent concentrated collagen-containing solution (MCCS) as a promising matrix for the formation of cell- and tissue-engineered constructs.

Materials and methods. A macroporous spongy carrier was obtained by cryostructuring of collagencontaining extract, prepared by acetic acid hydrolysis of chicken connective tissue (BIOMIR Service, Russian Federation). N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide (Sigma-Aldrich, USA) was used to make the cryostructurate water insoluble. The micromorphology of the sponge surface was studied using scanning electron microscopy. The cytotoxicity of the carrier was evaluated by reaction of the mouse NIH 3T3 fibroblast cell culture using automated microscope IncuCyte ZOOM (EssenBioscience, USA). Biocompatibility of the macroporous carrier was studied on cultures of human adipose tissue-derived mesenchymal stromal cells (AD-MSC), human hepatocellular carcinoma cell line HepG2 and human umbilical vein endothelial cell line EA.hy926. The metabolic activity of cells was determined using PrestoBlue™ reagents (Invitrogen™, USA). Cell population development during long-term cultivation of the cell-engineered construct (CEC) was assessed by fluorescencelifetime imaging microscopy over the entire surface of the sample using a Leica Dmi8 inverted microscope with Leica Thunder software (Leica Microsystems, Germany).

Results. Optical microscopy and scanning electron microscopy (SEM) showed the presence of pores of different sizes in the resulting biopolymer material: large pores with 237 ± 32 μm diameter, medium-sized pores with 169 ± 23 μm diameter, and small-sized pores with 70 ± 20 μm diameter; large and medium-sized pores were predominant. The studied media did not exhibit cytotoxicity. Cell adhesion and proliferation on the surface of the material and their penetration into the underlying layers during long-term cultivation were observed. The highest metabolic activity of the cells was observed for human AD-MSC on day 14, which corresponds to the normal dynamics of development of a population of cells of this type. The functional activity of HepG2 cells – albumin and urea production – was shown in the liver CEC model.

Conclusion. The good adhesion and active proliferation that were shown for the three cell types indicate that the resulting biopolymer carrier is biocompatible, and that the spread of the cells into the inner volume of the sponge and active population of the sponge under prolonged culturing indicates that this material can be used to create cell- and tissue-engineered constructs.

Objective: to study the effect of a conditioned medium of mesenchymal stromal cells (MSCs) from different sources on human chondrocyte proliferation.

Materials and methods. To confirm functional activity, chondrocytes were cultured in a cartilage cell-engineered construct (CEC), including 5 × 10⁵ cells and 5 mg of tissue-specific matrix from decellularized cartilage. The conditioned medium was obtained after culturing MSCs derived from human adipose tissue (AT), MSCs derived from the pulp of primary teeth and MSCs isolated from umbilical cord-derived Wharton’s jelly in a complete cell growth medium (CCGM). To evaluate the effect of MSC-derived secretome on chondrocyte proliferation, the conditioned medium, diluted 1 : 1 with CCGM, was added to wells containing chondrocytes. The effect of MSCs on human chondrocyte proliferation was studied by indirectly coculturing cells in CCGM using Transwell inserts. 5 × 10⁴ MSCs were applied to the bottom of the lower chamber, and 5 × 10⁴ human chondrocytes and 5 mg of matrix were placed in the upper chamber. Chondrocyte proliferation was assessed at days 7 and 14 by DNA quantification. Interleukin-6 content was determined as a marker of secretory activity of MSCs in the conditioned medium. The morphology of the samples was studied using histological staining methods.

Results. The ability of chondrocytes to produce cartilage-specific extracellular matrix was confirmed when forming cartilage CEC with tissue-specific matrix in a chondrogenic differentiation medium. When comparing the effect of the conditioned medium of MSCs obtained from different sources on the growth of human chondrocytes in vitro, increased proliferation was observed in all samples compared to controls. Indirect co-culture of MSCs with chondrocytes as part of CEC showed increased DNA amount in all samples at day 14, with the amount of DNA in the sample with MSC conditioned medium significantly higher than the control.

Conclusion. Studies on the effect of MSC conditioned medium on chondrocyte proliferation in 2D culture indicate a possible regenerative potential of MSCs for cartilage tissue repair. Within the scope of this work, we did not identify significant differences in the effect of secretome derived from MSCs that were obtained from different sources on chondrocyte proliferation. However, additional in vivo studies are warranted in the future.

Development of minimally invasive diagnosis techniques for complications in recipients, based on analysis of the levels of molecular and genetic biomarkers, is an urgent task facing modern transplantology. Transforming growth factor beta 1 (TGF-β1), which has multiple effects in the body, among the potential indicators of complications.

Objective: to assess the diagnostic significance of serum TGF-β1 in kidney recipients with graft dysfunction.

Materials and methods. The study included 129 kidney recipients aged 17 to 68 years and 35 healthy subjects. Serum TGF-β1 levels in the recipients were determined by immunoenzyme technique.

Results. Kidney recipients included 95 patients with laboratory and clinical signs of graft dysfunction, who underwent biopsy of the transplanted kidney, followed by morphological examination, and 34 recipients with normal graft function. Serum TGF-β1 levels in the kidney recipients were significantly higher than in their healthy counterparts (p = 0.00001); it did not correlate with most blood test parameters; with the glomerular filtration rate (GFR). Kidney recipients with graft dysfunction had significantly higher TGF-β1 levels than other recipients (p = 0.018). In recipients with graft dysfunction, morphological study revealed the following: acute tubular necrosis (ATN, n = 11), acute T-cell mediated rejection (ACR, n = 26), acute antibody-mediated rejection (AMR, n = 35), non-immune-mediated nephrosclerosis with signs of calcineurin inhibitor nephrotoxicity (CNI nephrotoxicity, n = 13), and recurrent glomerulonephritis (chronic graft rejection, n = 10). Recipients with immune-mediated graft injury (ACR, AMR and chronic rejection) had higher serum TGF-β1 levels than recipients with graft dysfunction resulting from other causes, p < 0.0001. Kidney recipients with serum TGF-β1 levels above the threshold value of 94.3 ng/mL had a higher risk of immune-mediated graft dysfunction than other kidney recipients (RR = 2.2 ± 0.22 [95% CI 1.46–3.46]) with 77.5% test sensitivity and 60.3% specificity.

Conclusion. The calculated threshold serum TGF-β1 level in kidney recipients can be considered as an auxiliary indicator of graft dysfunction resulting from acute or chronic rejection.

Patients with chronic kidney disease are susceptible to developing acute pancreatitis. We present a rare clinical case of acute pancreatitis with the formation of pancreatic necrosis in a patient on peritoneal dialysis (PD), debuted with PD–associated peritonitis. On hospitalization, there were no diagnostic criteria for acute pancreatitis; treatment for dialysis peritonitis was ineffective. Repeated ultrasound examination revealed signs of diffuse changes in the pancreas and multi-chamber formation of the small pelvis. Refractory peritonitis, inadequate ultrafiltration, and unclear nature of formation in the pelvic were the grounds for diagnostic laparoscopy and removal of the peritoneal catheter. Abdominal inspection revealed spots of stearin necrosis over the entire surface of the peritoneum and the greater omentum; in the pelvis there were adhesions between the uterus and the rectum. Development of pancreonecrosis was confirmed by abdominal CT scan. Treatment of acute pancreatitis was without effect, type 2 myocardial infarction developed, and with increasing symptoms of multiple organ failure, death occurred.

Objective: to carry out a comparative study of the efficacy of a 6-hour normothermic ex vivo heart and lung autoperfusion and cold cardioplegia using Bretschneider’s solution (Custodiol^®, Germany).

Materials and methods. Landrace pigs weighing 50 ± 5 kg at the age of 4–5 months (n = 10) were used as a model for a series of acute experiments. In the experimental group (n = 5), the cardiopulmonary complex was conditioned by autoperfusion for 6 hours. In the control group, the heart pumping function was restored after 6-hour cold cardioplegia using Bretschneider’s solution. The efficiency of graft preservation was assessed by measuring hemodynamic parameters, myocardial contractile function, and myocardial oxygen consumption.

Results. After reperfusion and repeated isolation of the working cardiopulmonary complex, cardiac output was 0.63 [0.37; 0.8] L/min and 0.37 [0.23; 0.37] L/min in the experimental and control groups, respectively (p < 0.05). Indicators – global left ventricular stroke work index and preload recruitable stroke work – were significantly higher in the experimental group (p < 0.05).

Conclusion. Normothermic autoperfusion is significantly more effective in preserving the morphofunctional status of a donor heart than static cold storage with Bretschneider solution for 6 hours.

Objective: to study in vitro survival and preservation of the proliferative activity of limbal stem cells (LSCs) in femtosecond laser-cut limbal tissue fragments.

Materials and methods. Limbal fragments were formed from donor cadaver eyes (n = 8) in the upper and lower limbus containing the highest number of limbal stem cells, using a Z8 femtosecond laser (FSL) (Ziemer, Switzerland). The limbal fragments were fragmented into 4 mini-grafts using different energy levels (100, 110, 120%). Mini-grafts from symmetrical sections of the cadaver eyes, which were manually isolated using a microsurgical blade, served as controls. The mini-grafts were cultured for two weeks in culture media intended for limbal epithelial stem cells (LESCs) (Epilife (0.06 mM Ca⁺⁺) and for multipotent mesenchymal stem cells (MMSCs) (DMEM/F12), with the addition of specific growth factors to selectively stimulate LESCs or MMSCs, respectively. The phenotype of the obtained cultured cells in the «laser» and «knife» groups was determined by flow cytometry using a set of markers (CD166, CD105, CD90, CD29, CD34) for the membrane proteins of LESCs and MMSCs. The ability of cultured cells to adhesion and proliferation in the «laser» and «knife» groups was determined by seeding the third passage of the resulting cultures on Bowman’s membrane of acellular corneas.

Results. Primary cell culture was obtained from mini-grafts of all donors in both groups. Cell morphology was consistent with the phenotype of corneal epithelial cells (cobblestone pattern). When cultured in the EpiLife medium (0.06 mM Ca⁺⁺), we determined the presence of LSCs proliferation from 38.6% of minigrafts; in the DMEM/F12 medium (1 : 1) the presence was determined from 31.8%. Two weeks later, cell yield from mini-grafts in the «laser» and «knife» groups was 77.2% and 63.6%, respectively. Cell growth by the end of week 2 of culturing of mini-grafts obtained by FSL at 120, 110 and 100% energies was 87.5, 71.4 and 71.4%, respectively. It was found that the resulting cell cultures in the «laser» and «knife» groups and in the «120%», «110%» and «100%» subgroups were not different phenotypically. Cytofluorimetric analysis showed that cell cultures in the groups had a mixed pattern of marker expression of both LESCs (CD29+) and MMSCs (CD90+, CD105+). Seeding of the third passage of cell culture in the test groups in all cases demonstrated adhesion and formation of a cell monolayer on the Bowman’s membrane of model corneas.

Conclusion. The use of FSL for cutting out limbal grafts seems to be effective and safe in comparison with the traditional mechanical (knife) technique. Cell cultures obtained from FSL-cut mini-grafts were able to grow and migrate for at least 21 days.

This article assesses the changes in the coverage of the problem of organ donation in Russia. The boundaries of the dialogue on posthumous organ donation are outlined, taking into account the current organ donation model in Russia. The paper defines the concept of social capital, the sociology of organ donation and their significance for the development of deceased organ donation (DOD). Steps to promote the DOD concept in Russia are proposed.