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Russian Journal of Transplantology and Artificial Organs

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Vol 22, No 4 (2020)
View or download the full issue PDF (Russian) | PDF
https://doi.org/10.15825/1995-1191-2020-4

Editorial

Clinical Transplantology

8-19 1049
Abstract

Introduction. Heart transplantation (HT) in patients with preexisting type 2 diabetes (T2D) is associated with high risk of infectious and non-infectious complications (renal dysfunction, multifocal atherosclerosis,  transplant coronary artery disease, etc.) that can negatively affect recipient survival in the early and late periods after HT.

Objective: to assess the effect of pre-transplant T2D on early and long-term outcomes of HT based on a  singlecenter retrospective study.

Materials and methods. The study enrolled 891 recipients who underwent HT within the period 2011 to 2018, and were divided into two groups: main group (T2D) – recipients with pretransplant T2D (n = 80, 9.0%) and the control group (T2D-free) – recipients without T2D (n = 811, 91.0%). Recipients from both groups did not differ in terms of HT urgency (UNOS status) and the need for pre-transplant mechanical circulatory support (MCS).

Results. At the time of the HT, recipients from the T2D group were older than the T2D-free recipients (54 [46; 59] years vs 48 [35; 56] years, p < 0.001), they had a higher weight (p < 0.001) and body mass index (p < 0.001), coronary heart disease was more often their main disease (65.0% vs 36.5%, p < 0.001), they had higher transpulmonary gradient (10.0 [7.0; 12.0] mm Hg vs 9.0 [6.0; 12.0] mm Hg, p = 0.024) and  pulmonary vascular resistance (2.9 [2.2; 4.0] Wood units vs 2.5 [1.8; 3.4] Wood units, p = 0.038). In the pre-transplant period, the T2D group had pronounced manifestations of renal dysfunction and increased comorbidity. Recipients in both groups did not differ in terms of cardiac donor parameters, graft ischemia time, cardiopulmonary bypass time, and incidence of severe early heart graft dysfunction requiring MCS (12.5% vs 10.7%, p = 0.74). In the early post-transplant period, the T2D group had high requirements (100% vs 28.0%, p < 0.001) and higher doses of insulin therapy. More pronounced manifestations of renal dysfunction and a greater need for renal replacement therapy (51.4% vs 27.9%, p = 0.003) did not affect artificial ventilation and ICU duration (6 [5; 10] days vs 6 [5; 10] days, p = 0.098), as well as hospital mortality ( 8.8% vs 8.5%, p = 0.895). The presence of pre-transplant T2D had no negative effect on the incidence of acute cardiac graft rejection, progression of transmissible coronary atherosclerosis, incidence and severity of cardiac graft vasculopathy, structure and severity of distant infectious and non-infectious complications, and post-transplant survival.

Conclusion. With correct selection of recipients and choice of optimal tactics for their post-transplant management, the presence of pre-transplant T2D has no negative effect on early and long-term outcomes of HT.

20-26 634
Abstract

Objective: to determine the diagnostic value of miRNA-101 and miRNA-27 expression levels for acute heart
transplant rejection.

Materials and methods. The study enrolled 46 heart recipients, among whom were 36 men (78.3%); the average age of recipients was 47.7 = 10.8 (16 to 67) years. Serum microRNA expression levels were measured via quantitative polymerase chain reaction (PCR). Graft rejection was verified through morphological analysis of endomyocardial biopsy specimens.

Results. The expression levels of miRNA-101 and miRNA-27 in recipients with acute graft rejection are significantly lower than in recipients without rejection (p = 0.04 and p = 0.03, respectively). When the miRNA-101 expression level is below the determined threshold value, the risk  of developing acute graft rejection increases 1.8 times (RR = 1.8 [95% CI 1.13–3.01]). When the miRNA-27 expression level is below the determined threshold value, the risk of developing acute graft rejection increases 1.9 times (RR = 1.9 [95% CI 1.12–3.37]). Simultaneous decrease in the expression levels of miRNA-101 and miRNA-27 below the determined threshold values increases the likelihood of acute graft rejection by 2.0 times (RR = 2.0 [95% CI 1.16–3.36]).

Conclusion. The serum miRNA-101 and miRNA-27 expression levels are of diagnostic value for acute graft rejection in heart recipients.

27-31 747
Abstract

Selection of heart donors is the most important stage on which the success of heart transplantation depends.

Objective: to create a donor heart scoring model based on a number of donor characteristics.

Materials and methodsThe study used data from 650 brain-dead donors who underwent organ explantations between January 1, 2012 and December 31, 2017. In binomial logistic regression, non-selection of heart donor was used as a dependent variable, while donor characteristics were used as factor features. In regression model, the odds ratio was determined for each donor factor, which was transformed into points. The sum of the points of each of the donor factors included in the model was taken as the score of the donor heart. The proposed model was validated on a sample of donors  for the period from January 1, 2019 to December 31, 2019; n = 218.

Results. The model includes donor characteristics, such as age, cause of death (traumatic brain injury (TBI)/stroke), history of hypertension and diabetes, cardiac arrest with subsequent recovery, own pathology and traumatic heart disease, as well as heart rate, systolic blood pressure, arterial lactate, and need for norepinephrine immediately before organ harvesting. Based on the average value of the sum of points, low-risk donors (LRD ≤17 points) and high-risk donors (HRD ≥18 points) were identified. In the validation pool of donors, the proportion of heart failure among LRD and HRD was 4.1% and 78.6%, respectively, p < 0.0001, Pearson’s χ2 – 130.9.

Conclusion. The presented donor heart scoring model accurately reflects the probability of using a donor’s heart for transplantation and creates conditions for optimal distribution of heart transplants, especially from high-risk donors. 

32-42 684
Abstract

Objective: to evaluate the immunological efficacy of haemophilus influenzae type b (Hib) vaccine in patients with severe bronchopulmonary condition waitlisted for lung transplantation.

Materials and methods. 16 patients (age 22–61 years) with severe bronchopulmonary diseases were vaccinated once against Hib infection. IgG antibody concentrations to Hib capsular polysaccharide before vaccination and 1 month after was measured by ELISA using a test system developed at Mechnikov Research Institute of Vaccines and Sera. Statistical data processing was carried out using stats (v.3.6.2), lme4 (v.1.1 – 21), and lmerTest (v.3.1 – 1) packages.

Results. Hib vaccine in patients with severe bronchopulmonary condition did not elicit any local or systemic reactions. The proportion of patients whose antibody (Ab) concentrations to Hib capsular polysaccharide exceeded the long-term protection threshold was 69% and 100% before and after vaccination, respectively (p = 0.02). There were differences in the formation of post-vaccination immunity depending on the nosological forms of patients’ diseases. In the group of patients with obstructive pulmonary diseases, the geometric mean level of antibodies to the Hib capsular polysaccharide after vaccination increased as compared to the baseline  value – from 1.3 [0.6–2.8] to 5.5 [1.9–15.4] AU/mL, (p = 0.05). In the group of patients with restrictive lung diseases, the level did not change – 2.8 [0.6–14.1] AU/mL before vaccination and 3.4 [1.3–8.5] AU/mL 1 month after vaccination. In the group of patients taking glucocorticosteroids, there was no increase in the level of antibodies to Hib capsular polysaccharide (2.7 [0.8–9.3] AU/mL before and 2.8 [1.2–6.5] AU/mL after vaccination). In the group of patients who did not take hormones, antibody concentrations to Hib capsular polysaccharide increased from 1.2 [0.7–2.1] AU/mL to 4.8 [2.2–10.1] AU/mL (p = 0.006).

Conclusion. Hib vaccination of waitlisted patients with severe bronchopulmonary disease is safe and immunologically effective. 

43-51 706
Abstract

Studies on the regenerative capabilities of tissues have shown that damaged liver can recover using hematopoietic stem cells (HSCs), which are able not only to replace cells in the target organ, but can also deliver trophic factors that support endogenous liver regeneration. There is practically no data on how organ-derived humoral signals involve such morphogenic/trophic cells in circulation.

Objective: to investigate the role of non-invasive vibromechanical percutaneous action on the liver in  cirrhosis by quantification of CD133+ lymphoid HSCs with specific hepatic marker alpha-fetoprotein (AFP) in patients awaiting liver transplantation.

Materials and methods. In order to increase the number of AFP+ part of CD133+ stem lymphoid cells in the blood, the patient’s cirrhotic liver was mechanically activated by transcutaneous microvibration using electromagnetic vibrophones in contact with the skin. This generated mechanical impulses with a 10 μm amplitude and a smoothly varying frequency from 0.03 kHz to 18 kHz and back to within one cycle lasting 1 minute. The amount of AFP+ lymphocyte fraction in the total content of CD133+ HSCs in lymphocytes of potential recipients was monitored by flow cytometry before and during daily 15-minute sonication of the skin zone corresponding to the liver projection for three weeks with eight synphased vibraphones.

Results. Sonication of the liver projection zone significantly increased the number of liver-specific CD133+ AFP+ lymphocytes by 2–3 times compared to the baseline values. Repeated similar sonication of the same site after a three-week break showed a statistically insignificant increase from the initial level. With a similar effect on the spinal projection in the control group of waitlisted patients with cirrhosis, there was no increase in CD133+ AFP+ lymphocytes.

Conclusion. Mechanical stress prompts the organ to secrete specific humoral signals that provoke the bone marrow to produce additional lymphoid stem cells committed to the liver and recruit them into circulation.

52-57 787
Abstract

Objective: to study liver transplantation (LT) outcomes in cirrhotic patients with hepatocellular carcinoma
(HCC), who underwent transcatheter hepatic arterial chemoembolization (THACE).

Materials and methods. From January 1998 to April 2020, we performed 245 orthotopic liver transplantation (OLTs) in 229 patients of which 25 (10.2%) had HCC in cirrhosis. In 9 (36%) patients, LT was performed without neoadjuvant therapy (Group 1). Group 2 consisted of 16 (66%) patients who underwent 49 THACE cycles before LT. 10 (62.5%) patients fell within the Milan criteria, while 6 (37.5%) were outside. According to the BCLC (Barcelona Clinic Liver Cancer) classification, 10 patients had A1–A4 stage, while 6 were in B stage. In 11 (68.5%) of 16 patients, increased serum alpha-fetoprotein (AFP) concentrations from 20 to 2463 (on average 493.8) ng/mL was revealed before treatment. In performing THACE, both the classical method (with lipiodol and hemostatic sponge) and the method with drug-eluting beads were performed 1 to 7 (on average 3) times. Doxorubicin was used in all cases.

Results. Group 2 recorded a 100% technical success. There were no complications. We performed radiofrequency ablation (RFA) in three patients as an adjunct. In two patients, we performed laparoscopic RFA-assisted atypical liver resection, and in one – sequential resection and RFA. Under the m-Recist criteria, complete response was observed in 6 (37.5%), partial response in 7 (43.75%), and stabilization in 3 (18.75%) patients. Change in AFP concentrations were as follows: in 5 out of 11 patients with increased concentrations, we were able to reduce their AFP concentrations to the reference values, their long-term outcomes are comparable to those of Group 1. Four patients showed a 13–84% decrease; a directly proportional relationship between the degree of AFP decrease and the time to tumor progression was  revealed. In 2 patients, there were 42% and 320% increase in AFP concentrations, the time to tumor progression was 3 and 1 month, both did not live up to 12 months. Among 9 (56%) of the living 16 patients, a maximum of 156 months and a minimum of 4 months (60.2 average) have elapsed since the surgery. Two of these nine have tumor progression (cases 4 and 14). Seven (44%) patients died within 9 to 54 months. The 1, 3, 5-year actuarial survival rates were 93, 50, 32%, two patients lived more than 10 years. The average life expectancy was 28.0 ± 3.0 months.

Conclusion. Serum AFP concentration is an important prognostic factor influencing the long-term outcomes of LT. Good biological response to THACE can be a positive predictor; LT outcomes in these patients are  comparable to those in patients who meet the Milan criteria. A decrease in AFP concentrations by less than  50% after neoadjuvant THACE is an unfavorable factor, and its increase is extremely adverse.  

58-64 818
Abstract

Objective: to study the outcomes of main surgical methods for stopping and preventing variceal hemorrhage in waitlisted cirrhotic patients.

Material and methods. In our prospective case-control study, the «case» cohort included 132 patients with cirrhosis complicated by recurrent varicose bleeding, while the «control» group consisted of 92 patients with  one episode of bleeding esophageal varices. Treatment included conservative therapy, endoscopic ligation, transjugular intrahepatic portosystemic shunt, and the original azygoportal disconnection technique.

Results. High MELD scores, severe hepatic encephalopathy, portal vein thrombosis, high degree of varices, and recurrent bleeding significantly affect the mortality of cirrhotic patients. Irrational use of nonselective  beta-blocker monotherapy has a negative impact on treatment outcomes. Combined use of drug therapy and surgical methods of stopping and preventing varicose bleeding, reduces the number of relapses, prolongs patients’ life to two years or more, which allows to move on to the next stage of cirrhosis treatment – liver transplantation.

Conclusion. The likelihood of recurrent variceal hemorrhage increases in patients who undergo passive surgical tactics. Azygoportal disconnection should be considered as the operation of choice if the patient has more than one episode of variceal bleeding. Timely and adequate treatment measures, clinical and diagnostic monitoring reduce waitlist mortality.

65-68 688
Abstract

Objective: to determine the indications for penetrating keratoplasty (PK) in the Kingdom of Jordan and evaluate
its clinical and functional outcomes.

Materials and methods. 213 patients underwent PK at the ophthalmology department of King Abdullah University Hospital (KAUH) in Jordan from January 1, 2010 to December 31, 2018. While 196 (92.2%) patients were operated on in one eye, 17 (8.8%) underwent PK in both eyes. For all patients, the best corrected visual acuity (BCVA) was checked using the Snellen table and compared with the BCVA before surgery; biomicroscopy of the anterior segment of the eye, as well as applanation tonometry, were carried out.

Results. Keratoconus was found to be the most common indication for PK – 154 patients (73.2%). For all patients, the BCVA improved from 0.08 before surgery to 0.25 after surgery.

Conclusion. Keratoconus is the most common indication for PK in both men (97, 71.3%, p < 0.05) and women (57, 74%, p < 0.05) in the Kingdom of Jordan. PK is an effective method for treating various corneal disorders.

69-74 3032
Abstract

The COVID-19 pandemic has had global consequences due to the wide spread of the infection in the world, lack of currently proven effective therapy, resistance to treatment in a significant proportion of those affected and, as a result, high mortality, especially among high-risk groups. Kidney transplant recipients with coronavirus-induced pneumonia are among the most problematic categories of patients. This patient cohort experiences a severe form of the disease, taking into account a combination of risk factors, such as long-term immunosuppression, comorbid background of patients, and consequences of chronic kidney disease. Difficulties in the management of recipients with COVID-19 are also down to the limitation of the use of drugs due to adverse drug-drug interactions.

Objective: to analyze the course of COVID-19 disease in organ recipients, to assess the factors influencing the prognosis of the disease, and to optimize approaches to treatment of these patients.

Materials and methods. During the period from April 15, 2020 to June 15, 2020, 68 people (38 men and 30 women) were hospitalized at our clinic. Their average age was 49.7 ± 9.2 years (22 to 70 years). COVID-19 diagnosis was verified by PCR. Multispiral computed tomography (MSCT) scans showed that in all cases, there were characteristic lung lesions of varying degrees of severity.

Results. Out of the 68 people treated, 61 (89.8%) were discharged with recovery, 7 patients died. So, the mortality rate was 10.2%. This indicator did not depend on age and gender. First of all, mortality depended on the severity of lung lesions: at CT4 it was 43% (3/7), at CT3 – 11.1% (4/36), there were no deaths in patients with CT2. There was a 100% mortality among patients who received mechanical ventilation. Severity of graft dysfunction was also an important prognostic factor: with moderate dysfunction, this indicator was 8% (5/63), while with severe dysfunction it was 40% (2 out of 5). Besides, a more severe prognosis was observed in patients in the early post-transplant period: 5 patients out of the 7 who died of COVID-19 (71%) lived for less than a year after kidney allotransplantation (ATP). Mortality in this category of patients was 24%, while in the period from 1 to 5 years, this indicator was 13.6%; no deaths were recorded among patients with a period of over 5 years after ATP. All patients received antibacterial (levofloxacin or azithromycin) and antiviral (hydroxychloroquine) therapy. In all cases, the baseline immunosuppressive  therapy (IST) was changed, including withdrawal of mycophenolic acid preparations, minimization of the calcineurin inhibitor dose (target concentration 1.5–3 ng/mL for tacrolimus and 30–50 ng/mL for cyclosporine), and increase in prednisolone dose by 5 mg relative to the current one. About 78% of cases received pathogenetic therapy with anti-interleukin monoclonal antibodies (mainly tocilizumab). These patients also received intravenous immunoglobulin at 10 g average dose. In severe COVID-19 accompanied in by clinical and laboratory signs of thrombotic microangiopathy 22% of cases, plasma exchange sessions and/or infusion of fresh frozen plasma and dose adjustment of low molecular weight heparins were performed.

Conclusions. COVID-19-induced pneumonia in kidney transplant recipients is characterized by a high risk of progressive lung damage and respiratory failure. Mortality in COVID-19 is independent of gender and age, but correlates with post-transplantation period, severity of pneumonia, and severity of graft dysfunction. The need for mechanical ventilation is associated with an extremely unfavorable prognosis of the disease.

75-82 1302
Abstract

Objective: to evaluate the short-term outcomes of surgical treatment of aortic valve and ascending aorta defects performed through mini-sternotomy using normothermic cardiopulmonary bypass and hyperkalemic cardioplegia via Calafiori technique from May 8, 2019 to May 14, 2020.

Materials and methods. The study enrolled 80 patients with isolated aortic valve disease and combined  pathology of the aortic root and ascending aorta. It lasted from May 8, 2019 to May 14, 2020. The patients were divided into two groups: Group 1 included 30 patients in whom the upper median J-shaped sternotomy was applied as an access, while Group 2 consisted of 50 patients in whom standard median sternotomy was used as an access. The patients consisted of 43 (53.7%) males and 37 (46.3%) females; the average age was 55.1 ± 11.6 years. All patients were examined before surgery. It revealed no statistically significant differences between the two groups.

Results. Group 2 had a 30-day mortality of 2% (n = 1) due to the development of acute heart failure against the background of heart rhythm disturbances. One patient in this group had a late mortality due to acute cerebrovascular accident occurring a month after discharge, which corresponded to 2% (n = 1). There were no deaths in Group 1. In Group 1, there were two conversions (6.7%) to longitudinal median sternotomy. In the first case, it was not possible to restore heart rhythm through repeated defibrillator discharges from mini-sternotomy access due to the presence of an adhesive process in the pericardial cavity. In the second case, ligation of the right internal thoracic artery was required after sternal wire sutures. Artificial ventilation (AV)  lasted for 170.9 ± 70.2 minutes in Group 1 and 358.2 ± 169.5 minutes in Group 2. Cardiac activity was independently restored in 23 patients (77%) in Group 1, and in 12 (24%) in Group 2 (p < 0.001). Intraoperative blood loss was 400 ± 150 mL and 850 ± 150 mL (p < 0.05) in Group 1 and Group 2, respectively. In the early postoperative period, it was 200 ± 150 mL in Group 1 and 350 ± 150 mL in Group 2. The length of stay at the intensive care unit and the duration of intensive therapy did not exceed 1 day in both groups. In the early postoperative period, 4 patients in Group 1 (13%) and 27 patients in Group 2 (54%) needed inotropic support (p < 0.001). The need for painkillers and non-steroidal anti-inflammatory drugs was within 3–4 days in Group 1 and 8–10 days in Group 2. In-hospital postoperative period varied from 10 to 16 days in both groups, depending on the severity of the initial condition, presence of concomitant diseases and the need to select an adequate anticoagulant dose. The patients were discharged in satisfactory condition  under the supervision of a cardiologist at their homes. There were no inflammatory complications in the access area in both groups during their in-hospital stay. Among the complications in the mid-term postoperative period, two months after discharge, mediastinitis was observed in Group 2. The patient was re-hospitalized, after a course of antibiotic therapy which resolved the mediastinitis; sternal osteosynthesis was performed.

Conclusion. Based on the study, it has been shown that this technique reduces the duration of mechanical ventilation, ensures early extubation, decreases blood loss, and, accordingly, ensures the use of replacement therapy, chest stability and a better cosmetic effect. It should be noted that there was no mortality and sternal complications in the patient group with a minimally invasive approach.

Heart Transplantation and Assisted Circulation

83-88 692
Abstract
Patients suffering from end-stage congestive heart failure are in the severe category of cardiac patients. For many decades, there has been active development of circulatory assist devices. However, despite significant progress made in this area, the use of such devices is associated with several dangerous complications, one of which is thrombosis. The problem of creating biocompatible materials still remains unresolved. Analyzing the mechanism and risk of this complication allows to determine the ways of solving this problem.

Regenerative Medicine and Cell Technologies

89-97 768
Abstract

Objective: to investigate the functional efficiency of a cell-engineered construct (CEC) of the liver based on tissuespecific matrix consisting of decellularized rat liver fragments, allogeneic liver cells and multipotent mesenchymal stromal cells (MSCs) isolated from the bone marrow on an experimental model of chronic liver failure (CLF).

Materials and methods. In creating liver CECs, the liver for decellularization and liver cells were obtained from male Wistar rats. MSCs were isolated from rat bone marrow. The functional efficacy of CEC was investigated on an experimental CLF model obtained by priming rats with CCl4 solution. At different periods after implantation, the outcomes were assessed based on the biochemical parameters of cytolysis.  Morphological changes in the liver were analyzed by histochemical methods in the control (administration of saline solution into the liver parenchyma) and experimental (administration of liver CEC into the liver parenchyma) groups.

Results. It was shown that implantation of the proposed CEC normalizes blood biochemical parameters and structural disorders of the damaged rat liver faster (by day 30 after introduction of CEC instead of day 180 in the control). The CEC was also shown to have reduced animal mortality from 50 to 0%, which is due to early activation of proliferation of viable liver cells and faster formation of new blood vessels. These effects are down to either stimulation of the internal regenerative potential of the damaged liver during CEC implantation or long-term functioning of the transplanted cells as part of the CEC based on the decellularized liver matrix.

Conclusion. The liver CEC, implanted into the liver parenchyma in laboratory animals with a CLF model, has a functional activity.  

98-104 750
Abstract

The development of effective and versatile microcarriers is a pressing issue in tissue engineering and regenerative medicine.

The objective of this work is to create biocompatible fiber microparticles from the cocoons of the Bombyx  mori silkworm, and to study their structure and biological properties. 

Materials and methods. In obtaining microparticles, the Bombyx mori cocoons washed from sericin were cryo-milled in liquid nitrogen. The structure of the resulting microparticles was analyzed via scanning electron microscopy. The cytotoxicity of the obtained fibers was assessed using MTT-cell culture assay of 3T3 mouse fibroblasts. Cell adhesion analysis was performed using the Hep-G2 human hepatocarcinoma cell line. Cell visualization was performed by staining the nuclei with DAPI fluorescent dye.

Results. Natural silk microparticles were obtained in the form of cylindrical fibers with 200–400 μm average length and 15 μm diameter. It was shown that the surface of the resulting microparticles has a rough relief; no pores were found. The microparticles are non-toxic for 3T3 mouse fibroblasts, they maintain a high level of adhesion by human hepatocellular carcinoma HepG2 cells.

Conclusion. The method developed by us for fabrication of biocompatible silk fibroin microparticles in the form of fibers without using toxic reagents and significant time costs is promising for cell cultivation and delivery to the damaged area for tissue and organ regeneration.

105-114 830
Abstract

Objective: to develop a method for obtaining scaffolds based on natural silk fabric and to study their biocompatibility in vitro.

Materials and methods. To obtain biodegradable scaffolds based on natural silk fabric, we propose treating natural silk fabric with a water-ethanol solution of calcium chloride. Differences in the structure of the resulting scaffolds were identified via scanning electron microscopy.

Conclusion. The resulting scaffolds are non-toxic to cells and support cell adhesion and proliferation. Our studies make it possible to consider the resulting biodegradable scaffolds as promising constructs for tissue engineering and regenerative medicine.

115-122 698
Abstract

Objective: to analyze the 3D micro- and nano-structure and quantitative morphological parameters of liver cells
cultured on biodegradable silk fibroin-based film scaffolds.

Materials and methods. Samples of biodegradable silk fibroin-based scaffolds with cultured Wistar rat liver cells were obtained for the study. The 3D structure of liver cells cultivated on the scaffolds was studied by scanning probe optical nanotomography using an experimental setup combining an ultramicrotome and a scanning probe  microscope in correlation with fluorescence  microscopy.

Results. Nanoscale images and 3D nanotomographic reconstructions of rat liver cells cultured on scaffold were obtained. The morphological parameters of liver cells (average roughness, specific effective area) were determined. The average surface roughness of the liver cells Ra was found to be 124.8 ± 8.2 nm, while the effective surface area σ was 1.13 ± 0.02. Analysis of the volume distribution of lipid droplets showed that they occupy 28% of the cell volume.

Conclusion. Scanning probe optical nanotomography can successfully analyze the nanostructure and quantify the nanomorphology of liver cells cultured on biodegradable scaffolds.

123-132 617
Abstract

Objective: to study the characteristics of mechanisms of the distant stimulating effect of full-thickness skin
autograft (FTSG) on microvascular perfusion in local and systemic microcirculation disorders.

Materials and methods. The experiment was carried out on 87 white male rats, divided into 5 groups: 1) control; 2) animals with local microcirculation disorders induced by sciatic nerve transection and neuroraphy; 3) animals with systemic microcirculation disorders caused by alloxan-induced diabetes; 4) animals that underwent FTSG after sciatic nerve transection and neurography; 5) animals that underwent FTSG in alloxan-induced diabetes. Laser Doppler flowmetry (LDF) was used to study microcirculation of the dorsal skin of the rear paw. Serum concentrations of vasoactive substances, including catecholamines (CA), histamine, and vasculoendothelial growth factor (VEGF) in the experimental animals were measured. A morphological study of the tissues of the autograft site was carried out on day 42 of the experiment.

Results. On day 42 of the experiment, FTSG normalized perfusion in local and systemic microcirculation disorders. FTSG decreases CA level in nerve injury, and to a greater extent in alloxaninduced diabetes. Serum  histamine increase under FTSG was more pronounced in rats with nerve injury. Serum VEGF in rats with nerve injury and FTSG increased, which was not observed in alloxan-induced diabetes. Histological assay of the  autograft site revealed degenerative changes in the epidermis and dermis of the autotransplant in both experimental models of microcirculatory disorders. Eosinophilic infiltration of the autograft site was more pronounced in nerve injury than in alloxan-induced diabetes.

Conclusion. FTSG has a distant stimulating effect on microcirculation, which manifests itself in the same degree in both local and systemic microcirculation disorders. The distant stimulating effect of FTSG on microcirculation is multicomponent in nature and includes a set of regulatory reactions, whose severity differs in local and systemic microcirculatory disorders.

133-139 677
Abstract
There are many different surgical techniques for bone reconstruction. However, biological reconstruction methods are being increasingly developed. The main purpose is not only to fill up defects, but to stimulate the processes of reconstruction and regeneration of bone as a complete organ. In this report, we describe the basic principles of orthobiology and the essential orthobiological materials. A clinical case is presented where a combination of allogeneic osteoplastic materials with autologous platelet-rich plasma is used to reconstruct a  cavity defect in the tibia.

Literature Reviews

140-148 1157
Abstract
Liver transplantation is the treatment of choice for patients with end-stage liver disease or acute liver failure. However, vascular complications, such as hepatic artery stenosis and/or thrombosis, graft portal vein stenosis and biliodigestive strictures following liver transplantation are still common despite improvements and innovations in surgical techniques. These complications can lead to graft damage or even death, and they are  caused by many factors. Although minimally invasive interventional radiology is an optional treatment for such post-liver transplant complications, there is little research on this method of treatment.
149-153 6520
Abstract
Living related liver transplantation has proved to be an effective, safe and radical method for treating end-stage liver diseases. In the last decade, a laparoscopic approach to donor hepatectomy has been gradually introduced into clinical practice. According to world literature, there are presently no uniform standards for performing laparoscopic liver resections in living donors. This literature review considers almost all methods for performing this surgery in living donors. These methods are described in transplant centers around the world.
154-161 790
Abstract
About 2,400 pancreas transplantations are performed every year worldwide, mainly pancreaticoduodenal  transplantations. Most clinics use the classical revascularization technique using a Y-shaped vascular prosthetic implant. However, it is not always possible to restore full blood supply to the graft in this way. Therefore, other options for arterial reconstruction are being developed – from isolated blood supply to the graft via the splenic artery to full blood flow restoration through all the main vessels of the organ to ensure the most physiological blood supply to the pancreas. This review is devoted to analysis of the used arterial reconstruction methods and pancreaticoduodenal graft revascularization techniques.

Clinical Cases

162-167 797
Abstract
Lung transplantation is the final treatment option for end-stage lung failure. In 2019, 63,530 lung transplants were performed worldwide [13]. Due to the variety of diseases causing patients to resort to lung transplant surgeries, there is a wide range of different complications and conditions that are subject to an individual clinical approach to determine treatment tactics. Each case is of great clinical interest due to the small amount of these operations and the complexity of postoperative rehabilitation, which requires a multidisciplinary approach [12]. We present a report on a surgical treatment of expiratory tracheal stenosis in combination with bronchiectasis in a lung recipient.
168-172 627
Abstract

Objective: to present our own experience of heart transplantation in a patient with persistent left superior vena cava (PLSVC). A clinical case of successful orthotopic heart transplantation using the biatrial technique in a patient with PLSVC drainage into the right atrium is presented. The clinical effect achieved as a result of the treatment fully justifies the chosen surgical tactics and allows us to recommend the proposed tactics for treatment of such a rare anomaly.

Conclusion. The clinical effect achieved as a result of the treatment fully justifies the chosen surgical tactics and allows us to recommend the proposed tactics for treatment of such a rare anomaly.

173-182 858
Abstract
Myocarditis has polymorphic clinical manifestations and is one of the main causes of heart transplantation. We present a clinical case of a 43-year-old female patient who was admitted to the clinic with biventricular heart  failure (NYHA class 3–4). She periodically noted exacerbations of bronchitis against the background of prolonged smoking. Twenty-one months prior to hospitalization, she first noted a shortness of breath without an obvious connection with the infection. Her ejection fraction (EF) decreased to 34%, pleural and pericardial effusion was revealed. Coronary angiography found no abnormalities. However, MRI showed subendocardial contrasting of the  left ventricular (LV) apex. The diagnosis was myocarditis. Within six months, the patient received therapy with 30 mg/day prednisolone and cardiotropic therapy. Her shortness of breath intensified, and the lower extremities swelled. Examination in the clinic showed a sharp decrease in QRS voltage, QS complexes in the V1–V6 leads, dilation of all heart chambers, thrombus in the LV apical aneurysm, 16% EF, 3.9 cm VTI, 454 mmHg dp/dt, and a sharp increase in anticardiac antibody titers (up to 1:320). Endomyocardial biopsy was not performed due to the patient’s rapidly deteriorating condition, the need for cardiotonics, and signs of multiple organ failure. She was transferred to Shumakov National Medical Research Center of Transplantology and Artificial Organs, where extracorporeal membrane oxygenation was performed; orthotopic heart transplant was successfully performed. The patient’s condition was stable for the next year. Investigation of the explanted heart revealed a picture of giant cell myocarditis. Issues of diagnosis, possibility of a long-term chronic course, as well as methods of treatment of this variant of myocarditis, including the key role of heart transplantation, are discussed.
183-191 790
Abstract
The vanishing bronchus intermedius syndrome is a type of peripheral bronchial stenosis that develops in lung recipients within two to nine months after transplantation. Lack of timely diagnosis and effective treatment leads to increased mortality and poor quality of life. The clinical case presented demonstrates the successful long-term treatment of vanishing bronchus intermedius syndrome in a lung recipient using interventional bronchoscopy.
192-196 669
Abstract
Progressive familial intrahepatic cholestasis type 2 (PFIC-2), formerly known as Byler’s syndrome, is an autosomal recessive disorder. In infancy or early childhood, this disease leads to end-stage hepatic disease, in which liver transplantation is the only radical treatment. In general, liver transplantation outcomes are good, but in the long term, PFIC-2 may reoccur. We present a case where a girl, aged 28 months, who suffered from cirrhosis resulting from PFIC-2, underwent a related transplantation of the left lateral sector of the liver (her grandmother as the donor). Punch biopsy was performed 8 years after the liver transplant due to graft dysfunction. Histopathology revealed a recurrent PFIC-2. F4. Increased liver failure was the reason for retransplantation of the left lobe of the liver also from a related donor (mother). Pathological pictures in the biopsy specimen and in the liver removed during retransplantation were identical, which once again confirmed PFIC-2 recurrence.
197-201 1704
Abstract

Elderly patients with diabetes, hypertension and obesity are at risk of severe course of the novel coronavirus infection COVID-19. Patients with chronic liver disease are also at high risk of severe course and death due to SARS-CoV-2.

Case report. Patient D., 65 years old, since 2010, was observed for Child-Pugh class B-C cirrhosis of mixed  etiology (alimentary and metabolic), type 2 diabetes. He was hospitalized on May 17, 2020 due shortness of breath, increased encephalopathy and CT signs of bilateral polysegmental pneumonia, involving about 75% of the lung tissue (CT-scan indicates possible COVID-19-associated pneumonia). Despite repeated negative results of PCR test targeting SARS-CoV-2 viral RNA, the clinical picture and CT scans pointed at the  novel coronavirus infection COVID-19 (virus not identified). Because of decompensated cirrhosis, the patient decided to refrain from antiviral and anticytokine therapy. Oxygen therapy, positional therapy, antithrombotic therapy (fondaparinux sodium), antibacterial therapy (ceftriaxone, then levofloxacin), infusion of 20% albumin solution and fresh frozen plasma were carried out. Due to increasing hypoxemia, the patient was transferred to the ICU and placed under mechanical ventilation. Despite all measures, he developed symptoms of multiple organ failure and died of asystole. 

Discussion. Mortality in chronic liver diseases, including cirrhosis, under the novel coronavirus infection caused by SARS-CoV-2, reaches 40% [4]. Factors aggravating the novel coronavirus disease in such patients include immune-mediated liver cell damage, direct cytotoxicity resulting from viral replication in hepatocytes, hypoxia, drug-induced liver injury, and reactivation of previously latent liver diseases (including hepatitis B and C virus).

Conclusion. In the above clinical case, end-stage lung disease (CT stage 3–4), complicated by disseminated  intravascular coagulation (DIC) syndrome, with progressive respiratory and multiple organ failure, led to the death of the patient suffering from cirrhosis and COVID-19.

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