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Russian Journal of Transplantology and Artificial Organs

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Vol 25, No 3 (2023)
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Editorial

8-30 2912
Abstract

Objective: to monitor the current trends and developments in organ donation and transplantation in the Russian Federation based on data from the year 2022.

Materials and methods. Heads of organ transplant centers were surveyed through questionnaires. Data control was done using the information accounting system of the Russian Ministry of Health. We performed a comparative analysis of data obtained over years from various federal subjects of the Russian Federation and transplant centers.

Results. Based on data retrieved from the National Registry in 2022, 46 kidney, 31 liver and 16 heart transplant programs were existing in the Russian Federation as of the year 2022. Organ donation activity in 2022 was 5.2 per million population (p.m.p.), with a 73.7% multi-organ procurement rate and an average of 2.8 organs procured from one effective donor. In 2022, 2,555 organ transplants were performed in the Russian Federation, which included 1,562 kidney, 659 liver and 310 heart transplants. Same year, the number of transplant surgeries performed in the Russian Federation increased by 10.0% compared to 2021. In Moscow, organ donation activity was 26.3 p.m.p. The city of Moscow and the Moscow Oblast alone had a total of 12 transplant centers, accounting for 52.6% of all kidney transplants and 64.8% of all extrarenal transplants in the country. The number of organ recipients in the Russian Federation exceeds 150 p.m.p.

Conclusion. The geographic distribution of transplant centers in the Russian Federation continues to expand. Five new centers were opened in 2022. Over the past year, the number of effective donors and organ transplants increased in the country. The resource potential of medical institutions has not been exhausted and this is set to further increase the number of organ transplants performed. Moscow is the powerhouse of Russian transplantology. However, other regional leaders have since appeared in the Russian Federation, such as in Kemerovo, Kazan, Rostov-on-Don, Tyumen, Irkutsk, and Volzhsky. In the Russian Federation, priority is being given to pediatric transplant care. It is expedient to implement a complex of measures aimed at identifying potential recipients.

Clinical Transplantology

31-37 510
Abstract

Bronchial complications, along with development and progression of chronic dysfunction on the background of chronic rejection, are factors that reduce the quality and life of lung and heart-lung recipients. They also increase the frequency of hospitalizations. Application of cryotechnology is based on the contact effect of extremely low temperatures on organs and tissues using a cryoprobe. This article demonstrates the experience of using cryotechnology in the diagnosis and treatment of complications in lung and heart-lung recipients.

38-49 527
Abstract

Graft-versus-host disease (GvHD) after liver transplantation (LT) occurs in 0.2–0.3% of liver transplant recipients. Each case is characterized by individual peculiarities of the clinical picture. There are no standards or clinical guidelines for the treatment of GvHD in solid organ recipients; mortality remains very high among these patients. We present two clinical cases of verified GvHD that developed early after LT, and we offer a brief review of the current state of the art in the study of this problem.

50-56 472
Abstract

The paper analyzes the literature on physical rehabilitation in transplantology. The medical and social aspects of rehabilitation and peculiarities of physical rehabilitation in child organ recipients are reflected. A rise in the number of organ recipients, including children, is noted. The role of physical rehabilitation in increasing the body’s adaptive reserves at the pre- and postoperative stage and improving the quality of life is described.

57-63 453
Abstract

Nephrolithiasis in a transplanted kidney is an important medical and social problem. The presence of renal calculi may not manifest clinically for a long time due to the peculiarities of the surgical intervention during organ transplantation. Development of chronic urinary tract infection and deterioration of the functional ability of the renal transplant in the presence of kidney stones can lead to graft death, which is an immediate threat to the patient’s life. Existing Russian guidelines on the treatment of urolithiasis currently lack a clear strategy for the management of kidney transplant recipients.

Objective: to systematize literature data on analysis of the outcomes of extracorporeal shock wave lithotripsy (ESWL) and other methods in patients with post-transplant kidney stones.

Results. Thirty-five publications on the research topic were selected. We summarized the information on various therapy options for patients with stones in transplanted kidney: endourological approach, ESWL, percutaneous nephrolithotripsy (PCNL), open surgical treatment (nephrostomy, pyelolithotomy). A modern foreign algorithm for the management of patients with post-transplant kidney stones depending on the severity of obstruction with sepsis and the size of the renal calculi is presented.

Conclusion. 1. The presence of stones in a kidney graft is a clinical situation that requires surgical treatment. 2. In clinical practice, different methods of treatment can be used, such as open intervention, ESWL, PCNL, retrograde transurethral manipulations. 3. In most cases, patient management tactics depend on the clinical picture (presence/absence of obstruction) and the size of the calculi. 4. The use of ESWL, as the most frequently used method, testifies to its efficiency and low-traumatic effect.

Heart Transplantation and Assisted Circulation

64-67 471
Abstract

Cardiac injury remains one of the most complex conditions in emergency surgery. Only 6% of patients with penetrating heart wounds manage to be delivered to the operating room for surgery, and the mortality rate is still extremely high. Unfortunately, such emergency interventions are often performed in institutions lacking the ability to provide the full range of reconstructive techniques, resulting in suboptimal correction and a high risk of developing postoperative complications. This paper describes a clinical case of successful repair of multiple stab wounds to the heart with concomitant anterior descending artery injury followed by severe heart failure requiring biventricular mechanical circulatory support.

68-75 425
Abstract

Heart transplantation (HT) is considered the optimal therapy for end-stage heart failure. In recent years, the number of operations performed has been growing, which has led to a rise in the number of heart transplant recipients requiring outpatient follow-up.

Objective: to evaluate the effectiveness of the model of dual personalized follow-up of heart transplant recipients in the consultative and diagnostic department of Shumakov National Medical Research Center of Transplantology and Artificial Organs.

Materials and methods. The study included 1,436 patients under outpatient follow-up from January 2008 to December 2022. Recipient data, results of laboratory and instrumental examination methods, nature and frequency of complications at different follow-up periods were analyzed.

Results: At the time of discharge from the hospital, 98.7% of patients had received triple-drug immunosuppressive therapy; 6 months later, methylprednisolone was discontinued in 72.2% of recipients. Mean tacrolimus level during the 1-year follow-up was 8.7 ± 2.7 ng/mL; in the period from 1 to 5 years of followup, the mean was 5.1 ± 2.4 ng/mL. At year 1 after transplantation, 23 (1.7%) recipients had been converted to everolimus; by the end of year 5 of follow-up, the number had increased to 8.6%. The most frequently detected complications during outpatient follow-up were: hypertension (48.65%), post-transplant diabetes mellitus (7.24%), nephropathy (35.97%), and malignant neoplasms (4.2%). Recipient survival, excluding in-hospital mortality, was 96.5%; and 88.0% at year 1 and 5 of follow-up, respectively.

Conclusion: The dual personalized approach model for outpatient follow-up and treatment of heart transplant recipients will improve recipient survival and quality of life in the long-term post-HT period.

Regenerative Medicine and Cell Technologies

76-86 417
Abstract

Objective: to study the effect of trypsin pretreatment in the porcine articular cartilage decellularization protocol on the ability to restore the biochemical composition and functional properties of the resulting finely dispersed tissue-specific scaffold when co-cultured with human adipose-derived stem cells (hADSCs).

Materials and methods. Porcine articular cartilage was micronized to a maximum size of 250 μm. The resulting porcine articular cartilage microparticles (CMps) were treated with trypsin (0.05, 0.25, 0.50%) / EDTA solution at +37 °C for 24 hours. Then, the CMps were successively incubated for 24 hours in three surfactant solutions containing 0.1% sodium dodecyl sulfate and increasing concentration of Triton X-100 (1, 2, 3%) at room temperature and in DNase I solution at +37 °C for 48 hours. The degree of change in the biochemical composition and the ability of decellularized CMps (DCMps) scaffolds within cell-engineered constructs (CECs) to support hADSC adhesion and proliferation, as well as their potential ability to exert a stimulatory regenerative effect, were then assessed. DNA, glycosaminoglycans (GAGs) and collagen content in the DCMps and CECs were examined. The morphology of the samples was examined using histological and immunohistochemistry staining.

Results. Histological analysis showed that there were no cells and detritus in the DCMp samples. Pretreatment of CMps samples гыштп a solution with the lowest content of trypsin (0.05%) / EDTA in the samples retained 5.14 ± 0.87 ng/mg DNA in the samples, while GAG content decreased to 5.34 ± 0.9 μg/mg and collagen to 154 ± 34 μg/mg. By day 28 of CEC cultivation, adherent cells had produced their own extracellular matrix (ECM) containing GAGs and collagen. The amount of DNA in it was 6.30 ± 0.11 μg/CEC and that of GAGs was 19.36 ± 0.73 μg/CEC.

Conclusion. Pretreatment with trypsin allows achieving uniformly complete decellularized CMps. At the same time, onset of changes in the ECM composition indicates a decrease in the ability of hADSCs to synthesize GAGs and type II collagen during co-culturing with DCMps. The increased proliferative activity of adherent hADSCs, as well as the tissue specificity of the DCMp scaffold will allow further research towards a hydrogel matrix capable of enhancing the specific and stimulating regenerative potential when co-cultured with cells of the same phenotype.

87-96 545
Abstract

High surgical porosity (SP) is one of the causes of significant blood loss, as well as hematoma formation. So, reducing the SP of small-diameter vascular grafts (VGs) is a crucial task.

The objective of this work was to develop a technology for the formation of polycaprolactone (PCL)-based small-diameter VGs with a bioactive coating with reduced SP.

Materials and methods. Porous VGs with an inner diameter of 3 mm were fabricated by electrospinning from 5% PCL solution with addition of 5–30% gelatin (PCL/G) on an NANON-01A unit (MECC CO, Japan). Bioactive coating was applied by sequential incubation of VGs in solutions of bovine serum albumin, heparin and platelet lysate with fixation in a glutaric aldehyde solution. The surface structure and mechanical properties of the samples were investigated. Functional properties of the bioactive VGs were evaluated in relation to their interaction with cell cultures in vitro.

Results. It was found that introduction of gelatin into the working solution reduces SP from 30.4 ± 1.5 mL/(cm2 ·min) to 2.8 ± 0.5 ml/(cm2 ·min). It was shown that at a PCL/gelatin ratio of 9 : 1, the outer and inner sides of the bioactive VGs samples are characterized by surface uniformity (no defects), mechanical properties close to blood vessels of the same diameter (Young’s modulus 6.7 ± 2.1 MPa, tensile strength 26.7 ± 4.9 N and elongation to break 423 ± 80%) and ability to support adhesion and proliferation of human umbilical vein endothelial cell line, EA.hy926.

Conclusion. Introduction of 10% gelatin content (by the polymer weight) into PCL solution reduces the SP of small-diameter VGs, leads to uniformity in their inner and outer surface, improvement in their mechanical properties without reducing their ability to support adhesion and proliferation of vascular endothelial cells.

Transplantomics

97-105 371
Abstract

Objective: to study the applicability of the neutrophil-to-lymphocyte ratio (NLR) for monitoring recipient status and for possible minimization of maintenance immunosuppression in the long-term period after liver transplantation (LT).

Materials and methods. Blood samples of 19 recipients with satisfactory graft function were examined by flow cytofluorometry at various time periods after LT using hematopoietic stem cell markers CD133, their CD31 derivatives, and alpha-fetoprotein (AFP), compared with the conventional NLR.

Results. The use of NLR equivalents with CD133 and CD31 to assess liver transplant status is due to their high representation in liver tissue. Their values change in the long-term posttransplant period (from 1.5 to 6–7 years following LT) ≈20-fold and in different directions, but only when measuring their commissural to the liver cell fractions bearing the AFP marker.

Conclusion. In contrast to the conventional NLR, maintenance of the lowest level of CD31 AFP, an NLR «equivalent», achieved at 1.5 years after LT, can be considered a criterion for the success of immunosuppressive therapy in the long-term post-LT period. The developed technique can be used to decide on whether to reduce or discontinue medication-assisted prophylaxis of graft rejection.

Organ Donation

106-112 357
Abstract

Small animal models are widely used in basic research. However, experimental hydrodynamic test benches, which include extracorporeal circuits, often have limitations associated with the size and filling volume of equipment. Thus, we aimed at developing and validating a miniature oxygenator as well as a low-volume hydrodynamic system for ex vivo perfusion of small animal lungs. A series of low-volume membrane oxygenators (n = 10) with 90–100 aligned microporous polypropylene hollow fibers, placed inside a sheath that is sealed at both ends to isolate the perfusing solution, was designed and manufactured. This design makes gas to flow through the hollow fibers and perfusate to circulate around the fibers. A low-volume hydrodynamic test bench was designed and assembled for isolated ex vivo lung perfusion and for evaluation of the performance characteristics of the oxygenators: gas and perfusate flow, perfusion pressure and temperature at 5–70 ml/min flow range.

113-121 645
Abstract

Objective: to present the successful experience with a donor with out-of-hospital cardiac arrest (OHCA) in whom a set of modern perfusion techniques was used to obtain kidneys suitable for transplantation.

Materials and methods. Automatic chest compression was resumed in an OHCA donor (after biological death has been confirmed in the hospital) to maintain minimal perfusion under mechanical ventilation with 100% FiO2. With femoral vein cannulation, an extracorporeal circuit with a centrifuge pump and oxygenator was connected and abdominal normothermic regional perfusion was initiated. After 215 minutes, kidney was explanted under normothermic machine perfusion. Next, the left kidney was placed in the LifePort Kidney Transporter for hypothermic machine perfusion of donor kidneys. Perfusion time was 285 minutes. The right kidney was transplanted without additional ex-vivo perfusion.

Results. Due to the complex use of perfusion techniques both in the donor body and ex-vivo, donor kidneys, after OHCA, with a total warm ischemia time of 110 minutes, were transplanted to recipients with good results. In the postoperative period, there was delayed function of the left and right renal grafts. The patients were discharged in a satisfactory condition under outpatient follow-up.

Conclusion. The possibility and efficiency of organ donation after OHCA, facilitated by modern perfusion techniques and devices, open up a new perspective in addressing the organ shortage crisis.

122-128 574
Abstract

Objective: to develop and approve the surgical technique for explantation of a functioning cardiopulmonary complex under normothermic autoperfusion.

Materials and methods. Landrace pigs were used as the experimental model for a series of acute experiments (n = 10). During the experiment, invasive pressure in the cavities of the heart and main arteries, blood gas composition, and myocardial contractility were monitored. The functioning cardiopulmonary complex was explanted through a median sternotomy. The explanted complex was conditioned at 37–38 °C for 6 hours.

Results. In the course of a series of experiments, it was shown that stable operation of the isolated heart-lung complex ex vivo for 6 hours was fundamentally possible provided that the parameters of the basic homeostasis constants are maintained. The technological solutions used made it possible to ensure safe hemodynamic and anatomical isolation of the working cardiopulmonary complex.

Conclusion. The developed protocol for isolating a functioning cardiopulmonary complex allows to provide stable graft function for 6 hours under normothermic autoperfusion. Implementation of this concept in the development of transport systems would significantly facilitate their design and eliminate the use of expensive components. This would contribute to widespread introduction into clinical practice.

Related Disciplines

129-138 707
Abstract

Endovascular surgery for aortic valve defects has proven itself well in elderly patients with severe comorbidities competing with the underlying disease. However, the risk of dysfunction resulting from structural degeneration of bioprosthetic heart valve and prosthetic valve endocarditis remains high. Repeated surgeries are associated with complications, but open surgery is the only method of treatment in this group of patients.

Objective: to describe a series of reinterventions for prosthetic valve dysfunction occurring after TAVI.

Material and methods. From 2015 to 2022, at the Department of Emergency Surgery for Acquired Heart Diseases (Head, Professor R.M. Muratov), Bakulev Research Center for Cardiovascular Surgery, 6 reoperations were performed in patients who had previously undergone transcatheter aortic valve implantation (TAVI). The average age of patients at the time of TAVI and at the time of reoperation was 70.6 years (62–83) and 74.3 years (70–84), respectively. The EuroSCORE II predicted risk of mortality at the time of reintervention was 42.2% (21.7–87.6). The mean time to reoperation was 42 months. Indications for reoperation were early active prosthetic endocarditis (4 cases) and structural valve degeneration (2 cases).

Results. At the hospital stage, 1 patient died of acute heart failure; the operation was performed for vital indications in conditions of extreme initial severity. In three patients, the early postoperative period was uneventful. One patient required intra-aortic balloon counterpulsation (IABP) due to heart failure, and 1 patient was implanted with permanent pacemaker. The average time of hospitalization was 14 days. Patients with active prosthetic endocarditis received a 6-week course of antibiotic therapy. The function of the implanted valves was satisfactory.

Conclusions. Aortic valve replacement after previous TAVI is an emergency operation and represents the only way to treat valve dysfunction. Under active prosthetic endocarditis, timely surgery can save this patient cohort.



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ISSN 1995-1191 (Print)