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Russian Journal of Transplantology and Artificial Organs

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Vol 23, No 2 (2021)
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EDITORIAL

ORGAN TRANSPLANTATION

8-12 663
Abstract

As a screening method for detecting coronary lesions, coronary angiography (CAG) is becoming increasingly important in the activities of transplant centers. Angiography examination of coronary arteries is performed in potential recipients of various organs, related donors, and annually in heart recipients. Given the grave condition of recipients in the early post-transplant period and annual angiographic studies, it is necessary to strive for reduction of radiation load on the body and reduction of dose of X-ray contrast agents used.

Objective: to assess the possibilities of using rotational CAG in the activities of transplant centers.

Materials and methods. We observed 254 patients who underwent CAG. Their ages ranged from 21 to 79 years (mean 46.92 ± 1), and 90% were men. All patients were divided into two groups: group 1 included 142 patients who underwent rotational CAG, while group 2 was the control group (where classical polyprojection CAG was performed) and included 112 patients. Group 1 was divided into 2 subgroups – the subgroup of patients after heart transplantation who underwent endomyocardial biopsy along with CAG (n = 51), and the subgroup of patients who underwent only rotational CAG.

Results. In 91% of patients, CAG was performed by radial access. In group 1, stenotic lesions were detected in 33 patients: 19 had single-vessel lesions, 9 had two-vessel lesions, and 5 had three-vessel lesions. A total of 56 hemodynamically significant stenoses were detected, 9 of which were chronic total occlusions. In 83 patients (60%), performing only 2 series of rotational scans (one left and one right coronary artery) was sufficient. In 32 (23%) patients, one more clarifying projection was required, in 17 patients two and in 9 – 3–5 additional projections. In 3 cases, we switched to polyprojection CAG. The average amount of contrast agent used was 24.4 ± 0.9 ml, the average X-ray dose was 34561.3 ± 1695.2 mGycm2. The need for a contrast agent was significantly higher in the comparison group – 24.4 ± 0.9 mL and 103.5 ± 1.7 mL, respectively. The average X-ray dose in the main group was 34561.3 ± 1695.2 mGycm2, in the comparison group 41430.9 ± 4141.7 mGycm2. However, there was no significant difference between the groups. Subgroup analysis showed that patients who underwent only rotational CAG had lower radiation exposure compared to patients who underwent CAG combined with endomyocardial biopsy biopsy (EMB), as well as significantly lower load compared to the control group.

Conclusion. Rotational CAG can be considered as the method of choice at transplant centers, where screening diagnostics of the state of the coronary bed is required, which is equivalent in terms of information content and safety. Rotational CAG allows to reduce the amount of injected contrast agent by more than three times, which in turn reduces the number of associated complications, as well as the radiation exposure of patients and medical personnel.

13-20 548
Abstract

 Introduction. To prevent post-transplant complications associated with unbalanced immunosuppression, objective indicators reflecting the state of the immune system and associated with the immunosuppressant dose are required. In pediatric liver transplantation, an important indicator of hepatocellular function and restoration of anthropometric characteristics is insulin-like growth factor 1 (IGF-1), which exhibits both nonspecific and selective immunomodulator properties.

Objective: to assess the correlation between growth hormone and IGF-1 levels and tacrolimus dose and blood concentrations in pediatric liver recipients and to determine the possibility of using the IGF-1 level in selecting the drug dose required to achieve its target concentration in the blood. Materials and methods. We examined 156 children aged from 2 to 105 (median – 8) months with liver cirrhosis of various etiology, who received liver from a living related donor. The concentration of growth hormone and IGF-1 was determined in blood plasma before, one month, and one year after transplantation using the enzyme-linked immunosorbent assay. Tacrolimus residual concentration was measured in the patient’s whole blood by immunochemical method.

Results. Growth hormone levels in the blood of pediatric liver recipients did not correlate with the dose or concentration of immunosuppressant tacrolimus one month or one year after transplantation, whereas the IGF-1 content was directly related to tacrolimus dose one year later (r = 0.41, p = 0.001), but not a month after surgery. The correlation coefficient was higher in uncomplicated post-transplant recipients (r = 0.51, p = 0.002) than in those with complications (r = 0.26, p = 0.17). The diagnostic efficiency of the IGF-1 level as an objective criterion for selecting the tacrolimus dose required to achieve its target blood concentration was 0.80 ± 0.11; 95% CI [0.58–1.00] (p = 0.007). In recipients with blood IGF-1 levels ≥115.7 ng/mL, the probability of prescribing a tacrolimus dose ≥0.25 mg/kg/day was 14 times higher than in children with lower blood IGF-1 levels. The estimated accuracy of the test was 83%, positive predictive value was 71%, and negative predictive value was 85%.

Conclusion. The IGF-1 level was found to correlate with tacrolimus dose in liver transplant recipients one year after transplantation. The diagnostic efficiency of IGF-1 as a potential indicator for choosing the tacrolimus dose required to achieve its target blood concentration is 80%, which suggests further study of the test to assess the effectiveness of immunosuppression and selection of an individual immunosuppressant dose.

21-29 1430
Abstract

Objective: to evaluate the 1- and 5-year graft and recipient survival after primary and second kidney transplantation, to compare the outcomes depending on the age of recipients.

Material and methods. The treatment outcomes for 364 patients who underwent kidney transplantation at Sklifosovsky Research Institute of Emergency Care, Moscow over the period from 2007 to 2019. Of these, 213 patients underwent kidney transplantation for the first time, while 151 patients were having a second transplantation. We analyzed the effect of previous transplants, as well as the age of the recipients on long-term survival rates.

Results. No significant difference in 1- and 5-year survival of kidney recipients after primary and second transplantations was found. In contrast, the long-term graft survival significantly depended on this criterion and turned out to be significantly higher after primary transplantations. The 1- and 5-year survival of older recipients was lower than the survival of younger recipients after primary and second kidney transplantation. The 1-year graft survival after primary kidney transplantation was higher in young recipients than in older recipients of the same group, however, but there were no significant differences in the 5-year graft survival. After second transplantations, there were no significant differences in the 1- and 5-year graft survival depending on the age of recipients.

Conclusion. A history of previous transplantation is an important factor in kidney transplantation outcome, which must be taken into account in clinical practice.

30-35 885
Abstract

Objective: to assess the incidence, determine the peculiarities of the course of invasive pulmonary aspergillosis (IPA) and identify risk factors for IPA in heart transplant recipients.

Materials and methods. From January 2010 to December 2019, 137 heart transplantations (HT) were performed: mean age 46 ± 14 years; male 102 (74%) and female 35 (26%). All patients received a three-component immunosuppressive therapy: calcineurin inhibitors, mycophenolate mofetil (MMF) and Glucocorticoid (GCs). Induction therapy consisted of Basiliximab (81%, n = 111) and antithymocyte immunoglobulin (15%, n = 20). A retrospective analysis of patients with identified post-HT invasive IPA was performed; risk factors for IPA were assessed. In patients with early IPA, the length of stay in the intensive care unit (ICU), the duration of mechanical ventilation, and the initial severity of the condition were studied. All patients with suspected pneumonia underwent bronchoscopy with examination of bronchoalveolar lavage (BAL) and chest computed tomography (chest CT scan).

Results. During the follow-up, there were 58 episodes of pneumonia, of which 16 (28%) were IPA (age 33 to 64 years). All patients had a target level of immunosuppressive drugs concentration in blood; basiliximab was used as induction therapy in 15 of 16 patients. Half of the recipients developed IPA in the early post-HT period (less than 3 months after HT), in the rest (n = 8) – at a later date (3 months to 1 year after HT). The diagnosis was verified: 14 out of 16 patients showed an increase in the Aspergillus antigen positivity in the BAL to 7.2 (2.8 ± 1.6); chest CT scan revealed specific changes. In two patients, there were no diagnostic criteria for IPA, but the diagnosis was made based on the results of histological examination after resection of the left lower lobe of the lung. All patients received voriconazole therapy for 2 to 6 months, their immunosuppressive therapy was adjusted (tacrolimus and MMF dose adjustment) and their white blood cell count was monitored. Complete cure of the disease was achieved in 13 (81%) patients. Two patients died within 30 days after HT in the intensive care unit, one died from urogenital diseases caused by bacterial flora and leading to urosepsis, 4 months after IPA treatment was initiated. All patients had risk factors for IPA: taking immunosuppression, including GCs (n = 16), prolonged ICU stay (n = 14), inotropic support exceeding 2 days in the early post-transplant period (n = 10), cachexia during HT (n = 6), leukopenia (n = 9) and neutropenia (n = 14).

Conclusion. In heart transplantat recipients, the incidence of IPA among respiratory tract infections is 28%. The risk of developing IPA was highest during the first year following HT. In the majority of recipients, the disease was detected at the early stages; diagnosis required surgical intervention in 12% of cases. A decrease in the risk of developing IPA was associated with correction of the following risk factors for this disease in all patients: volume of immunosuppressive therapy during the first year after transplantation and prevention of the development of neutropenia as a marker of infectious complications or immunosuppression overdose. Early diagnosis of IPA allowed for initiation of timely specific therapy in most recipients and achievement of a positive effect in 80% of them.

36-40 2292
Abstract

Kidney transplantation has been the best replacement therapy for end-stage kidney disease for over 60 years. The Republican Coordination Center for Transplantation reports that as of January 29, 2020, there were 2675 people on the kidney transplant waiting list in the Republic of Kazakhstan. The issue of deceased donation in Kazakhstan is problematic for various reasons. Over the past couple of years, the already low rates of deceased donors have fallen by more than 2 times.

Objective: to objectively assess the effectiveness of deceased-donor kidney transplant in order to indicate the need for development of cadaveric donation and reduce the number of patients in the transplant waitlist.

Materials and methods. Fifty-two kidney transplants from a deceased donor were performed at the National Research Oncology Center (NROC) from 2010 to 2020. The age group of recipients ranged from 20 to 75 years old. In most cases, end-stage chronic renal failure resulted in chronic glomerulonephritis (76%), pyelonephritis (1.9%), polycystic kidney disease (9.6%) and diabetic nephropathy (11.5%).

Results. The 1-year and 5-year survival rates were 96% and 86%, respectively. There was delayed graft function in 13 of cases. In one case (1.92%), there was intraoperative hyperacute rejection of the kidney transplant that could not be treated with high doses of glucocorticosteroids; the kidney graft was removed. Two patients (3.8%) in the early postoperative period, on days 2 and 7 after surgery, developed a clinic of acute renal transplant rejection; after the rejection crisis was stopped by drug therapy, graft function was restored. One patient (1.92%) died as a result of bilateral pneumonia, which led to sepsis and death.

Conclusion. Graft and recipient survival rates after deceased-donor kidney are comparable to those after living-donor kidney transplantation. The solution to the problems of increasing the number of deceased organ transplants should not rest entirely on the shoulders of transplant doctors; this task must also be addressed at the government level with constant propaganda to explain to the citizens the need for a deceased organ donation program.

41-51 1114
Abstract

Objective: to evaluate the early and long-term outcomes of cadaveric kidney allotransplantation (CKAT) based on a retrospective analysis of 71 cases treated at Krasnoyarsk Regional Clinical Hospital (KRCH).

Materials and methods. From March 2014 to June 2019, 71 kidney transplants were performed at KRCH – 42 (59.15%) men and 29 (40.85%) women. The age of the patients varied from 20 to 59 years (mean age 39.6 ± 8.14 years). The causes of end-stage chronic kidney disease which subsequently led to CKAT were chronic glomerulonephritis, chronic tubulointerstitial nephritis, hypertensive nephropathy (HN), diabetic nephropathy resulting from type I diabetes (DN), nephropathy of mixed genesis (HN + DN), vesicoureteral reflux, congenital angiodysplasia of the kidneys, and Alport syndrome. The mean number of HLA mismatches was 4.5 ± 0.9.

Results. Hospitalization lasted for an average of 34.05 ± 9.56 days. Primary function was observed in 32 (45.08%) patients, while 39 (54.92%) cases had delayed function. Post-transplant complications were noted in 23 (32.39%) patients, of whom 12 (16.9%) had early post-transplant complications, while 15 (21.13%) encountered complications in the late post-transplant period. The most frequently diagnosed were immunological, infectious, and urological complications. Vascular, surgical, oncological, and other complications were less frequent. The annual graft survival rate was 87.3%. Patient survival rate was 95.77%. One (1.4%) and 2 (2.81%) patients died in the early and late post-transplant periods, respectively. Hospital mortality – 1 case (1.4%).

Conclusion. Kidney transplantation is the most effective treatment for patients with irreversible chronic kidney disease. About 87.33% of transplants were found to be effective. However, 32.39% of patients had postoperative complications. The vast majority of complications were reversible and were corrected conservatively or surgically. Nevertheless, graft loss occurred in 12.67% of cases. The success of transplantation depends on a number of factors related to both the donor and the recipient, as well as the immunological status and surgical technique. A personalized approach to recipients helps to reduce postoperative complications, prevent nephrotoxicity and rejection reactions.

CARDIOVASCULAR ASPECTS OF TRANSPLANT SURGERY

52-59 2656
Abstract

Mitral annular calcification (MAC) is a chronic degenerative process involving the fibrous part of the mitral complex, characterized by calcium deposition and loss of valve function. MAC prevalence is 8–10%, but despite this, the clinical significance of MAC is underestimated. Currently, there are reports that complete decalcification leads to improved long-term outcomes in patients with severe MAC. An analysis of the immediate outcomes of mitral valve surgery in patients with severely calcified mitral annulus with decalcification was performed. The calcified annulus fibrosus underwent complete decalcification in all cases. Calcium deposits were removed in a single block, in 6 cases it was reconstructed with a xeno-pericardial patch; in 2 cases the annulus fibrosus was sutured. There were 2 cases of in-hospital mortality, caused by acute heart failure on day 8 in 1 patient and pulmonary embolism on day 30 after operation in the second patient. There were no complications associated with coronary artery injury and left ventricular posterior wall rupture. Experience in the treatment of severe mitral valve calcification with extensive annulus fibrosus decalcification and subsequent reconstruction is possible and gives satisfactory results.

CLINICAL REPORTS

60-66 1020
Abstract

Background. Focal segmental glomerulosclerosis (FSGS) of the graft in kidney recipients is a rare and difficultto-diagnose post-kidney transplant complication, which can lead to graft loss and death of the recipient. A unified protocol is required for the treatment of this disease.

Materials and methods. A 15-year-old female patient C. diagnosed with stage 5 chronic kidney disease as a result of steroid-resistant nephrotic syndrome with hematuria underwent a living related-donor kidney transplantation. On the third day after the operation, laboratory and imaging data showed kidney graft dysfunction. Patient examinations established the cause of the graft dysfunction – idiopathic nephrotic syndrome in FSGS.

Results. For the treatment of recurrent FSGS, the patient had her immunosuppressive therapy converted from tacrolimus to cyclosporin A, and received two 500 mg rituximab injections. Ten sessions of therapeutic plasma exchange (Plasauto Sigma) were performed to remove antibodies to podocytes. During the therapy, diuresis was restored, creatinine and urea levels decreased. Six months after the kidney transplant, graft function was fully restored. Conclusion. The absence of recurrent FSGS within six months during a single course of therapeutic plasma exchange with its subsequent cancellation after restoration of graft function allows to recommend the developed method for the treatment of FSGS in pediatric patients after kidney transplantation.

67-75 729
Abstract

Deep wound infection of the anterior chest wall tissues in patients after transsternal cardiac surgery despite intensive developments in surgical techniques and improvement of antibacterial chemotherapy, remains a genuine concern worldwide [1]. The incidence of this complication in the general population ranges from 0.5 to 4% [2, 3]. Despite developed approaches in the treatment of cardiac surgery patients, the treatment of deep sternal wound infection and surrounding tissues following a heart transplantation still remains a rather serious and pressing challenge. This paper presents a clinical observation of a heart transplant recipient, complicated by deep postoperative wound infection. The strategy of staged surgical treatment of sternal osteomyelitis consisted of surgical wound debridement, local wound debridement with vacuum dressings, and reconstructive surgery at the final stage (sternal reosteosynthesis, plasty of the anterior chest wall wound with displaced skin and fascial flaps).

76-83 741
Abstract

Background. Non-alcoholic Wernicke’s encephalopathy occurs in various somatic conditions with thiamine deficiency, excessive excretion of thiamine, or impaired thiamine metabolism. Very few cases of this pathology have been described in chronic kidney disease (CKD). We present a unique case of non-alcoholic Wernicke’s encephalopathy in a patient with a kidney transplant is presented.

Past medical history. The patient underwent kidney transplantation in 2008. Outpatient follow-up by a nephrologist was irregular. Renal graft function remained relatively stable: blood creatinine 200–240 μmol/L, estimated glomerular filtration rate 40–30 mL/min, tacrolimus plasma concentrations tended to increase (5.7–7.6–8.4–10.4 ng/mL); repeated graft biopsy (in 2015 and in 2017) determined the chronic toxicity of calcineurin inhibitors. The patient’s condition worsened in late January 2020: body temperature increased to 38°C, nausea, vomiting, loose, watery stools for up to 5 times per day, 8 kg weight loss, decreased diuresis. A few days later, double vision, shaky gait and then immobility appeared. Biochemical examination results: potassium 3.8 mmol/L, sodium 139 mmol/L, alpha-amylase 159 units/L (norm 0–100 units/L), creatinine 242 mmol/L, urea 13.2 mmol/L; ultrasound signs of pancreatitis. Magnetic resonance imaging (MRI) of the brain: bilateral diffuse lesions of the midbrain, thalamus, and cerebellum. Based on the clinical picture and on brain MRI results, Wernicke’s encephalopathy was diagnosed. Parenteral administration of thiamine had a good effect.

Conclusion. Possible mechanisms of the development of Wernicke’s encephalopathy in a patient were discussed. Vigilance is required regarding this disease when metabolic disorders occur in patients with CKD.

84-87 563
Abstract

We present a clinical case of urolithiasis. A patient diagnosed with stage 5 chronic kidney disease due to autosomal dominant polycystic kidney disease after bilateral nephrectomy underwent kidney transplantation with ureteral graft stenting. Two months after the operation, a stone was found in the upper third of the ureteral graft, complicated by necrosis in this area. Reconstructive plastic surgery on the ureter of the transplanted kidney with removal of the ureteral stone achieved the desired clinical effect.

88-94 728
Abstract

To date, liver transplantation remains the only effective treatment for patients with cirrhosis. Due to lack of other effective, alternative therapeutic methods, the search and development of new treatment technologies is problem number one. The development of cellular technologies is promising for use in clinical practice. Using this observation as an example, the safety and efficacy of cell therapy technology for prolonged stay on the liver transplant waiting list by a patient with cirrhosis is shown. After intraportal injection of autologous bone marrow-derived mononuclear cells, liver cirrhosis stabilized on the CTP and MELD-Na scales for 22 months of observation, which allowed the patient to wait for an organ and successfully undergo liver transplantation.

ARTIFICIAL ORGANS

95-103 611
Abstract

Objective: to justify the design of a self-expanding transcatheter aortic valve prosthesis based on a biomaterial stabilized with ethylene glycol diglycidyl ether using numerical simulation and a series of field experiments with working prototypes to determine the consistency of the proposed design solutions.

Material and methods. Numerical computer models of a developed aortic valve prosthesis intended for transcatheter implantation, as well as prototypes of the most promising concepts for a series of field tests, were used in the work. Computer 3D models were subjected to numerical analysis in the Abaqus/CAE environment (Dassault Systemes, France) based on the finite element method with iterative design optimization and repeated numerical experiments. Physical prototypes of the transcatheter prosthesis were subjected to a series of mechanical tests for axial and radial compression, as well as tests on a Vivitro hydrodynamic stand (Vivitro Labs, Canada) under simulated normal flow. All studies were carried out in a comparative aspect with a similar transcatheter aortic valve prosthesis (control), the CoreValve™ bioprosthesis (Medtronic, Inc., USA).

Results. Computer simulation demonstrates the stress-strain state values that do not significantly exceed the critical levels (628 and 756 MPa versus the threshold value 1080 MPa) for two basic concepts of support frames. The fatigue strength based on the calculation of the mean and alternating stresses corresponding to normo- and hypertensive states based on the Goodman diagrams, did not reveal any evidence that the threshold values (destruction area after 200 million cycles) were exceeded. The hydrodynamic characteristics of working prototypes made on the basis of computer models correspond to the testing data of CoreValve™ clinical bioprosthesis: the effective orifice area was 1.97 cm2, the mean transprosthetic gradient was 8.9 mm Hg, the regurgitant volume was 2.2–4.1 mL per cycle depending on the prototype model.

Conclusion. Generally, experiments carried out showed the consistency of the concepts, including from the point of view of implementation of the leaflet apparatus based on xenogeneic tissues treated with ethylene glycol diglycidyl ether.

REGENERATIVE MEDICINE AND CELL TECHNOLOGIES

104-113 738
Abstract

Objective: to investigate the efficacy of supercritical carbon dioxide (sc-CO2) for enhancштп the biocompatibility of biopolymer scaffolds from biodegradable materials and tissue-specific scaffolds from decellularized porcine liver slices (PLSs) or fine porcine cartilage particles (FPCPs).

Materials and methods. Biopolymer scaffolds of a polyoxy(butyrate-co-valerate) and gelatin copolymer composition, 4 mm in diameter and 80 mm in length, were formed by electrospinning (NANON-01A, MECC CO, Japan) and stabilized by incubation in glutaraldehyde vapor for 48 hours at room temperature. For decellularization, PLSs and FPCPs were incubated under periodic stirring in buffer (pH = 7.4) solutions of sodium dodecyl sulfate (0.1%) and Triton X-100 with increasing concentrations (1, 2, and 3%). Treatment in a sc-CO2 atmosphere was done at 150–300 bar pressure, 35 °C temperature, and 0.25–2.5 mL/min flow rate of sc-CO2 for 8–24 hours. 10% ethanol was introduced as a polarity modifier. Cytotoxicity was studied according to GOST ISO 10993-5-2011. The growth of NIH/3T3 in the presence of samples was studied using an interactive optical system IncuCyte Zoom.

Results. The effect of the sc-CO2 flow rate and pressure, and the effect of addition of ethanol, on the biocompatibility of scaffolds was investigated. It was found that treatment at a low sc-CO2 flow rate (0.25 mL/min) does not achieve the required cytotoxicity. Complete absence of cytotoxicity in biopolymer scaffolds was achieved in the presence of 10% ethanol, at a sc-CO2 flow rate of 2.5 mL/min, 300 bar pressure and 35 °C temperature after 8 hours of treatment. Effective removal of cytotoxic detergents from decellularized liver occurs already at a 150-bar pressure and does not require the addition of ethanol. Adding ethanol to sc-CO2 eliminates not only the cytotoxic, but also the cytostatic effect of tissue-specific scaffolds.

Conclusion. Sc-CO2 treatment is an effective way to enhance the biocompatibility of three-dimensional porous matrices produced using cytotoxic substances: bifunctional crosslinking agents for biopolymer scaffolds and surfactants in the case of tissue-specific matrices. Addition of ethanol as a polarity modifier improves the treatment efficiency by eliminating both cytotoxic and cytostatic effects.

114-121 768
Abstract

Introduction. Immunomodulator Galavit® is a promising domestic drug for the prevention and treatment of various infectious diseases. Earlier, the authors have developed and investigated in vitro its new dosage form – transdermal therapeutic system (TTS). Positive results from experiments made it possible to proceed to the study of the pharmacokinetic parameters of Galavit® TTS in animals.

Objective: to compare the pharmacokinetic parameters of intramuscular and transdermal administration of immunomodulator Galavit® in animal experiments.

Materials and methods. Sodium aminodihydrophthalazinedione was used as a substance in the form of a powder to prepare a solution for intramuscular administration of 100 mg (trade name Galavit®, manufacturer SELVIM LLC). The pharmacokinetics of transdermal and intramuscular injections were studied in male Chinchilla rabbits weighing 4.5–5.0 kg. Serum sodium aminodihydrophthalazinedione concentrations in animals were determined by highperformance liquid chromatography using a specially developed technique.

Results. In contrast to the injection method, a prolonged and uniform inflow of the drug substance (MP) into the body is observed for percutaneous administration of sodium aminodihydrophthalazinedione. The maximum serum Galavit® concentration for a 40 mg dose (0.172 ± 0.054 μg/mL) and for a 80 mg dose (1.16 ± 0.22 μg/mL) remained at a constant level for 9 and 8 hours, respectively. The relative bioavailability of the Galavit® transdermal therapeutic system was 0.65 and 1.06 for the same doses.

Conclusion. Application of Galavit® 80 mg transdermal therapeutic system provides bioavailability that is similar to the intramuscular administration of this drug at the same dose. At the same time, its maximum serum concentration significantly decreases and the retention time of Galavit® in the body increases by more than 10 times, which can contribute to prolongation of the drug effect. Due to the current growing interest in the use of immunomodulator Galavit® for coronavirus infection COVID-19, the development and study of a new dosage form is a promising task

122-136 710
Abstract

Creation of vascular grafts with atrombogenic and antimicrobial coating is a very important area.

Objective: to evaluate the biocompatibility and antimicrobial properties of biodegradable vascular grafts of various polymer compositions with atrombogenic and antimicrobial drug coating.

Materials and methods. Modification of the surface of the biodegradable vascular grafts was performed through complexation with polyvinylpyrrolidone, which was polymerized with polymer scaffold surface by means of ionizing radiation at 10 and 15 kGy. Physical and mechanical properties, as well as hemocompatibility were evaluated. Bacteriological studies were carried out using test strains of gram-negative and gram-positive microorganisms: Klebsiella pneumoniae spp. ozaena No. 5055, Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, Proteus mirabillis ATCC3177, Pseudomonas aeruginosa.

Results. There was no influence of modifying manipulations with ionizing radiation on the physical and mechanical characteristics of biodegradable prostheses. Vascular grafts with atrombogenic and antimicrobial coatings exhibited atrombogenic properties upon contact with blood, reducing platelet aggregation by 5–7 times (p < 0.05). Also decrease in adhesion and platelets deformation index was found on the surface of drug-eluting scaffolds (for PCL-based prostheses, the latter decreased by 1.9 times relative to unmodified counterparts (p < 0.05), for PHBV/PCL-based prostheses – by 1.3 times relative to unmodified counterparts and 1.5 times relative to scaffolds with polyvinylpyrrolidone (p < 0.05). Bacteriological studies revealed a local inhibitory effect in the place where scaffolds with cationic amphiphile were applied on agar. No growth retardation zones were identified. Polymeric composition of the scaffolds and the used dose of ionizing radiation did not lead to a difference in the bacteriostatic properties of the scaffolds with amphiphile.

Conclusion. A full cycle of surface modification of biodegradable polymer prostheses based on both PCL and РHBV/PCL composition resulted in significant increase in the atrombogenic and antimicrobial properties of prostheses and did not worsen the physical-mechanical and biocompatible properties of the structures being developed.

137-146 720
Abstract

Shortage of donor corneas is a burning issue in ophthalmology. That is why there is a search for new alternative ways for treating corneal diseases. Decellularization technologies make it possible to create corneal tissue-engineered constructs that can adrress the issue of donor corneal shortage. Objective: to conduct a comparative analysis of effective methods for treating the corneal lenticula and to create an optimized and standardized decellularization protocol. Materials and methods. Corneal stromal lenticules obtained after ReLEx SMILE surgery were chosen for the study. Lenticule parameters: thickness 77–120 microns, diameter 6.5 mm. We used 3 protocols for the treatment of lenticules: 1) treatment with 1.5 M sodium chloride with nucleases (NaCl); 2) 0.1% SDS (SDS); 3) treatment with Trypsin-EDTA solution, followed by double washing in a hypotonic Tris buffer solution with nucleases (Trypsin-EDTA). Optical properties of lenticles were determined spectrophotometrically, where the samples before decellularization served as a control. Fluorescence imaging of nuclear material in the original cryosections was performed using Hoechst dye. The state of collagen fiber ultrastructure was assessed by scanning electron microscopy. The quantitative DNA content in fresh lenticules and in lenticules after treatment was analyzed. Results. All three decellularization protocols effectively removed nuclear and cellular material; the residual DNA content was < 50 ng/mg. However, the Trypsin-EDTA protocol led to significant damage to the extracellular matrix structure, which negatively affected the transparency of corneal tissue-engineered constructs. Transparency of samples for the NaCl protocol was close to native lenticules. Conclusion. To create a corneal tissue-engineered construct, NaCl decellularization protocols appear to be optimized and can be used to treat various corneal diseases.

LITERATURE REVIEWS

147-157 611
Abstract

Kidney injury in heart transplant recipients is of a complex nature and bears the features of all types of cardiorenal interaction impairment. Pre-transplant renal dysfunction, perioperative acute kidney injury, as well as factors associated with graft and immunosuppression, determine the prevalence and severity of kidney pathology in this group of patients. This review examines the pathophysiology of kidney dysfunction in heart failure, the epidemiology, and criteria for acute kidney injury.

158-166 1555
Abstract

Background. Transplantation is presently the only treatment for end-stage liver and kidney failure. Up to 42% of liver transplant recipients and up to 30% of kidney transplant recipients have neurological complications from the transplantation. Acute symptomatic seizures (ACS) occupy an important place in the structure of early postoperative neurological complications. Verification of the causes of seizures and management of the risk of relapse is presently a critical task.

Objective: to review recent advances in ACS assessment, prevalence, and treatment approaches in liver and kidney transplant recipients.

Materials and methods. The causes of ACS after liver and kidney transplant are diverse. Nonspecific causes of seizures such as dysmetabolic and volemic changes associated with transplantation are widely known. There are also specific syndromes associated with seizures in liver and kidney recipients, such as posterior reversible leukoencephalopathy syndrome, neurotoxicity of calcineurin inhibitors, hyponatremia in the final stage of liver failure, hypocalcemia in kidney recipients, etc. Diagnosis is made based on general rules, and treatment depends on the identified causes of seizures. Management of acute symptomatic seizures involves prescribing anticonvulsants according to the risk of seizure recurrence; immunosuppression is converted when neurotoxicity is identified. Results. The diagnostic algorithm, and often the treatment strategies, in ACS cases in liver and kidney recipients, are not clearly defined.

Conclusion. Due to the multiple causes of ACS, there are differences in treatment tactics. Further accumulation and generalization of ACS outcome data will help in creating a convenient algorithm for rapid identification of the cause and the most effective treatment tactics.

167-176 571
Abstract

As the survival rate of cardiac recipients improves, higher incidence of malignancy in the late postoperative period becomes essential for their prognosis. Immunosuppressive therapy is one of the key prerequisites for successful transplantation. However, long-term use of immunosuppressive agents increases the incidence of malignant tumors compared to the general population. The risk of their development after organ transplantation increases by 2–4 times compared to the general population. For patients who have undergone transplantation since 2000, the risk of developing malignant neoplasms 1–5 years after surgery is estimated at 10–12%. Timely comprehensive examination of patients, development of new immunosuppression schemes, treatment of those predisposing to the development of malignant neoplasms and giving up harmful habits will reduce the risk of malignant tumors and help diagnose these serious complications at an early stage, which, in turn, will increase the life expectancy of solid organ (particularly the heart) recipients.

177-182 833
Abstract

Management of solid organ recipients requires a significant amount of research and observation throughout the recipient’s life. This is associated with accumulation of large amounts of information that requires structuring and subsequent analysis. Information technologies such as machine learning, neural networks and other artificial intelligence tools make it possible to analyze the so-called ‘big data’. Machine learning technologies are based on the concept of a machine that mimics human intelligence and and makes it possible to identify patterns that are inaccessible to traditional methods. There are still few examples of the use of artificial intelligence programs in transplantology. However, their number has increased markedly in recent years. A review of modern literature on the use of artificial intelligence systems in transplantology is presented.

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