Editorial
Aim. To analyse the status and trends in the development of organ donation and organ transplantation in the Russian Federation according to 2017 data.
Materials and methods. The survey of heads of transplantation centers was conducted. A comparative analysis of the data obtained in the dynamics of years, between individual subjects of the Russian Federation, the centers of transplantation is performed.
Results. According to the register in 2017 in Russia there were only 41 centers for kidney transplantation, 24 liver and 16 hearts. The waiting list for kidney transplantation in 2017 included 5,531 potential recipients, which is approximately 13.8% of the total number of 40,000 patients receiving dialysis. The level of donor activity in 2017 was 3.8 per million of the population, while the share of multiorgan seizures was 66.5%, the average number of organs received from one effective donor was 2.8. In 2017, the level of kidney transplantation was 8.0 per million of the population, the liver transplantation index was 3.0 per million of the population; the rate of heart transplantation is 1.7 per million of the population. In 2017 the number of transplants in Russia increased by 11.3% compared to 2016. There are 11 transplantation centers on the territory of Moscow and the Moscow Region, and half of all kidney transplants and 70% of all liver and heart transplantations are performed. The number of patients with transplanted organs in the Russian Federation is approaching 13,000.
Conclusion. In the Russian Federation there is a strong tendency to increase the number of effective donors and to increase the number of organ transplants, and the number of transplant centers is also increasing. In recent years, the country has created prerequisites for the development of organ donation and transplantation: the regulatory and legal framework, public donation funding, material and technical base, etc. In the coming years, positive experience and organizational patterns of organ donation and transplantation from successful regions in Other subjects of the Russian Federation for building effective programs. The leading role in this process should be played by the Academician V.I. Shumakov Federal Research Center of Transplantology and Artifi cial Organs.
Clinical Transplantology
Aim. Purpose of study was evaluated of early outcomes of HT performed from donors with LVEF <40%.
Materials and methods. The study included 18 (14 men and 4 women, age 29 to 59 (42.9 ± 2.7) years) recipients who received cardiac allograft from donors with LVEF <40%. The urgency of HT was 1A-B (n = 16) and 2 status (n = 2) UNOS. 11 (55,6%) patients needed peripheral VA ECMO.
Results. Heart donors (13 men and 5 women, 22 to 57 (39.1 ± 3) years) were the traumatic (n = 3) and non-traumatic (n = 15) brain damage. Maximal inotropic support was norepinephrine 433 ± 46.2 ng/kg /min (n = 14) and dopamine 5.6 ± 2.5 μg/kg/min (n = 4). Laboratory parameters of the heart donor blood: Hb 11.5 ± 0.7 g/l, total protein 72 ± 14 g/l, Na+ 139 ± 3 mmol/l, troponin I 0.3 ± 0.2 ng/ml, CK-MB 98 ± 18 U/l. ECG of the donor’s heart: LVEDV 134 ± 9 ml, LVEF 22–39 (35.3 ± 4.3)%, diffuse LV hypokinesis (n = 10), regional dyskinesis (n = 8). Ischemic time was 151 ± 27 min. 16 (88.9%) had acceptable cardiac allograft function. Primary graft failure treated by MCS (VAECMO (n = 2)) was in 2 (11.1%). ICU stay was 7.7 ± 1.2 days. All recipients were discharged at home.
Conclusions. Own experience demonstrates the satisfactory results of HT from donors with LVEF <40%. In more cases LV systolic function of cardiac allograft quickly normalized in early period after HT.
Aim: to estimate early and long-term outcomes in recipients under 18 years old who have been heart transplanted in Almazov National Medical Research Centre.
Materials and methods. From April 2011 to September 2017 we performed 5 heart transplantations (HTx) in recipients under 18 years old (female) old) from adults donors. The median of age were 15 years (range 10–16 years), LVEF prior HTx – 17% (10–33%). Causes of heart failure were dilated cardiomyopathy (n = 2), non-compacted myocardium (n = 1), arrhythmogenic ventricular dysplasia (n = 1) and Ebstein’s anomaly (n = 1). They spent in HT waiting list 76 days (12–684 days). One patient underwent biventricular assist device Berlin Heart EXCOR implantation (days on support – 250) as a «bridge» to transplant. Due to coronary angiography (CAG) results 1 patient underwent HTx and CABG simultaneously. All recipients treated by triple-drug therapy (steroids, calcineurin inhibitors, mycophenolate mofetil), induction (thymoglobulin – n = 4, basiliximab – n = 1). We evaluated retrospectively laboratory-instrumental investigations and frequency of complications after HTx.
Results. The median of survival after HT was 35,93 months (4,4–73,7 months), all of them are alive. Patients spent in ICU 12 days (4–18 days), but one – 18 days due to posterior reversible encephalopathy syndrome (PRES), tacrolimus was switched to cyclosporine. They required inotropic support during 3 days (3–8 days). In 1 yr after HT TTE results got to normal values, the same as VO2peak signifi cantly improved. According to EMB (n = 48) results there were no clinical signs of rejection, acute cellular rejection (R2) was diagnosed in 12,5% cases. In long-term follow-up there was no signifi cant post transplant complications and comorbidities.
Conclusion. Pediatric heart transplantation is an effective treatment of terminal CHF. There was no signifi cant clinical rejection under combined immunosuppressive regimens. All patients recovered and went back to normal life. Physical capacity improved in all recipients.
Heart Transplantation and Assisted Circulation
Aim. The optimal time for initiating of chronic dialysis remains unknown. The scale for mortality risk assessment could help in decision-making concerning dialysis start timing.
Methods. We randomly divided 1856 patients started dialysis in 2009–2016 into developmental and validation group (1:1) to create and validate scoring system «START» predicting mortality risk at dialysis initiation in order to fi nd unmodifi able and modifi able factors which could help in the decision-making of dialysis start. In the series of univariate regression models in the developmental set, we evaluated the mortality risk linked with available parameters: age, eGFR, serum phosphate, total calcium, hemoglobin, Charlson comorbidity index, diabetes status, urgency of start (turned to be signifi cant) and gender, serum sodium, potassium, blood pressure (without impact on survival). Similar hazard ratios were converted to score points.
Results. The START score was highly predictive of death: C-statistic was 0.82 (95% CI 0.79–0.85) for the developmental dataset and 0.79 (95% CI 0.74–0.84) for validation dataset (both p < 0.001). On applying the cutoff between 7–8 points in the developmental dataset, the risk score was highly sensitive 81.1% and specifi c 67.9%; for validation dataset, the sensitivity was 78.9%, specifi city 67.9%. We confi rmed the similarity in survival prediction in the validation set to developmental set in low, medium and high START score groups. The difference in survival between three levels of START-score in validation set remained similar to that of developmental set: Wilcoxon = 8.78 (p = 0.02) vs 15.31 (p < 0.001) comparing low–medium levels and 25.18 (p < 0.001) vs 39.21 (p < 0.001) comparing medium–high levels.
Conclusion. Developed START score system including modifi able factors showed good mortality prediction and could be used in dialysis start decision-making.
Aim. To evaluate the functioning of an implantable pediatric axial pump «DON-3» for bypassing the left ventricle of the heart in experiments on sheep.
Materials and methods. Five sheeps at the age of 12–18 months performed paracorporeal installation of the children’s axial pump «DON-3» according to the scheme «left ventricle – aorta».
Results. A technique was developed and 5 chronic experiments were conducted on sheep to assess the model of the children’s axial pump «DON-3». The duration of the experiments in this series averaged 9 ± 5 days. The main indicators of hemodynamics, acid-base balance were within the norm. Conducted morphological and histological studies of the kidneys, liver and lungs did not reveal the presence of zones of ischemia and thromboembolism.
Conclusion. The results of this series of experiments showed satisfactory results, suggesting further research on the development of prototypes of a pediatric pump for clinical practice.
Clinical Cases
Regenerative Medicine and Cell Technologies
Aim: to develop methods for obtaining islet cell cultures for the purpose of their further use as a suitable component of the pancreatic tissue engineered construct. As a source of islet cell cultures, pancreas of newborn rabbits was used as an accessible and well-studied donor model.
Materials and methods. For the obtaining of islet cell cultures, pancreas of 1–3-day-old newborn rabbits were used. Changes occurring during the cultivation of pancreatic tissue were recorded using an inverted microscope and a biostation. Morphological analysis of culture samples was carried out using histological and specifi c immunohistochemical methods. The insulin-producing activity of the cultures was determined by enzyme immunoassay.
Results. Three main types of cultures were obtained: isletlike organotypic, suspensionalcytotypic, and monolayered, consisting of progenitor cells. Greater morphological safety and adequate insulin-producing ability was revealed in fl oating islet-like cultures.
Conclusion. According to their morphofunctional properties, fl otation islet-like cultures obtained from pancreas of the newborn rabbits can be used as basal cell component of the experimental model of the tissue engineered construct of the pancreas.
Aim. A study of biocompatible and matrix properties of polylactide scaffolds as a materials for medical implanted articles as well as scaffolds for cell and tissue engineering constructions.
Materials and methods. Biocompatibility of polylactide scaffolds in the form of porous disks obtained by freeze drying method was estimated in vitro: by UV spectroscopy, pH measurements and cytotoxicity to NIH/3T3 mice fi broblasts in static conditions. Biocompatibility of scaffolds in vivo was investigated by its implantation under mice skin. Matrix properties of polylactide scaffolds (cell adhesion and proliferation) were studied in dynamic conditions with mesenchymal stromal cells of human adipose tissue (MSC ADh) in perfusion bioreactor.
Results. As a result of in vitro investigations it was shown that polylactide scaffolds obtained by freeze drying are satisfi ed to demands presenting biocompatible medical articles with respect to pH measurements, extraction tests and cyto toxicity to mice fi broblasts NIH/3T3. Cultivation of MSC ADh in perfusion bioreactor in hepatogenic media is accompanying by good adhesion and proliferation both on the surface and in the bulk of porous disks. However implantation of polylactide scaffolds under mice skin is accompanying by resorption and leads to the infl ammation reaction of adjacent tissues.
Conclusions. Positive results obtained only by in vitro testing of biocompatibility and matrix properties are not enough to recommend the material to be used as a scaffolds for cell and tissue engineering constructions. The preliminary study of biomechanical characteristics of the implant is recommended.