Editorial
Clinical Transplantology
Aim. To analyze approaches to pretransplant treatment of potential heart recipients and heart donation criteria, directed to reduction of mortality on a waiting list and to increase of volume and effi ciency of heart transplantations.
Methods and results. Data on 285 HT recipients (performed in 2008–2013) were analyzed. The analysis and comparison of patients with circulatory support before heart transplantation, using «high-risk» donors (aged over 40 years, with left ventricular hypertrophy ≥ 1.5 cm, after cardiopulmonary resuscitation, with the reduced systolic function of the left ventricle (< 40%), with potentially repair pathology of the heart valve and coronary arteries); to high risk recipients (over 60 years, with high pulmonary hypertension and earlier operated) were made.
Conclusion. The proposed scientifi c, technological and organizational solutions made possible the timely performance of heart transplantation to patients with an inevitable lethal outcome as a result of heart failure.
The analysis of clinical outcomes of cardiac transplantation is presented. The main directions of research on the development and implementation of methods for early diagnosis of adverse events and treatment of patients with heart transplant in V.I. Shumakov Federal Research Center of Transplantology and Artifi cial Organs of the Ministry of Healthcare of the Russian Federation are given. Among the non-invasive methods of forecasting, assessment of the risk of cardiovascular complications in heart recipients being developed are: analysis of laboratory biomarkers involved in the formation of relationship of the graft and the recipient; ultrasound diagnosis of functional and structural remodeling of peripheral arteries. The issues of improving drug therapy are discussed. The importance of multidisciplinary approach, continuity in management of the patients with heart transplant is emphasized.
Aim. To estimate opportunities, prospects and safety of using heart transplants from aged donors who are at high risk of coronary atherosclerosis.
Materials and methods. Over the period from March 1987 to May 2014
450 heart transplantations (HTx) were performed in V.I.Shumakov Federal Research Center of Transplantology and Artifi cial Organs. During the fi rst month after HTx coronarography was made to 152 (37,8%) recipients in
order to exclude/confi rm donor-transmitted coronary atherosclerosis (DTCA) and to identify tactics of treatment. Coronary atherosclerosis was detected among 16 patients (3,6% of total number of HTx), 15 (93,8%) men and 1 (6,2%) women. Mean age of recipients with DTCA at the moment of HTx was 48,3 ± 13,1 years.
Results. Hemodynamically relevant coronary atherosclerosis was not detected and percutaneous coronary intervention (PCI) was not made in the group of patients with the mean age of 42,24 ± 8,91 years. Using heart transplants from aged donors is connected with increasing risk of DTCA among the recipients. DTCA-dependent PCI is not connected with coronary mortality. Actuarial survival rate of patients who underwent PCI is comparable with the same one in the total population of HTx recipients and is equal to 87,5% at 5 years and less.
Conclusion. Hearts from aged donors (older than 50 years) may be used for HTx with suffi cient level of safety. Due to high level of DTCA using of hearts from such donors is preferable for completing urgent HTx to recipients 1А–В UNOS.
In this article we discuss the results of surgical treatment in patients with different acquired heart diseases. Procedures ranged from valve reconstruction, coronary artery revascularization, surgical repair or graft repair of the thoracic aorta to hybrid surgery in patients with combined acquired heart valve diseases and coronary artery diseases. The implementation of biological grafts for aortic repair in 147 cases was successfully performed with low in-hospital mortality (9.8%). Hybrid procedures in patients older than 70 years allowed reducing hospital mortality rate in 3 times in comparison with the standard surgery: 4% vs. 12%, respectively. We developed and introduced into clinical practice the original protocol for patients with aortal valve disease and low left ventricular
ejection fraction (mean – 24.3%). Due to this protocol 46 procedures were performed, in-hospital mortality was 4.4%. Cardiac surgery in patients on dialysis is one of the priorities in our practice. Our experience demonstrates that short waiting time of kidney transplantation after heart valve replacement improves long-term outcomes.
Aim of the study was to evaluate patient and graft survival after liver transplantation (LT) and to determine if primary disease diagnosis, early graft dysfunction or other factors affect it. Furthermore, we analyzed the reasons
of short-term and long-term deaths or retransplantations.
Materials and methods. 192 LTs from donors with brain death were performed from December 2004 until June 2014. Recipient age varied from 5 to 71 years. Most frequent diagnosis was liver cirrhosis (mainly due to hepatitis C), then hepatocellular carcinoma (HCC), liver graft dysfunction, etc.
Results and discussion. 1-year patient survival is 89.5%, graft survival is 87.7%, 3-year –87% and 84.6%, respectively, and 5-year – 83.5% and 83.0%, respectively. Early mortality (in fi rst 30 days after transplantation) was 8%, long-term mortality – 5.9%. Primary non-function graft (PNF) was the reason of 66.7% early deaths. In the long term, infections and oncology were the reasons of death with the same frequency – 36.4%. Early graft dysfunction including primary non-function signifi cantly decreases short term survival (p = 0.0002). Nevertheless, in the majority of cases graft function improves and doesn’t affect survival. Donor factors play role in outcomes: early dysfunction is higher (40.6%) in extended criteria donor group than in standard donor group (р = 0.0431). PNF has the same trend – 8.5% and 0.0%, respectively, but without signifi cance (р =0.0835). 5-year survival is remarkably lower in HCC group 40.8% (p = 0.003) than in other groups.
Conclusion: survival after liver transplantation in our Center is comparable with the results of the world’s centers.
Introduction. Over the past few decades in Russia and other countries there has been signifi cant progress in the development of liver transplantation in children. It became possible to operate recipients with very low body mass, to perform transplant from cadaveric and living donors with incompatible blood type, as well as to perform single-step transplantation of liver with kidney or pancreas in patients with combined diseases.
Aim: to investigate the 6-year experience of liver transplantation in children in V.I. Shumakov Federal Research Center of Transplantology and Artifi cial Organs.
Materials and methods. From May 2008 to June 2014 304 liver transplants
were performed in 297 children aged from 3 months to 17 years with body mass 4 to 32 kg. 241 living donor liver left lateral section transplants (including 2 in conjunction with kidney), 8 left lobe (including 1 in conjunction with kidney), 40 right lobe liver transplants (including 1 in conjunction with kidney), and 9 cadaveric whole liver transplants (including 1 case of simultaneous liver and pancreas transplantation) and 6 split liver transplants (4 – split left lateral section transplantations and 2 extended right lobe liver grafts) were achieved.
41 of these patients received a graft from AB0 – incompatible donors.
Results. A retrospective evaluation of surgical technique and analysis of results were carried out. Early mortality was 8.1%, 1-year survival rate – 86.4%, 5-year survival rate – 78.8%.
Conclusion. These results suggest the prospects of this procedure for pediatric
transplantation and require further investigation and promotion approaches in medical and social public.
Since 1999 living-donor kidney transplantation (LDKT) is one of the priorities in the work of our Center. More than 45% of kidney transplants performed annually are the LDKTs. Long-term outcomes of the fi rst 357 LDKTs demonstrate good 10-year patient and graft survival: 93,5% and 73,0%, respectively. In this group we identify the risk factors of poor graft survival: age of the recipient less than 18 years, duration of dialysis before transplantation more than 24 months and creatinine level at discharge more than 130 mmol/L. The next step was the introduction of laparoscopic donor nephrectomy in clinical practice in 2009. In 2011 we start the AB0-incompatible
LDKT (iAB0) program. Effective desensitization procedure and satisfactory results of iAB0 transplants (3-year patient and graft survival: 100% and 87.5%, respectively), as well as the availability of Luminex technology allowed us to start the clinical trials in patients with pre-existing high levels of anti-HLA antibodies. In this article we both analyze our current results, and focus on topical issues requiring further research.
Heart Transplantation and Assisted Circulation
The article brings up for the discussion main problems standing in the way of development of the mechanical circulatory support (MCS) technology. We give a short historical overview of the development of this technology in our country. Classifi cation of MCS systems for medical indications is given; methods and techniques for short-term and long-term therapy with MCS systems are considered. Main directions of the development of MCS methods are discussed. Using the example of personal experience the methods of design and research of MCS systems are investigated.
The experience of the introduction of convective methods since the eighties of the 20th century is described.
Aim: to evaluate the infl uence of convective transport supplementation on renal replacement therapy results.
Methods and results. The number of convective procedures was applied: hemodiafi ltration with commercial substituted fl uid, paired fi ltration dialysis, acetate-free biofi ltration, original hybrid methods, online hemodiafi ltration. The
main trend was the magnifi cation of substituted volume. In the long run after switching from conventional dialysis to convective therapy the increase of Kt/V, the decline of phosphate, the rise of serum albumin, the decrease of CRP level and ESA consumption, QOL improvement and the drop in severity of intradialysis complications were observed. Over last six years online hemodiafi ltration has become the standard of dialysis therapy in our Center.
Conclusion. The undoubted advantages of convective modalities and accessibility of online hemodiafi ltration make these methods the gold standard of dialysis therapy.
Regenerative Medicine and Cell Technologies
The paper presents the main fundamental and applied results obtained by the Department of Biomedical Technologies and Tissue Engineering over the period of 2010–2014.
Aim. To perform a study of three-dimensional micro- and nanostructure of porous biocompatible scaffolds and quantitative analysis of nanoscale porosity parameters.
Materials and methods. Three-dimensional porous scaffolds made from spidroin rS1/9 (recombinant analog of spider dragline protein) were produced by salt leaching technique. Dimensions of macropores in produced three-imensional scaffolds were in range from 200 to 400 microns. The study of three-dimensional structure of scaffolds was carried out by scanning probe nanotomography technique with the use of experimental setup combining ultramicrotome and scanning probe microscope.
Results. Three-dimensional nanotomographical reconstruction of scaffold macropore wall structure is obtained. The formation of three-dimensional network of interconnected pores and channels with characteristic dimensions in range from 20 to 700 nm in the volume of macropore walls of studied scaffolds is observed. Mean pore diameter is 150 nm. Volume porosity of macropore walls is 22% while volume fraction of pores interconnected in large pore clusters is about 20% of all pore volume.
Conclusion. Obtained as a result of the study quantitative characteristics of porous micro- and nanostructure of scaffolds show signifi cant degree of nanoscale porosity and percolation of macropore walls what correlates with reported high effi ciency of tissue regeneration on such scaffolds implanted in vivo. Use of scanning probe nanotomography technique for analysis of characteristics and topology of micro- and nanopore systems enables to improve effi ciency of development of novel biocompatible and biodegradable materials with predicted morphological, physical, chemical and biological characteristics.
TO ASSIST RESEARCHER
The structure of methodologies of the dissertation research (thesis) is given. Disclosure of the main structural elements in presenting the general characteristics of the study: the title of the dissertation; aim and relevance of the study; contradiction and problem statement; object and subject of the study; aim and hypothesis; novelty, theoretical and practical importance; provisions for the defense. The features of the formation of methodologies for medical research are shown. Tests to practice in formulating some methodological concepts are proposed. The content of the material presented can serve as a methodological guideline for scientifi c researchers to adjust basic ideas, refl ecting the main concepts and relationship between them in a generalized form.