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С. О. Шарапченко

V.I.Shumakov Federal Research Center of Transplantology and Artificial Organs

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ОП

О. П. Шевченко

V.I.Shumakov Federal Research Center of Transplantology and Artificial Organs

D. A. Velikiy

V.I.Shumakov Federal Research Center of Transplantology and Artificial Organs

N. I. Gabrielyan

Institute of Bioorganic Chemistry

ОЕ

О. Е. Гичкун

V.I.Shumakov Federal Research Center of Transplantology and Artificial Organs

АО

А. О. Шевченко

Pirogov Russian National Research Medical University

ИВ

И. В. Драбкина

V.I.Shumakov Federal Research Center of Transplantology and Artificial Organs

I. V. Pashkov

V.I.Shumakov Federal Research Center of Transplantology and Artificial Organs

ТБ

Т. Б. Сафонова

Ministry of Health

МИ

М. И. Петрухина

Ministry of Health

D. A. Saydulaev

V.I.Shumakov Federal Research Center of Transplantology and Artificial Organs

Cooperative Institutions

V.I.Shumakov Federal Research Center of Transplantology and Artificial Organs

Ministry of Health of the Russian Federation

Gause Institute of New Antibiotics Russian Academy of Medical Sciences

Sechenov University

Russian Academy of Sciences

Russian Medical Academy of Continuous Professional Education

Lomonosov Moscow State University

State Research Center for Applied Microbiology and Biotechnology

Academy of Medical Sciences

Ministry of Health

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Gram-negative hospital pathogens at risk of severe bacterial infection

Medical alphabet (2019)

N. I. Gabrielyan С. О. Шарапченко И. В. Драбкина Madina Kh. Kubanova Т. В. Крупенио

Background. Nosocomial infections remain an urgent problem of modern medicine. Along with bacterial infection of the bloodstream a special danger is posed by ventilation-dependent lung infection (VDLI), the main source which are still at the intensive care unit (ICU). Objectives. Assessment of the spread of bacterial infections in ICU over a five-year period. Analysis of the severity of postoperative complications depending on the infection location. Methods. A retrospective analysis of the frequency and form of blood flow and ventilation-dependent lung infection in patients, operated under cardiopulmonary bypass in the years 2013–2017. Results. The rate of blood contamination in the departments ranged from 8.0 to 9.8 %; against the ICU — from 17 to 24 % (p < 0,01). Gram-negative associated mortality was significantly higher than gram-positive (p < 0.001). Acinetobacter spp. and Klebsiella spp. are the most common agents. Analysis of the primary detection of the pathogen showed that in 73.6 % of cases, the trachea is the area of the initial localization of combined-form infection. Conclusions. The risk of bacterial complications in the early postoperative period is associated with gram-negative pathogen s (Acinetobacter spp. and Klebsiella spp.). Constant bacteriological monitoring in ICU is an effective prognostic tool of blood flow and ventilation-dependent lung infection.

Klebsiella

Acinetobacter baumannii

10.33667/2078-5631-2019-1-15(390)-31-35

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Profiling microRNA in the potential lung recipients

DOAJ (DOAJ: Directory of Open Access Journals) (2019)

О. П. Шевченко O. M. Tsirulniкova О. Е. Гичкун I. V. Pashkov С. О. Шарапченко

MicroRNAs are small RNA molecules stable in blood serum (plasma) samples. Their level of expression is associated with the severity and nature of physiological and pathological processes in the body. Aim : to evaluate the expression levels of five microRNAs (miR-27, miR-101, miR-142, miR-339 and miR-424) in potential lung recipients with end-stage chronic lung diseases of various etiologies. Materials and methods . The study included 16 patients with end-stage chronic lung diseases (potential lung recipients) aged 4 to 74 years (average 36 ± 18). Among them were two children (12.5%) – girls aged 4 and 14 years, and 14 adults aged from 21 to 74 (40 ± 16) years – 6 men (42.9%) and 8 women. The control group consisted of 12 healthy individuals. The main diseases that caused severe respiratory failure were: cystic fibrosis (n = 5), primary pulmonary hypertension (PPH; n = 4), pulmonary fibrosis of various etiologies (idiopathic pulmonary fibrosis – 1; pulmonary fibrosis associated with exogenous allergic alveolitis – 1; radiation-induced pulmonary fibrosis – 1), lymphangioleiomyomatosis (n = 2), histiocytosis (n = 1) and pulmonary emphysema (n = 1). MicroRNA expression was detected through real-time PCR. The level of microRNA expression in plasma was estimated in accordance with instructions for reagent kits (Qiagen, USA). Results . The levels of miR-27, miR-101 and miR-339 in potential lung recipients were significantly higher than in healthy individuals. The levels differed depending on the etiology of diseases: the levels of miR-27, miR-101, miR-142 and miR-339 were higher in patients with cystic fibrosis than in healthy individuals; in patients with other lung diseases, only miR-101 levels where higher than in healthy individuals. The miR-424 level in healthy individuals did not differ from that in potential lung recipients or in subgroups. Conclusion . Results obtained show the features of a number of microRNA levels (miR-27, miR-101, miR-142, and miR-339) under certain lung diseases and suggest a possibility of a diagnostic value in patients with chronic respiratory failure during pre-transplant examination.

Etiology

10.15825/1995-1191-2019-3-33-38

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Epidemiology issues in problem of antibiotic resistance of clinical pathogens

Medical alphabet (2021)

N. I. Gabrielyan С. О. Шарапченко О. V. Kisil V. G. Kormilitsina И. В. Драбкина

The relevance of the work is due to the increase in the number of hospital infections associated with antibiotic-resistant gram-negative pathogens on a global scale. For medical institutions, both from a clinical and economic point of view, the catastrophic situation is that the multidrug-resistant pathogens increasing leads to limited possible treatment options. Analysis of published scientific articles shows that today the strict epidemiological surveillance and the study of the pathogen resistance profile in each medical facility is an effective tool for controlling the growth of multidrug-resistant microorganisms, thus reducing morbidity and mortality.

10.33667/2078-5631-2020-34-6-8

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Comparison of clinical and cost effectiveness of accelerated study of sterility of intravascular catheters and drains

Medical alphabet (2021)

V. G. Kormilitsyna V. G. Zaletaeva С. О. Шарапченко R. Sh. Saidgareev M. Yu. Sinyak

The results of a new method for detecting the contamination of intravascular catheters and drains are presented to assess its clinical and cost-effectiveness. Catheters are one of the most widely used devices in critically ill patients. The insertion of a catheter into the central venous system is an invasive procedure that can potentially lead to life-threatening complications for the patient. Catheters are a gateway for infection as they connect the external environment to the internal parts of the human body, causing catheter-associated infections. More than 15 % of patients with an established IVC develop complications, of which the most frequent and requiring removal of the vascular catheter are infectious (5–26 %) and mechanical (up to 25 %). Risk factors for catheter-associated conditions are crucial for hospital mortality.

Central venous catheter

10.33667/2078-5631-2021-32-44-47

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Diagnostic value of microRNA-27 and -339 in heart transplant recipients with myocardial fibrosis

Russian Journal of Transplantology and Artificial Organs (2021)

О. П. Шевченко D. A. Velikiy С. О. Шарапченко О. Е. Гичкун А. В. Марченко

Myocardial fibrosis plays a key role in the pathogenesis of heart failure. A family of small non-coding signaling molecules, microRNAs (miRNAs), has been identified as promising profibrogenic biomarkers capable of signaling a possible risk of adverse events after heart transplantation. Objective : to identify and evaluate the diagnostic significance of miRNAs, as well as comprehensive miRNA-based tests in heart recipients with graft myocardial fibrosis. Materials and Methods . The study included 83 heart recipients aged 16 to 64 (48.4 ± 13.1) years. The expression levels of five microRNAs (miR-27, -101, -142, -339, -424) in venous blood plasma were measured by quantitative real-time polymerase chain reaction; galectin-3 serum levels were determined by enzyme immunoassay. Results . Morphological signs of graft myocardial fibrosis were verified in 48 recipients. The miR-27 and miR-339 expression levels were significantly higher in heart recipients with myocardial fibrosis than in those without myocardial fibrosis (p = 0.018 and p = 0.043, respectively). Diagnostically significant threshold levels of miR-27 and miR-339 for detection of myocardial fibrosis in heart transplant recipients were determined (–4.33 and –5.24 units, respectively). The relative risk of detecting graft myocardial fibrosis in recipients with miR-27 expression value above the threshold level was RR = 1.5 ± 0.157 [95% CI 1.104-2.039], p = 0.009; for miR-339, RR = 1.31 ± 0.130 [95% CI 1.018-1.692], p = 0.036. When miR-27 expression levels and galectin-3 serum levels simultaneously exceeded their estimated thresholds, the risk of transplanted heart myocardial fibrosis increased to RR = 2.7 ± 0.456 [95% CI 1.090-6.524], p = 0.032; when miR-339 and galectin-3 simultaneously exceeded threshold values, the risk was RR = 2.0 ± 0.316 [95% CI 1.076-3.717], p = 0.028). Conclusion . The miR-27 and miR-339 expression levels are associated with the presence of fibrotic changes in the graft myocardium. The combination of molecular-genetic and proteomic biomarkers in one test improves the diagnostic characteristics of these expressions with respect to post-transplant complications in heart recipients.

Myocardial fibrosis

Galectin-3

Pathogenesis

Cardiac Fibrosis

10.15825/1995-1191-2021-3-73-81

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Upregulated circulating mir-424 and its’ diagnostic value for gram-negative bacteremia after thoracic transplantation

Non-coding RNA Research (2022)

О. П. Шевченко O. M. Tsirulniкova С. О. Шарапченко О. Е. Гичкун D. A. Velikiy

Early post-transplant complications such as acute graft rejection and infections are associated with high morbidity and mortality of heart and lung transplant recipients who are in vital need of immunosuppressive therapy. MiR-424 is a member of the miR-16 family, which plays an important physiological role in the development of cardiovascular and respiratory pathology, is involved in the regulation of monocyte and macrophage differentiation, and has an immunosuppressive potential. The aim of the study was to determine the diagnostic value of circulating miR-424 as a potential biomarker of post-transplant complications in heart and lung transplant recipients.The study enrolled 83 heart transplant recipients, aged 18 to 70 (48 ± 13) years; 26 lung transplant recipients, aged 10 to 74 (36 ± 16) years. The miR-424 plasma expression was detected by real-time PCR (Qiagen, USA). Significance of miR-424 level was assessed through the ΔCt method. Acute graft rejection was verified by the results of endomyocardial or transbronchial biopsy. Post-transplant infectious complications were verified through microbiological identification of bacteremia from blood cultures.Our study shows miR-424 upregulation in plasma of patients with chronic heart or respiratory failure in comparison with healthy individuals (p = 0.003 and p = 0.04 resp.). There was a direct correlation of miR-424 expression with red blood cells and hemoglobin levels in patients before heart transplantation (p = 0.01 and p = 0.03 resp.). After transplantation the expression of plasma miR-424 correlated with the level of C-reactive protein (CRP) both in heart (r = 0.75; p = 0.02) and lung (r = 0.50; p = 0.04) transplant recipients. The expression of plasma miR-424 correlated with tacrolimus blood concentration after heart transplantation (r = 0.38; p = 0.04). The miR-424 level didn't differ in heart or lung transplant recipients with and without acute graft rejection (p = 0.47 and p = 0.78 resp.), but was significantly higher in heart and lung transplant recipients with gram-negative bacteremia (p = 0.002). When the miR-424 level is above a threshold value (-5.72 fold change), the relative risk of bacteremia is RR = 3.84 [95% CI 1.94-7.61]; Se = 60.0%; Sp = 89.2%. CRP concentration above 7 mg/L in duplex test with miR-424 improves the diagnostic characteristics of miR-424 for post-transplant gram-negative bacteremia in heart and lung transplant recipients up to RR = 9.17 [95% CI 1.37-61.46]; Se = 83.3% and Sp = 90.1%.MiR-424 plasma expression was upregulated in patients with chronic heart and respiratory failure and in heart and lung transplant recipients in the early post-transplant period. The duplex test, including miR-424 and CRP, has a diagnostic value for detecting the high risk of post-transplant gram-negative bacteremia in heart and lung transplant recipients.

Bacteremia

Monocyte

10.1016/j.ncrna.2022.08.001

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Diagnostic significance of TGF-β1 in kidney recipients with graft dysfunction

Russian Journal of Transplantology and Artificial Organs (2023)

О. П. Шевченко С. О. Шарапченко D. A. Velikiy О. Е. Гичкун E. S. Stolyarevich

Development of minimally invasive diagnosis techniques for complications in recipients, based on analysis of the levels of molecular and genetic biomarkers, is an urgent task facing modern transplantology. Transforming growth factor beta 1 (TGF-β1), which has multiple effects in the body, among the potential indicators of complications. Objective: to assess the diagnostic significance of serum TGF-β1 in kidney recipients with graft dysfunction. Materials and methods. The study included 129 kidney recipients aged 17 to 68 years and 35 healthy subjects. Serum TGF-β1 levels in the recipients were determined by immunoenzyme technique. Results. Kidney recipients included 95 patients with laboratory and clinical signs of graft dysfunction, who underwent biopsy of the transplanted kidney, followed by morphological examination, and 34 recipients with normal graft function. Serum TGF-β1 levels in the kidney recipients were significantly higher than in their healthy counterparts (p = 0.00001); it did not correlate with most blood test parameters; with the glomerular filtration rate (GFR). Kidney recipients with graft dysfunction had significantly higher TGF-β1 levels than other recipients (p = 0.018). In recipients with graft dysfunction, morphological study revealed the following: acute tubular necrosis (ATN, n = 11), acute T-cell mediated rejection (ACR, n = 26), acute antibody-mediated rejection (AMR, n = 35), non-immune-mediated nephrosclerosis with signs of calcineurin inhibitor nephrotoxicity (CNI nephrotoxicity, n = 13), and recurrent glomerulonephritis (chronic graft rejection, n = 10). Recipients with immune-mediated graft injury (ACR, AMR and chronic rejection) had higher serum TGF-β1 levels than recipients with graft dysfunction resulting from other causes, p < 0.0001. Kidney recipients with serum TGF-β1 levels above the threshold value of 94.3 ng/mL had a higher risk of immune-mediated graft dysfunction than other kidney recipients (RR = 2.2 ± 0.22 [95% CI 1.46–3.46]) with 77.5% test sensitivity and 60.3% specificity. Conclusion. The calculated threshold serum TGF-β1 level in kidney recipients can be considered as an auxiliary indicator of graft dysfunction resulting from acute or chronic rejection.

10.15825/1995-1191-2023-4-130-138

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К проблеме предупреждения послеоперационных инфекционных осложнений в хирургии высоких технологий. Состояние вопроса

Медицинский алфавит (2018)

С. О. Шарапченко Н И Габриэлян Р. Ш. Саитгареев В. М. Захаревич И. В. Драбкина

Background. The health care-associated infection in the hospital unit is one of the most important causes of morbidity and mortality in high-tech surgery and transplantology. Objectives. Analysis of special literature devoted to the problem of health care-associated infections and the importance of its prevention measures for patients of surgical departments, as well as the role of the bacterial state of the skin as an independent risk factor for postoperative bacteremia and mortality (based on our own findings). Methods. Analysis of the literature provided by PubMed resource in the period from year 2015 to 2017 on the relevant issues. A retrospective analysis of daily blood samples and swabs from the skin of patients after heart transplantation in the period from year 2013 to 2017. The criterion of group separation - the presence or absence of skin contamination. Results. 45 articles were selected. According to own data, 87 (76.3 %) of 114 cases of contamination were registered in the intensive care unit. The mortality and bacterial blood infection levels in the case of skin contamination were significantly higher (p < 0.05). Conclusions. Constant routine skin monitoring of its bacteriological condition is a necessary measure to reduce infectious complications.

Bacteremia

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Micro-RNA in lung transplant recipients: the prospects of clinical application

Russian Journal of Transplantology and Artificial Organs (2019)

D. A. Velikiy С. О. Шарапченко I. V. Pashkov О. Е. Гичкун О. П. Шевченко

This review summarizes the current literature devoted to the analysis of diagnostic role of biomarkers in rejection of the transplanted lung. Numerous researches have focused on small non-coding RNAs (micro-RNA) that regulate gene expression and affect various cell functions. Variations in the concentration of different micro-RNA have been shown in some pathological processes, including rejection of solid organs. Probably, measuring the level of micro-RNA in lung transplant may have value in the assessment of risk of rejection and possibility of minimizing immunosuppressive therapy. The accumulation of clinical data on the correlation of profiles of various biomarkers with clinical and laboratory parameters in lung recipients will help in finding non-invasive methods for the diagnosis rejection and improving long-term results of transplantation.

10.15825/1995-1191-2019-2-138-144

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Early determination of bacteriological status of biological fluid samples as effective method of diagnosing infectious complications in patients of transplant clinic

Medical alphabet (2020)

И. А. Милосердов И. В. Драбкина D. A. Saydulaev И. Р. Курбангулов С. О. Шарапченко

The concept of quality assurance in the health care system is popular for medical institutions all over the world. The problem of global multidrug resistance of pathogenic and opportunistic flora causes an urgent need for new approaches and methods of renal failure (particularly bacteriuria) rapid diagnosis. Objectives. Evaluate the benefits of laser light-scattering method in early diagnosis of renal failure and infectious complications after kidney transplantation. Methods. 220 urine samples from 129 patients were examined. Each sample was evaluated by traditional method and an automated laser light-scattering system simultaneously. Results. The automated method allowed to get the result in an average of 2 hours and give a result of bacteriuria availability with indicating the class of the pathogen by Gram. Discrepancy between the results of classical and automated methods was observed in 6.8 % of all samples, which is the standard for similar clinical trials. Conclusions. Laser light-scattering method has clear advantages over traditional methods. Diagnosis of urinary tract infections in kidney recipients in a shorter time (3.5 hours) is especially important. The economic benefit of automated process allows to reduce the costs of the hospital for bacteriological studies by 1.5 times.

10.33667/2078-5631-2019-3-32(407)-11-14

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