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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.

The objective was to improve the surgical treatment tactics in patients with non-small cell lung cancer (NSCLC) and coronary heart disease (CHD), requiring myocardial revascularization.Methods and materials. Two groups consisting of 24 patients operated on for NSCLC were examined. In one group, operations for NSCLC were performed in the second stage after coronary artery bypass grafting (CABG). Survival rates in both groups and factors influencing them were evaluated.Results. The number of postoperative complications in both groups was comparable: 20.8 % in patients with CABG and 16.6 % in the group operated only for NSCLC. Indicators of relapse-free and overall survival did not differ significantly from each other (p=0.90 and p=0.95). Only the stage of the disease (p=0.009) and the implementation of complex cancer treatment in case of its necessity (p=0.035) had a reliably impact on the long-term results of the operation. The first stage of myocardial revascularization surgery did not affect the results of treatment (p=0.94), as well as the age of patients, the volume of performed surgery, the morphological picture of the tumor.Conclusion. The staging approach to the treatment of patients with NSCLC and critical forms of CHD requiring myocardial revascularization is reliable, convenient and does not affect the long-term results of treatment.

We herein present our initial report from «ROKKOR-recipient», a national multicenter observational study. The prevalence, risk factors, clinical manifestations and outcomes of the novel coronavirus disease 2019 (COVID-19) in solid organ transplant recipients receiving immunosuppressive therapy were investigated. The study enrolled 251 COVID-19 patients (220 kidney recipients, 7 liver recipients, 1 liver-kidney recipient, and 23 heart recipients). The subjects came from 20 regions in Russia. The symptoms, clinical presentation, imaging and lab test results, therapy and outcomes of COVID-19 were described. It was established that solid organ transplant recipients with COVID-19 have a higher risk of developing adverse events. Predictors of adverse events include associated cardiovascular diseases, pulmonary diseases, diabetes, and kidney failure. Symptoms of the disease include dyspnea, rash and catarrhal signs, as well as initial low blood oxygen saturation (SpO2 10 × 109/L), elevated creatinine levels (>130 μmol/L) and a marked decrease in glomerular filtration rate, requiring hemodialysis. Performing organ transplant surgery in COVID-19 does not increase the risk of adverse events but could save the lives of waitlisted terminally ill patients.

Aim. To determine the clinical features of arrhythmogenic right ventricular dysplasia (ARVD) in recipients on heart transplant waiting list (WL) and after a heart transplantation (HTx).Material and methods. From January 2010 to December 2018, we included 192 recipients in heart transplant waiting list (HTx WL) on behalf of Almazov National Medical Research Center. ARVD was diagnosed in 4 subjects (F Marcus et al. criteria, 2010). All 4 patients (female, mean age 46,5 years-old (16-54-year-old)) underwent HTx. Prior to HTx, arrhythmias (atrial fibrillation, atrial flutter) were diagnosed in 3 recipients. In patient №2, pacemaker in VVI mode was implanted due to sick sinus syndrome (SSS) and tachycardia-bradycardia syndrome and others underwent ICD implantation.Results. Survival after HTx was 30,9 (3,9-46,2) months. All recipients were treated with triple-drug immunosuppressive therapy (calcineurin inhibitors, mycophenolic acid, steroids) and induction with Basiliximab. All patients experienced high sensitivity to immunosuppressive therapy (agranulocytosis), and therefore a colony-stimulating factor was administered to all of them. After immunosuppression reduction (Tacrolimus plus Methylprednisolone) agranulocytosis did not recur.Conclusion. ARVD is a rare disease in the structure of end-stage heart failure in recipients in HTx WL. An examination of this pathology is necessary to manage patients on-time with surgical treatment (ICD, HTx). According to our results, causal variants in desmosome genes were determined in 1 from 4 patients and simultaneous presence of two unique genetic variants in the RKR2 gene were found in one. A special feature of post-HTx management was the development of agranulocytosis, which once again underlines the need for a personalized approach to the selection of the immunosuppressive therapy.

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.

The objective of the study is to substantiate the applying of broncho- and angioplasty lobectomy as an alternative to pneumonectomy in NSCLC.Material and methods. The results of treatment of two comparable groups of patients with NSCLC were presented. In one group, patients underwent broncho- or angioplasty lobectomies (group A), in another – pneumonectomy (group B). The number of complications, overall and disease-free survival in both groups, as well as the factors affected the results were analyzed.Results. The number of postoperative complications in group A and group B was 12.5 % and 15.6 %, respectively. The median of disease-free survival and overall survival in both groups did not differ meaningfully, consisting of 20 months and 48 months in group A, and 19 months and 25 months in group B (p=0.91) and (p=0.97). The results of treatment were meaningfully affected only by the stage of the disease (p=0.017) and multidisciplinary treatment (p=0.007), including chemotherapy and radiation therapy.Conclusions. Performing of broncho- and angioplasty lobectomies can be justified as an alternative to lung removal in NSCLC within the multidisciplinary treatment.

Aim: to estimate physical capacity and quality of life (QoL) and defi ne factors which impact on their dynamic in recipients after heart transplantation (HTx).Materials and methods. From January 2010 to September 2016 we performed 76 HTx (mean age – 45,4 ± 1,6 yrs). Physical activity (PA) was evaluated by IPAQ questionnaire, QoL – by SF-36 (6 months and 1 yr after HTx). Patients underwent cardiopulmonary exercise test (Oxycon Pro, Germany) before, 6 months (n = 32) and 1 yr (n = 31) after HTx.Results. In 6 months after HTx PC improved (VO2peak – 12,6 ± 0,5 and 17,3 ± 0,6 ml/min/kg, p < 0,001). One yr after HTx physically active recipients (n = 21) showed better results (VO2peak – 18,7 ± 0,9 vs. 16,7 ± 0,4 ml/min/kg, p < 0,05). Moreover, 6 months 59,4% (n = 19) and 1 yr after HTx 77,4% (n = 24) of all patients reached normal values, 20 of them were physically active. We did not fi nd any difference in results depending on heart failure severity, duration of illness and of time spent in HT waiting list. In 6 months after HTx physical health (PH) increased (32,2 ± 1,1 vs. 48,2 ± 1,6, p < 0,001), on the other hand, results of mental health (MH) were the same and remained stable in 1 yr after HTx. In addition, QoL was higher in physically active patients than in sedentary lifestyle ones. There was correlations between PH and PA duration (r = 0,4; p < 0,05), VO2peak (r = 0,3; p < 0,05), VO2 at AT (r = 0,4; p < 0,05) and VE/VCO2 (r = –0,5; p < 0,05).Conclusion. After heart transplantation physical capacity and physical health improved but physically active recipients showed better results. Factors affecting the increase in physical capacity were improvement in the functional state of the cardiovascular system and physical activity.

An analysis of treatment results was made in 226 patients with multiple isolated intrapulmonary metastases of solid tumors. It appears that surgical removal of metastases was possible in patients with satisfactory functional resources and accurate evaluation in order to validate the indications for surgery. The operation shouldn’t result in considerable reduction of quality of life and didn’t prevent using other methods of treatment such as medicamental and radiation therapy. The indications to surgical intervention have to be set as individual in consideration of the number of metastases and potential of the patient to undergo the surgery.

The frequency of use of assist blood device as the «bridge» to the heart transplantation increased in last years. An assessment of results of first 7 implantations of assist circulation device using biventricular type «Excor» was made. The implantations were performed in Federal Almazov centre of the heart, blood and endocrinology. An observation period after implantation was since 11 till 301 days. The heart transplantation of 4 patients was carried out in different terms after implantation. One of the patients passed away on the fifth day due to the pulmonary embolism. Another patient died on the eleventh day after the implantation because of multiple organ failure against the background of severe chronic cardiac failure. The waiting list of heart transplantation includes 2 patients.

An analysis of results of 498 patients with malignant pleural effusion was made. All patients were divided into three groups depending on methods of treatment: in the first group of patients the puncture of pleural cavity and the evacuation of liquid were made against the background of complex treatment; in the second group of patients the thoracocentesis and suspension induction were performed; in the third group the video thoracoscopy was carried out. In an assessment of each method of treatment, the researchers came to the conclusion that in case when the patient had the sufficient functional capabilities, the doctors should give preference to the thoracoscopy operations and in case of severe somatic status the doctors should give preference to the drainage of pleural cavity with release from exudates and with subsequent introduction of talc as the most effective sclerosing agent.

The problem of antibody-mediated rejection of donor organ remains extremely relevant. The main targets of the antibodies are mainly donor HLA-antigens (Human Leucocyte Antigens), expressed, in particular, by the cells of graft vascular endothelium. This review describes the mechanisms of the development of humoral alloimmunity which are based on B-cell recognition of epitopes of donor HLA-molecules and affinity maturation of B-cell receptors in the germinal centers of peripheral lymphatic system. Monitoring of epitope load and cross-reactivity indicators to evaluate HLA-compatibility of donor and recipient plays an important role in the prevention of allograft humoral rejection.

Aim. To estimate the results of 6-year experience of heart transplantation (HT) in Federal Almazov North-West Medical Research Centre. Methods. From 2010 to 2015 we have performed 65 HT. Mean age was 44.3 ± 14 years old (from 10 to 64 years old). We used biventricular assist device (BIVAD, Berlin Heart Excor) support in 7 heart transplant candidates before HT. 19 patients (29%) received thymoglobulin, whereas 46 patients (71%) had basiliximab to induce immunosuppression.Results. Extracorporeal membrane oxygenation machines were implanted in 5 patients (7.7%) after HT due to acute right ventricular failure. Suture annuloplasty (the Batista procedure) for tricuspid valve repair was carried out in 3 cases (4.6%). Venovenous hemodiafi ltration was used in 11 patients (16.9%). A total of 598 endomyocardial biopsies (EMB) were performed after HT. Evidence of cellular rejection (R1 and R2) was presented in 286 biopsies (48%). The 30-day in-hospital mortality rate was 3.1%. The 6-month survival rate after HT was 92%, 1-year – 91% and overall survival for the 6-year period of observation – 89.2%. Maximum observation period was 71 months.Conclusions. The 6-year experience of HT in our Center has shown a high level of survival. BIVAD Excor support can be effectively used as a «bridge» to HT. Prevention of graft loss due to acute rejection in heart transplant recipients can be achieved only through regular EMB monitoring. The rate of viral infection increased in 2 months after HT.

The study included 61 patients with exudative neoplastic pleurisy of unknown primary localization. All patients underwent immunocytochemical study of pleural exudate to determine the etiology of effusion. Immunocytochemistry of 55 patients (90 %) of 61 ones was effective. The reason of exudation was both primary tumors — lung cancer (22), pleural mesothelioma (4) and pleural metastases of tumors of other localization - cancers of ovaries (9), breast (4), kidney (3), uterine body (2) , malignant lymphoma (2), colon (2), pancreas (2), thyroid gland (2), stomach (1), prostate (1), vagina (1). Immunocytochemical study of pleural effusions is the method of choice for the differential diagnosis of neoplastic pleurisies of unknown etiology.

Immunological allograft rejection is based on the process of recognition of donor antigens by T-cell receptors. Antigens are generally represented by molecules of major hystocompatibility complex (MHC), expressed by the donor organ tissue cells. Immune response to allogeneic transplant in its activity is greatly higher than response to conventional infection wherein the basic mechanisms of recognition of infectious antigens and alloantigens seem to be similar. In this review we have analyzed three main pathways of recognition of alloantigens. Those pathways are differentiated by the nature of antigen presenting cells, kinetics and duration of its influence on the formation of alloimmunity: direct, indirect and semidirect. Establishing the relationship between mechanisms of allorecognition and manifestations of graft rejection is of great clinical importance.

A comparative analysis of surgical treatment of non-small cell carcinoma of lung was made in 64 patients of senile age and more young patients. It was stated, that preference should be given to the partial lung resections (lob- and segmentectomies). The authors recommended to avoid pneumoectomy and typical resection of the lung as non-radical operations accompanied by high rate of local recurrences. The comorbidity background of patients should be thoroughly investigated before planning of surgery. If necessary, a surgical treatment of accompanied vascular pathology should be fulfilled as the first stage before oncology surgery.

Right heart catheterization (RHC) should be performed on all candidates in preparation for listing for cardiac transplantation. Patient, 64 y. o., with chronic heart failure NYHA III class, had developed a rare complication while performing that procedure – a rupture of segmental branch of pulmonary artery (PA) with pulmonary haemorrhage. The episode of pulmonary bleeding was stopped conservatively without surgical management. There was a pseudoaneurysm formation of segmental branch of PA 2,7 × 2,8 cm with signs of thrombosis. Afterfi ve months the patient underwent heart transplantation without severe complications in perioperative period. No more recurrent episodes of pulmonary haemorrhage were identifi ed.

Patients with congestive heart failure have an increased incidence of thromboembolic events. The choice of me- dical management in patients with antiphospholipid antibodies and generalized thrombosis due to hypercoagula- bility is complex issue. We report heart transplant outcome in 15 years old patient with dilated cardiomyopathy and secondary anti-phospholipid syndrome.

Purpose: to study the pathogenesis of retinopathy of prematurity.Patients and methods. 642 preterm infants born before 30 weeks gestation with the weight less 1500 grams were examined. The study included: indirect ophthalmoscopy; digital retinoscopy; calibrometry of retinal vessels; dopplerography; analysis of partial pressure of oxygen and carbon dioxide in the capillary blood. Results. The first phase of retinopathy of prematurity (ROP) occurred due to the immaturity of the mechanisms of autoregulation of the blood flow and the inadequate reaction of immature retinal vessels to oxygen. It was established: the less gestational age of a child, so there are less mechanisms of autoregulation of hemodynamics. The perverse reaction of autoregulation leads to pronounced arteriospasm, increasing the zone of hypoxia, and triggering pathological angiogenesis. In morphologically immature children, arteriospasm of retina vessels is more often detected, and narrowing degree of vessels is higher. Arteriospasm is defined in 82 % of children born at the age of gestation from 25 to 27 weeks, in 67 % — at a period from 28 to 29 weeks, in 54 % — from 30 to 32 weeks. In children with ROP in the preclinical period of the disease, retinal angiospasm is noted at values of pO2 in capillary blood less then 40 mm Hg or exceeding the upper limit of the norm values of pCO2 (the norm values of pO2 are 40–60 mmHg, pCO2 are 35–45 mm Hg). Autoregulation of blood flow is immature and inadequate. In the group before 30 weeks of post-conceptual gestational age without development of ROP, a spastic reaction of retinal arteries was revealed at the background of subnormal pO2 values in capillary blood. Biochemical autoregulation of blood flow is still immature. But from the 30 week of post-conceptual gestational age arteriospasm of retina is formed at values of pO2 of 45 mm Hg or higher (p < 0.05). The normal caliber of retinal arteries in children without development of ROP is revealed at the background of mean values of pO2 below 45 mm Hg and values of pCO2 below 42 mm Hg before 30 weeks of post-conceptual gestational age, and above 45 mm Hg from the 30th week of post-conceptual gestational age. In children without ROP from 30 weeks of gestational age biochemical autoregulation of blood flow functions. It is important the degree of an angiospasm for the development of ROP. Dopplerographic critical index of blood flow disturbance in the ophthalmic and anterior cerebral arteries has been established — the index of resistance (IR) exceeding 0.8. It is a precursor of the development of ROP and pathological angiogenesis. In the group of children with ROP, the IR of the anterior cerebral artery is 0.84 ± 0.02 (in av.). The IR of the ocular artery was 0.83 ± 0.03. In higher index (up to 0.9–1), the process in the eye was more active.