Almazov National Medical Research Centre Research Articles

Pharmacoresistant temporal epilepsy: the relationship of epileptiform activity and structural changes in the hippocampus

Background. Hippocampal sclerosis is one of the most common structural lesions associated with epilepsy. The standard medical care in the treatment of drug-resistant temporal lobe epilepsy associated with hippocampal sclerosis is surgery with anterior temporal lobectomy. The extent of resection depends on the involvement of hippocampal sclerosis in the epileptic system. Objective. Determine the relationship between the involvement of the hippocampus in the epileptic system (on the basis of the results of intraoperative electrocorticography (ECoG)) and the presence of structural changes in it, found on the basis of MRI data. Materials and methods. The present article presents an original retrospective study of the dependence of the signs of hippocampal sclerosis according to neuroimaging data and the formation of epileptiform activity in 36 patients treated at the Polenov Neurosurgical Institute — branch of Almazov National Medical Research Centre in 2015–2018. Results. Depending on the presence of hippocampal sclerosis and epileptiform activity, patients were divided into 4 groups: 1) patients with the presence of both hippocampal sclerosis and epileptiform activity in the mesiobasal structures (n = 15); 2) patients with identified sclerosis of the hippocampus, without registration of specific activity according to the results of ECoG (n = 8); 3) patients with epileptiform activity, while MR-negative (n = 10); 4) patients without epileptiform activity and without signs of hippocampal sclerosis according to MRI (n = 3). After a statistical check of the distribution of patients, it was found that the distribution was random. Conclusion. The fact of the presence of structural changes in the hippocampus could not be a pathognomonic sign of the inclusion of the hippocampal-entorial complex in the epileptic system.

Impact of physical training on functional and haemodynamic characteristics of “inotrope-dependent” patients with chronic heart failure at class III–IV

Objective . To assess and compare the impact of physical training (PT) on functional and hemodynamic characteristics in patients with chronic heart failure (CHF) depending on continuous inotropic support. Design and methods . Prospective randomized study included 120 men aged 18–65, admitted to the Almazov National Medical Research Center (St Petersburg, Russia) from 2014 to 2019 due to decompensated CHF of III–IV functional class (FC), with left ventricular ejection fraction (LVEF) ≤ 30 %; blood pressure (BP) ≥ 90/60 mmHg (with or without inotropic therapy). Patients receiving dopamine or dobutamine for ≥ 2 weeks were randomized into two groups: group 1 participated in program of physical training (PPT), and group 2 did not participate in PPT. Patients of group 3 had CHF of III–IV class without inotropic therapy and participated in PPT. Initially, all groups were comparable by clinical, functional and hemodynamic parameters. The follow-up lasted 6 months. During months 3 and 6, hemodynamic parameters — BP and heart rate (HR), respiration rate (RR) at rest and peak of exercise, echocardiographic and central hemodynamics at rest, parameters at rest, number of arrhythmias were evaluated. Results . Patients of group 1, after 3 and 6 months, showed no increase in systolic (BPs) and mean BP (BPm) at peak of exercise, in contrast to patients of group 3 who demonstrated a significant increase in BPs (p ≤ 0,002) and BPm (p ≤ 0,005) after 3 months, and BPs (p ≤ 0,001) and BPm (p ≤ 0,002) after 6 months. By 6-month follow-up, intergroup analysis did not show significant changes in HR, LVEF, end-diastolic volume, stroke volume and pulmonary pressure. Initially, ECG monitoring showed a higher number of unstable ventricular tachycardia (VT) in group 1 compared with group 3 (p = 0,01), after 3 and 6 months in all groups the number of VT was comparable. During 6 months, implantable cardioverter defibrillator (ICD) shocks were compared in all groups: 2 per group (5 %). Conclusions . “Inotrope-dependent” survivors with CHF at peak of exercise did not significantly increase BPs and BPm in contrast to “inotrope-independent” patients. Individually developed aerobic PPT of low and intermediate intensity in “inotrope-dependent” survivors did not influence negatively on echocardiographic parameters, parameters of hemodynamics at rest and during the peak of exercise, did not increase mortality and number of life-threatening cardiac arrhythmias and ICD shocks.

Sleep-related breathing disorders in patients with pulmonary hypertension

Abstract Introduction There are some evidences of sleep-related breathing disorders (SRBD) association with pulmonary hypertension (PH). Only limited information regarding the SRBD prevalence in pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) patients, is available. Purpose To estimate the features of SRBD and the asymmetric dimethylarginine (ADMA) level in PAH and CTEPH patients and their relationship with the severity of PH. Methods There were included 31 patients (45% male; 55% female) with a verified diagnosis of precapillary PH: 22.6% – with PAH; 9,7% with PAH associated with adult congenital heart disease; 64.5% – with CTEPH; 3.2% with PAH associated with connective tissue disease. Patients underwent a general clinical examination, questionnaires, a comprehensive assessment of respiratory function, a complete polysomnographic study, ECG and ECHO studies, assessment of clinical and biochemical blood tests, including an assessment of ADMA and NT-proBNP levels. Results SRBD of a predominantly obstructive nature were found in 74.2% of the examined: 38.7% were mild, 22.6% were moderate, 12.9% were severe. In 35% of patients, episodes of periodic breathing during sleep were recorded. There was no association SRBD with PH functional class and hemodynamic parameters. Moderate correlation was observed between the apnea-hypopnea index and remodeling indices of the heart chambers according to ECHO: for the end-diastolic size of the left ventricle (ρ=0.54; p=0.005); for an indicator of the ratio of the size of the ventricles (RV/LV) (ρ=−0.41, p=0.05). The presence of SRBD wasn't associated with the level of peripheral blood saturation according to pulse oximetry in sleep and during wakefulness. Negative moderate correlation was observed between NT-proBNP level and the average peripheral blood saturation at night in the entire examined group (ρ=−0.40; p=0.035). All patients showed an increase in ADMA, with no association between ADMA and SRBD severity. Conclusions The incidence of SRBD is extremely high in PAH and CTEPH patients. However, there no association between presence and severity of PH, including with right heart remodeling. But the severity of nocturnal hypoxemia is associated with an increase in NT-proBNP level, a proven marker of poor prognosis in PAH and CTEPH groups of patients. SRBD severity indices (apnea-hypopnea index and desaturation index) are associated with ECHO parameters characterizing remodeling of left heart chambers. Increasing ADMA level as a marker of endothelial dysfunction was related with PH severity, but not with SRBD. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Almazov National Medical Research Centre

New Approaches to the Integration of Science and Medical Education: Real Experience

We described key approaches to the realization of the pilot project, which is being carried out in Almazov National Medical Research Centre in order to implement basic medical education in close integration of science and education.

Arrhythmogenic right ventricular cardiomyopathy in recipients on heart transplant waiting list

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.

P0137FIRST RUSSIAN BOSIMILAR OF ECULIZUMAB IN THE TREATMENT OF AN ADULT PATIENT WITH ATYPICAL HEMOLYTIC UREMIC SYNDROME

Abstract Background and Aims The disease diagnostics results and the efficacy of pathogenetic treatment when transferring from the original drug to the biosimilar were evaluated during clinical observation of an adult patient with aHUS. Method A 46-year-old patient has a history of hypertension since 2012 and maximum ABP of 230/130 mmHg. In 2016, newly diagnosed azotemia was identified (blood creatinine — 140 μmol/L, GFR by EPI — 54 mL/min/1.73m2). In 2018, the patient suffered an acute cerebrovascular accident in the vertebrobasilar area. On admission to Almazov National Medical Research Centre, blood test showed: creatinine – 260 μmol/L (GFR by EPI — 28 mL/min/1.73m2), urea – 11.52 mmol/L, LDH – 130 U/L, complement system C3 – 1.32 g/L, С4 – 0.37 g/L, hemoglobin – 144 g/L, platelets – 302*109/L; urinalysis showed: daily protein loss – 2.6 g/day, RBC – 0–1 per field. Taking into account the kidney damage, the renal fine-needle aspiration biopsy was performed, revealing histopathological findings typical of chronic thrombotic microangiopathy of extreme severity, arteriolar arteriosclerosis with total or subtotal luminal occlusion, extensive secondary perihilar segmental glomerulosclerosis (27%); and global glomerulosclerosis (55%). According to the study results, the secondary genesis of TMA was ruled out, as well as STEC-HUS and thrombotic thrombocytopenic purpura (TTP), systemic diseases (systemic lupus erythematosus, antiphospholipid syndrome (APS), scleroderma), malignancies, HIV infection, sepsis, malignant arterial hypertension, adverse drug events, or disseminated intravascular coagulation (DIC). Plasma ADAMTS-13 levels were also assessed. Its activity was 64% (normal range 93–113%) of ADAMTS-13 activity in the control plasma, thus the diagnosis of thrombocytopenic purpura was ruled out. Due to the absence of anti-CFH-antibodies the antibody origin of aHUS was also ruled out. To assess the contribution of additional factors promoting the development of TMA, the polymorphism of hemostasis genes was studied to reveal homozygous genotypes of platelet collagen receptors (ITGA2: 807 С/Е), heterozygous genotypes of fibrinogen genes (FGB: 455 G/А), folate cycle enzymes (methylenetetrahydrofolate reductase (MTHFR: 677 C/T), methionine synthase (MTR: 2756 A/G (D919G)), responsible for a pronounced tendency towards hyperhomocysteinemia. In the clinical case the diagnosis of aHUS was obvious, which was supported by the classical symptom cluster of TMA and histopathological verification in the absence of data suggestive of other pathological conditions. The peculiarity of this clinical case is the late diagnosis, long-standing course, and severity (complications such as an acute cerebrovascular accident in the vertebrobasilar area, target lesions, kidneys in particular). Results Taking into account the primary diagnosis, treatment with a standard dose of eculizumab was initiated. After three months of treatment the patient was transferred to therapy with Russian biosimilar of eculizumab. After the switch from the original drug, the therapy with eculizumab biosimilar continued to be associated with a positive trend including a gradual decline in azotemia level (blood creatinine – 115 μmol/L (GFR by EPI – 52 mL/min/1.73m2), blood urea – 7.10 mmol/L), proteinuria (daily protein loss – 0.6 g/day). The comprehensive treatment including antihypertensive therapy also led to the normalisation of ABP values. No adverse events associated with the therapy were noted. Conclusion The obtained results demonstrate high efficacy and safety of eculizumab biosimilar in the treatment of the adult patient with aHUS.

Therapy of neonatal seizures: a two-year retrospective study at Almazov National Medical Research Centre

Introduction.Neonatal seizures are the most common pathological neurological symptom of the neonatal period, requiring immediate treatment. There are 2 directions in the treatment of seizures: relief of acute life-threatening seizures and supportive antiepileptic therapy of the chronic process. Worldwide phenobarbital is still the first-line medication for neonatal seizures. However, due to contraindications the doctors have to select and prescribe other antiepileptic therapy for both stopping seizures and supportive therapy.Objective.To introduce an algorithm for standardized phased treatment of neonatal seizures from stopping an acute debut to starting supportive chronic therapy according to clinical and electroencephalographic indications.Characteristics of children and research methods.The authors retrospectively analyzed 449 patients born in 2016 – 2017. The inclusion criteria: full-term term newborns with clinical and/or encephalographic verification of seizures in the neonatal period. The authors studied the time distribution parameters of the primary realization of seizures from the time of birth, the genesis of convulsive activity, the effectiveness of antiepileptic therapy.Results.Out of 449 treated children (full-term infants with somatic, surgical and cardiosurgical pathologies) 36 (8.0%) patients had neonatal seizures, 35 (97.33%) children of them had symptomatic seizures. Neonatal genetic epilepsy was diagnosed in 1 (2.77%) child (Otahar syndrome). The investigators revealed the prevalence of the primary realization of convulsive syndrome in newborns in the first 4 days of life. Occasionally the initial debut of seizures occurred in children older than 7 days with congenital metabolic disorders, represented by aminoaciduria. The seizures were stopped without anticonvulsants (correction of transient metabolic disorders – hypoglycemia, hypocalcemia) in 3 (8.33%) children, with phenobarbital monotherapy in 5 (13.89%) children, diazepam monotherapy in 4 (11.11%) children, monotherapy with sodium thiopental – in 5 children (13.89%), valproic acid preparations – in 8 (22.22%) children, a combination of first and second line drugs (sodium thiopental + diazepam; sodium thiopental + phenobrobital) – in 11 ( 30.56%) children. Supportive antiepileptic therapy was carried out using phenobarbital monotherapy in 16 (44.44%) children, valproic acid preparations in 7 (19.44%) children, levetiracetam in 4 (11.12%) children, oxcarbazepine in 2 (5.56 %) children; 7 (19.44%) children were discharged without supportive antiepileptic therapy.Conclusion.Currently anticonvulsant monotherapy is effective in less than 50% of neonatal seizures cases; phenobarbital or diazepam remain the first-line medications. 1/3 of the patients require a combination of antiepileptic therapy. It is of great importance to diagnose and correct transient metabolic disorders before the prescription of anticonvulsant therapy.

Experience with Selexipag to Treat Pulmonary Arterial Hypertension

Aim To present an own experience in using a medication selexipag in patients with pulmonary arterial hypertension (PAH) included into the V. A. Almazov National Medical Research Center registry and participating in the GRIPHON and GRIPHON OL clinical studies.Material and methods 26 patients with PAH were included into this study since 2010: 20 patients with idiopathic PAH, 4 patients with PAH associated with systemic scleroderma, and 2 patients with corrected congenital heart defects. At the time of randomization, 19 patients had been receiving therapy with phosphodiesterase type 5 inhibitors for at least one month. Among the patients treated with selexipag (n=14), 4 patients reached a high individual maintenance dose (1200-1600 µg b.i.d.), 4 patients reached a medium dose (600-1000 µg b.i.d.), and 6 patients reached a low dose (200-400 µg b.i.d.).Results The selexipag therapy exerted a positive effect on secondary endpoints, specifically, on changes in the functional class of pulmonary hypertension, serum concentration of NT-proBNP, and physical working capacity of patients. Adverse events associated with the selexipag treatment, which resulted in termination of study participation, were observed in one patient.Conclusion To achieve the main goal of drug therapy, low risk of death with selexipag it is critical to observe the titration schedule and to aim at reaching the highest individual maintenance dose.

Graphical Description of Left Ventricular Volumetric Characteristics in Selected Chronic Inflammatory Diseases

The combination of heart rate and stroke volume (SV) indexed (i) to body size provides an indication of adequacy of tissue blood perfusion. Both arterial compliance (AC) and arterial elastance (Ea) depend on SV. Understanding how pump function is performed requires determination of the prevailing working point of the heart. In practice we can look at end‐systolic volume (ESV) which is a key element in the characterization of ventricular functioning. Considering SV and ESV in unison offers a logical framework to study the cardiovascular system (Figure 1). This strategy allows the creation of two ratio‐based metrics: i) (SV/ESV) which is usually referred to as ventriculo‐arterial coupling (VAC) while assuming that the volume intercept vanishes, and ii) {SV/(ESV + SV)} which is known as ejection fraction (EF). As a consequence the EF and VAC are nonlinearly related, meaning that depending on the asymptotic region considered, one or the other is a more sensitive indicator. Being dimensionless ratios, EF and VAC do not consider body size.We retrospectively investigate the SV to ESV relationship in various diagnostic groups of patients (informed consent obtained), and calculated derived metrics. ESV and SV were determined in 145 patients (77% women) by echocardiography in Almazov National Medical Research Centre (Saint‐Petersburg). We created graphs of SV vs ESV to provide insight into VAC and EF differences in the following groups: scleroderma (Sc, N=55) and rheumatoid arthritis (RA, N=28) compared to atherosclerosis (Ath, N=62).Figure 2 shows data points for SV vs ESV in these 3 groups. SV is higher (P<0.0001) in Ath (69.6±12.3 mL) than in Sc (59.4±13.5 mL) or (P=0.01) in RA (61.8±16.0 mL), while ESV is only larger (P=0.0003) in RA (36.9±9.7 mL) than in Ath (30.3±6.8 mL). For the resulting ratio‐based metrics VAC is higher (P<0.0001) in Ath (2.35±0.36) compared to Sc (1.86±0.36) and RA (1.71±0.34), while EF is also higher (P<0.0001) in Ath (69.7±4.1) compared to Sc (64.4±4.8) and RA (62.5±5.2). Figure 2 clearly illustrates that VACC varies while VAC remains constant. The same observation obviously applies to EFC at any fixed level of EF.We conclude that EF, VAC, AC and Ea do not uniquely characterize properties of the cardiovascular system. Associated companion metrics (as proposed in Figure 1) are required to explore hemodynamic differences between various diagnostic groups in chronic inflammatory diseases. Such an extended analysis may contribute to enhanced insight into hemodynamics and connection with various pertinent biomarkers.Support or Funding InformationRussian Science Foundation (project No. 17‐15‐01177)Stroke volume (SV) versus end‐systolic volume (ESV) minus volume intercept (Vo). Ventriculo‐arterial coupling (VAC) corresponds with the slope, while the hypotenuse (c) refers to the companion associated with VAC.Figure 1Stroke volume (SV) versus end‐systolic volume (ESV), assuming that the volume intercept (Vo) vanishes. Ventriculo‐arterial coupling (VAC) is the ratio of SV and ESV.Figure 2

Chronic disorders of consciousness: terminology and diagnostic criteria. The results of the first meeting of the Russian Working Group for Chronic Disorders of Consciousness

Introduction. To date, patients with chronic disorders of consciousness (CDC) represent a serious problem from the medical, social, and economic points of view. Because of the relatively small incidence of this condition, accumulation of the sufficient experience in its diagnosis and treatment remains a complex task, while the lack of a unified approach among Russian specialists to classification of the CDC makes it even harder to solve. At the same time, there are widely used terms overseas that are accepted by the medical community and used in current recommendations. Aim. Specialists of the Federal State Funded Research Institution, Research Centre of Neurology, have put forward an initiative to create a Russian Working Group for Chronic Disorders of Consciousness, to discuss and approve unified Russian terminology for CDC and criteria for classifying CDC, and to then develop clinical recommendations for the diagnosis and treatment of patients with CDC. Results. The first roundtable meeting on the issues related to CDC took place at the ХI Russian Congress of Neurologists in June 2019. The attendees included staff members from the FSFRI Research Centre of Neurology, FSFRI Federal Research and Clinical Centre of Intensive Care Medicine and Rehabilitation Medicine, the Polenov Neurosurgical Institute - Branch of the FSFI Almazov National Medical Research Centre, FSFEI HE Ural State Medical University, SFI Saint Petersburg I.I. Dzhanelidze Research Institute of Emergency Medicine, FSAEI HE Pirogov Russian National Research Medical University, SFHI Research Institute of Emergency Paediatric Surgery and Traumatology of the Moscow Department of Health, and the SFHI N.I. Sklifosovsky Research Institute of Emergency Medicine of the Moscow Department of Health. Based on the results of the meeting and voting, a list of terms was composed to describe CDC and the corresponding diagnostic criteria were approved. The roundtable discussion also included the working group’s future plans, and the development of a plan for Russian recommendations for the diagnosis and treatment of the CDC. Conclusion. The terms and criteria mentioned in the article are recommended for use in clinical practice and research in Russia, for patients with CDC.

The number of oocytes as a predictor of pregnancy rates in the cycles of assisted reproductive technology

Background. Data on the effect of the number of received oocytes on the outcomes of assisted reproductive technology (ART) programs are contradictory. The frequency of obtaining a small number of cells ranges from 5.6 to 35.1 %. Identifying women who have chances of getting pregnant, despite this situation, is important for drawing up an adequate treatment plan.Objective of this study is to assess the pregnancy rate depending on the number of retrieved oocytes in ART cycles with ovarian stimulation, which ended with the transfer of embryos, as well as determining the characteristics of patients with a reduced response, in whom the pregnancy occurred.Design and methods. The study included 526 women who were treated for infertility in the department of ART of the Almazov National Medical Research Centre in 2017. Patients were divided into three groups depending on the number of oocytes retrieved: less than 5, from 5 to 9 and 10 or more. Group 1 (number of oocytes less than 5) included 126 women, group 2 (from 5 to 9) — 223 women and group 3 (number of oocytes 10 and more) — 177 patients. The average age of the patients was 33.37 years (from 22 to 48 years).Results. The frequency of obtaining a positive blood test and clinical pregnancy rate were comparable in groups 2 and 3 (53.81 % and 49.72 %, respectively) and significantly lower in group 1 (41.27 %, p > 0.05). Clinical pregnancy in group 1 occurred in 34.13 % of cases, which was significantly different from the indicators of group 2 + 3, where the gestational egg visualized in 47.5 % of cases (p < 0.05). In a group of women with a small number of oocytes, the most important predictors of pregnancy were obtaining 2 or more oocytes, and anti-mullerian hormone (AMH) level above 1 ng / L.Conclusion. The number of oocytes is an important predictor of pregnancy rate. The chances of becoming pregnant in women with a small number of oocytes depend on the level of AMH and the number of oocytes obtained.

Baseline pulmonary hypertension in heart transplant recipients: 9 years of experience at Almazov National Medical Research Centre

Objective: to assess the impact of baseline pulmonary hypertension (PH) on early and long-term outcomes following heart transplantation (HT). Materials and methods. From January 2010 to December 2018, 112 HTs were carried out. Based on right heart catheterization results, all recipients were divided into 2 groups: Group 1 with PH (n = 76; mean pulmonary arterial pressure (mPAP) ≥25 mm Hg), Group 2 – without PH (n = 36; MPAP <25 mm Hg). The average age of Group 1 patients was 46.4 ± 14.9 years, baseline pulmonary vascular resistance (PVR) was 3.5 ± 1.5 Wood units, PVR after reversion test (nitric oxide – 80 ppm, iloprost 20 μg) – 2.8 ± 1.0 Wood units, systolic PAP (sPAP) – 50.1 ± 13.4 mm Hg. The average age in Group 2 was 47.3 ± 12.2 years, baseline PVR – 2.1 ± 0.8 Wood units, sPAP – 27.4 ± 5.3 mm Hg. The dynamics in indicators of early postoperative period (duration of mechanical ventilatory support, use of vasodilators and inotropic support and the length of stay in intensive care unit (ICU), 30-day mortality) and long-term post-HT echocardiography results were assessed. Results. Due to acute right-ventricular failure (RVF) developing after heart transplantation, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) was done in 8 patients (11%) from Group 1 and one patient (3%) from Group 2. Presence of PH did not affect duration of mechanical ventilatory support, inotropic support, and length of stay in ICU. Levosimendan therapy in the early postoperative period was more often performed in Group 1 (n = 29) than in Group 2 (n = 6) (p = 0.048). Nitric oxide inhalation was also more often administered in Group 1 (n = 54); Group 2 (n = 7), (p = 0.003). Sildenafil therapy after HT was comparable in both groups Group 1 (n = 25); Group 2 (n = 6), (p = 0.048). In early post-HT stages, 14 patients died, 30-day mortality was comparable in both groups (p = 0.12). Six months after HT, no differences were found in the sPAP (p = 0.21) and PVR (p = 0.07) levels. Conclusion. Patients with baseline PH after HT have a more severe early postoperative period, including a higher RVF incidence, with the need for ECMO implantation. A PVR level >3.5 Wood units is not a threshold for HT. Patients with baseline PVR >3.5 Wood units following HT show comparable results with patients without baseline PH. This allows such patients (baseline PVR >3.5 Wood units) to be considered for inclusion in the heart transplant waiting list. In addition, 30-day mortality and duration of mechanical ventilatory support after HT in patients with and without baseline PH did not differ. Regardless of the baseline level of sPAP and PVR, all patients showed improvement in these parameters after HT. Six months after HT, no differences were found in sPAP and PVR levels in the patients, regardless of whether there was baseline PH or not.

Regional anaesthesia in pregnant women with cardiovascular diseases

Background. Currently in developed countries, up to 4 % of pregnant women have cardiovascular diseases, which are one of the leading causes of maternal mortality. Anesthesia method have an important role in the abdominal delivery in this category of patients. Objective. To summarize the experience of different anesthesia approaches to abdominal delivery in pregnant women with cardiovascular diseases.Materials and methods. A retrospective analysis of the use of various methods of anesthesia during abdominal delivery of pregnant women with cardiovascular diseases was performed.Results. In “Maternity Hospital № 13” and the Almazov National Medical Research Centre for the period from 2014 to 2018 2140 abdominal deliveries were carried out in pregnant women with heart diseases (1450 and 690, respectively). In the Maternity Hospital №13 1374 (94.8 %) of abdominal deliveries were performed under regional anesthesia, 76 (5.2 %) under general anesthesia. In Almazov National Medical Research Centre 513 (74.3 %) of abdominal deliveries were performed under regional anesthesia, 177 (25.7 %) under general anesthesia. The features of the hemodynamic profile of general and regional anesthesia in pregnant women with various heart disease are presented.Conclusion. In pregnant women with heart disease, up to 88 % of cesarean section are performed under regional anesthesia. General anesthesia is used for contraindications to regional anesthesia, as well as for obstetric indications. The use of advanced monitoring, methods of slow titration of local anesthetic dose and the use of vasopressors allow to avoid hemodynamic disorders in patients with concomitant heart disease.

SOCIO-PSYCHOLOGICAL AND BEHAVIORAL CHARACTERISTICS OF PATIENTS WITH CHRONIC HEART FAILURE AWAITING HEART TRANSPLANTATION

Aim. The article presents the results of psychological investigations of patients in the terminal stage of chronic heart failure (n = 105, average age 51.9 ± 0.9 years, males – 86.7 %) undergoing medical treatment at the Almazov National Medical Research Centre (St. Petersburg). The investigations were carried out before the medical commission for inclusion of patients into the waiting list for heart transplantation (HTWL). Materials and methods. After 6 months of treatment in a cardiology hospital, the patients were divided into 2 groups – the patients included in and retained their positions in the HTWL (n = 55) and the patients not included in or excluded from the HTWL (n = 55). That was done in order to identify the prognostically significant psychosocial characteristics of patients. Clinical, psychological and psychometric methods were used such as a structured interview, expert questionnaire for doctors, the Alcohol Use Disorders Identification Test (AUDIT), the Short Form-36 (SF-36). Results. Comparative analysis reveals a wide range of psychological characteristics, among which the indicators of adherence for treatment and willingness to change lifestyle have the greatest importance. Emotional support and relationships outside the family, an adequate understanding of the disease, an optimistic assessment of the outcome of surgery treatment, etc., as well as the presence of one's own family and minor children are essential in the structure of the psychosocial potential of patients during preparation for HT. Conclusion. Using the obtained results will improve the methodology and procedure for a comprehensive clinical assessment of patients with chronic heart failure before inclusion into the waiting list for heart transplantation, which is extremely important for advanced surgical technologies.

Skull defect repair in children using a 3D-printing technology

Currently, 3D-printing technologies are increasingly used in neurosurgery. Active development of this approach is valuable to improve preoperative planning, intraoperative navigation, and manufacturing of realistic training models. In this manuscript, the authors report an experience of the pediatric neurosurgical department of the Almazov National Medical Research Center regarding 3D-printing technologies in manufacturing of individual implants for skull defect closure. The main aspects of this technology, advantages and disadvantages are considered. Moreover, the authors describe several cases of creating individual implants for children with skull defects of various origins, dimensions and complexity.

Копинг-поведение в системе психосоциальной оценки пациентов, ожидающих трансплантации сердца

The paper presents the results of the study focusing on coping strategies and personal resources of patients with chronic heart failure (CHF) during the waiting period for heart transplantation (HT). The sample included 105 patients directed to the commission for inclusion in the waiting list of HT (WLHT) in the Almazov National Medical Research Centre. After 6 months of hospitalization, the patients were divided into two groups: those included in WLHT initially who kept their positions (n=55; Group 1), and those who were excluded or not included initially (n=50; Group 2). Methods: The Ways of Coping Questionnaire and Purpose in Life Test. It was found out that the most endorsed coping strategies were confrontation, positive reappraisal and self-control for Group 1, and distancing and escape/avoidance for Group 2. The significant increase in the life purposefulness general score, and subscale scores reflecting goals, time perspective and internal locus of control was observed in Group 1. We conclude that the obtained data can be used in planning psychological work with patients with CHF during the period of waiting for HT.

Clinical, structural and functional features of paroxismal syndrome in insular and temporal lobe tumors

To analyze the characteristics of paroxysmal syndrome in insular and temporal lobe tumors, to determine their relationship with the histological structure of tumor, to assess the effect of tumor growth nature on severity of disease. A retrospective analysis enrolled 80 patients aged 11 - 80 years with insular and temporal lobe tumors and symptomatic epilepsy. All patients underwent surgery at the Polenov National Research Neurosurgery Center in Almazov National Medical Research Center for the period from 2012 to 2018. The main group consisted of 29 patients with tumors of temporal and insular lobes. Control group of 51 patients with temporal gliomas was formed for comparative analysis. It was found that involvement of insular lobe into paroxysmal syndrome is characterized by attacks with a motor component, somatosensory paroxysms, vegetative manifestations (respiratory attacks, salivation, nausea), speech disorders and taste hallucinations. Derealization, motor arrest and déjà vu/jamis vu paroxysms were more common in patients with temporal lobe lesion. Neoplastic lesion of the insular lobe shortens the period between manifestation of paroxysms and surgical treatment. Moreover, this type of disease is characterized by higher incidence of seizures compared to isolated temporal lobe tumors.

Vitamin D and mineral metabolism after childbirth with the use of preventive doses of cholecalciferol

Hypothesis/aims of study. According to the literature, the prevalence of vitamin D deficiency and its deficiency in pregnant women reaches 6080%, which is a significant factor in reducing bone mineral density (BMD), osteopenia, and the risk of fractures after childbirth. Hormone-mediated changes in calcium-phosphorus metabolism during lactation are an independent factor in the reduction of BMD. Therefore, the study of the relationship between vitamin D deficiency and insufficiency after childbirth and the possibility of correction is relevant. The aim of this study was to evaluate the effect of prophylactic doses of cholecalciferol and calcium carbonate over time on calcium-phosphorus metabolism indicators after childbirth.
 Study design, materials and methods. A randomized controlled trial was conducted based on V.A. Almazov National Medical Research Center, Saint Petersburg. 64 puerperas, who lived in St. Petersburg from 2013 to 2014, were surveyed on the 35th day after childbirth. The age of women ranged from 20 to 35 years. Blood serum levels of calcium, phosphorus, magnesium, 25-hydroxycalciferol (25(OH)D), and parathyroid hormone (PTH) were determined for all the puerpera. Using the blind envelope method, the postpartum women were randomized into groups: group I received cholecalciferol 400 IU and calcium carbonate 1000 mg after delivery for 6 months; group II received cholecalciferol 900 IU and calcium carbonate 1000 mg after delivery for 6 months. Blood sampling was performed over time to assess the levels of 25(OH)D, PTH, calcium, phosphorus, and magnesium.
 Results. In group I after childbirth, the initial level of 25(OH)D in the blood serum was 22.46 4.35 ng/ml, which corresponds to vitamin D insufficiency. An increase in 25(OH)D level by 3.56 ng/ml was observed after 3 months from the start of taking cholecalciferol 400 IU. After 6 months, the level of 25(OH)D reached normal values in 20% of women (p = 0.0001). In group II after childbirth, the initial level of 25(OH)D in the blood serum was 20.64 5.37 ng/ml, which corresponds to vitamin D insufficiency. An increase in 25(OH)D level by 7.60 ng/ml was observed after 3 months from the start of taking cholecalciferol 900 IU. After 6 months, the level of 25(OH)D reached normal values in 56% of women, while the average level of 25(OH)D in these women corresponded to its normally low values. The levels of PTH, calcium, phosphorus, and magnesium remained within the reference values in both groups; however, there was an increase in PTH concentration 6 months after delivery, which may indicate that the cholecalciferol dose is insufficient to stabilize PTH.
 Conclusion. Vitamin D deficiency and insufficiency occurred in 80-97 % of those examined after delivery. The use of prophylactic doses of cholecalciferol has a positive effect on calcium-phosphorus metabolism; however, they are not sufficient to stabilize PTH level. The cholecalciferol dose of 400 IU is insufficient to normalize the level of 25(OH)D within 6 months of administration. The cholecalciferol dose of 900 IU leads to normally low values of 25(OH)D in 56 % of women after 6 months of administration, but this does not stabilize PTH level either.

Study of Phobic Manifestations and Anxiety in Patients with Coronary Heart Disease after Myocardial Infarction in View of Tasks of Psychological Rehabilitation

The study of the psycho-emotional features of patients with coronary heart disease (CHD) is important for the development of psychological rehabilitation measures. In particular, it is necessary to take into account the specifics of the experienced fears and anxiety states which can be manifested in patients after myocardial infarction (MI). Negative psycho-emotional experiences are known to influence the course and prognosis of the disease. Identification of the structure of phobic manifestations, anxiety and personal characteristics of patients is appropriate for optimizing psychodiagnostics and psychocorrection. The present research is aimed at studying the characteristics of phobic manifestations and the structure of anxiety in patients with coronary heart disease (CHD) after myocardial infarction (MI), considering the dominant state, indicators of quality of life and personal characteristics. In the course of the present study 67 patients were surveyed with gender distribution of 12 women (18%) and 55 men (82%): patients of the Almazov National Medical Research Centre of the Ministry of Health of the Russian Federation who had a history of myocardial infarction (up to 1 year) and had undergone myocardial revascularization. The average age of the patients was 58.95 years. Clinical interview and psychological testing (Dominant State Determining Method, Integrative Test of Anxiety, The 36-Item Short Form Health Survey (SF-36), The Big Five Personality Test) were used. In patients with CHD after MI with substantial fears the most frequently detected phobic manifestations are the fear of physical activity and the fears associated with the disease itself. In the group of patients with the presence of phobic manifestations more pronounced indicators of anxiety, lower indicators of quality of life (QoL) and emotional stability in the structure of personal characteristics were noted. When planning psychological rehabilitation for patients with CHD who have undergone MI, it is important to consider the likelihood of anxiety and phobic manifestations.

Psychosocial Status of Patients with Chronic Heart Failure Awaiting Heart Transplantation

A pilot study of psychosocial status of 80 patients (85% males) with terminal chronic heart failure (CHF), during the preparation for heart transplantation (HT) has been carried out in the Almazov National Medical Research Centre. The correlation of psychological, medical, biological and socio-demographic characteristics of patients as well as the dynamics of patients’ emotional state (anxiety and depression) during a long cardiology hospital stay (4 measurements over half a year) has been studied. The authors’ structured interview and a set of psychodiagnostic methods (“Index of General Well-being”, “Brief neuropsychological examination of cognitive sphere”, depression scale (SDS), scale of anxiety (STAI), personality questionnaire BIG-V) have been used in the study. For mathematical and statistical data processing the following methods included in the software package SPSS v. 20.0 have been used: the Pearson’s chi-squared test (χ2), the Mann - Whitney U test, the Spearman and Pearson correlations, and ANOVA. The results revealed the absence of clinically significant signs of depression, cognitive impairment, personality and system of significant relationships in the majority of patients at the first stage of the study (upon admission into hospital). The exception was the increased level of situational anxiety (M ± m = 43.2 ± 7.1). The study of the dynamics of the emotional state of patients reflected a systematic increase in the average group indices of the depression scale (upon admission M ± m = 46.9 ± 6.7; after 2 months M ± m = 48.9 ± 7.4; after 4 months M ± m = 51.1 ± 7.6; after 6 months M ± m = = 52.6 ± 7.5), as well as a decrease in the level of situational anxiety at the second stage of the study compared with the first and a further increase starting from the second period: after 2, 4, 6 months of the stay in hospital, respectively: M ± m = 41.3 ± 5.2; M ± m = 46.7 ± 6.8; M ± m = 50.8 ± 7.9). It was revealed that the level of situational anxiety at the second (F = 6.18; p < 0.05) and the third (F = 4.11; p < 0.05) stages of treatment is significantly higher in the patients after myocardial infarction(s). Also, the level of situational anxiety is higher at the first (F = 4.00; p < 0.05) and third (F = 3.68; p < 0.05) stages of hospitalization of the patients who have rare meetings with relatives as compared to the patients who are often visited by their relatives. The results reflect the psychosocial potential of patients waiting for HT, and may have a prognostic significance in relation to adherence to treatment in the postoperative period, which, in turn, largely determines the survival of patients.