[Transthyretin amyloid cardiomyopathy. Features of histological diagnosis: study design].

AIM: To compare efficiency and specific features of transthyretin amyloid staining by different histological dyes and thus to assess their suitability for diagnostic purposes. MATERIALS AND METHODS: Samples of left and right heart ventricles were taken from patients over 70 years-old of both genders (n=10) with immunohistochemically verified transthyretin amyloidosis (ATTR). All samples were stained with Congo red, Alcian blue, toluidine blue and methylene violet. RESULTS: Specificity and sensitivity of Congo red staining was comparable to those of immunohistochemical staining. For verification of amyloid presence after Congo red staining one could use fluorescent microscopy instead of polarization microscopy. It allows a more accurate diagnosis of amyloidosis. Confocal microscopy with spectral unmixing improves detection sensitivity of amyloid by elimination of background fluorescence of muscle tissue and autofluorescence of lipofuscin. Alcian blue staining gives the same result as Congo red. In addition, its less labor-intensive and free of false-positive and false-negative results caused by final processing of slide preparation. Toluidine blue and methylene violet develop metachromatic staining upon binding to transthyretin fibrils, likely due to specific biochemical features of these fibrils. CONCLUSION: The most reliable method for histochemical diagnosis of ATTR is the Congo red staining with subsequent analysis using fluorescence or confocal microscopy. For diagnostic screening, the use of Sodium sulphate-Alcian blue staining method is highly promising. Metachromatic stains are less effective for ATTR diagnosis.

[Practical guidelines for the diagnosis and treatment of transthyretin amyloid cardiomyopathy (ATTR-CM or transthyretin cardiac amyloidosis)].

This paper summarizes the data from updated international protocols and guidelines for diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM). The invasive and non-invasive diagnosis techniques and their combinations are briefly reviewed; the evidentiary foundations for each diagnostic option and tool are analyzed. The paper describes a customized algorithm for sequential diagnosis and differential diagnosis of patients with suspected ATTR-CM with allowance for the combination of clinical signs and diagnostic findings. Along with the awareness of primary care providers about the red flags of the disease and visualization criteria, as well as providing information to the patients about the possibility of performing therapy of ATTR amyloidosis and the risks of delayed diagnosis, the proposed algorithm enables timely patient routing and prescribing specific treatment.

[Informativeness estimation for the main clinical and laboratory parameters in patients with severe COVID-19].

AIM: To conduct a retrospective assessment of the clinical and laboratory data of patients with severe forms of COVID-19 hospitalized in the intensive care and intensive care unit, in order to assess the contribution of various indicators to the likelihood of death. MATERIALS AND METHODS: A retrospective assessment of data on 224 patients with severe COVID-19 admitted to the intensive care unit was carried out. The analysis included the data of biochemical, clinical blood tests, coagulograms, indicators of the inflammatory response. When transferring to the intensive care units (ICU), the indicators of the formalized SOFA and APACHE scales were recorded. Anthropometric and demographic data were downloaded separately. RESULTS: Analysis of obtained data, showed that only one demographic feature (age) and a fairly large number of laboratory parameters can serve as possible markers of an unfavorable prognosis. We identified 12 laboratory features the best in terms of prediction: procalcitonin, lymphocytes (absolute value), sodium (ABS), creatinine, lactate (ABS), D-dimer, oxygenation index, direct bilirubin, urea, hemoglobin, C-reactive protein, age, LDH. The combination of these features allows to provide the quality of the forecast at the level of AUC=0.85, while the known scales provided less efficiency (APACHE: AUC=0.78, SOFA: AUC=0.74). CONCLUSION: Forecasting the outcome of the course of COVID-19 in patients in ICU is relevant not only from the position of adequate distribution of treatment measures, but also from the point of view of understanding the pathogenetic mechanisms of the development of the disease.

[AL-amyloidosis with cardiac involvement. Diagnostic capabilities of non-invasive methods].

There are presented the literature data and a description of the clinical course of the disease in isolated/predominant cardiac amyloidosis. Amyloid cardiomyopathy is the most common phenocopy of hypertrophic cardiomyopathy. The modern possibilities of non-invasive diagnostics using osteoscintigraphy for the differential diagnosis between amyloid cardiomyopathy caused by AL- and transthyretin amyloidosis are described in detail.

[Characterisation of circulating microRNA-21 levels in patients with hypertrophic cardiomyopathy].

AIM: To study the levels of circulating microRNA-21 in patients with hypertrophic cardiomyopathy (HCM) of different ages. MATERIALS AND METHODS: The study included 49 patients with HCM. The proportion of females was 55.1%, males 44.9%. The average age was 50 [32; 65] (from 19 to 86 years). The control group for microRNA-21 included 44 healthy individuals, respectively, matched by the age and sex with the studied patients. Patients was made in accordance with the recommendations of the European society of cardiology. Plasma microRNA expression was determined by PCR with reverse transcription and real-time detection of results. The relative level of gene expression was calculated in accordance with the standard procedure 2-Ct. RESULTS: Septal wall thickness at end diastole has a significant negative correlation with age in patients with HCM (r=-0.56; р0.001). PWTd (posterior wall thickness at end diastole) has a significant positive correlation with age in patients with HCM (r=0.67, р0.001). The level of circulating microRNA-21 in plasma is higher in patients with HCM compared to healthy individuals (5.28 [2.64; 13.96] and 0.84 [0.55; 1.23], respectively; p0.001). Significantly higher levels of microRNA-21 were found in young patients aged from 19 to 45 years with the symptomatic course of HCM (36.76 [5.66; 42.22]) compared to patients with asymptomatic course 45 years of age (2.81 [1.45; 5.28]; p0.002) and symptomatic patients 45 years (3.88 [2.16; 8.63]; p0.002).) The calculated risk of SCD was significantly higher in young symptomatic patients with HCM (6.01 [3.64; 9.67]) compared to patients with asymptomatic course 45 years (2.41 [1.21; 3.89]; p0.001) and symptomatic patients 45 years (2.56 [1.67; 4.41]; p0.001). CONCLUSION: The level of circulating microRNA-21 is significantly in patients with HCM compared to control group. The maximum level of circulating microRNA-21 was detected in patients with symptomatic course of HCM at the age of 45 years.

[Left ventricular non - compaction: contemporary view of genetic background, clinical course, diagnostic and treatment].

This review highlights and discusses recent advances in understanding left ventricular non - compaction (LVNC). Clinical profile, prognosis and even diagnosis are still a great challenge faced by the world. The population prevalence of left ventricular non - compaction remains unknown. High variability of clinical manifestations, genetic heterogenity with overlap of different phenotypes, variability of hereditary patterns suggests that LVNC seems to be rather an isolated trait or a part of phenotypic expression of different cardiac diseases or complex genetic syndromes.

[Hypertrophic cardiomyopathy: modern aspects of pharmacologic treatment].

This article discusses recent advances in understanding genetic basis and classification of hypertrophic cardiomyopathy. Here, we review pharmacologic treatment strategies and new developments in disease - specific management of HCM.

[The problem of multiple somatic and/or psychiatric pathology basic concepts and prevalence]. / Problema mnozhestvennoi somaticheskoi i/ili psikhicheskoi patologii.

The literature of the last decades shows the growing interest to multiple pathologies in medicine including psychiatry and neurology. Multiple pathology is often determined as multimorbidity or comorbidity. Multiple pathology is a common phenomenon, which is the rule rather than the exception. In the medical care system, it is burden for the patient and for the physician in clinical, organizational and economic aspects. The review addresses all these issues in the aspect of terminology and prevalence.

[Transthyretin amyloidosis in a cohort of old and very old patients with chronic heart failure].

BACKGROUND: Life-time diagnostics of wild type transthyretin amyloidosis (ATTR(wt)-amyloidosis) is virtually absent, even though ATTR(wt)-amyloidosis is an underestimated cause for morbidity and mortality, particularly in the older age group. AIM: To study incidence, demographic characteristics, and morpho-functional features of ATTR(wt)-amyloidosis in patients with FC IV CHF and LV hypertrophy > 15 mm according to autopsy data. MATERIALS AND METHODS: Postmortem reports were retrospectively analyzed for patients (n=141; 19 % males, 81 % females) of cardiology departments aged ≥69 with the underlying CHF syndrome. From all formalin-fixed fragments of the myocardium embedded in paraffin were prepared 5-7 mkm cuts, which were stained with Congo red (Sigma, USA) and viewed under normal and polarized light. Immunohistochemical analysis was also performed using antibodies to AA-amyloid, transthyretin, kappa and lambda-light chains of immunoglobulins. RESULTS: deposits were found in both old and very old persons aged 91.25±9.67, mostly in women due to shorter life span of men. In different FCs associated with LV hypertrophy, according to autopsy data amyloid deposits were observed in virtually every fifth deceased (21 % of cases). The amount of myocardial amyloid deposits was generally small (56 % of cases had (+) and 27 % had (++) amyloid deposits); 17 % of cases had considerable amyloid deposits (7 % had (+++) and 10 % had (++++)). The presence of amyloid deposits did not influence indexes of myocardial hypertrophy, such as ventricular septum thickness, LV posterior wall thickness, and heart mass. In the presented cases we observed focal amyloid deposition in the myocardium typical for old age-related amyloidosis; in 97 % cases, amyloid was located in the interstitium, around cardiomyocytes and in 3 % of cases - exclusively around blood vessels. CONCLUSION: ATTR (wt)-amyloidosis was detected in every fifth patient in the old and very old cohort, primarily in women (83 %), and was not diagnosed during the life time. Characteristic morphological manifestations of ATTR(wt)-amyloidosis were focal amyloid deposits mostly in the myocardial interstitium.

[Suicidality in epilepsy: epidemiology and clinical risk factors]. / Suitsidal'nost' pri épilepsii: épidemiologicheskie aspekty i faktory riska.

The results of studies on the prevalence of suicidal behavior in patients with epilepsy are discussed in the article. The reasons for the high incidence of suicides among patients with epilepsy are given, with special attention paid to social, demographic, clinical and pathopsychological risk factors. Existing gaps in our knowledge about suicidal behavior in patients with epilepsy are analyzed.

Intravital and postmortem diagnostics of myocardial hypertrophy of the left ventricle:identity or convention?

AIM: The aim of the study is to assess the compliance of the results of electrocardiographic (ECG) and echocardiographic diagnostic methods of hypertrophy of left ventricular myocardium (LVH) with the postmortem finding of measurement of left ventricular myocardium mass (LVM). MATERIALS AND METHODS: We examined the data of intravital study of anthropometric measurements [age, height, weight, body mass index (BMI)], instrumental results [12-lead ECG, EchoCG], as well as the postmortem finding (direct measurement of LVM at autopsy) in 15 patients of general therapy department. While analyzing ECG we studied as conventional ECG criteria for the detection of LVH as well as the author's own criteria based on two models (regression and discriminant analyses), including voltage, sex and age criteria. Echocardiographic diagnostic method used to calculate LVM (according to ASE formula) and left ventricular mass index (LVMI). Postmortem finding of LVM was carried out according to the standard measurement method. According to the absence of the single conventional postmortem finding of measurement of LVH, we considered three different variants of the postmortem finding of LVH: the criterion of K. Bove et al. (CB); the criterion of A.M. Lifshitz, also called ventricular index (VI) and the criterion of P. Casale - the left ventricular mass index at autopsy (LVMI). RESULTS: Conventional ECG criteria for the detection of LVH showed high specificity (71-100%) using any method of the postmortem finding of measurement, but were characterized by extremely low sensitivity (0-37.5%). Their overall diagnostic accuracy was higher on using K. Bove or A.M. Lifshitz criteria (40-66.7%) and low - on using the criterion of P. Casale (13.3-40%). The author's ECG criteria were less specificity (50-100%) and had higher sensitivity (54-75%), and their diagnostic accuracy remained higher and showed small dependence on the method of the postmortem finding of measurement of LVH (60-66.7%). CONCLUSION: Usually the ECG criteria to diagnose left ventricular hypertrophy were expectedly showed low sensitivity using any method of the postmortem finding of measurement. Meanwhile, the author's own ECG criteria associated with the most sensitive electrocardiographic characteristics to LVH and sex and age-specific indexes of the examined patients exceeded the conventional ECG criteria in sensitivity and diagnostic accuracy.

[Subcortical laminar heterotopia 'double cortex syndrome']. / Podkorkovaia laminarnaia geterotopiia (sindrom 'dvoinoi kory').

This article presents a clinical case of a 29-year-old patient with 'Double cortex syndrome' with epilepsy, intellectual and mental disorders. Subcortical band heterotopia is a rare disorder of neuronal migration. Such patients typically present with epilepsy and variable degrees of mental retardation and behavioral and intellectual disturbances. The main diagnostic method is magnetic resonance imaging (MRI).

CHARACTERISTICS OF AMYLOID DEPOSITS DETECTED IN THE INTERNAL ORGANS OF mdx MICE.

The dystrophin-deficient mdx mouse is the most commonly used experimental model of Duchenne muscular dystrophy (DMD). Although the amyloid has been shown in the muscle biopsies of patients with different types of muscular dystrophies, there are no data on the amyloid accumulations in the biopsy of DMD patients or mdx mouse. Therefore, the aim of the present study was to testify the hypothesis of probable accumulation of amyloid in the visceral organs of mdx mouse. Specimens of myocardium, kidneys, and liver of male and female mdx mice aged from 2 months to 1.5 years (n = 9) were used in the study. The histochemical staining with Congo red demonstrated amyloid accumulations in the studied organs of the mdx mice. Morphology and localization of the found accumulations were described in details and analyzed. The mass-spectrometric study determined the vitronectin and apolipoprotein A-II as the most probable components of the amyloid accumulations in the mdx mouse.

[RAPID METHOD OF THE AMYLOID STAINING WITH CONGO RED FOR LIGHT AND FLUORESCENCE MICROSCOPY].

The aim of the present study was to optimize the histochemical method of amyloid staining using Congo red. The study was performed on specimens of the myocardium of left ventricle of the heart obtained at autopsy from the patients with amyloidosis of myocardium diagnosed postmortem. It was shown that a positive impact on the quality of the staining of amyloid is provided by a procedure of pre-heating the slides in the liquid, especially at an acidic pH. The staining protocol was developed allowing to obtain preparations characterized by high-contrast staining of amyloid at light microscopic level and by high intensity of its fluorescence. The advantage of the protocol presented is also a significant reduction in the total duration of staining, an increase in stability of the specific staining of amyloid and the absence of nonspecific background staining.

[RAPID METHOD OF THE AMYLOID STAINING WITH CONGO RED FOR LIGHT AND FLUORESCENCE MICROSCOPY].

The aim of the present study was to optimize the histochemical method of amyloid staining using Congo red. The study was performed on specimens of the myocardium of left ventricle of the heart obtained at autopsy from the patients with amyloidosis of myocardium diagnosed postmortem. It was shown that a positive impact on the quality of the staining of amyloid is provided by a procedure of pre-heating the slides in the liquid, especially at an acidic pH. The staining protocol was developed allowing to obtain preparations characterized by high-contrast staining of amyloid at light microscopic level and by high intensity of its fluorescence. The advantage of the protocol presented is also a significant reduction in the total duration of staining, an increase in stability of the specific staining of amyloid and the absence of nonspecific background staining.

[STEM CELLS PLAY NO CONSIDERABLE ROLE IN CARDIOMYOCYTE REPOPULATION OF ADULT HUMAN HEART].

There are two viewpoints concerning cardiac regeneration. One assumes that the myocardium of an adult human heart has a weak regenerative capacity. According to another, myocardium can renew at a high rate due to the presence of resident stem cells. This study was aimed to test the role of stem cells in myocardium repopulation in adult humans of different age by examining the distribution of cardiomyocytes as to their size and ploidy. Cytofluorimetry and interferometry were used to determine the dry weight, volume and ploidy of myocytes isolated from the left ventricle of the normal heart of 12 men aged 20-30 years (n = 7) and 40-50 years (n = 5). Dry weight of cardiomyocytes made up 6906 ± 182 pg (10(-12) g) aged 20-30 years and 9126 ± 263 pg in men aged 40-50 years. There were no cells with an intermediate volume between amplifying and mature myocytes. The number of candiomyocytes in the left ventricle made up (3.18 ± 0.05) x 10(9) cells in the age group 20-30 years and (2.06 ± 0.6) x 10(9) cells in the age group 40-50 years. Most of the myocyte population was represented by mononucleate cells with tetraploid nuclei (41.3%). Proportion of myocytes of different ploidy classes did not change in the interval from 20 to 50 years. Our results strongly suggest that stem cells of the heart are not involved in the regeneration of human myocardium during aging. The function of the aging heart is mostly compensated by the hypertrophy of the remaining myocytes.

[The «Dialogue¼ or the «Conflict of interests¼ between psychiatrists and neurologists: results of a focus group interview]. / «Dialog¼ ili «konflikt interesov¼ psikhiatrov i nevrologov (rezul'taty fokusirovannogo gruppovogo interv'yu).

OBJECTIVE: To determine the characteristics of interdisciplinary interactions between neurologists and psychiatrists in treatment of anxiety and depressive disorders, including prognostic aspects, and the responsibility of the doctor. MATERIAL AND METHODS: A scenario of an interview included similar questions related to diagnosis, examination and the treatment of patients with anxiety and depressive disorders. Ten neurologists and 10 psychiatrists have completed the interview. RESULTS: The characteristics of the management of patients, the absence of the joint management and interactions, subjective adherence to definite drugs and methods were shown. CONCLUSION: The intersection of professional interests for both specialties because of the similarities of the groups of patients in the conditions of concurrent interdisciplinary interactions makes up the reason for the conflict between them. An introduction of an interdisciplinary model of interactions between the physicians and specified continual education in adjacent fields of medicine will resolve this situation.

[The role of autonomic dysfunction in pathogenesis of irritable bowel syndrome].

This article presents the results of a comparative study of autonomic disorders in patients with differernt types of irritable bowel syndrome (IBS). We used several clinical and instrumental methods, including the Veyn questionnaire, Kerdo autonomic index, skin sympathetic response and heart rate variability analysis. The results show a prevalence of sympathetic tone in all groups of patients (more pronounced in IBS with constipation), as well as an elevated stress index and decreased arterial baroreflex sensitivity. In the IBS with diarrhea group there was a reliable increase of power spectral density alvery low frequency and a lowered respiratory sinus arrhythmia.

[Nuclear lamins regulate osteogenic differentiation of mesenchymal stem cells].

Nuclear lamins are the major proteins of nuclear envelope and provide the strength of nuclear membrane as well as the interaction of extra-nuclear structures with components of cell nucleus. Recently, it became clear that lamins not only play a structural role in the cell, but could also regulate cell fate, for example lamins could influence cell differentiation via interaction with components of the Notch signaling pathway. Human mutations in LMNA, encoding lamin A/C lead to diseases commonly referred to as laminopathies. Different mutations cause tissue specific phenotypes that affect predominantly a tissue of mesenchymal origin. The nature of this phenomenon, as well as the mechanisms by which lamins regulate cell differentiation remain poorly understood. The aim of this study was to investigate the effect of different mutations of the LMNA on human mesenchymal stem cell (MSC) osteogenic differentiation, and to explore a possible interaction of lamins and Notch signaling pathway. We modified human MSC with mutant LMNA bearing known mutations with tissue specific phenotype associated with different laminopathies. We have shown that mutations associated with different diseases have different effects on the efficiency of MSC osteogenic differentiation and on the expression of specific osteogenic markers SPP1, IBSP and BGLAP. We have also shown that one of the mechanisms involved in the regulation of MSC differentiation may be an interaction of lamins A/C with components of Notch signaling.

[A feedback method in clinical practice].

The authors reviewed a history of development of a feedback method, its physiological basis, essence, methodological aspects of its practical application and factors related to its effectiveness. This method may be used in studies of basic functional disorders, syndromes and diseases. Perspectives of its using in restorative and preventive health care are considered.