THE ROLE OF ENDOMYOCARDIAL BIOPSY IN DIAGNOSTICS OF INFLAMMATORY MYOCARDIUM DISEASES

Literary review focuses on the role of endomyocardial biopsy in diagnostics of inflammatory diseases of myocardium. The article discusses indications for biopsy, its informativity, and diagnostical value; the list of possible complications is provided, the clear algorithm defined for histological, histochemical, immunehistochemical investigation of the specimens with differential diagnosis of the pathological findings. The review provides with the analysis of molecular-biological methods, that are in use for verification of myocarditis etiology, recent morphological criteria provided for different types of the disease

Rationale for endomyocardial biopsy in the diagnosis of heart disease in children and adults

Endomyocardial biopsy (EMB) is the method of choice for diagnosing a wide range of myocardial diseases.Aim. To assess the rationale for diagnostic EMB in children and adults.Material and methods. Morphological and statistical analysis of 2803 diagnostic EMBs in adults (n=811) and children (n=83), including those in heart transplantation (n=1909), was carried out.Results. In 231 (28%) cases, adults were diagnosed with myocarditis, of which in 6 patients — granulomatous, in 5 — eosinophilic and in 6 — lymphocytic-macrophage myocarditis after coronavirus infection. In children, myocarditis was found in 22 cases (27%). Arrhythmogenic right ventricular dysplasia took the second place in detection rate in children and adults. Immunohistochemical study revealed viral envelope protein 1 (VP1) antigen of enteroviruses in one third of myocarditis cases, and in half — other cardiotropic viruses. Dotted dystrophin expression was observed in myocarditis. A correlation was established between the perforin expression and myocarditis presence (Pearson χ2=27,8; Fisher's exact test=27,3; p=0,01).Conclusion. Analysis of diagnostic EMB results confirmed its rationale in adults and children not only for heart transplantation, but also for identifying cardiac pathology, including for myocarditis diagnosis. It has been shown that immunohistochemical study with antiviral antibodies can be considered as an alternative method for detecting viral infection. An immunohistochemical analysis for perforin and dystrophin can be recommended as additional morphological markers of myocarditis

Congenital hyperinsulinism in newborns and young children: the state of the problem and the results of surgical treatment

Congenital hyperinsulinism causes irreversible damage to the cerebral cortex with subsequent disability in children. The article presents the features of etiopathogenesis, clinical picture of the disease. The histological variants of pancreatic lesions are analyzed in detail. The principles of correct diagnosis are formulated. A new in Russia method for the preoperative determination of the histological form of the disease, which is carried out at the y, Almazov National Medical Research Centre since 2017, – PET/ CT with 18F-DOPA, explained the biochemical basis of its clinical application and the examination technique. The principles of the selection of drug therapy with possible complications, the need for an adequate assessment of its effectiveness are described. If it is impossible to achieve a stable target euglycemia without the need for intravenous glucose infusion, surgical correction of the disease is indicated. In schematic drawings and intraoperative photographs, approaches to surgical treatment are described, the stages of operations and possible complications are clearly disassembled. The results of surgical interventions at the N.N. V.A. Almazov for 01.2017–02.2021, where 39 children with congenital hyperinsulinism were operated on. According to PET/CT with 18F-DOPA, 15 diffuse and 24 focal forms were diagnosed. After surgery, in 12 (31%) patients, a diffuse lesion of the gland was confirmed, in 23 (59%) – a focal nature of the lesion, in 4 (10%) – an atypical form was diagnosed intraoperatively. Of 39 children, 36 (92%) have complete relief of hyperinsulinism, a significant improvement in psychomotor development, of which 9 (23%) need insulin replacement therapy with minimal dosages, these are 8 children with a diffuse form of the disease and 1 child with an atypical one. Intraand postoperative complications were not observed. Thus, partial pancreatectomy for focal forms, subtotal for atypical and near total for diffuse forms, can cope with hypoglycemia due to congenital hyperinsulinism and prevent damage to the central nervous system of newborns and infants

Импульсный режим воздействия полупроводникового лазера с длиной волны 445 нм в фонохирургии: экспериментальное исследование

The study presents the results of an experimental study devoted to the choice of the most optimal mode of pulsed contact laser exposure of semiconductor laser with a wavelength of 445 nm in phonosurgery, which implies maximum preservation of anatomically and functionally significant structures of the larynx combined with a radical approach to the pathological process. From the standpoint of the mucoundular theory of voice formation, wave-like oscillations of the vocal folds are possible due to the mobility of the cover layer of the vocal fold (epithelium, superficial layer of the lamina propria) relative to its body (deep layer of the lamina propria, vocal muscle). Thus, any injury at the level of the integumentary layer is associated with the risk of excessive scarring and loss of the ability to wave-like sliding. Pig vocal folds, according to a number of authors, have a structure similar to human ones in terms of both histological structure and acoustic parameters, which justifies the rationality of their use as an experimental model. In a series of experiments using a 445 nm laser, contact pulsed impacts on a biological model were carried out with pulse durations of 10, 20, 50, and 100 ms, followed by evaluation of the following parameters based on the data of histological sections: the depth and width of the ablation crater, the width of the zone of lateral thermal damage. Thus, the most optimal for phonosurgical interventions modes of pulsed laser exposures with a wavelength of 445 nm are described.В работе представлены результаты экспериментального исследования, посвященного выбору наиболее оптимального режима импульсного контактного лазерного воздействия полупроводникового лазера с длиной волны 445 нм в хирургии голосовых складок (фонохирургии). Эндоларингеальная фонохирургия подразумевает собой максимальную сохранность анатомически и функционально значимых структур гортани в сочетании с радикальностью в отношении патологического процесса. С позиции мукоундулярной теории голосообразования волнообразные колебания голосовых складок возможны за счет подвижности покровного слоя голосовой складки (эпителий, поверхностный слой собственной пластинки) относительно ее тела (глубокий слой собственной пластинки, голосовая мышца). Таким образом, любая травматизация на уровне покровного слоя сопряжена с риском его избыточного рубцевания и потерей способности к волнообразному скольжению. Голосовые складки свиньи, по данным ряда авторов, имеют схожее строение с человеческими как по гистологическому строению (толщина слоев, соотношение коллагеновых и эластических волокон), так и по акустическим параметрам, что обосновывает рациональность их использования в качестве экспериментальной модели. В серии экспериментов с использованием лазера 445 нм проведены контактные импульсные воздействия на биологическую модель с длительностью импульсов 10, 20, 50 и 100 мс с последующей оценкой по данным гистологических срезов следующих параметров: глубина и ширина кратера абляции, ширина зоны бокового термического повреждения. Таким образом, описаны наиболее оптимальные для фонохирургических вмешательств режимы импульсных воздействий лазера с длиной волны 445 нм

Effectiveness of immunosuppressive therapy for lymphocytic myocarditis according: data from actual clinical practice

Aim. To compare the effectiveness of standard heart failure therapy with and without combined immunosuppressive therapy in patients with documented lymphocytic myocarditis (LM) based on data from actual clinical practice.Material and methods. This observational study included 70 patients with documented LM, 40% (n=28) of whom received immunosuppressive therapy. All patients underwent standard echocardiographic and laboratory investigations, endomyocardial biopsy with histological, immunohistochemical and molecular genetic analysis. Contrast-enhanced cardiac magnetic resonance imaging was performed in 74% of patients. All patients received standard therapy for heart failure at baseline.Results. The groups did not differ in demographic and echocardiographic characteristics. The appointment of immunosuppressive therapy was accompanied by an increase in ejection fraction by 12,2% compared to 6,4% (p=0,02). There were no significant differences in combined endpoints (survival and the need for heart transplantation) depending on therapy regimen (log-rank p=0,97).Conclusion. The prognosis of patients with chronic LM depends on the process activity, the severity of impaired hemodynamics and ventricular arrhythmias, as well as on the presence of persistent viral infection. Compliance with patient selection algorithm before prescribing immunosuppressive therapy is associated with the improvement in myocardial global contractility

Clinical, morphological and molecular biological examination of the myocardium in COVID-19 patients

The presence of coronavirus-associated myocarditis remains controversial despite elevations in cardiac troponin and natriuretic peptide in many patients.Aim. To assess the morphological changes in the myocardium of patients who died due to coronavirus disease 2019 (COVID-19) and compare them with the intravital level of cardiac biomarkers.Material and methods. A total of 420 hospital charts and 77 autopsies of those who died from COVID-19 were analyzed. In 15 of 77 cases (19%) with histologically suspected myocarditis, an immunohistochemical examination of the myocardium with antibodies to CD3, CD45, CD8, CD68, CD34, Ang1, VWF, VEGF, HLA-DR, MHC1, C1q, VP1 of enteroviruses was performed, and in 8 patients with immunohistochemically confirmed myocarditis (10%) — polymerase chain reaction for SARS-CoV-2.Results. Hemorrhage, intramural thrombosis, necrosis of non-coronary origin, myocardial infarction and lymphocytic myocarditis were detected in 43%, 10%, 17%, 19% and 10% of cases, respectively, without coronavirus N and E gene sequences in the myocardium. Dysplasia, hyperplasia and hypertrophy of the vascular endothelium, expression of Ang1, VWF, VEGF, MHC1, C1q, VP1 of enteroviruses were determined in 100, 100, 87, 100, 75 and 62% of cases of myocarditis, respectively. There were no significant correlations between inflammatory biomarkers and myocarditis.Conclusion. The main morphological manifestation of COVID-19 in the myocardium is the so-called endotheliitis with dysplasia and endothelial activation, leading to hemorrhages, intramural thrombosis and necrosis. There is no convincing evidence of a direct involvement of coronavirus in myocarditis induction

Neurodevelopmental outcomes and neurophysiological parameters in children with congenital hyperinsulinism

Introduction. Congenital hyperinsulinism is a rare group of genetic disorders resulting in persistent hypoglycemia which can lead to delay of neurodevelopment.Aim. To assess psychomotor development and certain neurophysiological parameters of children treated for congenital hyperin-sulinism.Materials and methods. This prospective and retrospective cohort study included 73 infants with congenital hyperinsulinism admitted to the National Almazov Research Centre from 2017 to 2021. All subjects underwent standard clinical examination including physical and neurological assessment as well as 18F-DOPA PET/CT, genetic testing, electroencephalography. Developmental screening was performed using “Ages and Stages” questionnaire in 33 subjects. Possible risk factors for neurode-velopmental sequelae due to hypoglycemia were analyzed.Results and discussion. Normal neurodevelopment in general was observed in 23 subjects (69%), 10 patients had developmental delay. Focal form of CHI had the greatest modifying effect on positive neurodevelopmental outcome in general. Individual skills such as communication, fine and gross motor, problem solving in children with a focal form of CHI were significantly better than those with a nonfocal forms. Age of manifestation and verification of the disease, the minimum level of glycemia and the maximum level of glucose utilization did not significantly affect the formation of either individual skills (with the exception of gross motor skills) or psychomotor development in general. The indicators of gross motor skills in children with a lower level of glucose utilization turned out to be significantly better. Kaplan-Meier survival analysis showed that the alpha rhythm appearance was significantly earlier in patients with a focal form of CHI and with earlier verification of the diagnosis (<28 days of life).Conclusion. The focal form of the disease has the greatest modifying effect on the positive outcome of the psychomotor development. The age-appropriate gross motor skills were observed more often in the group of children with low glucose disposal rates. The association of the early occurrence of the alpha rhythm with the focal form of congenital hyperinsulinism, as well as with the early verification of the disease, was found

НЕДИФФЕРЕНЦИРОВАННАЯ ПЛЕОМОРФНАЯ САРКОМА СЕРДЦА: ВОЗМОЖНОСТИ СОВМЕЩЕННОЙ ПОЗИТРОННОЙ ЭМИССИОННОЙ И РЕНТГЕНОВСКОЙ КОМПЬЮТЕРНОЙ ТОМОГРАФИИ ДЛЯ ДИАГНОСТИКИ МЕСТНОГО РЕЦИДИВА ОПУХОЛИ И ОТДАЛЕННЫХ МЕТАСТАЗОВ (КЛИНИЧЕСКОЕ НАБЛЮДЕНИЕ)

The paper presents a case of a 52-year-old female patient with pleomorphic malignant fibrous histiocytoma/ undifferentiated pleomorphic sarcoma of the left atrium. One year after surgical resection of the primary tumor, microsurgical removal of the right parietal lobe metastatic tumor was performed. PET/CT with 11C-methionine and 18F-FDG performed 2 months after surgical resection of brain metastasis revealed local recurrence of sarcoma in the left atrium and left lateral ventricle metastases. This clinical case demonstrates high diagnostic accuracy of PET/CT with 18F-FDG and 11C-methionine in detecting local recurrence of cardiac undifferentiated sarcoma, however, PET/CT with 11C-methionine appears to be superior to PET/CT with18F-FDG in detecting brain metastasis.Представлено клиническое наблюдение пациентки 52 лет с плеоморфной злокачественной фиброзной гистиоцитомой / недифференцированной плеоморфной саркомой левого предсердия. Через год после хирургического лечения первичной опухоли выполнено микрохирургическое удаление метастаза саркомы, локализованного в коре правой теменной доли головного мозга. При проведении ПЭТ/КТ с 11С-метионином и 18F-ФДГ через 2 мес после удаления метастаза головного мозга выявлен местный рецидив саркомы в левом предсердии и метастаз в области латеральной стенки левого бокового желудочка головного мозга. Данное клиническое наблюдение иллюстрирует высокую эффективность ПЭТ/ КТ с 18F-ФДГ и 11С-метионином в определении местного рецидива недифференцированной саркомы сердца. Следует отметить диагностическое преимущество ПЭТ/КТ с 11С-метионином в определении метастатического поражения головного мозга

Клинико-морфологическая дифференциальная диагностика форм врожденного гиперинсулинизма до этапа иммуногистохимического исследования залитых препаратов поджелудочной железы у детей

Introduction.Differential diagnosis of various forms of congenital hyperinsulinism (CH) is required at the stage of urgent histological examination, but the difference between the exo- and endocrine parts of the pancreas in frozen sections is visualized very poorly.The objective was to search for differential diagnostic criteria of focal and diffuse forms of CH, suitable for urgent histological examination.Methods and materials. Pancreatic surgery material from 25 children with CH, of which 15 cases of focal form (FCH) and 10 cases of diffuse (DСH), and autopsy material from 10 children without CH (K). Frozen and paraffin sections stained with hematoxylin-eosin and histochemical stains were made from the tissue of the pancreas. The number of endocrinocytes with large nuclei was estimated in 10 fields of view for each case.Results. The average proportion of endocrinocytes with large nuclei was significantly (p <0.01) higher compared to the control both with FCH (in the affected area) and DCH (FCH – (1.82±0.50) %, DCH – (4.68±1.66) %, K – (0.34±0.21) %). We found a tendency to detect a higher absolute number of cells with large nuclei in DCH ((4.95±1.24) DCH and (3.71±1.56) FCH). Staining with azure-eosin, picro Mallory and the PAS reaction gave unstable result, and staining with toluidine blue and May-Grunwald did not allow differentiating exo- and endocrine parts of the pancreas.Conclusion. An increase in the size of the endocrinocyte nuclei was the unsuitable criterion for the differential diagnosis of CH forms, and histochemical stains did not give a stable qualitative result. For urgent biopsy examination, new immunohistochemical methods are needed.Введение. Дифференциальную диагностику между различными формами врожденного гиперинсулинизма (ВГ) требуется проводить на этапе срочного гистологического исследования, но на замороженных срезах различие между экзо- и эндокринной частями поджелудочной железы (ПЖ) визуализируется очень плохо.Цель – поиск дифференциально-диагностических критериев очаговой и диффузной форм ВГ, пригодных для срочного гистологического исследования.Методы и материалы. Операционный материал ПЖ от 25 детей с ВГ, из них 15 случаев очаговой формы (ОВГ) и 10 – диффузной (ДВГ), и аутопсийный материал от 10 детей без ВГ (К). Из ткани ПЖ были изготовлены замороженные и парафиновые срезы, окрашенные гематоксилин-эозином и гистохимическими окрасками. Было оценено число эндокриноцитов с крупными ядрами в 10 полях зрения для каждого случая.Результаты. Средняя доля эндокриноцитов с крупными ядрами была статистически значимо (р<0,01) больше по сравнению с контролем как при ОВГ (в зоне поражения), так и при ДВГ (ОВГ – (1,82±0,50) %, ДВГ – (4,68±1,66) %, К – (0,34±0,21) %). Была выявлена тенденция к обнаружению бóльшего абсолютного числа клеток с крупными ядрами при ОВГ ((4,95±1,24) ОВГ и (3,71±1,56) ДВГ). Окрашивание азур-эозином, пикро Маллори и PAS-реакция давали непостоянный результат, а окраски толуидиновым синим и по Май – Грюнвальду не позволяли дифференцировать экзо- и эндокринные части ПЖ.Заключение. Критерий увеличения в размерах ядер эндокриноцитов непригоден для дифференциальной диагностики форм ВГ, а гистохимические окраски не дают стабильно качественного результата. Для срочного биопсийного исследования необходимы новые скоростные иммуногистохимические методики

ЦИТОМЕГАЛОВИРУСНАЯ ИНФЕКЦИЯ У РЕБЕНКА СО СПИНАЛЬНОЙ АМИОТРОФИЕЙ

This article describes a clinical case, representing the diagnostic difficulties. The baby of 4 months with bright neurological symptoms that appeared after vaccination, and coming with a diagnosis of "post-vaccination complications" in the survey diagnosed active cytomegalovirus infection and spinal muscular atrophy type 1. The role of the infective matter within the underlying disease was analyzed. В статье описан клинический случай, представлявший диагностические трудности. У ребенка 4-х месяцев с яркой неврологической симптоматикой, появившейся после проведения вакцинации, и поступавшего с диагнозом «поствакцинальное осложнение», в процессе обследования диагностирована активная цитомегаловирусная инфекция и спинальная амиотрофия 1 типа. Проанализирована роль инфекционного агента в течении основного заболевания.