Cardiac amyloidosis (amyloid cardiomyopathy) is a disease damage to the heart caused by extracellular amyloid deposition. In some cases, there may be local damage to the structures of the heart, for example, the atria; more often, heart damage is part of a systemic (generalized) pathology. Depending on the amyloid precursor protein, 36 types of amyloidosis are described, among which hereditary and acquired forms are distinguished. Cardiac amyloidosis is diagnosed 1) in the case of the amyloid infiltration in the myocardial bioptates or 2) in the case of non-cardiac amyloid deposition and the left ventricular wall thickening >12 mm without arterial hypertension and other reasons. The heart is most often affected in AL-, ATTR-, AA-, AANF-types of amyloidosis. Cardiac amyloidosis should be considered in patients with a heart failure with an unclear etiology, especially with preserved left ventricular ejection fraction, refractory to treatment, with proteinuria and CKD 4-5, in patients with idiopathic atrial fibrillation and conduction disturbances, in patients with left ventricular wall thickening of unclear etiology, low ECG voltage, unexplained arterial hypotension and pulmonary hypertension. Screening for cardiac amyloidosis should include non-invasive methods such as electrophoresis and immunofixation of blood and urine proteins, the free light lambda and kappa chains of immunoglobulins, 99Tc-DPD scintigraphy, genetic testing (if hereditary variants of amyloidosis are suspected), as well as a histological examination of biopsy samples stained with Congo red and polarizing microscopy.

55-62. DOI: 10.21508/102755-62. DOI: 10.21508/ -4065-2017 Abstract: The article reports clinical case of early neonatal manifestation of a rare genetic disease -mitochondrial DNA depletion syndrome, confirmed in laboratory in Russia. Mutations of FBXL4, which encodes an orphan mitochondrial F-box protein, involved in the maintenance of mitochondrial DNA (mtDNA), ultimately leading to disruption of mtDNA replication and decreased activity of mitochondrial respiratory chain complexes. It's a reason of abnormalities in clinically affected tissues, most of all the muscular system and the brain. In our case hydronephrosis on the right, subependimal cysts of the brain, partial intestinal obstruction accompanied by polyhydramnios were diagnosed antenatal. Baby's condition at birth was satisfactory and worsened dramatically towards the end of the first day of life. Clinical presentation includes sepsis-like symptom complex, neonatal depression, muscular hypotonia, persistent decompensated lactic acidosis, increase in the concentration of mitochondrial markers in blood plasma and urine, and changes in the basal ganglia of the brain. Imaging of the brain by magnetic resonance imaging (MRI) demonstrated global volume loss particularly the subcortical and periventricular white matter with significant abnormal signal in bilateral basal ganglia and brainstem with associated delayed myelination. Differential diagnosis was carried out with hereditary diseases that occur as a «sepsis-like» symptom complex, accompanied by lactic acidosis: a group of metabolic disorders of amino acids, organic acids, β-oxidation defects of fatty acids, respiratory mitochondrial chain disorders and glycogen storage disease. The diagnosis was confirmed after sequencing analysis of 62 mytochondrial genes by NGS (Next Generation Sequencing). Reported disease has an unfavorable prognosis, however, accurate diagnosis is very important for genetic counseling and helps prevent the re-birth of a sick child in the family.

Т ромбоэмболия легочной артерии (ТЭЛА)-патологическое состояние, характеризующееся полной или частичной окклюзией тромбом просвета легочной артерии или ее ветвей. Известно, что первое описание ТЭЛА, датированное позапрошлым веком, принадлежит французскому ученому Рене Лаэннеку (René Laënnec), который назвал ее «легочной апоплексией». Впоследствии уже выдающийся немецкий патолог Рудольф Вирхов (Rudolf Virchow) экспериментально доказал, что тромбы в венах нижних конечностей служат источником эмболии ветвей легочной артерии. Первой русской фундаментальной работой, посвященной этой проблеме, была монография И.Ф. Клейна «О тромбозе, эмболии», опубликованная в 1863 г. В современном мире ТЭЛА, возникающая как осложнение тромбоза вен нижних конечностей и таза, достаточно распространенная патология, регистрируемая у 35-40 человек на 100 тыс. населения [1]. В 20-30% случаев (0,1% населения в экономически развитых странах) ТЭЛА приводит к гибели пациента [2].

Transthyretin amyloidosis (ATTR-amyloidosis) is a systemic disorder associated with extracellular deposition in the tissues and organs of amyloid fibrils, transthyretin-containing insoluble protein-polysaccharide complexes. The change in transthyretin conformation, leading to its destabilization and amyloidogenicity, can be acquired (wild type, ATTRwt) and hereditary due to mutations in the TTR gene (variant, ATTRv) [1, 2]. Hereditary ATTR-amyloidosis has an earlier onset and greater phenotypic diversity. The age of the manifestation, the predominant phenotype, and the prognosis are often determined by the genetic variant. To date, more than 140 variants in the TTR gene have been identified; however, most of them are described in single patients and do not have clear evidence of pathogenicity. The prospects of a new pathogenetic treatment of ATTR-amyloidosis [3], especially effective in the early stages of the disease, increases the relevance of timely diagnosis, which is challenging due to physicians' lack of awareness. This article presents a clinical case of ATTRv-amyloidosis associated with a rare pathogenic variant in the TTR gene and a newly described skin symptom. This article is a literature review.

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Background. Many studies concerning molecular-biological markers in colorectal cancer (CRC) were performed over the past decade. Вcl-2 protein (B-cell lymphoma 2) was one of the most studied molecular-biological markers and attracted the attention of different specialties as on studying carcinogenesis and the relationship with prognosis. Aim. To study in details the characteristics of Bcl-2; to study Bcl-2 role in the mechanisms regulating apoptosis; to show update data concerning the prognostic significance of this protein in CRC. Materials and methods. To write this literature review we have studied domestic and foreign publications from Russian and international systems of search (PubMed, eLibrary, etc.) over the past 2-30 years. Results. The evaluation of the expression of antiapoptopic protein Вcl-2 in tumor can give additional information about the course of malignant process independently of therapeutic effects, the biological behaviour of the tumor: the rapidity of growth, the ability of invasion and metastasis (i.e. the prognosis of a disease). Conclusion. The results concerning the impact of abnormal expression of apoptosis inhibitor Вcl-2 on the course and prognosis of CRC have been accumulated in the scientific literature, but there have been only several studies, analyzing the relationship between Вcl-2 and metastasis of CRC and factors influencing the invasive potential of tumor cells. Nowadays, there is no consensus about the prognostic significance of protein Вcl-2 in patients with CRC. In some studies, concerning CRC, have been shown the correlation between Bcl-2 overexpression in tumor cells and a favorable course of disease and good survival in patients. Other authors have been shown that tumors with Bcl-2 overexpression, by contrast, are more aggressive in comparison with tumors without Bcl-2 expression. There are a number of studies in which the prognostic significance of Bcl-2 protein is not proved. Many issues, concerning the correlation between this molecular-biological marker and clinico-morphological characteristics of tumor, might also need to be itemized. All shown in the article is a subject to further research.

Background.The evaluation of clinical and morphological characteristics is not sufficient to predict the prognosis of metastatic colorectal cancer (mRCC). Tumor aggressiveness may vary significantly even in patients with similar clinical and morphological disease characteristics. These differences are believed to be associated with molecular tumor characteristics and can be used as additional prognostic factors for patient survival.Objective:to evaluate the effect of topoisomerase IIα overexpression (topoIIα) in primary colon tumor on the mRCC prognosis.Materials and methods. The study cohort included patients with mRCC that have not previously received treatment for disseminated disease. All participants had a morphologically verified diagnosis of colon adenocarcinoma and received first-line chemotherapy with oxaliplatin and capecitabine. We evaluated both short-term and long-term treatment outcomes. We also assessed the expression of topoIIα in primary colon tumors (biopsy/surgical specimens obtained prior to initiation of first-line treatment) using immunohistochemical methods. We aimed to evaluate the association between the level of topoIIα expression and short-term/long-term treatment outcomes. We analyzed the impact of topoIIα expression in the primary tumor on the efficacy of first-line chemotherapy, progression-free survival (PFS) and overall survival (OS) in patients with mRCC.Results. Immunohistochemical evaluation of topoIIα expression in the primary tumor was conducted for 39 patients with mRCC. We found no correlation between topoIIα expression and PFS, i.e. median PFS did not differ significantly between patients with topoIIα-positive and topoIIα-negative tumors (p >0.05). Individuals with low levels of topoIIα expression in the primary tumor and those with topoIIα-negative cancer demonstrated significantly higher OS than patients with topoIIα overexpression (median OS 16.30 ± 2.0 months; 95 % confidence interval 12.32–20.28 vs 7.7 ± 4.98 months; 95 % confidence interval 0.00–17.46; p = 0.007).Conclusion.Overexpression of topoIIα is a factor of poor prognosis associated with poorer OS in patients with mRCC that received first-line chemotherapy with oxaliplatin and capecitabine.

Behçet's disease (BD) is a systemic vasculitis of unknown origin, characterized by recurrences of the ulcerative process in the oral cavity and on the genitals, inflammatory damage of the eyes, joints, vessels and other organs. The severity and prognosis of BD determines organ pathology. Intestinal manifestations of BD (intestinal BD) are the least studied. Its verification in BD is complicated by the variety of clinical manifestations, their similarity with inflammatory bowel diseases, the lack of informative laboratory tests, pathognomonic endoscopic and histological signs. Intestinal BD can lead to serious complications (massive bleeding, intestinal perforation and fistula formation), which can not only significantly reduce the quality of the patient’s life, but also cause death. Treatment of intestinal BD is not standardized; it is mainly empirical and conducted courses. The purpose of therapy is to achieve clinical remission, healing of intestinal ulcers and prevention of surgery. The article presents a case of severe refractory intestinal BD, requiring twice emergency surgical care - removal of half and then the whole of the colon because of multiple perforations. A brief review of the literature is given and diagnostic difficulties of intestinal BD are discussed.