Malignant neoplasms cells are characterized by clonal evolution that is resistant to the applied antitumor drug and evasion from the effects of the immune system. Therefore, a promising direction in modern oncology is the stimulation of the immune response against neoplasms. This method can be used in combination with other anticancer drugs and alone. Tumor cells produce CTLA4 (CTLA4 — cytotoxic T-lymphocyte protein 4) and PD-1 (programmed cell death) checkpoints that inhibit the activity of T-lymphocytes and their production of antitumor cytokines. The clinic uses antibodies against CTLA4, PD-1 and PD-L1, monotherapy with which increases the effectiveness of the chemotherapy used, but significantly aggravates the development of adverse reactions, which limits their use. Monotherapy with anti-PD/PD-L1 showed low efficacy and also a high risk of pulmonary, hepatic, and thyroid complications. In this regard, it is necessary to develop new methods of tumor immunotherapy. The most promising in this regard is the method of viral mimicry, when double-stranded RNA formed from transcripts of retroelements serve as a trigger for the production of interferon and activation of T-killers. For artificial activation of retroelements, inhibitors of DNA methyltransferases, deacetylases, and histone methyltransferases are used. Since retroelements are located in gene introns, viral mimicry can be used in spliceosomal targeted therapy. Transposons serve as drivers of carcinogenesis, therefore, in addition to their artificial activation, oncology uses methods for silencing retroelements using reverse transcriptase inhibitors. The use of non-specific methyltransferases and inhibitors of histone demethylases for this can lead to suppression of the expression of other genes, with possible side effects. Therefore, this technique is the most promising with the use of guides that direct histone modification enzymes to the loci of the location of retroelement genes in the genome. Guides can also be used to activate the most significant retroelements in the development of the immune antitumor response and exclude the expression of elements involved in the initiation and maintenance of carcinogenesis. MicroRNAs, long non-coding RNAs, and antisense oligonucleotides can be used as guides.

Medication-overuse headache (MOH) is a highly prevalent secondary headache, developing in patients with frequent and chronic cephalalgias due to excessive use of “acute” medications for headache, and significantly affecting patients’ quality of life. Treatment of MOH demands high compliance physician-patient, and the result is satisfactory not in all cases. For this reason, the prophylaxis of overuse of symptomatic medications for headaches is important. The review presents contemporary data on MOH, its treatment and prophylaxis.

Introduction and purpose. Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular (LV) wall thickening not associated with increased afterload (hypertension and aortic stenosis), is usually caused by mutations in sarcomeric protein genes, and is inherited in an autosomal dominant manner. Unlike HCM, myocardial hypertrophy in its phenocopies is associated with the accumulation of substances such as amyloid, glycogen, etc. in the myocardium. The aim of our work was to analyze the features of the diagnosis and course of HCM in real clinical practice. Material and methods. A retrospective analysis of medical records of 80 patients (56.3 % of men) discharged with a diagnosis of HCM from a multidisciplinary hospital in Moscow in the period from 2007 to 2021 was carried out. The diagnosis of HCM in all patients was established on the basis of echocardiography data. The median age (25th and 75th percentiles are indicated in brackets) was 57 (48.5; 63) years. The duration of hospitalization was 8 (6; 12.5) days. Results. The reason for hospitalization was angina syndrome in 35 %, suspicion of acute coronary syndrome in 16.3 %, paroxysmal atrial fibrillation (AF) in 11.3 %, decompensation of chronic heart failure in 11.3 %, syncope in 7.5 % %, hypertensive crisis in 3.8 %, coronary angiography in 3.8 %, pacemaker implantation in 2.5 %, consultation with an arrhythmologist in 2.5 %, implantation of a cardioverter-defibrillator in 1.2 %, medical examination to resolve the issue of fitness for military service in 1.2 %, acute cerebrovascular accident in 1.2 %, hypotension in 1.2 %, drug bradycardia in 1.2 % of patients. Before hospitalization, a history of myocardial infarction was diagnosed in 15 %, arterial hypertension — in 53.8 %, chronic heart failure — in 77.6 %, chronic kidney disease — in 21.3 % of patients. Prior to the analyzed hospitalization, a history of myocardial infarction was diagnosed in 15 %, arterial hypertension in 53.8 %, chronic heart failure in 77.6 %, chronic kidney disease in 21.3 % of patients. LV wall thickness ≥1.5 cm was detected in 91.2 %, symmetrical form of hypertrophy — 22.1 %, apical — 5.2 %, papillary muscle hypertrophy — 1.3 %, interventricular septum — 71.4 % of patients. Permanent obstruction of the LV outflow tract (LVOTO) was detected in 62.8 % (9.0 % of patients had a history of septal reduction), transient LVOTO — in 1.3 %, non-obstructive HCM — in 35.9 %. The ejection fraction (EF) of the LV (according to Simpson) was 63 (55-70) %, CHF with reduced LV EF <40 % was detected in 3.8 %, with a moderately reduced LV EF (40-49 %) — in 5 %, with preserved LV EF — in 68.8 % of patients. Anterior systolic movement of the anterior leaflet of the mitral valve occurred in 47.5 %, prolapse of the anterior leaflet of the mitral valve was described in 7.14 %. Mitral regurgitation was registered in 75 % of patients. 45 % of patients with HCM suffered from AF: permanent 15 %, paroxysmal 23.8 %, persistent 6.2 % of patients. During hospitalization, ventricular tachycardia was registered in 7.5 %, supraventricular tachycardia — 3.8 %, conduction disturbances were noted in 36.3 % of patients, of which atrioventricular block in 6.3 %, blockade of the right bundle branch block in 21.3 %, left bundle branch block in 15 %, and Wolff-Parkinson-White syndrome in 1.3 % . Implantation of a pacemaker in history was in 5 %, including in connection with MorgagniAdams-Stokes attacks — in 3.8 % of patients. During a median follow-up of 87 (interquartile range 45–131.5) months, 13.8 % of patients with HCM died. In deceased patients, LVOTO was significantly more common (in the dead 100 %, in the living 58.2 %, p = 0.006) and AF (in the dead 72.7 %, in the living 40.6 %, p = 0.047). Genetic testing and exclusion of HCM phenocopies was not performed during hospitalization and was not recommended for any patient. Conclusion. In real clinical practice, in most cases, only phenotypic diagnosis of HCM is carried out according to echocardiography, and screening for genetic mutations and HCM phenocopies is not performed. It is necessary to widely introduce genetic testing and screening for HCM phenocopies for the timely diagnosis of pathology that requires the appointment of specific pathogenetic therapy to improve the prognosis of patients

Non-alcoholic fatty liver disease (NAFLD) is a widespread disease closely associated with obesity and metabolic disorders. Noninvasive instrumental markers are of great importance in the diagnosis of NAFLD. The aim of the present investigation was to study the correlation of Hamaguchi score with the prevalence of peripheral arterial atherosclerosis and to evaluate the diagnostic value of Hamaguchi score in relation to the presence of carotid and lower limb arterial stenoses. Materials and Methods. All the participants underwent duplex scanning of the arteries of the carotid basin and the arteries of the lower extremities, and abdominal ultrasound examination. Results. The study involved 175 patients, including 72 men and 103 women. Median age of the patients was 50 years. Combined atherosclerosis of carotid arteries and the arteries of the lower extremities was detected in 76 (43,4 %) patients. Median severity of hepatic steatosis according to Hamaguchi score was 2 points. Significantly higher Hamaguchi score values (p=0,026) were observed in the group of patients with combined atherosclerosis of carotid arteries and lower limb arteries. According to logistic regression analysis, a one unit increase in Hamaguchi score was associated with a 1,192-fold (95 % CI 1,023-1,387) increase in the relative risk of finding combined atherosclerosis of two basins (carotid and lower extremity arteries). According to ROC-analysis, increasing Hamaguchi score>2 points allowed to diagnose combined stenoses of carotid and lower limb arteries with sensitivity of 52,6 % and specificity of 63,6 % (AUC=0,596; p=0,024). Conclusion. In patients with NAFLD the Hamaguchi score>2 made it possible to diagnose combined stenoses of the carotid and lower extremity arteries with a sensitivity of 52,6 % and specificity of 63,6 %.

Hepatopulmonary syndrome is a severe complication of chronic liver diseases, significantly reducing the quality and duration of patient’s lives, the pathogenetic manifestation of which is hypoxemia and intrapulmonary vasodilation. The disease is widespread enough: according to some authors, up to 35 % of patients with the terminal stage of liver damage suffer from this syndrome. The main clinical manifestation is progressive dyspnea with possible occurrence of platypnea and orthodexia. Diagnosis is difficult, since the “gold standard” — transthoracic echocardiography with intravenous injection of contrast agent — is an invasive procedure requiring specific equipment, that’s why it is poorly used in medical institutions of the Russian Federation. Physical examination is used as an additional method, in which we see dyspnea, cyanosis, spider nevi, digital clubbing, but these manifestations are not highly specific. Therefore, there is an urgent need for minimally invasive, widespread diagnostic methods and clinical markers that can provide early verification of the diagnosis. This review presents data on the prevalence, pathogenesis, clinical presentation, diagnosis and treatment of this syndrome. The aim of this review is to structure the current data and the accumulated experience for an earlier verification of the diagnosis and accordingly, to apply the optimal management tactics for patients with this pathology. Liver transplantation is currently the main effective method of treatment. Patients with hepatopulmonary syndrome who underwent liver transplantation have been proven to have better survival rate.

Background. Chronic obstructive pulmonary disease (COPD) is one of the most significant diseases due to its high prevalence and impact on prog- nosis. The frequency of exacerbations and comorbidity are important factors influencing the course of COPD. It is believed that local and systemic inflammation may underlie this heterogeneous course of COPD. In this regard, assessment of local inflammation activity in the respiratory tract may be useful to assess the course of COPD. Aim. To study molecular mechanisms of COPD and assess inflammation biomarkers in the exhaled breath condensate (EBC) in patients with COPD with the phenotype of frequent exacerbations combined with peripheral atherosclerosis. Materials and Methods. Bioinformatic analysis of data from Gene Expression Omnibus (GEO) was performed to examine gene ontology of differentially expressed genes in COPD. Proinflammatory cytokines interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNFα) in EBC in COPD patients without concomitant atherosclerotic cardiovascular disease (ASCVD) in the stable course phase, in patients with COPD with the phenotype of frequent ex- acerbations and peripheral artery disease (PAD) compared with healthy controls were examined. Results. Differentially expressed genes are involved in biological processes and signaling pathways according to the Kyoto Encyclopedia of Genes and Genomes (KEGG pathway) associated with the immune response that may link the development and progression of COPD and atherosclerosis. Patients with COPD combined with atherosclerosis had higher values of IL-1β and TNFα in EBC compared with controls (p <0.001). COPD patients with frequent exacerbations and PAD had the highest levels of IL-1β and TNFα in EBC compared with patients without ASCVD (p=0.0038 and p=0.0005, respectively). Conclusion. TNFα and IL1-β levels in EBC are elevated in COPD patients with frequent exacerbations and PAD, which may indicate the presence of local inflammation in the airways, the severity of which is associated with the clinical course of COPD.

Gastroesophageal reflux disease is a widespread chronic disease in which stomach or duodenal contents rise up into the esophagus. Esophageal spasm and achalasia cardia are poorly studied disorders associated with impaired neuromuscular impulse transmission and motor discoordination of the esophagus, manifested by chest pain and dysphagia. The article presents a clinical case of a young patient with gastroesophageal reflux disease and a history of atypical chest pain requiring differential diagnosis between variants of impaired esophageal motility.

Scabies is an infectious skin disease caused by the human-specific ectoparasite Sarcoptes scabiei var. hominis. Despite the comprehensive study of scabies, the problem of its timely diagnosis in low-mobility patients with neurological and cognitive impairments remains relevant all over the world. Simultaneous administration of a large number of medications to patients with limited mobility may mask the clinical manifestations of scabies and mistakenly attribute itching to manifestations of skin allergic reactions or other dermatoses. The authors observed patient K., who was admitted in FCBRN of FMBA of Russia from 14.11.2022 to 15.11.2022. Clinical diagnosis upon admission: I69.3. The consequences of a stroke. Early recovery period of ischemic stroke in the basin of the left middle cerebral artery from 09.08.2022, atherothrombotic subtype according to TOAST criteria. Right-sided hemiparesis. Gross aphasia. Violation of the pelvic organs function. RMS 5. Comorbid diseases: arterial hypertension, controlled, the risk of CVE 4 (very high). The target blood pressure is less than 135/85 mmHg. Occlusion of the left anterior cerebral artery, middle cerebral artery. Toxic-allergic dermatitis (medicinal) in the acute phase. Based on a set of clinical data and laboratory detection of the pathogen, patient K. was diagnosed with B86 — scabies. Even though the patient was under medical supervision at the ambulatory step, scabies was not diagnosed timely. Late diagnosis of scabies leads to the spread of the disease and an unfavorable epidemiological situation.