Anton Pavlovich Chekhov gained worldwide fame as a writer, but he was also a doctor by education and dedicated a signifi cant part of his life to medicine. At the university, his studied under outstanding scientists — therapist Grigory Antonovich Zakharyin, surgeon Nikolai Vasilyevich Sklifosovsky, hygienist Fyodor Fyodorovich Erisman. Chekhov began his medical practice as a second-year student at the Chikinskaya Zemstvo Hospital in the Moscow Region town of Voskresensk, where he secured a position as a district physician after graduating from the university. Later, he practiced privately in Moscow. According to colleagues, Anton Pavlovich Chekhov was an excellent diagnostician and a talented psychotherapist. He was distinguished by exceptional kindness, patience and tact in relation to patients. In 1890, he went to Sakhalin, where he was the fi rst to conduct a population census, studied the living conditions of exiles, collected data on diseases and causes of death. Based on the results of his research, he wrote a fundamental work, Sakhalin Island. In the 1890s, he acquired an estate in Melikhovo, 70 km from Moscow, where he served as a zemstvo doctor, fought cholera, built four schools, a fi re station, a post offi ce, a bell tower and a road to the railway station, and organized a public library. In his literary works, Chekhov created a vast gallery of realistic portrayals of doctors. Thanks to his medical experience and knowledge, he professionally accurately depicted clinical portraits of patients with such various diseases as tuberculosis, typhus and typhoid fever, depressive disorder, persecution mania, etc. In 1897, Chekhov suffered from severe pulmonary hemorrhage and was diagnosed with tuberculosis. From 1899, following medical advice, Anton Pavlovich moved to Yalta, where he continued to help everyone who turned to him for medical help. He initiated the construction of a tuberculosis sanatorium and personally contributed a large sum, made numerous charitable donations to the sick. In 1904, Anton Pavlovich’s condition worsened signifi cantly, he was recommended treatment in Germany, at the Badenweiler resort, where Chekhov died on July 2, 1904.

Current treatment of hemorrhagic fever with renal syndrome (HFRS) is primarily based on expert opinion and data from small observational studies, the results of which are not always confirmed in clinical practice. Due to the lack of effective antiviral agents for the treatment of HFRS, the search for optimal supportive therapy continues. The clinical course of HFRS is characterized by the sequential development of phases of fever, hypotension, oliguria, polyuria and convalescence; each of these phases is characterized by certain pathophysiological mechanisms, knowledge of which is necessary for the correct management of patients with HFRS. This narrative review provides the pathophysilogic rationale and practical experience of using treatment methods for HFRS, such as anti-inflammatory therapy, correction of fluid, electrolyte, hemodynamic and hemocoagulation disorders, as well as, renal replacement therapy and symptomatic therapy.

Nonalcoholic fatty liver disease (NAFLD) is currently a serious medical and social problem for public health systems due to its high prevalence, potential development of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). In addition, the presence of NAFLD in the patient’s somatic continuum is associated with a significantly higher incidence of cardiovascular events and type 2 diabetes mellitus (T2DM). The most frequent NAFLD is registered in patients with excessive body weight. Patients with normal body weight deserve special attention of researchers and clinicians. Despite the seemingly relatively favorable profile of “metabolic health”, the risk of progression of NAFLD to CKD and HCC, as well as conjugation with cardiovascular events in this group of patients is no less than in the group of patients with NAFLD and high body mass index (BMI). The absence of early symptoms and abnormalities of some indicators characterizing “metabolic health” in patients with NAFLD and normal body weight contributes to late and untimely diagnosis of liver disease and, as a consequence, its progression and the formation of severe vascular and metabolic disorders in the future. In the presented review the authors offer some epidemiological data on the prevalence of NAFLD in patients with normal body weight, variants of the clinical course of NAFLD in the discussed group of patients and propose to make a special emphasis on the obvious need for a much wider involvement of patients with normal body weight in clinical and scientific studies devoted to a detailed study of the pathogenesis, issues of organization of medical care and treatment of NAFLD.

This review provides information on recent advancements in the treatment of cystic fi brosis and presents interim results from ongoing clinical trials. Various scientifi c databases, including Scopus, Web of Science, and EMBASE, were utilized during the preparation of this review.

The results of studies on new drugs such as acebilustat, LAU-7b, JBT-101 designed for anti-infl ammatory therapy of this disease are also presented.

The review describes various approaches to cystic fi brosis therapy — substance ABO401, SP-101. It includes clinical trial results for the adeno-associated vector 4D-710, liposomal nanoparticles, including the drugs MRT5005, RCT2100, the corrector galicaftor, as well as the drugs lumacaftor+ivacaftor, tezacaftor+ivacaftor, tezacaftor+ivacaftor+elexacaftor и tezacaftor+vanzacaftor+deutivacaftor.

Special attention is given to transgene delivery using vectors with a detailed discussion of the advantages and disadvantages of this method. The main modern genome editing techniques, their capabilities, advantages and disadvantages are also described.

The results of the study on the oligosaccharide structures, which reduces sputum viscosity in patients with cystic fi brosis, are presented. This reduction in viscosity enhances the effectiveness of the antibiotic aztreonam, which is active against the Burkholderia cepacia complex — a group of pathogens, which is often responsible for infl ammation in cystic fi brosis patients.

The role of targeted therapy as a factor capable of signifi cantly reducing disease severity was highlighted. Targeted therapy drugs can partially restore the function of the abnormal protein in cystic fi brosis patients, thereby reducing symptom severity and signifi cantly improving the patient’s quality of life. The necessity of further development in this fi eld was emphasized.

Objective: to assess the state of the collagenolysis system in patients with long-term post-COVID syndrome, to determine the features and risk factors of its changes. Materials and methods. The study included 178 patients who had had a new coronavirus infection (NCVI) 12 weeks or more ago, depending on the presence or absence of symptoms of long-term post-COVID syndrome, patients who had NCVI 12 or more weeks ago were divided into 2 groups: the first group consisted of 88 patients with Long-covid symptoms; the second group consisted of 90 subjects without any symptoms of Long-covid. Results. The median period after NCVI was 8.5 [3.6; 12.4] months. In all patients who underwent NCVI, tissue inhibitor of matrix metalloproteinase type 1 (TIMP1) was higher than the reference value (135 pg/ml). In the patients of the first group, TIMP1 was lower than in the second group: 315.5 [145.0; 620.0] pg/mL vs. 513.5 [220.0; 865.0] pg/mL (p < 0.001). Therefore, in long-term post-COVID syndrome, a collagenolytic pattern develops against the background of an increased risk of fibrosis. Conclusion. In patients who have undergone NCVI with a long-term post-COVID syndrome, the state of the collagenolysis system is characterized by the development of a collagenolytic pattern against the background of the prevailing processes of collagen formation in comparison with asymptomatic patients who had NCVI 12 weeks ago or more, which can be considered as a pathogenetic mechanism for the formation of “Long Covid”.

The aim of the study was to investigate differences in the content of unsaturated fatty acids (UFA) in blood plasma in men living of rural areas of the Novosibirsk region, depending on their alcohol status. Materials and methods: as part of a single-stage epidemiological study in the Novosibirsk region, rural residents (men) aged 60.04±10.55 (from 35 to 74 years) were examined. The alcohol status of the participants was determined by means of a questionnaire. The number of different alcoholic beverages was recalculated in doses of pure alcohol. All study participants were divided into three groups based on alcohol consumption per week: group 1 — low alcohol consumption (LC); group 2 — moderate alcohol consumption (MC); group 3 — high alcohol consumption (HC). The levels of omega-3, -6, and -9 UFA in blood plasma were determined by high-performance liquid chromatography. Results: It was found that the group of men with HC had higher concentrations of omega-3 alpha-linolenic acid (p=0,041) and omega-6 digomo-gamma-linolenic (p=0,002), docosatetraenoic (p=0,017), docosapentaenoic (p=0,023) UFA in blood, compared with group of men with LC. Conclusions: In the study, we found statistically significant differences in blood concentrations of alpha-linolenic acid, digomo-gammalinolenic acid, docosathetraenoic acid, and docosapentaenoic acid unsaturated fatty acids were obtained in men aged 35-74 years living in rural areas of the Novosibirsk region, depending on alcohol consumption.

Takotsubo Syndrome (TS) is an acutely developing and typically reversible myocardial dysfunction, predominantly affecting the left ventricle, which clinically and electrocardiographically resembles acute coronary syndrome. Among the etiological factors of this pathology, severe emotional stress and physical conditions, including severe brain diseases, are noted. The most common symptoms in the acute phase include chest pain and dyspnea, while palpitations and syncope occur less frequently. Severe cases of TS may be complicated by cardiogenic shock, pulmonary edema, acute cerebrovascular accident, cardiac arrest. The presented clinical case demonstrates an atypical course of TS, in which the severity of the patient’s condition was determined by central nervous system involvemen.t

A 68-year-old man was admitted in critical condition to the intensive care unit: after experiencing severe emotional stress, he was found unconscious at home. Upon examination, the patient was in a state of sopor with right-sided gaze paresis, right-sided mouth corner drooping, and severe neurological deficit, as assessed by NIHSS.

Computed tomography of the brain revealed a poorly defined ischemic lesion in the vascular territory of the left middle cerebral artery. Electrocardiography showed biphasic and negative T waves in AVL, V3-V6. Echocardiography revealed a reduction in left ventricular ejection fraction to 32 % and the regional walls motion abnormality including circular hypokinesis. Elevated levels of myocardial necrosis markers were observed. A diagnosis of combined ischemic brain and myocardial injury was established, and treatment was initiated. The following day, significant positive dynamics were observed—the patient regained consciousness, had no neurological deficit. Magnetic resonance imaging of the brain did not reveal evidence of stroke. There are no negative and biphasic T waves on the electrocardiogram, echocardiography demonstrated normalization of left ventricular ejection fraction and the absence of hypokinetic zones. The correlation between disease onset and severe emotional stress, the discrepancy between the regional walls motion abnormality and the vascular territory of a single coronary artery with circular involvement of the left ventricle, the absence of a morphological substrate explaining the pronounced neurological deficit in the acute phase, and the quick, complete recovery of cardiac and neurological function led to the conclusion of a primary form of TS. A catecholamine surge induced acute left ventricular dysfunction, which was further complicated by cerebral hypoperfusion with progressive brain edema.

So, in the acute phase TS may mimic not only the typical anginal form of myocardial infarction but also a cerebral event.

Guillain-Barré Syndrome is a severe autoimmune disease of the peripheral nervous system, representing the most common cause of acute flaccid tetraparesis, which can lead to life-threatening respiratory failure in the absence of adequate therapy. The relationship between GBS and infective endocarditis is not well studied.

A 54-year-old patient experienced increasing numbness and weakness in the lower extremities two weeks after an acute respiratory viral infection, and was hospitalized with suspected ischemic stroke. Brain computed tomography revealed no data for acute focal pathology but showed left-sided sinusitis and ethmoiditis. Cerebrospinal fluid analysis showed protein at 0.8 g/L (normal up to 0.2 g/L), with cytosis within normal limits. The neostigmine test was negative. The clinical and instrumental picture was assessed as Guillain-Barré Syndrome. Echocardiography revealed vegetations on the mitral valve (MV) leaflets, rupture of the anterior leaflet chordae (“flail leaflet” of the MV), and grade 3 mitral regurgitation. Despite ongoing therapy, including antibacterial and immunomodulatory treatment, the patient continued to exhibit neurological symptoms, developed pulmonary artery thromboembolism, nosocomial bilateral polysegmental pneumonia, and sepsis, leading to a fatal outcome. Autopsy confirmed infective endocarditis with rupture of the MV chordae, abundant growth of Pseudomonas aeruginosa, scant growth of Klebsiella pneumoniae and Acinetobacter baumannii, and right atrial thrombosis. No pathological changes were found in the brain substance.

Thus, Guillain-Barré Syndrome in rare cases can be associated with infective endocarditis and negatively impact the course and prognosis of the disease.