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Vol 75, No 2 (2020)

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INTERNAL DISEASES: CURRENT ISSUES
Patterns of esophageal acidification and impairment of esophageal motility in gastroesophageal reflux disease and Barrett’s esophagus
Maev I.V., Barkalova E.V., Kucheryavyy Y.A., Ovsepyan M.A., Andreev D.N., Movtaeva P.R., Shaburov R.I.
Abstract

Background. Gastroesophageal reflux disease (GERD) has a high prevalence worldwide and plays a major role in the development of Barrett’s esophagus (BЕ) and, as a consequence, esophageal adenocarcinoma.

Aims: to evaluate the patterns of esophageal acidification and esophageal motility in patients with BЕ in comparison with various GERD phenotypes and control subjects.

Methods. 100 patients were examined: 31 patients with nonerosive reflux disease (NERD), 20 patients with erosive reflux disease (ERD), 17 patients with BE, 32 healthy individuals who made up the control group. All patients underwent 24-hours pH-impedance and high-resolution esophageal manometry.

Results. According to the 24-hour pH-impedanсe, the total time with pH < 4 in the esophagus was 1.9% (95% CI: 1.1−2.7) in control patients, 11.6% (95% CI: 8.76–13.4) in the NERD group, 19.35 (95% CI: 12.70−26.05) in the ERD group and 28% (95% CI: 10.04–40.96) in patients with BE (p < 0.05). The average number of acid refluxes was 18.0 (95% CI: 10.99−23.0) in the control group, 58.0 (95% CI: 42.34−71.0) in the group with NERD, 78.5 (95% CI: 65.34−103.93) in the group with ERD and 89.0 in patients with BE (95% CI: 67.03−118.72). Significant differences in the listed indicators were noted when comparing patients with BE and control individuals, as well as the NERD group (p < 0.05). The number of acidic refluxes was significantly correlated with the time on the acidification of the esophagus (r = 0.5439; p < 0.05). The median time of chemical clearance was 1.55 min (95% CI: 1.19−2.0) in control subjects, 2.4 min (95% CI: 1.65−2.94), in the NERD group, 2.85 min (95% CI: 1.80−3.84) in the ERD group, and 3 min (95% CI: 2.1−4.68) in the BE group. The analysis of the mean nocturnal baseline impedance (MNBI) revealed a tendency to decrease the values in patients with GERD relative to the control subjects, and there was a decrease in the values of MNBI as the severity of GERD ― from NERD to ERD and BE (p < 0.05). Manometric signs of hiatal hernia and/or hypotension of the lower esophageal sphincter were more often registered in the groups of patients with ERD (70%) and BE (65%) than in patients with NERD (32%) and in control group (12%). In addition, the frequency of such esophageal motor disorders as ineffective motility and absent contractility were significantly more often observed in patients with ERD and BE (75% and 77%, respectively) compared with patients with NERD (22.5%) and control subjects (12,5%).

Conclusions. Increase in level of total time with pH < 4, number of acid refluxes, slowing chemical clearance, reduced values of MNBI, as well as disorders of the structure and function of the esophagogastric junction and motility of the esophagus are associated with the severity of аcid pathology of the esophagus.

Annals of the Russian academy of medical sciences. 2020;75(2):96-105
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IMMUNOLOGY: CURRENT ISSUES
A review: quality of life of patients with allergic rhinitis receiving various treatment
Tyufilin D.S., Deev I.A., Kobyakova O.S., Tagina E.K., Kulikov E.S.
Abstract

The high prevalence of allergic rhinitis in a population, the link between this disease and asthma, and a significantly higher economic burden of the disease, causing a negative impact on the patients’ quality of life, have resulted in increased attention to the problem of allergic rhinitis at the global level. Nowadays optimal allergic rhinitis treatment and management include disease control, consisting of assessing the level of disease control and selecting a treatment scheme based on this assessment. Current studies are focused on the development of questionnaires and testing systems for assessing the level of disease control, especially given the absence of a standardized control assessment procedure tool. Studies also address the possibility of using the indicators of quality of life to measure the level of disease control. The present review deals with the issue of understanding of using this parameter to measure the effectiveness of pharmacotherapy of different groups of patients with allergic rhinitis. The review includes randomized clinical trials covering the period 2010−2019 including the following keywords: “Rhinitis Quality of Life”, “Allergic Rhinitis Quality of Life”, “Allergic Rhinitis Questionnaire”, “RQLQ”. In total, 4.407 publications were identified and analyzed, only 60 publications were selected for comparative analysis after a second review. According to the results, in general, it can be concluded that the indicator of the quality of life allows us to identify the advantages of pharmacotherapeutic regimens in the long term (for example, allergen-specific immunotherapy, alternative therapy). Moreover, it demonstrates a correlation with objectivistic indicators in randomized clinical trials of standard treatment. It is still necessary, however, to address the question of whether it would be possible to use the assessment of the quality of life as a part of allergic rhinitis treatment in everyday clinical practice to select a group of drugs, their dosages, and correct regimes in dynamics. Using the indicator of the quality of life for managing patients with allergic rhinitis in Russia requires tremendous work in terms of cross-cultural adaptation of questionnaires and large-scale population-based pharmacoepidemiological studies.

Annals of the Russian academy of medical sciences. 2020;75(2):106-114
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INFECTIOUS DISEASES: CURRENT ISSUES
A new look at the COVID-19 pathogenesis: the disease is a generalized viral vasculitis, and the lung tissue damage is a variant of angiogenic pulmonary edema
Kubanov A.A., Deryabin D.G.
Abstract

Based on the data about angiotensin-converting enzyme 2 (ACE2) as the main receptor for severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), hematogenous spread of the virus is hypothesized, followed by killing of ACE2-expressed cells in the microvessel walls. Damage to the blood vessels (primarily arterioles) leads to the development of microthromboses and results in the exit of the blood liquid phase in perivascular space, which is pathogenetically similar to the angiogenic edema development. In fact, this disorder is multi-organ in nature, and in the lung tissue its occur as “pulmonary edema” variant, the signs of which during CT scan precede predicts the development of severe respiratory failure. The hypothesized COVID-19 pathogenesis allows us to explain the causes and stages of occurrence of many symptoms of this disease. Possible changes in COVID-19 diagnostic and therapeutic protocols are discussed.

Annals of the Russian academy of medical sciences. 2020;75(2):115-117
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COVID-19, septic shock and syndrome of disseminated intravascular coagulation syndrome. Part 1
Bitsadze V.O., Khizroeva J.K., Makatsariya A.D., Slukhanchuk E.V., Tretyakova M.V., Rizzo G., Gris J.R., Elalamy I., Serov V.N., Shkoda A.S., Samburova N.V.
Abstract

The pandemic of a new coronavirus infection (Coronavirus Disease 2019, COVID-19) caused by SARS-CoV-2 became a real challenge to humanity and the medical community in 2020 and raised a number of medical, social and even philosophical questions. An almost avalanche-like increase in the number of infected people in a short time, due to the high contagiousness of viral infection, allowed us to identify groups of patients with mild, moderate and severe forms of the disease. Doctors around the world are faced with an acute problem of treating a large number of patients in critical conditions caused by COVID-19. From the currently available information on clinical cases of COVID-19, it follows that COVID-19 patients in critical condition have a clinical picture of disseminated intravascular coagulation (DIC), septic shock with the development of multiple organ failure. The first part of the article discusses the pathogenesis of non-specific universal biological responses of the body in critical condition ― from the Sanarelli-Schwartzman phenomenon to the DIC, septic shock, systemic inflammatory response syndrome and the so-called neutrophil extracellular traps (NETs). The questions of cytokine storm in severe forms of systemic inflammatory response syndrome (SIRS), the role of inflammation in the activation of coagulation, and the relationship between inflammation and thrombosis are discussed. Modern ideas about the mechanisms of so-called NETosis, their role in the occurrence of immunothrombosis and inflammation-induced thrombosis in autoimmune diseases ― vasculitis, antiphospholipid syndrome, and systemic lupus erythematosus is highlighted. The article discusses the possibility of participation of ADAMTS-13 metalloproteinase in the pathogenesis of multiple organ failure in severe endotheliopathy in patients with viral septic shock.

Annals of the Russian academy of medical sciences. 2020;75(2):118-128
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Detection of the RNA for new multicomponent virus in patients with Crimean-Congo hemorrhagic fever in southern Russia
Ternovoi V.A., Gladysheva A.V., Sementsova A.O., Zaykovskaya A.V., Volynkina A.S., Kotenev E.S., Agafonov A.P., Loktev V.B.
Abstract

Background. Recently, a new multicomponent RNA-containing virus was described and called as Jingmen tick virus (JMTV) supposedly belonging to flaviviruses. A virus contains of four viral particles and JMTV was firstly isolated from ticks in China.

Aims. Detection viral RNA specific for JMTV complex, sequencing genome fragments and taxonomy identification novel virus from JMTV complex in patients with Crimean-Congo hemorrhagic fever (CCHF) from southern European part of Russia.

Methods. Panel of 20 randomly selected sera from patients with confirmed Crimean-Congo hemorrhagic fever was collected in 2016 and was used for detection JMTV and CCHF viral RNA by PCR with experimental primers. Subsequent sequencing of isolated fragments of viral genomes was used for identification JMTV and CCHF virus genetic materials and phylogenetic analyses.

Results. The RNA of the CCHF virus and JMTV were detected in sera of four patients. Sequencing of the PCR fragments from S segment CCHF virus were identifying these isolates as members of Europa 1 clade. The nucleotide sequences of segment 2 (GP glycoprotein) of novel JMTV isolates clustered together by phylogenetic analysis. The level nucleotide identity for discovered JMTV isolates was only about 81−82% with comparison to the previously described European variants (Kosovo) of JMTV.

Conclusions. The results allow us to conclude that in CCHF patients the RNA of the CCHF virus and RNA of the novel multicomponent JMTV flavivirus were detected in serum.

Annals of the Russian academy of medical sciences. 2020;75(2):129-134
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CARDIOLOGY AND CARDIOVASCULAR SURGERY: CURRENT ISSUES
Spectral analysis of heart rhythm variability in atrial fibrillation patients using sotalol and bisoprolol
Popova E.P., Bogova O.T., Chandirli S.A., Shueb A.A., Puzin S.N., Sychev D.A., Fisenko V.P.
Abstract

Background. Atrial Fibrillation is one of the most common arrhythmias. Despite the different attitude to the pharmacotherapy of Atrial Fibrillation, the problem of selection of adequate antiarrhythmic therapy for the prevention and treatment of persistent Atrial Fibrillation remains relevant and is of great interest to researchers. For the effective selection of drugs in the treatment of arrhythmia can be successfully used the method of spectral analysis of heart rhythm variability.

Aims: to study the effect of antiarrhythmic drug Sotalol and β-adrenoblocker Bisoprolol on the spectral parameters of heart rhythm variability in patients with Atrial Fibrillation.

Methods. 167 patients with Atrial Fibrillation of both sexes aged 46 to 94 years were examined. The study included patients with the first diagnosed Atrial Fibrillation, and with persistent Atrial Fibrillation during of 6 months to 8 years. Arterial hypertension has diagnosed in all patients. Also, patients were diagnosed with coronary heart disease with a history of myocardial infarction and without myocardial infarction. Spectral analysis of heart rhythm variability was conducted in patients with Atrial Fibrillation. Therapy in patients was performed with the antiarrhythmic drug Sotalol (80−160 mg, orally) and Bisoprolol (2.5−5 mg, orally).

Results. Spectral analysis of heart rhythm variability in patients Atrial Fibrillation using Sotalol showed that the proportion of VLF in patients with the first diagnosed Atrial Fibrillation is more than half of the spectrum, whereas in patients with persistent Atrial Fibrillation this parameter is 18%, the proportion of LF is higher in patients with persistent Atrial Fibrillation. The coefficient LF/HF in patients with persistent Arial Fibrillation is two times lower than in patients with the first diagnosed Atrial Fibrillation. Spectral analysis of heart rhythm variability in patients Atrial Fibrillation using Bisoprolol, it was shown that the proportion of LF in patients with the first diagnosed Atrial Fibrillation was 2 times lower, and the proportion of HF was twice higher than in patients with persistent Atrial Fibrillation.

Conclusions. In this study, a spectral analysis of heart rate variability in patients with Atrial Fibrillation, who receive antiarrhythmic drug therapy with sotalol and bisoprolol, was carried out. It was found that humoral factors play a significant role in patients with the first diagnosed Atrial Fibrillation during sotalol therapy, the role of the vagus in this group of patients is minimal, while in patients with bisoprolol therapy the vagus has a dominant effect on the activity of the heart.

Annals of the Russian academy of medical sciences. 2020;75(2):135-143
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HEALTH CARE MANAGEMENT: CURRENT ISSUES
The role of modern information technologies in the educational programs for children with normal visual functions and with ophthalmopathology
Tahchidi H.P., Gracheva M.A., Kazakova A.A., Strizhebok A.V., Vasilyeva N.N.
Abstract

Today, in the educational process, the usual paper sources of information are increasingly giving way to electronic devices: smartphones, tablets, E-readers and computer monitors. Currently, in the field of cognitive activity continues active development in the field of cognitive science. Extensive opportunities in the use of interactive training programs, a positive impact on the cognitive functions of students, increasing the concentration of active attention on educational material, increasing motivation for learning are important advantages of electronic devices. Of particular importance are modern electronic devices for visually impaired students, allowing them to receive an education that is fully consistent with the education of students who do not have restrictions on health opportunities. The review describes the existing types of displays, lists their main characteristics that can affect the state of visual functions and visual performance. The current sanitary and hygienic requirements for the visual work of students with normal visual functions, and with severe ophthalmopathology, containing the basic provisions, but not taking into account, however, the diversity of currently used and emerging new electronic devices. In this regard, it emphasizes the prospects of research in the field of the impact of modern technology on the visual system and the development of appropriate recommendations for their use in the organization of the educational process.

Annals of the Russian academy of medical sciences. 2020;75(2):144-153
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PHTHISIOLOGY: CURRENT ISSUES
Prevalence of polymorphisms in N-acetyltransferase 2 gene among patients of Yakut ethnicity newly diagnosed with pulmonary tuberculosis
Krasnova N.M., Alekseeva E.A., Rudykh Z.A., Chertovskykh Y.V., Klimova T.M., Efremova E.N., Kravchenko A.F., Val N.S., Suvorova O.A., Suleymanov S.S., Vengerovsky A.I., Sychev D.A.
Abstract

Background. Tuberculosis therapy can lead to considerably dissimilar outcomes among individual patients. Some patients benefit from anti-tuberculosis chemotherapy leading to a desired therapeutic effect, while other patients show insufficient or absent response, or develop adverse side effects. Individual response to isoniazid is affected by mutations in the gene encoding N-acetyltransferase 2 (NAT2). Wide variations were observed in distributions of polymorphic NAT2 alleles in human populations depending on race, ethnicity, or geographical origin. No data are available to date on prevalence of NAT2 gene polymorphic variants and acetylation types in Yakut (Sakha) patients with newly diagnosed pulmonary tuberculosis.

Aims: the frequencies of NAT2 polymorphic SNPs as well isoniazid acetylation phenotypes were evaluated in the patient’s cohort of Yakut ethnicity with newly diagnosed pulmonary tuberculosis (PTB). The comparison with, other ethnic groups of Asian origin was done.

Methods. Cross-sectional study was conducted among Yakut patient cohorts with newly identified pulmonary tuberculosis. Using real-time PCR the following SNPs were explored: NAT2*5 (rs1801280, Т341С), NAT2*6 (rs1799930, G590A), NAT2*7 (rs1799931, G857A), NAT2*11 (rs1799929, C481T), NAT2*12 (rs1208, A803G), NAT2*13 (rs1041983, C282T). Genetically determined metabolic rates were calculated using NATpred online tool.

Results. NAT2 SNPs were assessed, namely *5, *6, *7, *11, *12, and *13. The most frequent in Yakut patients were NAT2*6 and NAT2*13 SNPs (40.9% and 64.4%, respectively). Significant differences were detected in frequencies of NAT2 *5, *11, *12 polymorphisms; all studied NAT2 gene polymorphisms showed meaningful differences in genotype and minor allele prevalence rates after comparison between Yakut population and other Mongoloid ethnic groups (populations of China, Japan, Vietnam). High prevalence of intermediate acetylation type among ethnic Yakuts (58.3%) was established.

Conclusions. Certain distinct differences in allelic variants of NAT2 gene and acetylation type prevalence in patients of Yakut ethnic origin newly diagnosed with pulmonary tuberculosis let conclude that the existing genotyping and phenotyping data from studies among other Mongoloid populations cannot be implicitly extrapolated on Yakut people. Pharmacogenetic data on individual response to drugs in Yakut patients should be made use of in clinical practice, to develop personalized isoniazid administration algorithms, with a final goal to make treatment more effective and safe.

Annals of the Russian academy of medical sciences. 2020;75(2):154-161
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SURGERY: CURRENT ISSUES
The lasers in urology
Enikeev D.V., Laughtin E.А., Arshiev M.R., Taratkin M.S., Alyaev Y.G., Rapoport L.M., Glybochko P.V.
Abstract

A very rapid development of laser technology lead to the fact that many of them have already replaced surgeons with their usual scalpel. Laser technology has taken a place among the methods of treatment of various urological diseases. The features of the physical effect of laser exposure make it possible to characterize laser surgery as safe for the patient and convenient for the doctor. Therefore, along with the improvement of old laser devices, also the development and testing of new ones is constantly carried out. Nowadays the most commonly used lasers in urology are Nd:YAG, Greenlight, diode, Ho:YAG, Tm:YAG lasers and novel thulium fiber laser (TFL). Laser technology is taking place among the recommended methods for the diagnosis and treatment of various urological diseases, such as benign prostatic hyperplasia, urolithiasis, and bladder tumors. The aim of our review was to talk about laser devices that have already taken a place in the arsenal of urologist and about the most interesting developments in the field of laser surgery.

Annals of the Russian academy of medical sciences. 2020;75(2):162-168
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ENDOCRINOLOGY: CURRENT ISSUES
Gastric neuroendocrine neoplasias: literature review
Mikhaleva L.M., Vasyukova O.A., Birukov A.E., Midiber K.Y., Akopyan E.P., Khovanskaya T.N., Guschin M.Y.
Abstract

Introduction: The gastric neuroendocrine neoplasias (NEN) are being diagnosed more and more often due to the wide spread of endoscopy methods and an increase in the imaging range, despite the rarity of the gastric neuroendocrine tumors (NETs) (which amounts to about 9% of all gastrointestinal neuroendocrine tumors and 0.3% of all gastric tumors). It is extremely important to distinguish in which case clinician and pathologist should suspect a neuroendocrine tumor and to classify it correctly, both at the stage of esophagogastroduodenoscopy and during pathological examination, because all these components affect the choice of the surgery extent, subsequent drug therapy, as well as the possibility of more accurate metastasis prognosis and the patient outcome.

Aim: The aim of this literature review is to systematize, generalize and discuss the recent data on gastric neuroendocrine tumors with a focus on current classifications including their critical analysis, and to show promising ways in the endoscopic and morphological diagnostics of these tumors, which, in turn, will have an effect on patient management. The search was performed among articles in the PubMed database (in English and German) and among Russian articles published on the eLibrary and Cyberleninka platforms using the following keywords: gastric neuroendocrine tumor, gastric carcinoid, gastric NET pathology, gastric NET morphology, gastric NET morphology, gastric NET diagnostics. The papers on surgical treatment methods, adjuvant therapy, as well as drug therapy with somatostatin analogues and other drugs were excluded. A brief retrospective journey into the history of neouroendocrine neoplasias serves to remind the histology and distribution of neuroendocrine cells in the gastric mucosa, followed by chronological review of NEN discovery and theory development up to the present moment. The morphological classification of gastric NET consisting of 4 possible types is highlighted: the correct interpretation of the pathological findings, taking into account not only the histological features of the tumor itself, but also of the adjacent mucosa, allows to suggest the appropriate managment, which fundamentally affects patient survival. The review provides other current classifications of the gastric neuroendocrine neoplasia depending on its location, embryogenesis, functional activity, histological grade (with a focus on the Ki-67 labeling index counting, and ways to improve the interobserver reliability in routine practice). Moreover, the differences in the gastric NET and NEC TNM classification are emphasized. The drawbacks of all classifications are discussed and the possibilities for their further development are considered. An important part of the review is the description of a possible immunohistochemical markers, since immunohistochemistry is widely used to confirm the diagnosis. In addition, INSM1 (insulinomaassociatedprotein 1), the new immunohistochemical and molecular marker for NEN is discussed: according to the literature, it contributes to more accurate assessment of the tumor malignant potential and the metastatic risk. Furthermore, modern methods of endoscopic and PET/CT imaging (68-gallium DOTATATE PET/CT, molecular imaging using SSTR (somatostatin receptor) PET/CT or GLP-1R (Glucagon-like peptide-1 receptor) SPECT (single photon emission computed tomography)/CT), which allows the clinician to suspect a NEN even before morphological analysis of the resected specimen and adequately select the extent of surgical intervention are shown.

Conclusion: We would like to reiterate the importance of further research on the gastric NET subtype pathogenesis and their clinical behavior, also of the correlation of the endoscopic, morphological, and immunohistochemical picture with the patient prognosis to improve managment tactics.

Annals of the Russian academy of medical sciences. 2020;75(2):169-177
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TO THE MEMORY OF
Mind and heart in scientific research
Paltsyn A.A.
Abstract

The article presents the opinions of prominent native and foreign scientists about the psychology of scientific creativity, the role of interest, love, and almost always, even a passion to the subject of research. Not all scientists discuss this topic, but when we get acquainted with the available information, we become convinced that great scientific achievements are created only by people who are in love with their work. Pushkin’s words are confirmed: «Inspiration is needed in geometry, as in poetry». In the topic under discussion, a special place is occupied by the work of Donat Semenovich Sarkisov. Firstly, because of the structure of his mind, he turned out to be especially susceptible to rapidly forthcoming and developing methodological achievements into the theory and practice of medicine of the twentieth century. Electron microscopy, light and electron autoradiography, cyto- and immunochemistry became the technical basis for D.S. Sarkisov’s theory of intracellular regeneration. His specialty: pathologist, general pathologist, general morphologist, happily coincided with the variety of scientific and clinical topics of the Institute of Surgery named after A.V. Vishnevsky of the Soviet years. Patriotism, love of science, widespread social activity, and the post of Scientific Secretary of the RAMS contributed to the implementation of the achievements of the mind and heart of Donat Semenovich in the practice of domestic medicine. A unique event in science — the discovery (officially recognized) of the law of philosophy, of course, he applied to understand and describe the history of Russia. A lot of «heart» was spent by the patriot D. S. Sarkisov on this understanding and description!

Annals of the Russian academy of medical sciences. 2020;75(2):178-182
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