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Aim. These recommendations are developed for practitioners in order to familiarize them with modern diagnostic methods, management features and pharmacotherapy of patients with gastroesophageal reflux disease (GERD).General provisions. GERD is the most common reason for patients to visit clinics. There are esophageal and extraesophageal manifestations of GERD. Patients' complaints of heartburn and regurgitation remain the most sensitive and specific clinical manifestations of GERD. The diagnosis of GERD is established on the basis of anamnestic data, instrumental examination (detection of reflux esophagitis during upper gastrointestinal endoscopy, detection of pathological gastroesophageal reflux with 24-hour pH-metry or/and 24-hour pH-impedance monitoring). Patients with suspected GERD and the absence of erosive and ulcerative changes in the mucous membrane of the esophagus or the presence of erosive esophagitis of Grade A according to Los Angeles Classification of Gastroesophageal Reflux Disease are recommended to conduct 24-hour pH-metry on PPI off to exclude or confirm the diagnosis of GERD. Patients with extraesophageal manifestations of GERD without classic symptoms (heartburn, regurgitation) are recommended to undergo 24-hour pH-impedance monitoring with discontinuation of proton pump inhibitor therapy. When deciding on surgical treatment, all patients need to perform high-resolution esophageal manometry and 24-hour pH-impedance monitoring. Complications of GERD include bleeding, strictures, Barrett’s esophagus and esophageal adenocarcinoma. The main groups of medications used in the treatment of GERD are proton pump inhibitors (PPIs), potassium-competitive acid blockers (P-CABs), alginates, antacids, and prokinetics. PPIs are the drugs of choice in the treatment of both symptoms of gastroesophageal reflux disease and existing erosive esophagitis. Combination therapy Rebamipide with PPIs increases the effectiveness of relief of GERD symptoms, as well as reduces the frequency of relapses.Conclusion. These clinical recommendations will improve the quality of medical care for patients with GERD.

Background. Comorbidity as the presence of two or more pathological processes in a patient is one of the most discussed topics in medical forums around the world and in Russia. Meanwhile, the breadth of discussion of this problem carries the risk of losing the true meaning of comorbidity, set out by the ideologist of this problem, A. R. Fainstein, namely: a combination in one patient of two and/or more chronic diseases, pathogenetically interrelated. (with an unconditional understanding of the variety of options for these connections).Results. This article offers the reader a detailed look at comorbidity in its original/true understanding, based on a deep understanding of the pathogenesis of diseases and pathomorphological analysis of completed cases of comorbidity. Various options for comorbidity (causal, complicated, iatrogenic, specified and unspecified) with pathomorphological confirmation are considered. Pathomorphological illustrations of the analyzed variants are offered – preparations from the clinical and morphological archive of the Department of Therapy, Clinical Pharmacology and Emergency Medical Care of the Moscow State Medical and Dental University (now the Russian University of Medicine). Inseparable from the understanding of comorbidity is an accurate, uniform presentation of diagnoses – clinical and pathomorphological – by doctors of all specialties, to ensure continuity in the provision of medical care and improve the quality of diagnosis and treatment. The article updates the rules for formulating a clinical and pathomorphological diagnosis in a comorbid patient, namely: a clear reflection of the presence of the main disease and comorbid ones (competing, combined and background diseases), complications of the main disease and concomitant diseases. In the finale, algorithmized "comorbidity postulates" are proposed, facilitating the perception and use of the proposed methodological approaches.

The aim of this work was to study the risk factors for severe COVID-19, comorbid diseases, and the structure of mortality in patients who died in a hospital from a new coronavirus infection. The study included 180 patients with bilateral viral polysegmental pneumonia caused by SARS-CoV-2. In patients with viral pneumonia, the degree of lung tissue damage, the frequency and severity of comorbid diseases were studied: arterial hypertension, coronary heart disease, cerebrovascular diseases (chronic cerebral ischemia, cerebral stroke), atrial fibrillation, chronic heart failure, chronic kidney disease, diabetes mellitus type 2, obesity, malignancy and anemia. In patients with COVID-19-associated pneumonia, severe lung damage was observed – pneumonia with CT3 (36.1%) and CT4 (33.0%) prevailed, less often CT2 (30.9%). A high frequency of comorbid diseases was found in deceased patients with viral pneumonia: arterial hypertension (98.9%), cerebrovascular disease (96.9%), coronary heart disease (83.9%), chronic kidney disease (96.7%), type 2 diabetes mellitus and atrial fibrillation – in almost half of patients (42.2%), and in every third patient – obesity (36.6%). The main causes of death in patients with COVID-19-associated pneumonia were: acute respiratory distress syndrome (83.3%), less often acute myocardial infarction (7.2%), cerebral infarction and edema (5.6%), thromboembolism pulmonary artery (3.9%). In patients with viral pneumonia caused by SARS-CoV-2, there is a high frequency of comorbid conditions leading to a severe course of the disease: arterial hypertension, coronary heart disease, severe chronic heart failure, advanced age (> 75 years), lack of vaccination, chronic kidney disease, obesity of the 3rd degree, diabetes mellitus type 2. Among women who died from COVID-19-associated pneumonia, such risk factors as age over 75 years, type 2 diabetes, lack of vaccination, a history of myocardial infarction with the development of chronic heart failure stages 2A and 2B, and chronic microcytic anemia prevailed; among the dead men – obesity of the third degree, a history of cerebral stroke, lack of vaccination and severe chronic heart failure.

The purpose of the review: to summarize the main data of the literature and our own accumulated practical experience of everyday diagnosis of inflammatory bowel diseases (IBD) to better represent the morphological features and histological conclusions.Key points. The microscopic picture of IBD is often represented by a combination of basic histological characteristics that can be detected in other diseases and only in rare cases can be considered pathognomonic. No single histological feature can be used in isolation to diagnose ulcerative colitis or Crohn’s disease. Diagnostic accuracy is improved if several signs are taken into account at once, if changes within one or more parts of the intestine are analyzed, it is necessary to compare the identified changes with the clinical picture of the disease.Conclusion. The presented stages of the morphological study of biopsy specimens in patients with IBD and the exact characteristics of the detected changes will help to increase the diagnostic value of the study of ileo- and colonobiopsies, as well as improve mutual understanding between gastroenterologists and pathologists and, as a result of interaction between specialists, will increase the accuracy of the diagnosis.

Aim. Current clinical recommendations aim to provide gastroenterologists, general practitioners (family doctors), endoscopists and infectionists with modern methods for diagnosis and treatment of infectious esophagitis.Key points. Infectious esophagitis is an esophageal disease of fungal, viral, bacterial or parasitic origin. Esophagus may be affected per se or conjointly in a common gastrointestinal infection. All patients suspected for infectious esophagitis, unless contraindicated, are advised an esophagogastroduodenoscopy with biopsy to confirm diagnosis. Selected incidents of infectious esophagitis require a histological, immunohistochemical examination or polymerase chain reaction-based diagnosis to verify the infectious agent. Uncomplicated infectious esophagitis requires a conservative therapy, mostly on an outpatient basis. However, cases of severe odynophagia, dysphagia, severe pain syndrome, high complication risks (e.g., esophageal ulcer bleeding in thrombocytopenia), severe immunodeficiency, generalised forms of disease and severe concomitant disorders are considered for hospital care. The clinical recommendations outline criteria for the medical care quality assessment and provide relevant information to the patient.Conclusion. Diagnosis of infectious esophagitis capitalises on the clinical picture (odynophagia, dysphagia), presence of immunosuppression, endoscopic and histological evidence. All patients with infectious esophagitis of verified origin are recommended a suitable etiotropic therapy.

Aim. Determine the primary antibiotic resistance of Helicobacter pylori (H. pylori) strains isolated from patients living in the European part of the Russian Federation. Materials and methods. As part of a clinical laboratory study, from 2015 to 2018, 27 gastrobiopsy samples obtained from H. pylori-infected patients were analyzed. H. pylori infection was verified using a rapid urease test or a 13C-urea breath test. The values of the minimum inhibitory concentration (MIC) of antibiotics were determined by the diffusion method using E-test strips (BioMerieux, France) according to the recommendations of the manufacturer. The sensitivity of the isolates was determined for 6 antibacterial drugs (amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline, rifampicin). Results. According to the data obtained, resistance to amoxicillin was 0%, clarithromycin 11.1%, metronidazole 59.3%, levofloxacin 3.7%, tetracycline 0%, and rifampicin 14.8%. Dual resistance to clarithromycin and metronidazole was recorded in two isolates (7.4%). Conclusion. Thus, the first results of the evaluation of H. pylori antibiotic resistance in the European part of the Russian Federation indicate a low resistance of the microorganism to clarithromycin and quite high to metronidazole.

Aim. Current recommendations of the Russian Gastroenterological Association are developed to acquaint medical practitioners with modern diagnostics, treatment and trends in rational drug therapy for gastroesophageal reflux disease (GERD).General provisions. Incidence rate of GERD in the Russian Federation varies from 11.3 to 23.6%. GERD is diagnosed with medical history and laboratory examination evidence. Esophagogastroduodenoscopy (EGDS) allows detection of reflux esophagitis of various severity and cylindrical epithelial metaplasia of esophagus. The refractory form of disease (lack of conclusive clinical and endoscopic remission during 4-8 weeks of standard-dose PPI therapy), presence of strictures and Barrett's esophagus require EGDS with esophageal biopsy and bioptic histological examination. Patients should be conclusively performed esophageal 24-hour pH-metry or pH-impedance monitoring, high-resolution manometry to thoroughly examine functionality of esophagus, esophagogastric junction and assess disease prognosis and therapy outcomes.Treatment of GERD should be personalised accounting for clinical manifestations and severity, as well as aimed at symptom improvement, lesion healing in erosive esophagitis, averting complications, Barrett's esophagus progression, dysplasia and esophageal adenocarcinoma.Proton pump inhibitors (PPIs) are most effective agents in primary (4-8 weeks) and maintenance anti-GERD therapy. Antacids are recommended in monotherapy for occasional nonerosive heartburn and complex anti-GERD settings for fast symptom improvement. Prokinetics can be used in combination with PPIs for their properties to recover normal functionality of esophagus through affecting pathogenetic mechanisms of GERD.Complicated patients (repeated bleedings, peptic esophageal strictures) are recommended anti-reflux surgery with prior examination of esophageal functionality using pH-impedance and high-resolution manometry.Conclusion. Current recommendations provide an up-to-date evidential medicial review of GERD and guidelines to advance special medical care and timely preventive measures.

The differences in mortality rates between Moscow and St. Petersburg require study.Aim. Ranking and comparison of cardiovascular mortality in Moscow and St. Petersburg in 2015 and 2018.Material and methods. Data on the population and mortality rates was assessed according to the Brief nomenclature of causes of death of Federal State Statistic Service. Eleven out of 35 nomenclature lines related to cardiovascular disease (CVD) are represented by 4-digit ICD codes, the rest are represented by groups with 3- and/or 4-digit codes. Standardized mortality rates (SMRs) were calculated based on the European standard. Comparison of SMR differences between Moscow and St. Petersburg in 2015 and 2018 was carried out using the nonparametric Wilcoxon test.Results. The proportion of CVD in all-cause SMR in both cities is about 50%. There were no significant differences in SMR (2018-2015) between Moscow and St. Petersburg for 35 CVDs. The first 3 ranking places in the CVD pattern both in Moscow and St. Petersburg were occupied by CAD, different types of chronic CAD, and stroke. In 2015, their proportion was 58,3% and 48,9% and in 2018, 52,7% and 58,7%. Other causes varied significantly in relation to SMR and ranks in different years, which is probably due to different approaches to determining the code of death cause. The SMR and myocardial infarction contribution to cardiovascular mortality decreased.Conclusion. Differences in cardiovascular mortality between Moscow and St. Petersburg remain. To understand the mortality causes and to develop effective programs to reduce it, it is necessary to eliminate the identified defects.

Aim of publication. To present the latest data on adequate diagnostic methods, treatment approaches and features of rational pharmacotherapy of gastroesophageal reflux disease (GERD) based on the principles of evidence­based medicine to general practitioners. Summary. The prevalence of GERD occupies the first place of other gastroenterological diseases. The heartburn that is a leading GERD symptom is present at 20-40% of the population of developed countries. The prevalence of GERD in Russia ranges 18­46%. Diagnosis of GERD early stages is based on the primary appealability and clinical presentation evaluation. Esophagogastroduodenoscopy (EGDS) gives the chance to define the presence of reflux esophagitis, to estimate severity grade, to reveal development of esophageal epithelium columnar metaplasia. At the refractory course (lack of conclusive clinical and endoscopic remission within 4-8 wks of treatment by standard dose of proton pump inhibitor - PPI), and development of complications (strictures, Barret's esophagus) examination within specialized hospital or gastroenterological clinic is required, including their out­patient departments. Under certain indications the patient should undergo EGDS with esophageal biopsy and histological examination of biopsy specimens to rule out the Barret's esophagus, esophageal adenocarcinoma and/or eosinophilic esophagitis; intraesophageal 24­hour pH­metry or pH­impedance measurement; high resolution esophageal manometry; X­ray study of the esophagus and stomach. The treatment of GERD has to be individualized according to the pattern and severity of clinical symptoms. The goal of treatment is symptom relief, at erosive esophagitis - healing of erosions and complication prevention, at Barret's esophagus - prophylaxis of disease progression and dysplasia and adenocarcinoma development. Nowadays PPIs are considered as the most effective and safe agents for GERD treatment. PPIs are applied for the long­term baseline treatment (no less than 4-8 wks) and maintenance therapy (6-12 months). Intake of alginates is pathogenically reasonable therapeutic approach for reduction of «acid pocket» and acid neutralization in the area of gastro­esophageal junction in GERD patients by formation of mechanical barrier raft which prevents reflux of the stomach content into the esophagus. Antacid monotherapy is recommended for the cases of rare heartburn which is not accompanied by esophagitis and in complex modes of GERD treatment for achievement of rapid symptom relief. Adsorbents are applied as monotherapy at non­ erosive reflux disease, and as a component of comprehensive GERD treatment, especially of the cases of mixed (acid + biliary) refluxes. Prokinetic drugs promote recovery of a normal physiological state of the esophagus, controlling the pathogenic mechanisms of GERD, reducing the number of transient lower esophageal sphincter relaxations and improving esophageal clearance due to stimulation of the lower gastrointestinal motor function. Prokinetics can be applied as a component of comprehensive treatment of GERD along with PPI. Anti­reflux surgery is indicated in complicated cases (recurrent bleeding, peptic esophageal strictures, development of Barret's esophagus with high­grade epithelial dysplasia, frequent aspiration pneumonias). Surgical treatment of GERD is more effective in patients was typical manifestations and positive treatment response to PPIs. Conclusion. Implementation of clinical guidelines can promote improvement of healthcare quality for GERD patients and prevent complications, in particular if terms of treatment will be observed, at active outpatient follow­up for certain groups of patients.

In case of severe burn leukomas when keratoplasty is ineffective, the only way to restore vision is keratoprosthetics. Low biomechanical characteristics of leukoma make the surgery significantly more difficult and affect the development of complications, for their prevention and treatment the techniques strengthening cornea using autologous tissue are elaborated. However, their use has a number of difficulties, such as the selection and simulation of grafts in necessary form, weak adaptive capacity of the material and its lysis in the postoperative period. In this paper a new method is presented to improve biomechanical properties of the corneal leukoma using the implantation of collagen membrane with the growth factor of bone rhBMP-2 inthe corneal stroma. An increase of the strength characteristics of cornea 2-3 weeks after the implantation of collagen membrane with rhBMP-2 was proved experimentally.Purpose. To assess the impact of rhBMP-2 in a collagen membrane composition of the carrier on morphological and biomechanical characteristics of the cornea.Material and methods. The study was performed in 18 rabbits of the chinchilla breed. For a preparation of the implants (collagen membranes) we used a sterile 2% solution of the purified native rat collagen of the type I («IMTEK»), to which a sterile solution of rhBMP-2 (produced by the N.F. Gamaleya Center of Epidemiology and Microbiology) was added. The obtained collagen membrane was implanted into the intrastromal «from limbus to limbus» corneal pocket. The experimental period was 90 days. Corneal samples were investigated for morphology and biomechanics.Results. In the postoperative period an intense angiogenesis was observed with a moderate inflammatory reaction, which subsided on the 8th day. Histological examination revealed a graft retention followed by its replacement by young connective tissue. A study of the biomechanical properties showed a significant increase in the strength characteristics of the cornea i n the site of implant ation.Conclusions. The feasibility of morphological and biomechanical properties changes of the corneal tissue under the action of growth factor rhBMP-2 is proved. This is a promising direction for leukoma strengthening at various stages of keratoprosthetics and requires a further study.

The objective. To assess the effectiveness of the selective progesterone receptor modulator ulipristal (Esmya) in presurgicaltherapy of patients with uterine myoma.Patients and methods. The examination included 23 patients with uterine myoma aged 37 to 42 years, 13 patients with uterine myoma aged 21 to 41 years who received Esmya (5 mg/day for 3 months) as a presurgical treatment, 10 patients with uterine myoma aged 33 to 48 years - control group. Removed myoma nodules underwent complex histological examination that included immunohistochemical testing with the use of monoclonal antibodies to estrogen and progesterone receptors; Кi-67; phospho-histone; Вах; Bcl-2; cleaved caspase-3; VEGF.Results. After a 3-month Esmya therapy in 13 patients, the sizes of uterine myoma decreased to correspond to 2-3 wks of gestation, the sizes of the dominant nodule were reduced on the average by 3±0,4 cm in diameter, amenorrhea developed as soon as in the first cycle (complaints of profuse menstrual bleeding stopped). No undesirable effects were noted, the women pointed out to the convenient use of the drug. A morphological examination found large sites of dystrophic changes of leiomyocytes; low-active perivascular growth areas; pseudocapsule sclerosis, single mitotic figures, and marked apoptosis. Analysis of the results of immunohistochemical examination found the following results: phospho-histone and Ki-67 - in single cells; Bax - marked induction; cleaved caspase-3 - distinct expression; VEGF - weak-to-moderate expression; expression of progesterone - 78-87%.Conclusion. As has been demonstrated a decreasing of proliferation and hypertrophy of smooth muscle cells of uterine myoma, under the influence of Esmya; while the surrounding myometrium does not change. The mechanism of the regression effect of Esmya on uterine myoma has been confirmed as a selective tissue-specific «noneffective» receptor protein conformator, inhibiting transcription of progesterone in cells of uterine myoma.