[Study of the resistome of human microbial communities using a targeted panel of antibiotic resistance genes in COVID-19 patients].

AIM: To study overall drug resistance genes (resistome) in the human gut microbiome and the changes in these genes during COVID-19 in-hospital therapy. MATERIALS AND METHODS: A single-center retrospective cohort study was conducted. Only cases with laboratory-confirmed SARS-CoV-2 RNA using polymerase chain reaction in oro-/nasopharyngeal swab samples were subject to analysis. The patients with a documented history of or current comorbidities of the hepatobiliary system, malignant neoplasms of any localization, systemic and autoimmune diseases, as well as pregnant women were excluded. Feces were collected from all study subjects for subsequent metagenomic sequencing. The final cohort was divided into two groups depending on the disease severity: mild (group 1) and severe (group 2). Within group 2, five subgroups were formed, depending on the use of antibacterial drugs (ABD): group 2A (receiving ABD), group 2AC (receiving ABD before hospitalization), group 2AD (receiving ABD during hospitalization), group 2AE (receiving ABD during and before hospitalization), group 2B (not receiving ABD). RESULTS: The median number of antibiotic resistance (ABR) genes (cumulative at all time points) was significantly higher in the group of patients treated with ABD: 81.0 (95% CI 73.8-84.5) vs. 51.0 (95% CI 31.1-68.4). In the group of patients treated with ABD (2A), the average number of multidrug resistance genes (efflux systems) was significantly higher than in controls (group 2B): 47.0 (95% CI 46.0-51.2) vs. 21.5 (95% CI 7.0-43.9). Patients with severe coronavirus infection tended to have a higher median number of ABR genes but without statistical significance. Patients in the severe COVID-19 group who did not receive ABD before and during hospitalization also had more resistance genes than the patients in the comparison group. CONCLUSION: This study demonstrated that fewer ABR genes were identified in the group with a milder disease than in the group with a more severe disease associated with more ABR genes, with the following five being the most common: SULI, MSRC, ACRE, EFMA, SAT.

[Efficacy of Saccharomyces boulardii CNCM I-745 probiotic drug in the prevention and treatment of diarrhea in hospitalized patients with new coronavirus infection COVID-19].

AIM: To evaluate the efficacy of Saccharomyces boulardii (S. boulardii) CNCM I-745 probiotic drug in preventing and treating diarrhea in hospitalized patients with COVID-19. MATERIALS AND METHODS: A prospective comparative study was conducted in two parallel groups. The study included males and females aged 18 to 60 with the following diagnosis confirmed by polymerase chain reaction: U07.2 Coronavirus infection COVID-19, caused by SARS-CoV-2 virus (grade 1-3 pneumonia according to CT scan). All patients received antibiotic therapy. The patients were subdivided into two equal groups (n=60) depending on the administration of S. boulardii CNCM I-745 probiotic drug in addition to standard treatment. The probiotic was prescribed by the attending physician; the dose was 2 capsules per day (500 mg/day) 30 min before the meal for 10 days. All patients were monitored for main clinical, laboratory, and instrumental parameters during the study. In addition, the symptom of diarrhea (stool with a frequency of more than 3 times a day of type 6 and 7 according to the Bristol stool scale), including its frequency, duration, and the number of bowel movements of loose stool per day were precisely evaluated in both groups. RESULTS: In the overall patient pool, diarrhea was reported in 21.7% of in-patients during the observation period (95% confidence interval [CI] 14.2-29.1) with a mean duration of 4.6154 days (95% CI 3.7910-5.4398). The incidence of diarrhea in group 1 was 13.3% (95% CI 4.5-22.2), and in group 2, it was 30.0% (95% CI 18.1-41.9). Relative risk showed that the use of the S. boulardii CNCM I-745 probiotic drug leads to a significant reduction in the risk of diarrhea in hospitalized patients with COVID-19 infection receiving antibiotic therapy (odds ratio [OR] 0.3590, 95% CI 0.1421-0.9069; p=0.0303). In group 1, the duration of diarrhea was 3.1250 days (95% CI 2.5892-3.6608) versus 5.2778 days (95% CI 4.2290-6.3265) in group 2, p=0.0112. The mean daily frequency of loose stools in patients with diarrhea in group 1 was 3.2500 (95% CI 2.6588-3.8412) versus 4.3889 (95% CI 3.7252-5.0525) in group 2, p=0.0272. The secondary endpoint, duration of hospital stay, was also significantly shorter in group 1 patients - 11.6833 days (95% CI 11.2042-12.1625) versus 12.7333 days (95% CI 12.1357-13.3309) in group 2, p=0.0120. CONCLUSION: The present prospective comparative study demonstrated that adding S. boulardii CNCM I-745 probiotic drug into the standard treatment regimen of patients with new coronavirus infection COVID-19 receiving antibiotic therapy helps reduce the incidence of diarrhea and its severity during hospitalization, as well as the duration of hospital stay.

[Composition of oropharyngeal microbiota in patients with COVID-19 of different pneumonia severity].

AIM: To identify features of the taxonomic composition of the oropharyngeal microbiota of COVID-19 patients with different disease severity. MATERIALS AND METHODS: The study group included 156 patients hospitalized with confirmed diagnosis of COVID-19 in the clinical medical center of Yevdokimov Moscow State University of Medicine and Dentistry between April and June 2021. There were 77 patients with mild pneumonia according to CT (CT1) and 79 patients with moderate to severe pneumonia (CT2 and CT3). Oropharyngeal swabs were taken when the patient was admitted to the hospital. Total DNA was isolated from the samples, then V3V4 regions of the 16s rRNA gene were amplified, followed by sequencing using Illumina HiSeq 2500 platform. DADA2 algorithm was used to obtain amplicon sequence variants (ASV). RESULTS: When comparing the microbial composition of the oropharynx of the patients with different forms of pneumonia, we have identified ASVs associated with the development of both mild and severe pneumonia outside hospital treatment. Based on the results obtained, ASVs associated with a lower degree of lung damage belong predominantly to the class of Gram-negative Firmicutes (Negativicutes), to various classes of Proteobacteria, as well as to the order Fusobacteria. In turn, ASVs associated with a greater degree of lung damage belong predominantly to Gram-positive classes of Firmicutes Bacilli and Clostridia. While being hospitalized, patients with severe pneumonia demonstrated negative disease dynamics during treatment significantly more often. CONCLUSION: We have observed differences in the taxonomic composition of the oropharyngeal microbiota in patients with different forms of pneumonia developed outside hospital treatment against COVID-19. Such differences might be due to the presumed barrier function of the oropharyngeal microbiota, which reduces the risk of virus titer increase.

[Prevalence and prognostic value of gastroenterological manifestations of COVID-19: data from the Russian University Clinic].

AIM: Assessment of the prevalence and prognostic value of gastroenterological manifestations in patients with COVID-19. MATERIALS AND METHODS: A single-center retrospective cohort study was carried out. Only cases with laboratory confirmed detection of SARS-CoV-2 virus RNA using polymerase chain reaction in oro-/nasopharyngeal smear samples were subject to analysis. Patients with documented (according to anamnestic data and/or according to examination data during hospitalization) organic pathology of the gastrointestinal tract (GIT) and/or hepatobiliary system, malignant neoplasms of any localization, as well as pregnant patients were excluded from the general register of retrospective data. The final cohort was divided into two groups depending on the presence of gastrointestinal symptoms: COVID-19 with gastrointestinal symptoms (cases) and COVID-19 without gastrointestinal symptoms (control). RESULTS: The final sample consisted of 3764 patients, including 2108 (56%) women and 1656 (44%) men. The average age of the subjects included in the analysis was 58.0 years (95% confidence interval CI 48.663.0). In the study cohort, gastroenterological manifestations (alone or in combination) were recorded in 885 (23.51%) patients. Calculation of the odds ratio (OR) of unfavorable and lethal outcomes between the analyzed groups showed that the presence of gastroenterological symptoms significantly increases the chances of lethal outcome in a cohort of elderly and senile patients (OR 1.6817, 95% CI 1.03352.7364; p=0.0364), determines a higher risk of hospitalization or transfer to the intensive care unit (OR 1.2959, 95% CI 1.05471.5922; p=0.0136), development of acute respiratory distress syndrome (OR 1.5952, 95% CI 1.31641.9329; p0.0001), as well as the need for mechanical ventilation (OR 1.2849, 95% CI 1.0771.5329; p=0.0054). CONCLUSION: The present study has demonstrated that gastroenterological symptoms are detected in about one in four patients infected with the SARS-CoV-2 virus and multiply the risk of adverse and life-threatening complications of COVID-19.

[Combined therapy of acid-dependent gastrointestinal disorders with the use of antacidic drug Relcer].

The aim of the study was to evaluate clinical efficiency of antacidic drug Relcer included in combined therapy of gastroesophagal reflux disease (GERD) and ulcer disease (UD). Group 1 comprised 47 patients with GERD and group 2 49 patients with gastric and duodenal UD. Each group was divided into study (A) and control (B) subgroups. All GERD patients were given rabeprazole and metoclopramide, patients with UD received rebaprazole, clarithromycin and amoxicillin. Relcer was additionally prescribed to 24 patients in group 1A and 26 in 2A. Duration of therapy in all groups was 14 days. By the end of the study, all symptoms of GERD were eliminated in 100% of the patients in group 1A and in 78.3% in 1B. Pain and heartburn in group 1A were reduced or eliminated within 5 and 7.8 min respectively after the first dose of Relcer. The same complaints in 69.9% of 1B patients were resolved by the end of the first day. The remaining ones benefited from combined treatment on day 2 Rapid and complete elimination of UD symptoms was finally achieved in 21.7-26.1% of 2A patients whereas moderate dyspeptic syndrome persisted in those of subgroup 2B. Ulcer scarring completed by day 14 in 88.5 and 87% of the patients in subgroups 2A and 2B respectively. Eradication of H. pylori was achieved in 92.3 and 87% of the patients in these groups. It is concluded that introduction of Relcer into combined therapy of GERD and UD improves its results and accelerates elimination of clinical symptoms.

[Helicobacter pylori infection as additional risk factor of the development of NSAID-gastropatia effects at the patients with osteoarthritis].

Prevalence of osteoartrosis disease is high among the population. The main places in treatment of this pathology occupy NSAID. Intake of NSAID is lead to the development of NSAID-gastropatia. During last years H. pylori infection was numbered with risk factors of the NSAID-gastropatia development. In this review considered researches which are devoted to studying ties between H. pylori and NSAID. Data of the using eradication therapy with purpose of prevention and treatment of NSAID-gastropatia associated with H. pylori are shown in this review.

[Early symptoms of hepatic encephalopathy in patients with chronic diffuse hepatic diseases].

Four hundred and twenty-three patients with chronic diffuse hepatic diseases (hepatitis and viral hepatic cirrhosis) underwent complex clinico-instrumental examination; the control group consisted of 30 healthy individuals. Hepatic encephalopathy syndrome was a much more frequent finding in patients with hepatic cirrhosis. Association of chronic viral hepatic lesion with alcohol abuse increased the frequency of latent central nervous system lesions.

[Etiology of chronic diffuse liver damages].

Patients with chronic diffuse liver damages have cases of chronic hepatitis associated with alcoholic liver disease being transformed to cirrhosis 2.1 times more often when having mostly equal frequency of chronic damage of viral and alcoholic origin on the stage of chronic hepatitis or in the case of pure viral damage against a background of significant prevalence (3 times) of viral etiology. Infection associated with HCV in patients with alcoholic liver cirrhosis doesn't significantly influence the course of disease, aftereffects and prognosis of patients.

[Use of ednit in the treatment of portal hypertension in patients with chronic hepatitis and liver cirrhosis]. / Opyt primeneniia édnita dlia lecheniia portal'noi gipertonii u bol'nykh khronicheskim gepatitom i tsirrozom pecheni.

AIM: To study ednit (ACE inhibitor) effectiveness in the treatment of portal hypertension in patients with chronic hepatitis (CH) and hepatic cirrhosis (HC). MATERIAL AND METHODS: The examination of 87 patients with active CH and 54 patients with HC at the preascytic stage included two-dimentional ultrasonic scanning of the abdominal organs with doppler fluometry of the vessels in the territory of the portal vein, tetrapolar rheohepatography, ultrasound investigation, angiography of the abdominal vessels. The patients received combined therapy with ednit in a dose 5 mg twice a day for at least 5 weeks. RESULTS: Patients with active CH and HC having portal hypertension treated with adjuvant ednit in the above dose achieved marked clinicobiochemical remission quicker, portal-hepatic circulation improved. CONCLUSION: The addition of ednit to therapy of active CH and HC with portal hypertension is effective as it lowers total peripheral vascular resistance which eventually results in a fall of pressure in the territory of the portal vein and improvement of hepatic circulation. The highest effect is reached in administration of 5 mg twice for 24 hours.

[24-hour monitoring of gastric juice pH in assessment of anti-ulcer treatment]. / Ispol'zovanie sutochnogo monitorirovaniia pH zheludochnogo soka dlia otsenki éffektivnosti protivoiazvennoi terapii.

AIM: Comparison of various schemes of three-component eradication of duodenal ulcer (DU) using 24-h monitoring of gastric juice pH. MATERIALS AND METHODS: 62 DU patients in aggravation period have undergone 24-h monitoring of gastric juice pH and esophagogastroduodenoscopy with biopsy and H.pylori test of the treatment beginning and end. Patients of group 1 (n = 28) received ranitidin, metronidazole and amoxicillin while patients of group 2 (n = 34) took quamatel, metronidazole and amoxicillin. RESULTS: 24-h monitoring of pH of the gastric juice demonstrated that three-component therapy consisting of quamatel (20 mg/day, metronidazole (500 mg 4 times a day), amoxicillin (750 mg 3 times a day) maintains the level of intragastric acidity optimal for quick scarring of duodenal ulcer defect and led to eradication of H.pylori in 91.2% of cases. CONCLUSION: 24-h monitoring of gastric juice pH is a significant method of assessment of antiulcer treatment efficacy.

[Liver function in biliary tract dyskinesia]. / Sostoianie pecheni pri diskinezii zhelchevyvodiashchikh putei.

The authors analyze data obtained in a complex clinico-instrumental study of the functional activity of the liver, portal and hepatic blood flow in 77 patients with different forms of dyskinesias of the biliary tract. Obtained data evidence in these patients development (against the background of cholestasis) functional insufficiency of the liver and involvement of its parenchyma associated with a moderate pressure increase in the portal vein, reduction of the hepatic blood flow intensity, increase of its lability that may be a proof of development (in patients with functional bile secretion disorders) of chronic diffuse inflammatory process in the liver with subsequent appearance of clinically clear portal hypertension.

[Drug therapy of pulmonary and portal hypertension in liver cirrhosis]. / Farmakoterapiia legochnoi gipertenzii pri tsirroze pecheni.

Detailed examination of hemodynamics in patients with portal and pulmonary hypertension was performed upon acute drug tests and course administration of nitrosorbide++, corinfar and propranolol. Ultrasound and rheography investigations were employed to elucidate the relations between portal and pulmonary hypertension in cirrhosis patients. Criteria of early diagnosis are discussed. Nitrosorbide++ produced positive effect on hepatic blood flow, corinfar improved pulmonary hemodynamics in lack of its influence on hepatic blood flow, while propranolol resulted in the drop of both portal and pulmonary hypertension, normalization of general hemodynamics.