[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.

[Zonulin and I-FABP are markers of enterocyte damage in celiac disease].

AIM: To evaluate the level of serum I-FABP (Fatty-Acid-Binding Protein a protein that binds fatty acids) and fecal zonulin as markers of the permeability of the mucous membrane of the small intestine in celiac patients. MATERIALS AND METHODS: A total of 151 celiac patients (25 men and 126 women) were examined. The median age was 42 years. Group I included 58 patients with newly diagnosed celiac disease; in group 2 38 patients, knowingly or unknowingly violating the gluten-free diet; group 3 consisted of 55 patients strictly observing gluten-free diet. The control group consisted of 20 healthy volunteers: 4 men and 16 women. All patients underwent esophagogastroduodenoscopy by biopsy of the mucous membrane of the small intestine and assessment of duodenobioptates according to Marsh. In the blood serum, the level of antibodies to tissue transglutaminase IgA and IgG was determined by the enzyme-linked immunosorbent assay using kits manufactured by Orgentec Diagnostics GmbH (Germany), the concentration of I-FABP in blood serum was determined using Hycult Biotech kits (Netherlands). The content of zonulin in feces was investigated by enzyme-linked immunosorbent assay using kits from Immundiagnostik AG (Germany). Statistical analysis was performed using the Statistica 13.3 software (StatSoft Inc., USA). RESULTS: There was a significant increase in the level of antibodies to tissue transglutaminase IgA [120.0 (41.1200)] IU/ml and IgG [31.4 (5.578.9)] IU/ml in patients of group 1 compared with group 2 [IgA 9.1 (2.987.6)] and IgG [3.8 (2.219.7)] IU/ml and group 3 [IgA 1.6 (1.03.2)] and IgG [2.2 (1.152.53)] (p0.01). The level of I-FABP in blood serum in patients of group 1 averaged 2045 pg/ml, in patients in group 2 1406 pg/ml, in patients in group 3 1000 pg/ml. All patients showed a significant increase in the mean I-FABP values compared to controls (1, 2 and control p0.01, 3 and control p=0.016). In patients with Marsh grade III AC atrophy, the I-FABP level depended on the degree of damage to the mucosa and significantly differed from the control: March IIIA (median: 1310 pg/ml, interquartile range: 12121461 pg/ml), March IIIB (median: 2090 pg/ml, interquartile range: 18122322 pg/ml) as well as Marsh IIIC (median: 2058 pg/ml, interquartile range 18582678 pg/ml). The concentration of zonulin in feces in patients of group 1 averaged 111.6 pg/mg, in patients of group 2 90.5 pg/mg. In patients of group 3 50 IU/ml. The concentration of zonulin in feces increased as the degree of mucosa atrophy increased (r=0.585, p0.01). However, despite the fact that both of these markers may indicate impaired permeability, each of them indicates damage to a certain level of the intestinal barrier, which is not always associated with the degree of mucosa atrophy. CONCLUSION: Determination of serum I-FABP and fecal zonulin levels in celiac patients allows for the assessment of intestinal permeability and can serve as non-invasive markers for monitoring ongoing structural changes in the mucosa without the need for endoscopy.

[Frequency and risk factors for thromboembolic complications in patients with inflammatory bowel diseases].

BACKGROUND: Inflammatory bowel diseases (IBD) are characterized by chronic immune inflammation of the mucous membrane and/or the thickness of the intestinal wall, and are also accompanied by disorders of the blood clotting system and the development of a hypercoagulation state. AIM: To identify the frequency of thromboembolic complications (TEC) in IBD patients and to determine the influence of acquired and inherited hypercoagulation factors that contribute to the development of TEС. MATERIALS AND METHODS: The clinical status of 1,238 IBD patients who were treated in 2019 was evaluated. Of these, 748 patients with ulcerative colitis (UC) and 490 patients with Crohn's disease (CD). Among UC patients, there were 369 (49.3%) men and 379 (50.7%) women. In 10.1% of patients with UC, there were clinically significant feasibility studies. There were 227 (46.3%) men and 263 (53.7%) women among patients with CD; 7.3% of patients with CD had clinically significant feasibility studies. RESULTS: In general 112 (9.0%) of 1,238 IBD patients had clinically significant feasibility studies. Among patients with UC (n=748), 76 (10.2%) showed clinically significant feasibility studies. Among patients with CD (n=490), 36 (7.3%) had a feasibility study. Of 112 IBD patients with clinically significant TEC, 45 (40.2%) had genetic polymorphisms that increase affinity for fibrinogen, increase platelet aggregation, and contribute to a decrease in the activity of folate cycle enzymes, including methylenetetrahydrofolate reductase, which may be manifested by a moderate increase in homocysteine levels. Of the 45 IBD patients with clinically significant TEC due to inherited factors, 30 (66.6%) patients had UC, 15 (33.7%) patients had CD (hazard ratio 1.038, 95% confidence interval 0.7461.444; 2=0.049; p=0.83921); 67 (59.8%) patients with IBD who had clinically significant TEC did not have genetic polymorphisms leading to hypercoagulation. CONCLUSION: Based on the analysis, we can conclude that such risk factors for the development of TEC as the status of a smoker, long bed rest, taking hormonal contraceptives, varicose veins of the lower extremities, high activity of the disease, glucocorticoids therapy, the extent of intestinal damage in patients with IBD, genetic factors, should be taken into account by gastroenterologists in the treatment of patients with UC and CD. The hereditary factor of hypercoagulation equally affects the development of TEC, both in patients with UC and CD.

[Enteropathy with impaired membrane digestion and the prospects for cytoprotective therapy].

The article describes enteropathy with impaired membrane digestion (EIMD) as a new nosological form. The main clinical manifestation of EIMD is the poor tolerance of food products, in particular carbohydrates and a decrease in the activity of membrane enzymes, in particular, carbohydrates, in the mucous membrane of the small intestine. The cause of the disease can be acute intestinal infections, viruses, drugs and other agents that damage the small intestine. The pathophysiology, clinical picture and diagnosis of EIMD are described. The basis of therapy is rebamipide, which has the ability to reduce the symptoms of carbohydrate intolerance and increase the activity of disaccharidases.

[Screening for celiac disease among patients of the gastroenterological profile].

AIM: To determine the frequency of celiac disease (CD) among gastroenterological patients and criteria for its active detection. MATERIALS AND METHODS: 1.358 patients referred for gastroenterologist consultation from 2016 to 2019 was conducted, of which 140 had CD (339 males 24.9%; 1019 females 75.1%). The average age was 40.415.4 (1886 years). All patients were determined anti-TTG IgA, IgG, and analyzed the clinical symptoms and analysis. The results were subjected to statistical processing Statistica 13.3 (StatSoft Inc., USA). RESULTS: In patients without CD (1218 people), high level of anti-TTG IgA and IgG was observed in 59 (4.8%), an increase in anti-TTG IgA in 54 (4.4%), and anti-TTG IgG in 38 patients (3.1%). The CD diagnosis confirmed in 51 patients (4.2%). The main symptoms were diarrhea (88%), abdominal pain (60.7%), bloating (73.8%), nausea (40.3%), weight loss (44.3%). Anemia was determined in 31.6%, serum iron 33%, hypoproteinemia 12.6%, hypoalbuminemia 12%, hypokalemia 5.48%, hypocalcemia 21.9%. An increase in the level of AST 14.5%, ALT 14.6%. Comparative analysis showed that in the group with newly detected CD, anemia, malabsorption syndrome, increase AST, ALT were significantly more frequent than in patients with normal antibodies, which confirms the need to detect CD among patients with these laboratory abnormalities. CONCLUSION: The incidence of CD among patients with a gastroenterological symptoms was 4.2%. Analysis of clinical and laboratory data has shown that a comprehensive analysis of clinical symptoms and laboratory indicators at the stage of primary treatment will allow timely identification of CD patients and prescribe GFD.

[Celiac crisis in patients with celiac disease. Case report].

Celiac crisis (CC) is a rare life-threatening course of celiac disease, observed mainly in children. In adults, CK can be the first manifestation of the disease and, very rarely, a relapse that occurs in patients who do not follow the gluten-free diet (AGD). Triggers can be stress, surgery, childbirth, etc. A clinical observation of CC developed in a 49-year-old patient with previously established latent celiac disease with subtotal villous atrophy, stage Marsh III C is presented. The patient did not comply with AHD. After severe angina, she developed anorexia, diarrhea, emaciation, coagulopathy, bilateral pulmonary embolism, infarction pneumonia, and enterogenic sepsis. As a result of intensive therapy with prednisolone, Fraxiparine, antibiotics, fresh frozen plasma and strict adherence to hypertension, remission of the disease was achieved.

[Loss of response and frequency of adverse events in patients with ulcerative colitis and Crohn's disease when switching from the original infliximab to its biosimilars].

AIM: To define the frequency of adverse events and loss of the response in patients with ulcerative colitis (UC) and Crohn's disease (CD), treated with original medicine infliximab (IFX) "Remicaide" and its biosimilars. MATERIALS AND METHODS: We included 154 patients with IBD: 78 UC patients (50.6%) и 76 CD patients (49.4%), treated with original medicine IFX Remicade and its biosimilars. In our study we did not include patients, who previously underwent induction treatment with IFX and its biosimilar. RESULTS: Among 78 UC patients, IFX was cancelled in 25 (32.0%) patients and they were switched to the other anti-TNF inhibitor or medicine with the another mechanism of action; in patients group, treated with biosimilar ­ 16 (20.5%) and 9 (11.5%) patients, who were interchanged biosimilar and/or original IFX. Among 76 CD patients IFX was cancelled in 20 (26.3%) patients: 11 (14.5%) patients in group, treated with similar trade name biosimilar, 8 (10.5%) patients, who were interchanged biosimilar and/or original IFX and 1 patient (1,3%), receiving original IFX. We found no difference in the secondary loss of response and adverse events in patients with CD and UC, switched from original IFX to biosimilar (p=0.6257 and p=0.6635, correspondingly). The frequency of the secondary loss of response or adverse events in patients with UC and CD, switched from original IFX to IFX biosimilar, was similar (p>0.05). CONCLUSION: Approximately 30% of IBD patients, receiving IFX biosimilar, will be switched to the other anti-TNF therapy or medicine with the another mechanism of action because of secondary loss of response or adverse events.

[Resected bowel syndrome: clinical course and treatment options].

The current concepts of the short bowel syndrome and malabsorption after intestinal surgery are generally accepted, but do not fully reflect the patients condition, making it difficult to diagnose and treat it. AIM: The purpose of the study is to analyze the clinical course of the patients after bowel resection, to create a classification based on the variants identified to allow for a differentiated treatment and to introduce the concept of the resected bowel syndrome. MATERIALS AND METHODS: We observed 239 patients (96 men and 143 women) aged 18 to 80 who underwent intestinal resection for 1 month to 16 years (from 2002 to 2018). The 1st group included 96 patients with small bowel resection (40 men and 56 women). The 2nd group included 39 men and 58 women with small bowel resection, including the resection of the ileocecal valve and the right-hand side of the colon (n=97). The 3rd group included 17 men and 29 women with the resection of the right-hand side of the colon or colectomy (n=46). The survey included the NRS-2002 (Nutritional Risk Screening 2002) screening test to identify nutritional risk, a clinical assessment of the symptoms that occurred after the surgery, instrumental methods (esophagogastroduodenoscopy, colonoscopy with biopsy, ultrasound of the abdominal cavity organs and the kidneys, a plain radiography of the abdominal cavity organs, an X-ray examination of the small intestine and the intestinal passage), serum citrulline and short-chain fatty acids in faeces. RESULTS: Based on the analysis of the clinical symptoms and the nutritional status of the patients, a new concept is proposed the resected bowel syndrome with two variants of its progression: either with or without the development of nutritional insufficiency of three types: the dehydration type, the protein-energy insufficiency type and a mixed type. Type 1 requires the use of antimicrobials with the control of SCFA concentrations in faeces. Type 2 requires the introduction of an optimal amount of easily digestible protein to correct protein-energy deficit. The 3rd (most severe) mixed type requires prescription of a parenteral nutrition component with the control of citrulline concentration in the blood serum. CONCLUSION: The proposed concept the resected bowel syndrome makes it possible to improve its diagnosis, take into account the variants of its progression and allow for a differentiated treatment.

[Bile acids are a risk factor for colorectal cancer].

Bile acids were first considered carcinogenic in 1939. Since then, accumulated data have associated colon cell changes with high levels of bile acids as an important risk factor for developing colorectal cancer, which is more common among people who consume large amounts of dietary fat. Secondary bile acids formed under the influence of the intestinal microbiota can cause the formation of reactive forms of oxygen and nitrogen, disruption of the cell membrane, mitochondria, DNA damage, reduction of apoptosis, increased cell mutation, turning them into cancer cells. High-fat diet, intestinal microflora, bile acids are a risk factors for colorectal cancer.

Rebamipide increases the disaccharidases activity in patients with enteropathy with impaired membrane digestion. Pilot study.

AIM: To evaluate the effectiveness of enteroprotector Rebamipide in the treatment of enteropathy with impaired membrane digestion (EIMD). MATERIALS AND METHODS: We examined 102 patients aged 18 to 50 years (41 men and 61 women) with clinical signs of irritable bowel syndrome (n=65), functional diarrhea (n=33), and functional constipation (n=4) according to Rome IV criteria (2016). The activities of glucoamylase (GA), maltase, sucrase and lactase were determined by Dahlquist-Trinder method in duodenal biopsies obtained during esophagogastroduodenoscopy. The control group consisted of 20 healthy people aged 23-47. They showed following average enzyme activity: lactase - 42±13 ng glucose on 1 mg of tissue per minute, GA - 509±176, maltase - 1735±446, sucrase - 136±35 ng glucose on 1 mg of tissue per minute. These numbers were taken as the norm. RESULTS: The activity of the disaccharidases was reduced in 89.2% out of 102 patients, and they were diagnosed with EIMD. Thirteen patients with EIMD were recommended to maintain the FODMAP diet and take enteroprotector Rebamipide 100 mg 3 times a day for 12 weeks. After 3 months 11 patients reported decreased or no flatulence, abdominal pain, stool disorder; 2 patients reported no change. The activity of GA increased to an average of 149±82 (by 78%, p=0.016), maltase - to 864±472 (by 131%, p=0.0019), sucrase - 63±35 (by 95%, p=0.0041) and lactase - 10±8 ng glucose on 1 mg of tissue per minute. The activity of lactase did not change. CONCLUSION: We discovered a previously unknown phenomenon of the disaccharidases activity increase in duodenal mucosa and improved carbohydrates tolerance in the patients with EIMD taking Rebamipide in the dose 300 mg/day for 12 weeks.