Glucagon-like peptide-1 receptor agonists (arGLP-1) demonstrate considerable efficacy in the management of obesity and type 2 diabetes mellitus. Nonetheless, their clinical application is often restricted due to gastrointestinal adverse events, such as dyspepsia, nausea, and constipation, as well as an elevated risk of biliary sludge and gallstone disease – particularly in the context of rapid weight loss. The present review posits a multifaceted adjuvant therapy strategy that systematically modulates multiple pathophysiological pathways. At the initiation of therapy, prokinetic agents such as itopride and acotiamide are recommended to alleviate nausea and dyspepsia. Concurrently, the administration of psyllium (10–15 g/day) is recommended as a prebiotic substrate to normalize stool consistency and stimulate endogenous short-chain fatty acid synthesis. In the second stage of treatment (within 1 to 3 months), butyric acid in an enteric-coated formulation is introduced to restore intestinal barrier integrity and enhance endogenous GLP-1 secretion. Rebamipide may be used in conjunction with butyric acid to strengthen the intestinal barrier throughout the gastrointestinal tract synergistically. During the transition from the second to the third month of treatment, or when weight loss exceeds 1 kg per week, ursodeoxycholic acid (10–15 mg/kg per day) should be added. This compound is effective in preventing cholelithiasis and reducing steatosis and inflammation associated with non-alcoholic fatty liver disease. A notable advantage of the adjuvant agents discussed is their pleiotropic nature – the ability to target multiple pathophysiological mechanisms inherent to obesity and related gastroenterological conditions. Psyllium, recognized for its efficacy in managing irritable bowel syndrome, is also endorsed for the treatment of uncomplicated diverticular disease, as it normalizes intraluminal pressure and enhances colonic evacuation. Butyric acid, in addition to strengthening the intestinal barrier, offers symptomatic benefits in irritable bowel syndrome and may aid in the remission of diverticulitis by attenuating localized inflammation. Ursodeoxycholic acid, on the other hand, not only prevents cholelithiasis but also improves biochemical markers of steatosis and inflammation in non-alcoholic fatty liver disease, modifies the intestinal microbiota, and relieves symptoms associated with duodenogastric and duodenogastroesophageal reflux. The proposed therapeutic strategy aims to amplify the metabolic effects of arGLP-1 while minimizing adverse events and requires further validation through randomized controlled trials.
Aim. To evaluate the efficacy of combination therapy with rifaximin and Saccharomyces boulardii CNCM I-745 versus rifaximin monotherapy in patients with small intestinal bacterial overgrowth (SIBO) associated with long-term proton pump inhibitor (PPI) use. Materials and methods. A prospective comparative study with two parallel groups was conducted. Eligible patients were those on continuous long-term PPI therapy ( 3 months) with confirmed SIBO. SIBO was diagnosed in all patients using a lactulose Hydrogen/Methane Breath Test (HMBT). Symptom severity was assessed using the validated "7 × 7" Questionnaire, and Quality of Life (QoL) was evaluated using the SF-36 Health Status Survey. Enrolled patients were randomized into two groups based on a 7-day treatment regimen: Group 1 received rifaximin (400 mg twice daily); Group 2 received rifaximin (400 mg twice daily) plus the probiotic Saccharomyces boulardii CNCM I-745 (Enterol® drug product, Biocodex, France; 500 mg twice daily). SIBO eradication was confirmed via repeat lactulose HMBT, and symptom severity/QoL were reassessed 4 weeks after treatment completion. Results. 108 patients were enrolled (mean age 38.7 ± 8.9 years; 65.7% female). Mean PPI treatment duration at enrollment was 4.81 months (95% confidence interval 4.15–5.46). At 4-week follow-up, repeat lactulose HMBT showed SIBO persistence in 41.5% of Group 1 (n = 22/53) versus 21.8% in Group 2 (n = 12/55; p = 0.038). Statistically significant resolution of diarrhea was observed only in Group 2 (p = 0.033). The final median "7 × 7" Questionnaire score was significantly lower in Group 2 (p = 0.0010). Both groups showed significant trends toward QoL improvement on the SF-36 survey. Conclusion. This prospective comparative study demonstrates that combination therapy with rifaximin and Saccharomyces boulardii CNCM I-745 appears more effective than rifaximin monotherapy for SIBO eradication, symptom regression, and QoL improvement in patients with PPI-associated SIBO.
The majority of metagenomic studies are based on the study of bacterial biota. At the same time, the COVID-19 pandemic has prompted interest in the study of both individual fungal pathogens and fungal communities (i.e., the mycobiome) as a whole. Here, in this work, we investigated the human gut mycobiome during COVID-19. Stool samples were collected from patients at two time points: at the time of admission to the hospital (the first time point) and at the time of discharge from the hospital (the second time point). The results of this study revealed that Geotrichum sp. is more represented in a group of patients with COVID-19. Therefore, Geotrichum sp. is elevated in patients at the time of admission to the hospital and underestimated at the time of discharge. Additionally, the influence of factors associated with the diversity of fungal gut microbiota was separately studied, including disease severity and age factors.
Over the past decades, acid production in the stomach has been regulated mainly by proton pump inhibitors (PPIs). However, despite their widespread use and solid evidence base for efficacy, PPIs have pharmacokinetic and pharmacodynamic limitations, such as a slow onset of action, response variability (dependent on CYP2C19 polymorphisms), and the need for activation in an acidic environment. These restrictions underscore the need for innovative molecular approaches to inhibiting acid production, which led to the development of a fundamentally different mechanism of action – potassium-competitive acid blockers (P-CABs), first introduced into clinical practice in 2015. The mechanism of action of P-CABs is based on a reversible ionic interaction with hydrogen potassium adenosine triphosphatase (H+/K+ATPase) in parietal cells of the stomach. Direct inhibition of the active enzyme enables more rapid and sustained control of gastric secretion, including nocturnal and postprandial acid production, making this class of drugs particularly relevant in the treatment of gastroesophageal reflux disease, peptic ulcers, and in the eradication ofHelicobacter pylori. Recent meta-analyses demonstrate the clinical benefits of P-CABs over PPIs for these indications.
Aim: to discuss current views on the clinical significance, diagnostic opportunities, and therapeutic approaches in the treatment of small intestinal bacterial overgrowth (SIBO) as an important component in the gut microbiota function assessment, to assess the awareness of physicians and the opportunities in the diagnosis and treatment of this disease in patients in the Federal districts of the Russian Federation, as well as to present the proceedings of the Expert Council held on December 16, 2023 in Moscow.Key points. SIBO is a common syndrome often associated with irritable bowel syndrome, liver cirrhosis, asthma, and congestive heart failure, being also a predictor of early death in the elderly. Today, in many regions of the Russian Federation, there are limitations for instrumental diagnosis of this disease — lack of awareness among doctors, unavailability of gas analyzers for diagnosing SIBO, lack of information about the need to diagnose SIBO in the standards of compulsory health insurance. Rifaximin is the first-line treatment due to the highest therapeutic efficacy. One of the ways to increase the efficacy of SIBO treatment is to include strain-specific probiotics in the treatment regimen. Saccharomyces boulardii CNCM I-745 is thought to be the most studied, promising probiotic. The review also presents statistical data on the issues in the diagnosis and treatment of SIBO in the regions of the Russian Federation.Conclusion. Optimization of approaches to the diagnosis and treatment of SIBO, the development of domestic gas analyzers, increasing the awareness of physicians in all regions of the Russian Federation, as well as the development and optimization of clinical recommendations appear to be necessary measures to increase the effectiveness of medical care, the duration and quality of life of the Russian population. These goals can be achieved within the framework of Federal programs under the supervision of specialized reference centers of the Ministry of Health of the Russian Federation.
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.
The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has significantly impacted global healthcare, underscoring the importance of exploring the virus’s effects on infected individuals beyond treatments and vaccines. Notably, recent findings suggest that SARS-CoV-2 can infect the gut, thereby altering the gut microbiota. This study aimed to analyze the gut microbiota composition differences between COVID-19 patients experiencing mild and severe symptoms. We conducted 16S rRNA metagenomic sequencing on fecal samples from 49 mild and 43 severe COVID-19 cases upon hospital admission. Our analysis identified a differential abundance of specific bacterial species associated with the severity of the disease. Severely affected patients showed an association with Enterococcus faecium, Akkermansia muciniphila, and others, while milder cases were linked to Faecalibacterium prausnitzii, Alistipes putredinis, Blautia faecis, and additional species. Furthermore, a network analysis using SPIEC-EASI indicated keystone taxa and highlighted structural differences in bacterial connectivity, with a notable disruption in the severe group. Our study highlights the diverse impacts of SARS-CoV-2 on the gut microbiome among both mild and severe COVID-19 patients, showcasing a spectrum of microbial responses to the virus. Importantly, these findings align, to some extent, with observations from other studies on COVID-19 gut microbiomes, despite variations in methodologies. The findings from this study, based on retrospective data, establish a foundation for future prospective research to confirm the role of the gut microbiome as a predictive biomarker for the severity of COVID-19.
Introduction: For people with allergies, it is not always possible to prevent allergens admission to the body. For this reason, it is essential to create a long-acting drug that can prevent an allergic reaction. The very promising option is a transdermal therapeutic system (TTS), with H1 blockers. The aim of the study: To create a technology for the production of desloratadine-based TTS, suitable for routine use with prolonged drug releasing. Materials and Methods: Polyvinylpyrrolidone K30 (PVP) was used as the main matrix polymer for TTS, and the Kruofilm polymer membrane was used as the adhesive layer. The formation of the polymer membrane was carried out by drying a water-alcohol solution of the components at a temperature of 60ºC. Characterization of the obtained dosage forms was made by spectrophotometry. The resulting micelles size was measured by dynamic light scattering. Results and Discussion: Round shaped TTS (patches) with water-dissolved DL and its micellar form were obtained. The size of micelles with DL was 22.8±5.2 nm. The spectrophotometric method for determining DL has been developed. The containing of DL in the patches ranged from 5 to 25 mg per patch, depending on the manufacturing technology. Conclusion: We have developed TTSs containing DL by a solution and a micellar form. A top adhesive layer has been selected that has moisture resistance, strength and reliable fixation of the matrix with the active substance on the skin. A method for the spectrophotometric determination of DL in solutions and patches was developed and validated.
IntroductionThe new coronavirus disease, COVID-19, poses complex challenges exacerbated by several factors, with respiratory tissue lesions being notably significant among them. Consequently, there is a pressing need to identify informative biological markers that can indicate the severity of the disease. Several studies have highlighted the involvement of proteins such as APOA1, XPNPEP2, ORP150, CUBN, HCII, and CREB3L3 in these respiratory tissue lesions. However, there is a lack of information regarding antibodies to these proteins in the human body, which could potentially serve as valuable diagnostic markers for COVID-19. Simultaneously, it is relevant to select biological fluids that can be obtained without invasive procedures. Urine is one such fluid, but its effect on clinical laboratory analysis is not yet fully understood due to lack of study on its composition.MethodsMethods used in this study are as follows: total serum protein analysis; ELISA on moderate and severe COVID-19 patients’ serum and urine; bioinformatic methods: ROC analysis, PCA, SVM.Results and discussionThe levels of antiAPOA1, antiXPNPEP2, antiORP150, antiCUBN, antiHCII, and antiCREB3L3 exhibit gradual fluctuations ranging from moderate to severe in both the serum and urine of COVID-19 patients. However, the diagnostic value of individual anti-protein antibodies is low, in both blood serum and urine. On the contrary, joint detection of these antibodies in patients’ serum significantly increases the diagnostic value as demonstrated by the results of principal component analysis (PCA) and support vector machine (SVM). The non-linear regression model achieved an accuracy of 0.833. Furthermore, PCA aided in identifying serum protein markers that have the greatest impact on patient group discrimination. The study revealed that serum serves as a superior analyte for describing protein quantification due to its consistent composition and lack of organic salts and drug residues, which can otherwise affect protein stability.
Background. Cavernoma of cavernous sinus is a fairly rare benign neoplasm, accounting for less than 3 % of all neoplasms in this area. Due to the rarity of this pathology, a standardized protocol for diagnosis or treatment has not been developed. Surgical and radiosurgical methods are used for treatment.Aim. Analysis of the results of treatment of patients with cavernous sinus cavernomas operated at the N. N. Burdenko National Medical Research Center of Neurosurgery from 2000 to 2022 using endoscopic transnasal access.Materials and methods. We present our own experience in the treatment of 9 patients who underwent transnasal endoscopic removal of cavernous sinus cavernoma.Results. A total of about 300 cases of treatment of patients with cavernous sinus cavernomas have been described in the literature, and endoscopic removal has been described in only 12 cases.As a result, subtotal removal was achieved in 7 cases. In 2 cases, the removal was partial. The postoperative period proceeded in all patients without peculiarities and without complications.Conclusion. Endoscopic transnasal access allows partial or subtotal removal of the formation without risk of injury to cranial nerves and with minimal soft tissue injury, which has a positive effect on the postoperative period of patients. In combination with radiosurgical methods, it is possible to achieve satisfactory treatment results.
Aim. To determine the phenotypic variants of patients with symptoms of gastroesophageal reflux disease (GERD), non-erosive reflux disease (NERD), hypersensitive esophagus (HSE), functional heartburn (FH) using 24-hour pH-impedance testing and high-resolution esophageal manometry (HSEM). Materials and methods. Fifty-five treatment-native symptomatic patients with newly diagnosed GERD and 48 control group subjects (CG) were examined. The mean age of the subjects was 45.0 years (95% confidence interval [CI] 41.0–48.9). Patients were grouped based on typical symptoms (heartburn, belching, regurgitation, odynophagy, dysphagia), medical history, endoscopy results, and 24-hour pH-impedance testing. Patients with typical symptoms of GERD and Grade B, C, D erosive esophagitis (EE) according to the Los Angeles Classification (LA) based on endoscopy were excluded from the further study. All patients without changes in the esophageal mucosa on endoscopy or with LA grade A EE (presumably NERD) underwent 24-hour pH-impedance testing and HSEM without proton pump inhibitors. Acid exposure, acid reflux count, symptom association with reflux (with symptom index and symptom association with reflux), mean nocturnal impedance, and post-reflux swallow-induced peristaltic wave index were assessed. The structure (presence or absence of a hiatal hernia) and function (presence or absence of the lower esophageal sphincter hypotonia) of the esophagogastric junction, as well as the motor function of the thoracic esophagus, were assessed using HSEM. The results of the HSEM were interpreted according to the Chicago Classification, 3rd edition (2015). Results. The number of acid refluxes in patients with NERD was 71.0 (95% CI 58.4–83.7), in subjects with HSE – 38.5 (95% CI 28.3–49.0), with FH – 13.0 (95% CI 6.5–18.2), in CG – 16.5 (95% CI 9.0–21.0). The average nocturnal basal impedance was 1300 ohms (95% CI 1000–1986) in patients with NERD, 1725 ohms (95% CI 1338–2261) in patients with HSE, 2760 ohms (95% CI 2453–3499) in FH, 2515 ohms (95% CI 2283–2700) in CG. The index of post-reflux swallow-induced peristaltic wave in patients with NERD was 61% (95% CI 57–71), with HSE – 85% (95% CI 82–88), with FH – 71% (95% CI 64–78), in CG – 66% (95% CI 63–69). Hiatal hernia and/or hypotonia of the LES were more common in patients with NERD (23%) than in CG (13.3%). Ineffective motility was detected in 34% of patients with NERD, in 23% of subject with FH and in 66.7% of patients with HSE. Conclusion. The results support the hypothesis that patients with GERD symptoms represent a heterogeneous population. 24-hour pH-impedance testing and HSEM helps to differentiate endoscopically negative patients with GERD symptoms and patients with Grade A EE by LA to NERD, HSE and FH.
Helicobacter pylori (H. Pylori), microaerophilic spiral-shaped Gram-negative bacteria which colonize the gastric mucosa of human population, is the leading causal factor in the development of a whole range of diseases of the gastroduodenal region (chronic gastritis, gastric and duodenal ulcer disease, MALT lymphoma and gastric adenocarcinoma). Since the discovery of H. pylori infection and the identification of its leading role in the development of a range of gastroenterological diseases, researchers have begun to actively study the potential trigger significance of this pathogen in the development of extragastric pathology. At the epidemiological level, H. pylori infection has been shown to be frequently associated with skin diseases such as rosacea, acne, chronic urticaria and psoriasis, although the clinical significance of these associations remains clouded. In fact, recent meta-analytic studies (2019–2024) demonstrate an increased risk of developing the above diseases in H. pylori-infected individuals with odds ratios ranging from 1.19 to 3.00. On the other hand, not all studies have showed that eradication therapy of this microorganism helps reduce the clinical severity of symptoms of skin diseases, which is hypothetically explained only by the trigger role of infection within the complex pathogenesis. In a modern light, such associations can be viewed in terms of pathogenetic findings through the implementation of the syndrome of increased epithelial permeability (SIEP). The chronic gastritis caused by H. pylori infection is believed to lead to increased permeability of the epithelial lining of the stomach, as well as the walls of the mucosal vessels and a higher exposure of bacterial and nutritional antigens in the systemic circulation, which can induce both local release of inflammatory mediators in tissues and systemic immunological reactions (autoimmune and inflammatory processes, formation of molecular mimicry-induced immune complexes and cross-reactive antibodies).
Aim: to provide the basic points of the Expert Panel of the Russian Gastroenterological Association with discussion of measures to improve diagnostics, treatment and management of chronic gastritis patients.Key points. In the Russian Federation in 2021 more than 30 million patients diagnosed with “Gastritis and duodenitis” were recorded (K29 in accordance with International Classification of Diseases-10). H. pylori incidence rate in the Russian population has reduced and presently is about 40 %. In chronic gastritis pattern H. pylori-associated gastritis has still dominated though gastritis percent after successful H. pylori eradication, reactive gastropathy (including reflux gastritis) and autoimmune gastritis, has increased. Endoscopic and histologic examinations serve as key diagnostic techniques that provide a means for assessing the ethiology of gastritis, topography and degree of atrophic changes, gastritis staging as per OLGA/OLGIM system that properly correlates with the risk of stomach cancer and determines endoscopic examination strategy. H. pylori eradication therapy of gastritis serves as an etiotropic treatment and makes it possible to prevent progression of atrophy and stomach cancer. Conventional triple therapy combined with bismuth tripotassium dicitrate allows for achieving optimal cure rates of H. pylori eradication. Addition of rebamipide to regimens of H. pylori eradication improves their efficiency. Rebamipide arrests symptoms of dyspepsia in the case of chronic gastritis and functional dyspepsia. The administration of rebamipide for chronic gastritis makes it possible to influence the syndrome of increased epithelial permeability and inflammation, which makes it advisable to study it as a means of preventing stomach cancer and the progression of atrophy in various types of chronic gastritis.Conclusion. Members of the Expert Panel has approved the algorithm of diagnosis and treatment of H. pylori-associated gastritis, gastritis after H. pylori eradication and H. pylori-negative gastritis at the diagnostic stage in the case of initial presentation and long-term follow-up when needed.
Introduction. The presence of dyssynergic defecation in a cohort of patients with overlap syndrome of functional disorders is poorly studied.Aim. To assess the motor function and sensitivity parameters of the anorectal zone, to identify dyssynergic defecation and to analyze the frequency of correlation in patients with overlap syndrome of functional gastrointestinal disorders associated with constipation.Materials and methods. A one-stage examination was conducted in four parallel groups. The study included 100 patients aged 30 to 40 years with the following diagnoses: constipation-p redominance irritable bowel syndrome (IBS-C) (group 1), IBS-C combined with functional dyspepsia (group 2), IBS-C combined with functional biliary disorder (group 3) and healthy volunteers (group 0). All patients underwent a balloon expulsion test and high-resolution anorectal manometry to determine the presence of dyssynergic defecation.Results. Based on the analysis of parameters according to anorectal manometry data, dyssynergic defecation was not detected in group 0, in group 1 dyssynergic defecation was detected in 8 people – 32.0% (95% CI 12.3–51.6), in group 2 – in 14 people – 56.0% (95% CI 35.0–76.9), in group 3 – in 16 people – 64.0% (95% CI 43.7–84.2). A negative evacuation test was detected in 8 (32%) patients in group 1, in 14 (56%) patients in group 2, and in 17 (68%) patients in group 3, which confirmed the presence of dyssynergic defecation.Conclusions. This study demonstrated the presence of dyssynergic defecation in three groups of subjects, more often with a combination of irritable bowel syndrome with predominant constipation with functional dyspepsia, and most often with a functional disorder of the gallbladder.
The article presents an original method for personalized predicting surgical outcomes in patients with tumors of diencephalic and suprasellar localization based on a clinical and epidemiological approach and the use of intelligent analysis (Data Mining) of clinical and electroencephalo-graphic data. Use of the methods allowed us to programmatically select nosologically specific test for making surgical outcome prognosis, including sensitivity and specificity calculations.
Aim. To systematize data on the prevalence of gastroesophageal reflux disease (GERD) in the adult population of Russia. Materials and methods. The search for studies was conducted in the electronic databases MEDLINE/PubMed, EMBASE, and RSCI (Russian Science Citation Index) from January 2000 to December 2022. The review included relevant publications in peer-reviewed periodicals in English or Russian, publications with data from cross-sectional epidemiological studies assessing the prevalence of GERD in the Russian population, studies on adult patients with GERD, and publications with detailed descriptive statistics that allow using the data in the meta-analysis. Results. The final analysis included 6 studies involving 34,192 subjects. The overall prevalence of GERD (prevalence of heartburn ± regurgitation once a week or more frequently) in the analyzed studies was 25.605% (95% confidence interval [CI] 17.913–34.147). The analysis used a random effect model, as there was significant heterogeneity between the results in both groups (I2=99.63%; p0.0001). The overall mean age of GERD patients in the study population was 48.14 (95% CI 32.25–4.03) years. The prevalence of GERD in the male population was 23.653% (95% CI 13.351–35.832) and 25.457% (95% CI 17.094–34.849) in females. Conclusion. This meta-analysis demonstrated that GERD is a common esophageal disease in the Russian population, affecting approximately one in four country residents.