Aim: to present literature data on the genetic underpinnings of inflammatory bowel disease (IBD), focusing on key genetic variants such as NOD2, ATG16L1, and IL23R; The objective of this was to understand how these genetic factors contribute to immune dysregulation, epithelial barrier dysfunction, and mucosal homeostasis in IBD.

Key points. IBD, encompassing Crohn's disease and ulcerative colitis, is intricately shaped by a nexus of genetic and environmental factors, and its global prevalence is increasing. Genetic research has identified pivotal variants — NOD2, ATG16L1, and IL23R — linked to IBD, influencing key pathways, such as autophagy, interleukin signaling, and bacterial management. These genetic variants, integral to IBD's etiology of IBD, have functional significance because they perturb immune regulation, compromise epithelial barrier integrity, and disrupt mucosal homeostasis, collectively contributing to intestinal inflammation through diverse mechanisms. Early detection of IBD is paramount for arresting disease progression and underscoring the importance of prognostic testing and genetic screening, especially in cases with familial predispositions or very early onset IBD. Additionally, the use of certain IBD medications, such as corticosteroids, azathioprine, and infliximab, may have implications for male fertility, necessitating a nuanced understanding of these potential effects for informed decision-making in IBD management. This comprehensive understanding of the genetic landscape, functional implications, and diagnostic strategies is vital for advancing personalized treatments and improving outcomes in individuals with IBD.

Conclusion. IBD is a complex gastrointestinal disorder influenced by a combination of genetic and environmental factors. Genetic variants, including NOD2, ATG16L1, and IL23R, contribute to dysregulation of immune responses, epithelial barrier function, and mucosal homeostasis. While progress has been made in understanding the genetic landscape of IBD, ongoing research is needed to elucidate the functional consequences of these variants, identify causal genes, and explore gene-environment interactions. This deeper understanding holds the potential for more precise diagnostics and personalized treatments, ultimately improving outcomes in individuals living with IBD.

The introduction of digital technologies into the learning process for medical university students represents a new paradigm in medical education since high level of criteria for assessing the quality of learning of a medical student require the application of modern technologies in training fundamental disciplines and, in particular, anatomy. Thanks to virtual technologies, conditions are created for modeling and integrating the student into conditions close to real ones, which increases the interest and involvement of students in the educational process and, as a result, a subjective improvement in the process of assimilation of the material. Traditional education based on dissection materials cannot fully provide for the massive training of students, as biological materials cannot be restored or preserved and are quickly damaged. 3D models are devoid of these limitations.

Aim: to evaluate the effectiveness of digital dissection in the educational trajectory of clinical anatomy using interactive anatomical tables and the need of students for the active use of these aids.

Materials and methods. Four groups of students were formed: three groups were studying the material using various anatomical tables and one group used the traditional method. To control the effectiveness of the educational process, before the start of training, entrance testing was conducted in all groups. At the end of classes on individual topics, participants completed exit testing, as well as a questionnaire.

Results. The analysis of learning outcomes shows a significantly higher level of absorption of the material among students in groups where 3D anatomical models were used during classes. This indicates that students’ subjective experience of the learning process has improved due to their increased involvement in the class and their interest in innovative teaching methods.

Conclusion. We plan to study learning outcomes in more detail to identify any differences in the formation of general and professional competencies among students. This information will help us make informed decisions about the widespread use of anatomical models in educational practice.

Aim: to demonstrate an artificial intelligence model that optimises the differential diagnosis of achalasia.

Material and methods. The study included 75 patients: 52 % men (mean age 44.5 ± 17.8 years) and 48 % women (mean age 45.6 ± 16.6 years,) with a preliminary diagnosis of achalasia. Patients were divided into four groups: type I, II, III achalasia and a group of patients whose results did not correspond to a diagnosis of achalasia according to HRM performed based on Chicago Classification version 4.0. On the basis of a set of data from 750 swallows and therefore 6750 manometric parameters, the artificial intelligence models DecisionTreeClassifier, RandomForestClassifier and CatBoostClassifier have been trained to provide a manometric diagnosis. The comparison criteria were the training time and the f1_score metric. The technical characteristics of the model (hyperparameters) were selected using the GridSearchCV method. The model with the best results was integrated into a web application.

Results. The RandomForestClassifier was chosen as the best performing model to compare. Its technical characteristics were “decision trees” and branching depth the number of which was 14 and 5 respectively. With a maximum possible value of 1.0, these hyperparameters achieved f1_score=0.91 in 27 seconds. The web application, developed on the basis of this model, is capable of analyzing manometric data and establishing one of three types of achalasia in patients. Alternatively, it can exclude the diagnosis of achalasia. The output of an image corresponding to the diagnosis is produced for each manometric type of the disease.

Conclusions. For the first time in Russia, a machine learning model based on high-resolution esophageal manometry data was developed at the V. Kh. Vasilenko Clinic of Internal Disease Propedeutics, Gastroenterology, and Hepatology of Sechenov University. The model has been applied to the creation of a web application which has the ability to substantiate the manometry diagnosis of patients. The Federal Service for Intellectual Property (Rospatent) issued a certificate of state registration of the computer program No. 2024665795 dated July 5, 2024. This artificial intelligence programme can be used in clinical practice as a medical decision support tool to optimize the process of differential diagnosis of achalasia and early detection of the disease, to determine the patient's prognosis and to select the method of further treatment.

Aim: to evaluate the significance of a positive polymerase chain reaction result for hepatitis D virus RNA (HDV RNA) in liver biopsy specimens of patients with chronic hepatitis D (CHD) after completion of antiviral therapy (AVT) as a predictor of infection relapse.

Materials and methods. The study included 21 patients with CHD who received combined AVT with peginterferon alpha and bulevirtide for 48 weeks, followed by bulevirtide monotherapy for 48–96 weeks, making the total duration of antiviral therapy 96–144 weeks. In all patients HDV RNA became undetectable in serum 24–96 weeks from the start of treatment, with aviremia maintained for at least 48 weeks until the end of AVT. At the end of treatment, all patients underwent liver biopsy to detect HDV RNA in liver tissue.

Results. Out of 21 patients with sustained complete virological response (negative polymerase chain reaction result for HDV RNA in serum), 8 (38 %) had HDV RNA detected in liver tissue, indicating that a tissue virological response was not achieved. All 8 patients experienced a relapse of CHD within 24 weeks after discontinuing AVT.

Conclusions. In patients with chronic hepatitis D who have achieved a complete virological response in serum, the absence of a virological response in liver tissue (detection of HDV RNA in liver biopsy) is a predictor of relapse, providing a rationale for the continuation of antiviral therapy.

Aim: to evaluate the effects of the probiotic Symbiosys Alflorex (Bifidobacterium longum longum 35624®) on the symptoms and quality of life in patients with irritable bowel syndrome (IBS).

Materials and methods. A multicenter, observational program (SAGA) was conducted to evaluate the effects of Symbiosys Alflorex on symptoms and quality of life in patients with IBS, which enrolled 3,116 patients and 246 physicians from 48 cities of Russia. Eligible patients were diagnosed with IBS according to the Rome IV Criteria and clinical guidelines of the Russian Association of Gastroenterology and the Association of Colorectal Surgeons of Russia. Patients received standard-of-care treatment and add-on therapy with Symbiosys Alflorex 1 capsule once daily for 28 days, followed by Symbiosys Alflorex alone for 2 months. The intensity of symptoms and severity of IBS were assessed using the 7 Symptoms in 7 Days (“7 × 7”) and the Irritable Bowel Syndrome Severity Scoring System (IBS-SSS) questionnaires, respectively. The Irritable Bowel Syndrome Quality of Life (IBS-QоL) questionnaire was used to assess the quality of life. Stool abnormalities were assessed using the Bristol Stool Scale.

Results. After the course of standard-of-care treatment and add-on therapy with Symbiosys Alflorex, 25.8 % of patients achieved clinical remission. After 3 months of probiotic treatment, 76.9 % of patients achieved clinical remission. A significant decrease in the “7 × 7” score was observed, with the mean total score decreasing from 15.8 to 9.77 after the main treatment course and to 3.44 by the end of the study. Stool consistency became normal in 40.1 % of patients by the end of the first month and in 76.8 % after 3 months of follow-up. Changes in the IBS-QoL score showed a significant improvement in the quality of life.

Conclusions. Add-on treatment with Symbiosys Alflorex 1 capsule once daily for 3 months helps to improve IBS symptoms and quality of life of patients. Symbiosys Alflorex has a favorable safety profile.

Aim:  demonstration of basic molecular biological, metabolic and immunological effects of fecal microbiota transplantation (FMT), on the example of a rare case of acute graft-versus-host disease (GVHD) with intestinal damage in a patient after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Materials and methods. To monitor the basic effects of FMT, we performed targeted DNA sequencing of 16S rRNA gene (V3–V4) using MiSeq platform as well as multiplex real-time PCR, MS/gas chromatography technique, immunophenotyping of blood lymphocytes, histological and immunohistochemical techniques.

Clinical case. A 40-year-old female patient diagnosed with myelodysplastic syndrome, with a history of two unsuccessful allo-HSCTs due to graft failure, underwent the third haploidentical HSCT (haplo-HSCT) from her father as ‘salvage’ therapy. Due to early viral/bacterial colitis post-transplant associated with a multidrug-resistant strain of K. pneumoniae and herpes virus type 6, FMT was performed on days 46 and 47 after allo-HSCT. Complete resolution of the enteropathy symptoms was noted following FMT. However, immunosuppressive therapy was canceled on D+106 after haplo-HSCT due to the detection of minimal residual disease causing development of the ‘overlap’-type GVHD with damage skin lesions grade 4, and intestinal mucous membranes grade 3. This complication required resumption and subsequent intensification of immunosuppressive therapy with complete resolution of GVHD symptoms. Following FMT treatment, the patient showed complete resolution of clinical colitis symptoms. According to results of 16S rRNA sequencing, the species-specific diversity of fecal microbiota increased significantly, along with decreased relative contents of opportunistic bacteria (Klebsiella, Enterococcus, Streptococcus genera). A significant growth was revealed for commensal Bacteroidota, and re-emergence of Faecalibacterium, Blautia, Roseburia. Acute gastrointestinal GVHD promoted by tacrolimus withdrawal was associated with repeated depletion of intestinal microbiota. Upon resolution of GVHD and resumed immunosuppression, increased microbiota diversity (Shannon index) was again recorded, and the parameters of patient’s fecal microbiota reached the donor values. The microbiota shifts at all clinical stages (before and after FMT, at the peak of acute intestinal GVHD and intensive immunosuppressive therapy) showed some relations with metabolism of bile and fatty acids in blood plasma and immune parameters.

Conclusions. FMT may be a component of complex therapy aimed at early reconstitution of immune system and organic acid metabolism in patients after allo-HSCT. The composition of fecal microbiota, metabolic profile and spectrum of lymphocyte subpopulations may be markers for monitoring complex rehabilitation after allo-HSCT.

Aim: to develop and describe the technique of primary retroperitoneal approach to the superior mesenteric vessels for D3 lymph node dissection in minimally invasive surgical treatment of the right colon cancer; to evaluate the shortterm results of the first series of patients operated by this technique.

Materials and methods. Patients with adenocarcinoma of the right colon were included in the study. The technique of primary retroperitoneal approach consisted in mobilization of the right mesocolon along the posterior surface in the direction of the superior mesenteric vessels, D3 lymph node dissection with crossing of the feeding vessels from the retroperitoneal side using a single-port access system and consisted of five consecutive steps. At the last step of the procedure the peritoneum and the remaining part of the mesentery were crossed laparoscopically to the intended borders of the colon resection. The specimen was extracted through the incision for the single port, followed by the formation of an anastomosis extracorporeally. The endpoints of the study were the short-term results of surgical treatment.

Results. The study presents data of the first 5 patients with adenocarcinoma of the right colon who underwent surgical treatment with D3 lymph node dissection using primary retroperitoneal approach to the superior mesenteric vessels. The duration of the retroperitoneal step averaged 110 (90–140) min. The average blood loss was 62 (10–100) mL. The first two patients underwent a three-stage retroperitoneal portion of the surgery. The other three patients were successfully operated by primary retroperitoneal approach with performing of all five steps of the operation. The number of removed regional lymph nodes was on average 36 (18–57), apical lymph nodes — 6 (4–5), metastatic regional lymph nodes — 3 (2–4). One patient developed a Class 1 Clavien — Dindo complication, which did not require a change in treatment tactics. The average postoperative hospital stay was 8 (5–12) days.

Conclusion. The technique of primary retroperitoneal approach to the superior mesenteric vessels to perform D3 lymph node dissection was described for the first time. The obtained results demonstrated the possibility of using this method for minimally invasive radical treatment of right colon cancer.

Aim: to present a modern view on the combination of functional dyspepsia (FD) and gastroesophageal reflux disease (GERD) and to evaluate the effectiveness of acotiamide in patients with FD and GERD.

Key points. The high frequency of the combination of FD and GERD is caused by common pathogenetic mechanisms and presents an urgent problem in clinical practice. The concurrent occurrence of these diseases alters the clinical picture, complicates differential diagnostics, and leads to inadequate prescription of drugs. Medical treatment for patients with FD and GERD includes the use of proton pump inhibitors (PPIs) and prokinetics. Currently, acotiamide is recognized as an effective drug that affects the motility of the upper gastrointestinal tract. Acotiamide is an antagonist of muscarinic M1 and M2 receptors and a reversible inhibitor of acetylcholinesterase. The clinical efficacy of this drug has been demonstrated not only in patients with FD but also in those with a combination of FD and GERD.

Conclusion. Administration of acotiamide is pathogenetically justified in patients with the combination of GERD and FD.

Aim: to present disorders of mineral and bone metabolism in patients with chronic liver diseases through clinical observations.

Key points. The liver plays an important role in mineral metabolism: metabolic activation of vitamin D, synthesis of vitamin D-binding protein and albumin, metabolism of parathyroid hormone, etc. However, data on the development of mineral metabolism disorders, particularly hyperparathyroidism, in this population are very limited. Bone diseases such as osteoporosis and osteomalacia are quite common in chronic liver disease, especially in cirrhosis and cholestatic diseases; however, the pathogenesis of these disorders and their relationship with mineral metabolism remain poorly understood. The article presents cases of severe primary hyperparathyroidism (PHPT) in patients with chronic liver disease. In one patient with a long history of viral hepatitis C and cirrhosis, PHPT manifested with severe bone complications, including multiple vertebral compression fractures and a subsequent femoral neck fracture. Imaging studies revealed lesions of all four parathyroid glands, and the removal of the largest lesion did not result in disease remission. In the second case described, PHPT was diagnosed in a patient with bone pain and osteoporosis following orthotopic liver transplantation for Budd — Chiari syndrome with cirrhosis. One year after the initial surgical treatment for PHPT, the patient experienced a recurrence of the disease, with confirmed multiglandular lesion.

Conclusion. In patients with chronic liver diseases, disorders of mineral and bone metabolism remain a significant yet not fully understood problem. Further studies are needed to develop therapeutic approaches for this group of patients to prevent the onset of late, disabling complications.

Aim: to highlight the challenges of diagnosing and treating a patient with severe intrahepatic cholangiolithiasis.

Key points. Primary sclerosing cholangitis is a chronic progressive liver disease characterized by destructive inflammation and fibrosis in the bile ducts, leading to biliary strictures, secondary biliary cirrhosis, portal hypertension and liver failure. Cholangiolithiasis occurs in more than half of cases of primary sclerosing cholangitis and can be both a complication and a cause of secondary sclerosing cholangitis, maintaining inflammation in the ducts and facilitating stone formation. Genetic mutations are known to contribute to the development of gallstones in young patients, including low phospholipid-associated cholelithiasis. Despite the wide range of modern methods of radiological and endoscopic diagnostics, there are still difficulties in differential diagnostics of bile duct diseases. This article presents a clinical case of a 39-year-old male patient with primary sclerosing cholangitis, dyslipidemia and multiple cholangioliths in the gallbladder, intraand extrahepatic bile ducts.

Conclusion. The presented clinical case demonstrates the difficulties in assessing pathogenesis, choosing diagnostic and therapeutic approaches in patients with severe intrahepatic lithiasis that may mimic hepatic neoplasm. Combination of non-invasive and endoscopic methods, such as magnetic resonance imaging, magnetic resonance cholangiopancreatography, endoscopic retrograde cholangiopancreatography, and cholangioscopy, appears to be the most effective both diagnostically and therapeutically.

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.