Aim: to present the principles and distinctive features of the innovative educational program “Health Modeling” for the General Medicine specialty, aimed at refocusing medical training toward proactive health preservation and disease prevention.

Key points. The “Health Modeling” profile was introduced in 2023 at Sechenov University in response to the need to shift the focus of physicians’ work from treating existing diseases to effectively preventing the development of pathologies. This approach aligns with the global healthcare strategy of maintaining population health and increasing the duration of healthy life. The program seeks to equip students with a comprehensive set of competencies for preserving patient and public health using the latest advances in medical science and technology. Distinctive features of the curriculum include interdisciplinary modules structured by organ systems and a spiral progression of content, early immersion of students into clinical practice from the first year, and the translation of cutting-edge scientific knowledge into education through hands-on laboratory practicums. In the senior years, the learning trajectory is individualized, and students acquire healthcare management skills through internships in federal and regional healthcare institutions. Sechenov University is the first in Russia to implement such an integrated, organ system-based curriculum within the General Medicine specialty.

Conclusion. The “Health Modeling” educational program represents a significant step forward in modernizing medical education with an emphasis on preventive care. This model prepares a new generation of physicians oriented toward health preservation at both individual and population levels and should be of interest to medical educators and administrators seeking to update training programs in line with contemporary global health challenges.

Aim: to systematize literature data and the authors’ own findings regarding the endoscopic features of eosinophilic esophagitis.

Key points. Eosinophilic esophagitis is a chronic inflammatory disease of the esophagus characterized by marked eosinophilic infiltration of the esophageal mucosa, as well as subepithelial and submucosal fibrosis. These changes lead to functional impairment of the esophagus, stricture formation, and luminal narrowing, clinically manifesting as progressive dysphagia and episodes of luminal obstruction by a food bolus. Timely diagnosis and appropriate treatment of eosinophilic esophagitis help prevent the development of strictures and other complications.

The diagnosis relies on endoscopic evaluation with the procurement of multiple biopsies (at least six) from the esophageal mucosa to confirm a characteristic histological picture. The main and additional endoscopic findings in eosinophilic esophagitis include edema, linear furrows, rings, exudates, strictures, so-called “feline” esophagus, narrow-caliber esophagus, and the “crepe-paper” esophagus. In recent years, new endoscopic signs have been proposed, such as multiple polypoid lesions, esophageal changes resembling “ankylosaur back” and a “caterpillar track” pattern. Despite the range of possible endoscopic findings, they exhibit relatively low specificity and may be overlooked by endoscopists, leading to delayed diagnosis. High-resolution endoscopic equipment and the development of artificial intelligence programs for image processing hold promise in improving diagnostic accuracy.

Conclusion. Esophagogastroduodenoscopy is the key method for diagnosing eosinophilic esophagitis: awareness of the disease’s endoscopic signs and taking multiple biopsies from the esophagus when eosinophilic esophagitis is suspected allow early diagnosis — prior to the onset of complications — thereby enabling timely treatment to prevent stricture formation.

Aim: to analyze the role of nucleotide sequence variants (NSVs) of ABCG5 and ABCG8 genes in gallstone disease (GSD) and gallbladder cancer (GBC).

Key points. ABCG5 and ABCG8 are key sterol efflux transporters that regulate hepatic secretion and intestinal absorption of cholesterol. ABCG5/G8 is the human LITH9 gallstone gene. One of the major genetic risk factors for GSD rs11887534 (D19H) ABCG8, as a ‘gain-of-function’ NSV, increases the activity of this transporter by 3.2 times, which leads to supersaturation of bile with cholesterol and an increased risk of GSD. On average, rs11887534 increases

the risk of GSD in children by 4 times, in adults — by 2 times, which has been proven in population, genome-wide studies and meta-analyses worldwide. The presence of the H allele D19H (rs11887534) is associated with a two-fold risk of recurrence of GSD after cholecystectomy. The results of the studies of the associations of GSD with other NSVs of ABCG8 (T400K, A632V, M429V, C54Y) and ABCG5 (E604Q, R50C) genes are contradictory.

In population studies, rs11887534 was associated with a 4-fold increase in the risk of GBC, and the risk is more prominent (4.9 times) in patients with GBC and gallstones. We found no studies of the NSVs of the ABCG5 and ABCG8 genes in biliary pathology in Russia.

Conclusion. Most studies confirm the role of the rs11887534 ABCG8 gene as a predictor of GSD and GBC; however, replicating studies of NSVs of ABCG5 and ABCG8 genes in biliary pathology in Russia are needed.

Aim: to compare various methods of intraarterial therapy for hepatocellular carcinoma (HCC) in terms of survival, adverse events, and cost-effectiveness.

Key points. Hepatocellular carcinoma is a malignant liver tumor that originates from hepatocytes. This form of liver cancer is the most common and accounts for 85 % of cases. HCC is the seventh most common cancer and the third leading cause of cancer death worldwide. Unfortunately, the majority of patients with HCC are diagnosed at an advanced stage, when surgical treatment is impossible. Thus, new methods of therapy (including intraarterial) appear, which allow saving the lives of these patients. At present, new intraarterial methods of treatment include transarterial chemoinfusion (TACI), conventional transarterial chemoembolization (cTACE), drug-eluting-beads-TACE (debTACE) and radioembolization (RE).

Conclusion. As a result of studying various sources of world literature about comparing intraarterial methods of HCC treatment, a final table was compiled, which presents the main characteristics of each method. The methods have their advantages and disadvantages, however, according to the criteria of overall survival and progression-free survival, debTACE is in the lead. The most inexpensive method of those presented is TACI, however, in terms of economic efficiency, the method is not a priority, because for treatment with this method, a greater number of cycles is required, compared, for example, with TACE. The radioembolization is associated with the lowest risk of adverse events.

Aim: to assess the data on the most common surgical interventions for rectal prolapse.

Key points. At present, there are more than 100 methods of surgical correction of rectal prolapse that are carried out by means of the perineal or abdominal approach. Perineal surgical approaches are mostly performed in elderly patients who suffer from severe concomitant diseases, as well as in cases of recurrent rectal prolapse. In other cases, the abdominal approach is preferred for surgical interventions. Currently, the most popular surgery is laparoscopic recto(colpo)sacropexy.

Conclusion. It is important to consider that the descending perineum syndrome is accompanied by a variety of clinical symptoms; therefore, patients with rectal prolapse require a personalized approach. Underestimation of these factors may lead to an unfavorable outcome of functional treatment and recurrence of rectal prolapse.

Aim: to evaluate the effect of combined therapy with a proton pump inhibitor and rebamipide on clinical manifestations and morphofunctional changes in the esophageal mucosa in patients with non-erosive reflux disease.

Materials and methods. The study included 39 patients with non-erosive reflux disease randomized into the main group (omeprazole 20 mg/day + rebamipide 300 mg/day) and the comparison group (omeprazole 20 mg/day). The duration of treatment was 4 weeks. Histological examination of esophageal mucosa biopsies (hematoxylin-eosin staining), morphometry of intercellular spaces, and immunohistochemical assessment of tight junction protein expression (claudin-1, -4, occludin) were performed. Symptoms were evaluated using the Likert scale.

Results. The combined therapy group showed significant reductions in heartburn severity (p < 0.001) and belching (p = 0.004), with absent/mild symptoms in 63.7 and 72.4 % of patients, respectively. In the proton pump inhibitor monotherapy group, 53 % of patients retained moderate or severe heartburn. Morphologically, the combined group demonstrated reduced eosinophilic infiltration (p = 0.030). Occludin expression increased in both groups but reached statistical significance only in the monotherapy group (p = 0.046).

Conclusion. The combined therapy with proton pump inhibitor and rebamipide improves symptoms and morphological outcomes in non-erosive reflux disease. Increased occludin expression suggests restored integrity of intercellular junctions. Further studies with larger cohorts and extended follow-up are needed to confirm these findings.

Aim: to evaluate results of follow-up of patients with pancreatic non-functioning neuroendocrine tumors of the stage T1–T2 using a medical registry.

Materials and methods. A retrospective analysis of the medical registry data of the Loginov Moscow Scientific Center was conducted, which included 312 patients with pancreatic neuroendocrine tumors from 2014 to 2023. Observation was recommended for 115 (36.9 %) patients. The inclusion criteria: diagnosis of pancreatic neuroendocrine tumor; non-functioning tumor status; asymptomatic disease; tumor size less than 3 cm; patient’s consent. The exclusion criteria were patient’s refusal of observation; tumor growth of more than 3 mm/year of observation; appearance of disease symptoms. Based on the registry data, gender and age of patients, size and location of tumors, TNM stage, tumor growth dynamics (mm/year), biochemical markers of neuroendocrine tumors, and the presence of concomitant pathology were studied. Whole genome sequencing was performed on 53 patients with first diagnosed pancreatic neuroendocrine tumors.

Results. Six patients (5.2 %) were excluded from the study: three refused to be observed, three demonstrated tumor growth. 109 patients diagnosed with non-functioning pancreatic neuroendocrine tumor were included in the analysis: 78 (71.6 %) women and 31 (28.4 %) men aged from 22 to 86 years (58.5 ± 10.8 years) at the time of presentation. The median follow-up time was 34.0 (2.0–86.0) months. The most common location of tumors was in the head of the pancreas — 45.5 % (n = 51). Of the 109 patients observed, 103 were diagnosed with stage T1 tumors (94.5 %), 6 — with T2 (5.5 %). The average tumor size was 11.9 ± 3.8 mm (3.1–29.0 mm) (n = 118). An increase in biochemical markers of neuroendocrine tumors (gastrin, chromogranin A) was associated with atrophic gastritis. Germline mutations were detected in 24.0 % of patients (n = 12). The most common mutations in the sample were the CHEK2 gene (n = 4).

Conclusions. According to the registry data, active observation is an acceptable tactic for managing patients with T1 non-functioning pancreatic neuroendocrine tumors. Likely it is not the size of the tumor but its growth rate that has prognostic significance, and therefore a protocol for monitoring this group of patients is required. The effect of estrogens on tumor growth inhibition and the role of CHEK2 gene mutations are perspectives for future research.

Aim: to determine the distribution of the three most significant single nucleotide polymorphisms (SNPs) of the TGFB1 gene (rs1800469, rs1800470, rs1800471) and their haplotypes in children with liver fibrosis.

Materials and methods. The study included 107 pediatric liver recipients (45 boys, 62 girls) aged from 3 to 73 months (median — 8 months). The control group consisted of 199 healthy individuals (78 men, 121 women) aged 32.7 ± 9.6 years. During histological examination of the liver removed before transplantation, fibrosis of different severity grades was diagnosed in all children in accordance with the criteria of the METAVIR scale: 5 cases — Grade F1, 9 cases — Grade F2, 14 cases — Grade F3 and 79 cases — Grade F4. The indication for liver transplantation was end-stage liver disease: biliary atresia (n = 61) and hypoplasia (n = 8), Alagille syndrome (n = 8), Caroli disease (n = 8), Byler disease (n = 6) and other liver diseases (n = 16). SNPs were determined by real-time polymerase chain reaction using TaqMan probes in genomic DNA, isolated from peripheral blood.

Results. In children with liver fibrosis of different severity grades, the frequency distribution of the studied TGFB1 gene SNPs was: for rs1800469 — 38 % GG homozygotes, 42 % AG heterozygotes and 20 % AA homozygotes; for rs1800470 — 50 % AA, 29 % AG, 21 % GG; for rs1800471 — 93 % CC, 7 % GC, 0 % GG. The distribution of SNPs rs1800469 and rs1800471 corresponded to the Hardy — Weinberg equilibrium and did not differ from that in healthy individuals. The distribution of rs1800470 in children with fibrosis, in contrast to healthy controls, did not correspond to the Hardy — Weinberg law (p = 0.00026). For the studied SNPs, linkage disequilibrium was shown; five main combinations were observed: three haplotypes, including two most common ones, were distributed, in total, in about 55 % of children with fibrosis and 91 % of healthy individuals; these frequencies were not statistically different in the group of patients and healthy individuals. Significant differences were detected in the distribution of two rarer haplotypes — A-A-C and G-G-C (respectively rs1800469, rs1800470, rs1800471), which were observed more often in patients with liver fibrosis than in healthy individuals: respectively, in 6.03 (95% CI: 3.06–11.89; p < 0.0001) and 3.71 (95% CI: 1.94–7.08; p = 0.0001) times.

Conclusions. In children with liver fibrosis, the distribution of single nucleotide polymorphism rs1800470 and two rare haplotypes rs1800469, rs1800470, rs1800471 of the TGFB1 gene differs significantly from that in healthy individuals. Polymorphism of rs1800470, as well as haplotypes A-A-C or G-G-C at positions rs1800469, rs1800470, rs1800471, may predispose to the development of liver fibrosis in children with liver failure.

Aim: determination of alleles of HLA genes associated with autoimmune hepatitis (AIH) and overlap syndrome (OS) in the Russian population.

Materials and methods. The study included 160 adult patients with a verified diagnosis of AIH or OS. The control group consisted of 320 conditionally healthy participants. A custom NGS panel was used to type the alleles of the HLA class I and II genes. The statistical analysis was carried out using Pearson’s χ² test with multiple FDR correction (p < 0.05). A logistic regression model was used to evaluate HLA alleles as predictors of the disease.

Results. Alleles and haplotypes which frequencies have statistically significant difference in the study and control groups were identified. In the study group, alleles HLA-A*01:01:01 (OR = 2.15; 95 % CI: 1.43–3.23), HLA-B*08:01:01 (OR = 3.38; 95 % CI: 2.10–5.44), HLA-C*07:01:01 (OR = 1.90; 95 % CI: 1.30–2.78), HLA-DPB1*01:01:01 (OR = 3.22; 95 % CI: 1.58–6.55), DQB1*02:01:01 (OR = 3.11; 95 % CI: 2.06–4.70), HLA-DRB1*03:01:01 (OR = 3.03; 95 % CI: 2.02–4.55) were more common. Frequency of occurrence of the DQB1*03:01:01 allele in the study group was lower than in the control group (OR = 0.49; 95 % CI: 0.34–0.71). A logistic regression model was built, which was characterized by an accuracy of 0.688, a sensitivity of 0.487, and a specificity of 0.887.

Conclusion. Alleles and haplotypes of HLA genes associated with AIH and OS were identified in a representative sample of the Russian population.

Aim: to present data on the main components of gastric mucosal protection and the possibilities of H. pylori eradication and cytoprotective pharmacotherapy for its restoration.

Key points. The various components of the protection system correspond to the pre-epithelial, epithelial and post-epithelial levels in accordance with the structural organization of the gastric mucosa. Colonization of the gastric mucosa by H. pylori and the development of acute and chronic gastritis are possible due to a number of factors, including the form of the bacterium, the presence of virulence factors (CagA, VacA, OipA), and adhesion proteins (BabA, SabA). H. pylori has a negative effect on all levels of protection of the gastroduodenal mucosa, for example, it affects the secretion of mucins, disrupts the tight junction proteins functioning. Eradication of H. pylori infection eliminates its negative effects. An increase in the effectiveness of H. pylori eradication therapy is achieved by including rebamipide in therapy regimens. In the Russian Federation the eradication efficiency with the addition of rebamipide to treatment was 90.38 % compared with 81.68 % without rebamipide. The inclusion of rebamipide in the treatment regimen when prescribing standard triple therapy with bismuth tricalcium dicitrate allows achieving successful eradication rates of more than 95 %. The cytoprotective properties of rebamipide are due to an increase in the synthesis of endogenous prostaglandins, mucins containing O-glycans, and a decrease in oxidative stress and inflammation.

Conclusion. Eradication of H. pylori infection helps restore the protective properties of the gastric mucosa. Rebamipide, when included in H. pylori eradication therapy regimens, increases its effectiveness. The cytoprotective effects of rebamipide make it possible to prescribe it for long-term treatment of post-eradication gastritis.

Aim: to demonstrate the differential diagnosis of recurrent ascites in a patient without chronic liver disease.

Key points. The patient came to the clinic with complaints of an increase in the volume of the abdomen, shortness of breath during moderate physical activity, weight loss, and severe general weakness. The increase in the volume of the abdomen, accompanied by pain, had been occurring periodically for 12 years without any obvious cause. This condition was assessed as a manifestation of portal hypertension. Laboratory signs of systemic inflammation were noted, while liver function remained intact. Laparoscopy and therapeutic and diagnostic laparocentesis were performed repeatedly — the ascitic fluid was an exudate (serum-ascitic albumin gradient — dance of deformed mesothelial cells was also noted. According to the instrumental examinations (ultrasound, computed tomography with intravenous contrast), signs of liver cirrhosis and portal hypertension were not reliably detected. However, thickening of the parietal peritoneum and infiltration of the peritoneal sheets were noteworthy. This clinical picture was suspicious for mesothelioma/peritoneal carcinomatosis. To clarify the nature of the changes, positron emission tomography with computed tomography (PET-CT) was performed. The results showed increased accumulation of the radiopharmaceutical agent along the peritoneum. The patient underwent therapeutic and diagnostic laparoscopy with biopsy. Based on the biopsy and immunohistochemical study, a diagnosis of epithelioid mesothelioma of the peritoneum was made. Polychemotherapy was started, five courses have been completed to date. The patient’s condition has improved, ascites has completely regressed, and abdominal pain practically does not bother him. In dynamics, PET-CT shows significant regression of mesothelioma foci and its metabolic activity.

Conclusion. The presence of ascites in a patient without signs of independent liver disease and portal hypertension serves as a reason for conducting an extensive differential diagnosis with a step-by-step examination to exclude malignant lesions of the peritoneum, in particular its primary tumor — mesothelioma.