LEADING ARTICLE
Purpose of the study. To determine clinical, morphometric, genetic predictors of non-refractory and refractory variants of the course of irritable bowel syndrome (IBS).
Materials and methods. We examined 148 patients with non-refractory (41 people) and refractory (107 people) the course of irritable bowel syndrome. The control group consisted of 36 healthy volunteers. The analysis of the symptoms of the current exacerbation of the disease, verifi cation of comorbid gastroenterological pathology (taking into account the Roman criteria- IV and Russian recommendations), assessment of signs of psychological maladaptation (The Four-D imensional Symptom Questionnaire), fi brocolonoscopy, immunohistochemical, morphometric study of colobiopts, determination of the expression area of colonocytes immunopositive to motilin and sirtuin-1, determination of genotypes of polymorphic marker rs4680 of the СOMT gene by polymerase chain reaction.
Results. The intensity of abdominal pain, the severity of “intestinal” symptoms was higher in refractory IBS compared with non-refractory. Functional comorbidity (functional dyspepsia, functional disorder of the gallbladder) was more common in the refractory variant of the course of the disease, mainly with diarrhea. Indicators of distress, depression, anxiety, somatization in the refractory course of the disease were higher compared to non-refractory, did not diff er signifi cantly in IBS with constipation and diarrhea. The indicators of the expression area of motilin-p ositive colonocytes were reduced in IBS with constipation, increased in IBS with diarrhea (the maximum changes were in the refractory variant of the course of the disease). The expression area of sirtuin-1-positive colonocytes was reduced in IBS with diarrhea compared to IBS with constipation and with the control group. Associations of genotypes of the polymorphic marker rs4680 of the СOMT gene with a refractory variant of the course of IBS, as well as with the severity of abdominal pain syndrome and signs of psychological maladaptation were found.
Conclusion. Patients with irritable bowel syndrome are characterized by functional comorbidity, signs of psychological maladaptation, more pronounced in the refractory variant of the course of the disease. Patients with IBS, in comparison with the control group, are characterized by a change in the expression area of motilin- and sirtuin-1-positive colonocytes, correlating with the variant of intestinal dysfunction and maximally expressed in the refractory course of the disease. Variants of the course of irritable bowel syndrome are associated with polymorphic markers rs4680 of the gene of the enzyme СOMT.
CLINICAL GASTROENTEROLOGY
The frequency and clinical course of chronic generalized periodontitis against the background of liver cirrhosis of various etiologies were studied. 70 patients with chronic generalized periodontitis of varying degrees in combination with liver cirrhosis were examined (23 patients (32.9%) had liver cirrhosis class A, 25 (35.7%) — class B, 22 (31.4%) — class C. Comparison group — 17 patients with periodontitis without somatic pathology. Control group — 20 practically healthy volunteers. A signifi cantly reduced level of oral hygiene was revealed in patients with liver cirrhosis of classes B and C. Periodontal pathogenic microorganisms were signifi cantly more common in the contents of periodontal pockets with cirrhosis. With an increase in the class of CP, the frequency of bacterial expansion increased. The severity of periodontal damage in patients with liver cirrhosis is associated with a loss of bone mineral density by the type of osteopenia (47.2%) or osteoporosis (31.4%), increasing according to the class of liver cirrhosis and the severity of periodontal disease The degree of resorption of the alveolar process is associated with a systemic decrease in bone mineral density. The eff ects of generalized osteopenic syndrome and resorption of the alveolar processes are characteristic of patients with alcoholic liver damage and liver cirrhosis with cholestasis syndrome.
This article is devoted to the comorbidity of diseases of the digestive tract and respiratory system in children. Comorbidity (polymorbidity) in the pathology of the gastrointestinal tract is widely described in modern scientific literature, however, the relationship between the digestive and respiratory systems seems to be less studied.
The purpose of the study was to analyze the endoscopic signs of refl ux pathology of the digestive tract in children with a comorbid condition — GERD and respiratory diseases occurring with broncho-o bstructive syndrome (BOS).
Materials and methods. An in-depth examination of 180 children from 6 to 16 years old with comorbid pathology (respiratory diseases with BOS and GERD) was carried out. Performed: X-ray examination, spirometry, intracavitary pH-metry, EFGDS and ultrasound of the gastrointestinal tract. To study the morphological features of the esophageal mucosa in this comorbidity, biopsies were examined 1 cm above the Z-line; at the same time, a biopsy of the mucosa of the antrum of the prepyloric part of the stomach was performed.
Results. Respiratory diseases with biofeedback in the examined groups of patients were most often (43.9%) combined with GERD at the age of 12–14 years. The predominance of endoscopically positive grade 1 GERD is typical for patients with broncho- obstructive syndrome caused by moderate and severe persistent BA, acute and prolonged pneumonia, and recurrent bronchitis. Infl ammatory diseases of the digestive system (chronic gastritis, chronic gastroduodenitis) in BA were detected in 40.6% of patients, in pneumonia — in 45.7%, in recurrent bronchitis — in 33.3% of patients. Based on the data of a general morphological study of biopsy specimens, regardless of age and type of bronchopulmonary pathology, two variants of infl ammation were identifi ed, which are more common than others — with a predominance of dystrophic changes and with a predominance of infl ammation itself, which largely depended on the duration of the disease. In patients suff ering from both BA and pneumonia with biofeedback, morphological changes in the esophageal mucosa corresponded to the catarrhal nature of the infl ammation.
Purpose of the study: to establish the clinical and diagnostic signifi cance of structural and functional changes in the colon in NAFLD against the background of obesity, type 2 diabetes, arterial hypertension.
Materials and methods: 138 patients with NAFLD and intestinal pathology, 36 patients without intestinal dysfunction were examined. The clinical and endoscopic features of lesions of the colon mucosa in patients with NAFLD were studied, taking into account the underlying pathology (obesity, type 2 diabetes, arterial hypertension). Changes in intestinal microbiocenosis were revealed in patients with NAFLD, depending on the underlying pathology. The morphometric parameters of the expression of colonocytes immunopositive to the vascular endothelial growth factor, as well as to leptin, were studied in comparison with the clinical and endoscopic features of the colon and liver, and the presence of a background disease.
Results: It has been established that the background diseases in NAFLD — type 2 diabetes and obesity — make a certain contribution to the structural and functional changes in the colon. In turn, changes in the intestinal microbiota in NAFLD against the background of obesity, type 2 diabetes lead to aggravation of dyslipidemia, glycemia with the progression of chronic systemic infl ammation and fi brosis in the liver.
Research objective. To study the effect of vegetative nervous system dysfunction on mechanisms of peptic ulcer of gastroenteroanastomosis formation and to improve the results of treatment of patients after gastric resection for peptic ulcer disease.
Material and methods. The study included 30 patients with peptic ulcers of gastroenteroanastomosis being operated on for gastric ulcer and duodenal ulcer. Instrumental research included: cardiorhythmography, esophagogastroduodenoscopy, intragastric pH-metry, electrogastrography, laser Doppler fl owmetry.
Results. In patients with peptic ulcers of gastroenteroanastomosis, according cardiorhythmography, parasympathicotonia prevailed in 20 (66,7%) patients, sympathicotonia was observed in 8 (26,7%) patients, eutonia — in 2 (6,6%) patients. Microcirculation data against the background of sympathicotonia were signifi cantly lower than in the control group (p<0,05) and lower than those in parasympathicotonia and eutonia. With the hyperkinetic type of motility, the predominance of parasympathicotonia(87,5% patients), while the acid-producing function of the stomach was increased in 70% patients (рН 0,9±0,3). Autonomic dysfunction and helicobacteriosis were observed in 26 patients (86,6%). Correlation analysis between cardiorhythmography data and gastric acidity established positive correlation of average strength (r=0,726), which determined the important role of acid-peptic exposure against the background of an increase in the tone of the parasympatic part of the vegetative nervous system. With the predominance of parasympathicotonia, M-anticholinergic Нyoscine butylbromide was included in the complex therapy. After the treatment, the results of cardiorhythmography showed the normotensive nature of the cardiorhythmograms, motor data improved in 60% patients, the acidity data corresponded to the normality (рН 1,2–2,0).
Conclusions. The results of the study showed the predominance of parasympathicotonia in patients with peptic ulcers of gastroenteroanastomosis, which contributes to impaired microcirculation, motor- evacuation and secretory functions of the gastric stump and creates conditions for persistence. The сardiorhythmography made it possible to objective assess of the state of the vegetative nervous system. The inclusion of hyoscinebutylbromide in complex treatment with the predominance of parasympathicotonia has a modulating effect on the vegetative nervous system.
The aim of the work was to study the relationship of selectins with hepatic fi brosis in nonalcoholic fatty liver disease (NAFLD).
Material and methods. In 40 patients with histologically confi rmed NAFLD (42.5% of women, 57.5% of men) aged 19 to 65 years (mean age — 40.93±1.95 years), the levels of E-, P- and L-selectins in the blood was studied. Severe liver steatosis was present in 47.5% of patients, nonalcoholic steatohepatitis was observed in 57.5% of cases, and severe liver fi brosis was detected in 22.5% of patients. The control group consisted of 60 practically healthy people.
Results. The increase of plasma levels of all selectins was observed in NAFLD. The blood levels of E-selectin elevated with increasing of histological signs of hepatic steatosis. The concentration of E- and P-selectins in the blood was higher in patients with nonalcoholic steatohepatitis than in cases of its absence. The maximum values of E- and P-selectins in the blood were present in severe liver fi brosis. Correlation of soluble E- and P-selectins with fi brosis index was determined. The risk of severe fi brosis in NAFLD increased 27-fold with E-selectin values above 89 ng/ml and 33-fold in cases of P-selectin values greater than 166 ng/ml. The accuracy of the above levels of E- and P-selectins in predicting severe fi brosis in NAFLD was 80.0 and 82.5%, respectively. The probability of severe liver fi brosis in NAFLD was related with the presence of insulin resistance and increased levels of P-selectin in the blood.
Conclusion. Determination of the profi le of soluble selectins in NAFLD allows us to state the severity of liver fi brosis and stratify patients into groups with its diff erent severity.
Aim: to study the immunological characteristics of patients with H. pylori-unassociated chronic gastritis with its comorbidity with allergic rhinitis.
Materials and methods. The study included patients aged 18 to 40 years: 47 healthy individuals (comparison group) and 140 people, of which 66 people had chronic gastritis, 43 people had seasonal allergic rhinitis in remission, 31 people had a combination of both. Conducted a clinical examination, determination of serum concentrations of IL-4, IL-5, IL-6, IL-8, IL-10, IL-18, MCP-1, total IgE, detection of IgG to the nuclear antigen of the Epstein-Barr virus.
Results: During the study, we showed that H. pylori-non-associated chronic gastritis is characterized by a decrease in the level of monocyte-macrophage cytokines (IL-6 and IL-18, but not IL-8), but an increase in the production of Th2-dependent cytokines (IL-5 and IL-4), as well as total Ig E. In addition, H. pylori-non-associated chronic gastritis in patients without allergic rhinitis is associated with an increased frequency of detection of IgG to the nuclear antigen of the Epstein-Barr virus in blood serum (80.0% vs 48–55% of cases in other groups, p<0, 05).
Conclusion. Thus, H. pylori-non-associated chronic gastritis is a multidisciplinary problem, which, from an immunopathogenetic point of view, is characterized by a Th2-phenotype of the immune response in such patients, including in the absence of allergic pathology, which determines the need for a wider involvement of data in the examination. patients of specialists of other profiles (allergists, infectious disease specialists, etc.).
Objective: to evaluate circadian rhythms of the act of defecation in obese patients, depending on the presence or absence of concomitant constipation syndrome.
Materials and methods: in the period from October 2020 to April 2022, 251 patients were examined. The average age of the patients was 49.8 ± 11.4 years. The ratio of men and women was 1:1.14 (117:134 people). The study included patients aged 18 to 75 years inclusive, obese: body mass index (BMI) 30 and above and waist circumference >94 cm in men and >80 cm in women who do not have organic diseases of the colon. All patients were assessed for gastroenterological complaints, stool frequency (number a week), stool type according to the Bristol scale (1–7), the time of defecation during the day to identify possible disorders of circadian rhythms, measurement of anthropometric parameters (height, body weight), calculation of BMI. Statistical data processing was performed using Statistica 10 and SAS JMP 11 programs.
Results: in the study population, constipation was detected in 45.8% of obese patients. Patients with constipation were signifi cantly more concerned about pain along the colon, bloating, as well as the need for severe straining and pain in the perianal region and along the rectum after defecation (p<0.05). Patients with obesity and constipation syndrome, compared with those without obesity, had signifi cant changes in the frequency, consistency of stool and circadian rhythms of defecation: the frequency of defecation (number a week) 2.8 and 6.9, the average value of the type of stool on the Bristol scale 1.8 and 3.5, defecation in the morning 42.6% and 58.8%, respectively (p<0.05).
Conclusions: in patients with obesity and the presence of constipation, pronounced disorders of circadian rhythms of defecation are determined. This can contribute to the progression of chronic constipation, the formation of disorders of the gut microbiota, which leads to the development of the leaky gut syndrome, the maintenance of chronic infl ammation and, as a result, to the progression of obesity and metabolic changes. Restoration of physiological rhythms of the act of defecation is an important component of non-drug treatment in the complex therapy of obesity, metabolic syndrome, chronic constipation.
EXPERIMENTAL GASTROENTEROLOGY
Increasing the effectiveness and safety of pharmacotherapy of hyperlipidemia is an urgent task of gastroenterology and cardiology. Statin drugs can differ signifi cantly not only in the effectiveness of lipid profile normalization, but also in the spectrum of side effects. The paper presents the results of a comparative chemoreactomic analysis of “natural” statins (monacolins K, J, L, simvastatin) and synthetic statins (atorvastatin, fl uvastatin). It is important to note that “natural” monacolin K does not cause the negative metabolic changes characteristic of synthetic statins. In general, the assessments of the accumulation of the studied molecules in various human cells and tissues, effects on the human metabolome and proteome, and assessments of the side effects of therapy indicate a more favorable safety profile of the “natural” statin monacolin K.
Hepatoprotectors are necessary for the treatment of alcoholic and non-alcoholic (including medicinal) liver damage. This paper presents the results of a study of the Laennec hepatoprotector, produced on the basis of pharmaceutically standardized human placental hydrolysates (HPH). The use of HSP in toxic liver damage with alcohol or paracetamol led to a significant decrease in markers of liver dysfunction (AST, ALT, bilirubin, MDA), which increase when the models are reproduced. The hepatoprotective effect of Laennec was confi rmed by the results of histological studies, indicating a reduction in infl ammation and preservation of the liver parenchyma. Histological studies also indicated the nephroprotective and cardioprotective effects of Laennec in liver damage with both alcohol and paracetamol.
REVIEW
Th e article presents a review on a cystic fibrosis-r elated diabetes, a severe complication of cystic fi brosis in children, which has acquired increasing importance and revealed to contribute in prognosis of the disease in recent years. Which include resent and historical epidemiology, pathophysiology, diagnostic methods, features of the course and the latest aspects of the targeted therapy effect on endocrine function of the pancreas. The authors presented a retrospective analysis of the carbohydrate metabolism condition in two groups of children with cystic fi brosis investigated in 1993 and 2021. These groups diff ered signifi cantly in baseline enzyme therapy, diet and nutritional support (the intake of supplementary medical nutrition). The study confi rmed that present-day patients have a lower percentage of impaired carbohydrate metabolism on the background of complete therapy. The authors proved that carbohydrate metabolism disorders occur earlier in nowadays children with cystic fi brosis, at the age before 10 years. This fi nding provides strong evidence that prediabetes is a period they should be diagnosed. These changes can be identifi ed only by a complete examination of the glycemic profi le of the patient, rather than, as previously thought, an oral glucose tolerance test. The study identifi ed that the indicator of continuous glucose monitoring — 6.42 mmol/l could be a predictor of the possible transition of prediabetic stage into cystic fi brosis related diabetes. The obtained results are confi rmed by the clinical case given by the authors.
The purpose of the review: to summarize the information available in the literature and to present to the practitioner information on the relationship of diseases of the gastrointestinal tract with cardiovascular pathology.
Basic provisions. The comorbidity of diseases of the gastrointestinal tract and cardiovascular pathology (CVP) is due to similar risk factors and pathogenetic mechanisms. The results of scientifi c studies of patients with gastrointestinal tract pathology indicate higher cardiac risks and the incidence of CVP in comparison with the general population.
Conclusion. Gastrointestinal disorders can act as risk factors, links in pathogenesis, elements of the clinical picture of CVP. A multidisciplinary approach is needed in the treatment of patients with chronic gastrointestinal pathology in order to best address the underlying problems and existing cardiovascular diseases in this category.
Background. The problem of comorbidity is becoming increasingly important in modern medicine and healthcare. A combination of infl ammatory bowel diseases (IBD) and spondyloarthritis (SpA), the genesis of which is closely related to immune infl ammation, can be attributed to the number of comorbid mutually aggravating pathology. In real clinical practice, there is often a late diagnosis of these comorbid processes, which aff ects the quality and eff ectiveness of treatment and worsens the outcomes of diseases.
Aim. In order to attract the attention of specialists of various profi les to immuno-i nfl ammatory comorbidity, the article presents current data on the association between IBD and SpA with an analysis of the frequency of joint and spine lesions in ulcerative colitis (UC) and Crohn’s disease (CD), as well as the frequency of detection of intestinal lesions in various SpA phenotypes.
Basic provisions. It has been shown that joint lesions in IBD and intestinal lesions in SpA, as a rule, occur in severe and moderate forms of these diseases, occurring with high or moderate activity. The HLA B27 genotype is more typical for individuals with manifest SpA, including developed against the background of IBD. The combination of IBD and SpA is caused by similar disorders of immunoregulation, the functional state of cells of native and adaptive immunity, and an imbalance of cytokines. These mechanisms have become the basis for the use of biological and targeted therapy in IBD and SpA, as well as in their combination. It has been shown that approximately half of patients resistant to standard drugs can achieve clinical remission on biological therapy.
Conclusions. Thus, in order to objectify the severity of the immuno- infl ammatory process and improve outcomes, it is advisable to diagnose the most likely comorbid pathology in a timely manner and take this factor into account to optimize treatment.
The article presents a review of publications in in Russian and foreign literature devoted to modern views on the role of intestinal microbial metabolites as risk factors for cardiovascular diseases. The technical capabilities of the last decade made it possible to accurately characterize the intestinal microbiota, which contributed to a deeper understanding of the processes occurring during the development of a number of diseases and to establish that the outcome of their treatment is aff ected by pronounced changes in the composition, diversity and metabolic activity of the human intestinal microbiota. A number of questions on the interaction of the intestinal microbiota and the host organism remain open. Further research on the relationship of the intestinal microbiota, its metabolic products with risk factors for cardiovascular diseases opens up unique opportunities in the treatment and prevention of diseases of the cardiovascular system using manipulative technologies with the composition of the microbiota and its function.
COVID-19
The global pandemic of the new coronavirus infection (COVID-19) has become an extreme challenge for the health care of the whole world since 2020.
The main target of the SARS-CoV-2 virus is the lungs, but at the same time, more and more evidence is accumulating that the new coronavirus can also aff ect other organs and systems, such as the heart, blood vessels, kidneys, intestines, and brain.
Thus, adequate management of a coronavirus patient means not only the therapy of viral pneumonia, but also the timely diagnosis and treatment of damage to other organs.
The analysis of predictor factors of severe course and fatal outcome in COVID-19 indicates the aggravating role of comorbid pathology, such as cardiovascular diseases, diabetes mellitus, chronic obstructive pulmonary disease, chronic gastrointestinal diseases. Therefore, in addition to measures to prevent infection with SARS-CoV-2, measures should also be taken to control the comorbid conditions present in the patient.
ACE2 receptors, which the virus uses to penetrate human cells, can also be expressed in the esophagus, stomach, small and large intestines, liver and pancreas. This makes the frequency of gastroenterological symptoms in COVID-19 high, which is caused both by the defeat of the digestive organs by the coronavirus itself and by the exacerbation of chronic gastrointestinal diseases against the background of infection and its aggressive therapy. At the same time, the presence and severity of digestive diseases signifi cantly affect the clinical course of COVID-19.
This article is devoted to the pathogenesis, clinical picture, approaches to the diagnosis and therapy of erosive ulcerative lesions of the stomach and duodenum against the background of a new coronavirus infection.
Remaxol was evaluated as a means of hepatotropic support for patients with COVID-19 receiving antiviral therapy. Patients were observed in two groups of 30 people each and received intravenous infusions of Remaxol (400.0 ml) or “active placebo” (400.0 ml. 0.9% sodium chloride) for 10 days. In these groups of patients, an analysis was made of the dynamics of clinical parameters and laboratory tests that characterize the functionality of the liver. The results of the analysis made it possible to state that the use of the corrector of cellular and energy metabolism metabolism Remaxol as a hepatoprotector in complex therapy contributes to favorable clinical dynamics, stabilization of biochemical parameters of liver function and allows completing the course of etiotropic therapy in all patients.
Good tolerability of the drug “Remaxol” and the absence of pronounced side effects were noted. The course of Remaxol made it possible to carry out therapy with antiviral agents without dose adjustment and duration of treatment.
CLINICAL CASES
Purpose of the study: to present a description of the clinical observation of chronic aspiration bronchiolitis in a patient with a large diverticulum of the upper esophagus and gastroesophageal refl ux disease (GERD).
Materials and methods: a brief review of the literature on the modern concept of extraesophageal respiratory manifestations of GERD, the features of the course of upper esophageal diverticula, clinical and radiological symptoms of chronic aspiration bronchiolitis is presented. In the above clinical case, chronic aspiration bronchiolitis was a manifestation of gastroesophageal pathology.
Results: The development of fi brosing interstitial lung disease in a patient with a large upper esophageal diverticulum and GERD is presented.
Conclusion: the problems of differential diagnosis of respiratory symptoms in esophageal pathology are shown. The authors hope that the described observation will increase the attention of doctors regarding comorbid fi brosing interstitial lung diseases in esophageal pathology; the need for timely detection of a progressive fi brotic phenotype and determination of indications for antifi brotic therapy.
The article presents a clinical case of a combination of celiac disease with diagnosis in the adult period and infl ammatory bowel disease, which had the phenotype of ulcerative colitis in its debut and transformed into indeterminate colitis during observation. Gastroenterological pathology was accompanied by adrenal insufficiency and demyelinating disease of the central nervous system, which can be considered as extra-intestinal manifestations of autoimmune intestinal diseases according to literature data.
We present a rare clinical case of Wilson-C onovalov disease in a patient after a new coronavirus infection. The development of her neurological symptoms, which allowed to specify the etiology of the already existing liver damage, may have been provoked by the COVID-19 infection, in which the central nervous system is frequently involved in the pathological process. Wilson-C onovalov disease was suspected due to the presence of neurological manifestations and signs of liver cirrhosis. Subsequently, the diagnosis was confi rmed genetically, copper metabolism disorders were identifi ed and pathogenetic therapy was prescribed to eliminate excess copper from the body.
In the article, the authors provide brief information about a rather rare problem of pediatric gastroenterology — bezoars of the gastrointestinal tract. The data on the classifi cation of these pathological formations are presented, the problems of the pathogenesis of the formation of various types of bezoars are briefl y highlighted. Using the example of a clinical case of the detection of two giant bezoars in a teenage girl with high intestinal obstruction, the problem of the complexity of timely diagnosis of this condition in a patient with trichotillomania and trichophagia is discussed. The conclusion is made about the expediency of a comprehensive interdisciplinary approach to this problem in pediatric practice in order to reduce the risks of subsequent severe surgical interventions.