FUNCTIONAL GASTROINTESTINAL DISEASES
This article provides present-date knowledge on irritable bowel syndrome (IBS) and different approaches to therapy. The method of presenting the materials is based on a specific clinical case, which includes the diagnostic algorithm, a list of modern medicines, defines pharmacological targets and, based on them, describes an approach to the selection of an adequate pharmaceutical drug. In the presented case, patient S. (37 years old) had a functional bowel disorder (stool disorder) for seven years, and short-term pharmacotherapy courses did not produce a lasting effect. The course of the disease had become more alarming over time. The medical examination confirmed irritable bowel syndrome (IBS) in the patient – a mixed variant with pain syndrome during exacerbations. The drug of choice was otilonium bromide, an intestinal antispasmodic, which differed from other intestinal antispasmodics in its complex mechanism of action and practically zero absorption (3%). It allowed for a long-term therapy reducing a risk of side effects. The duration of treatment was 15 weeks (40 mg 3 times a day), of which the last three weeks were regarded as the maintenance therapy at a dose of 40 mg once a day. Pain and dysbiosis were completely relieved at 4 weeks of treatment. Motility and stool were restored, which resulted in the improvement of the quality of life and the symptoms of anxiety were resolved almost completely after 12 weeks of treatment. Thus, otilonium bromide had an effect on all pharmacological targets that were established before treatment.
ESOPHAGEAL AND GASTRIC DISEASES
Epigastric pain can have a variety of etiologies, including not only diseases of the upper gastrointestinal tract (GIT): gastroesophageal reflux disease, hiatal hernia, gastritis and duodenitis, gastric and/or duodenal ulcers, polyps and stomach cancer, functional dyspepsia, but also other gastrointestinal diseases, somatic diseases of other organs and systems, vascular pathology, infections and invasions, medications and a number of other reasons. More than 10 years have passed since the publication of our previous article on the issues of differential diagnosis of pain in the stomach. In the Elibrary.ru information base, both in the period of time preceding the publication and to this day, we have not found similar publications. This explains its placement in full or in fragments on specialized gastroenterological sites and guidelines for differential diagnosis in gastroenterology. Over the past 10 years, new consensuses and clinical recommendations have been published on diseases and conditions associated with epigastric pain, and the number of publications on other diseases and conditions that were previously considered very rare, but which today must be taken into account when carrying out differential diagnosis, has increased. Several foreign publications on the problem in recent years were found in the PubMed electronic database. In this regard, we consider it appropriate to consider the current aspects of the differential diagnosis of epigastric pain from the perspective of today. The list of diseases and conditions presented in the review, in which epigastric pain occurs in the clinical picture, indicates that the differential diagnosis of this syndrome is an interdisciplinary problem and is of interest not only to the gastroenterologist and therapist, but also to doctors of other specialties.
Introduction. The inefficiency of proton pump inhibitors (PPIs) in patients with symptoms of gastroesophageal reflux disease (GERD) may be caused by functional esophageal diseases, which should be diagnosed by using pH-impedance monitoring.
Aim. To evaluate the clinical efficacy of therapies in patients with symptoms of gastroesophageal reflux disease after phenotyping based on 24-h pH-impedance monitoring.
Materials and methods. A total of 61 patients with GERD symptoms were observed in a prospective study. The patients were categorized into 3 phenotypes based on the Lyon Consensus 2.0 and Rome criteria IV: nonerosive reflux disease (NERD), hypersensitive esophagus (HSE), functional heartburn (FH). The 5-point Likert scale was used to measure the severity of symptoms. NERD patients received PPI (omeprazole 20 mg twice daily), HSE patients received PPI (omeprazole 20 mg twice daily) and a selective serotonin reuptake inhibitor (SSRI) (citalopram 20 mg daily), FH patients received tricyclic antidepressant (TCA) (amitriptyline ¼ tablet at the bedtime). The entire length of treatment in all groups was 4 weeks.
Results. The severity of heartburn in patients with NERD, HSE and FH before treatment averaged 3.23 (95% CI 3.02–3.43) points on the Likert scale (strong). Due to therapy, the average score in the NERD group decreased from 3.48 (95% CI 3.23–3.74) to 0.77 (95% CI 0.53–1.01), in the HSE group from 2.92 (95% CI 2.41–3.42) to 0.83 (95% CI 0.30–1.36), and in the FH group from 2.86 (95% CI 2.41–3.30) to 0.86 (95% CI 0.41–1.30). The efficacy of therapy in NERD patients was 85%. The efficacy of PPI + SSRI and TCA in patients with HSE and FH was 83% and 79%, respectively.
Conclusion. A differentiated approach to the treatment of patients with heartburn symptoms based on phenotyping using 24-h impedance-pH findings can help optimize the therapy and improve its efficiency.
Introduction. Gastroesophageal reflux disease is the most common gastrointestinal disease. In recent decades, various questionnaires have been used to study the prevalence of gastroesophageal reflux disease: GERD-Q, QUEST, FSSG, RDQ, GERD-HRQL, the use of which has allowed us to establish a clear trend towards an increase in the frequency of gastroesophageal reflux disease throughout the world, including in Russia.
Aim. To study the prevalence and features of the clinical course of gastroesophageal reflux disease in residents of the Makhachkala- Caspian agglomeration of the Republic of Dagestan.
Materials and methods. A survey was conducted of 496 residents of the Republic of Dagestan (308 women and 188 men, average age ‒ 40 ± 0.7 years) using the GERD-Q and EFGERD (Epidemiology and Risk Factors for the Development of Gastroesophageal Reflux Disease in Dagestan) questionnaires.
Results. The prevalence of gastroesophageal reflux disease in residents of the Makhachkala-C aspian agglomeration of the Republic of Dagestan according to the GERD-Q questionnaire was 11.8%, according to the EFGERD questionnaire – 26.2%. The most common residents of the Republic of Dagestan who suffer from gastroesophageal reflux disease are Dargins (39.8%), Avars (38.2%) and Kumyks (37.0%). Somewhat less common are Lezgins (30.7%) and mestizos (31.6%). Laks (12%) and Tabasarans (8.9%) suffer from gastroesophageal reflux disease much less frequently. It has been established that in addition to esophageal symptoms of the disease, patients with gastroesophageal reflux disease often have symptoms of gastrointestinal tract diseases, as well as otolaryngological, bronchopulmonary, cardiac and dental symptoms.
Conclusion. The prevalence of gastroesophageal reflux disease in residents of the Makhachkala-C aspian agglomeration of the Republic of Dagestan according to the EFGERD questionnaire was 26.2%. At the same time, the EFGERD questionnaire has shown its high diagnostic value, which makes it possible to recommend it for the purpose of early diagnosis of gastroesophageal reflux disease and its extraesophageal manifestations.
Introduction. The heterogeneity of GERD pathogenesis determines the differences in diagnostic and therapeutic tactics. The personalization of therapy includes individual nuances of the metabolism of proton pump inhibitors and modification of risk factors: reduction of excess body weight, the abolition of tobacco smoking, alcohol intake, optimization of the pattern of eating behavior, the exclusion of drugs affecting the lower esophageal sphincter, normalization of the permeability of the mucous membrane of the esophagus.
Aim. To investigate pathological changes in the esophagus according to endoscopic examination protocols and the frequency of factors predisposing to the occurrence of reflux symptoms in the esophagus.
Materials and methods. In retrospective study of the EGDS protocols (n = 208), esophagitis was assessed (Los Angeles classification, 1994) and at the same time, risk factors for heartburn were investigated by questionnaire in a hospital cohort of patients (n = 50). The analysis of these protocols and respondents’ responses took into account differences by gender and age (WHO).
Results and discussion. Among patients with convincing endoscopic signs of GERD in a random sample of EGDS protocols, men predominated. The frequency of detection of pathological changes in the esophagus associated with GERD was at the level of 19.5%, stage C esophagitis was recorded 2 times more often, while stage D esophagitis and Baretta esophagus were recorded only in men. Age-related patterns have been established: stage D esophagitis, Barette’s esophagus and peptic stricture of the esophagus were detected among elderly and senile patients. Among the triggers of heartburn, respondents most often chose a certain pattern of eating behavior. Obesity was a significant risk factor in women, while smoking and taking calcium channel blockers were significant in men.
Conclusion. Prolonged use of proton pump inhibitors is indicated in a limited proportion of patients suffering from heartburn. To diversify GERD therapy, diagnostic measures are needed to clarify the mechanism of reflux into the esophagus.
Introduction. Students are a risk group for the development of chronic diseases. Clinical manifestations of gastroesophageal reflux disease, as a chronic disease, are often masked by diseases of other organs, which complicates diagnosis and reduces the effectiveness of treatment.
Aim. To identify clinical symptoms characteristic of gastroesophageal reflux disease among students of medical university and to propose a set of measures to prevent the identified disorders.
Materials and methods. We conducted a survey of 120 students of the 3rd year of medical university, including oral examination, original questionnaire and GerdQ questionnaire-questionnaire.
Results. According to the questionnaire data, only 13.9% regularly eat 3–4 times a day, 56.4% have a diet consisting mainly of fast food. 22.2% of students smoke, alcohol is occasionally consumed by 70.8%. Constant stress is experienced by 47.2% of surveyed students. The examination revealed the following: pain at swallowing in 2.8%; feeling of a lump in the throat, attacks of nausea in 13.9%, heartburn in 3%, frequent belching in 9.7%, complaints of pain in the epigastric region in 18.1% of students. Chronic infections of the oral cavity and pharynx (laryngitis, pharyngitis) were registered in 11.1%, cough, hoarseness of voice in 5.6%, caries and changes in the oral mucosa were diagnosed in 4.2% of students. According to the analysis of the GerdQ questionnaire, the presence of 8 or more points was found in 13.3% of students who were recommended to undergo an in-depth examination by a gastroenterologist.
Conclusion. Clinical manifestations characteristic of gastroesophageal reflux disease were revealed in the examined students. A comprehensive approach to diagnosis, proposed measures aimed at correcting risk factors, conducting educational and preventive activities will help to reduce the prevalence of the disease and improve the quality of life of young people.
DISEASES OF THE BILIARY SYSTEM AND LIVER
Introduction. The use of hypoammonemic agents to treat sarcopenia in liver cirrhosis has the potential to positively affect muscle mass, strength and function, given the pathogenetic basis of sarcopenia in liver cirrhosis.
Aim. To compare muscle mass, strength and function, as well as capillary blood ammonia levels in patients with decompensated liver cirrhosis in two groups with and without use of L-ornithine-L-aspartate (LOLA).
Materials and methods. A prospective cohort study was conducted. The treatment group included patients with decompensated liver cirrhosis of various etiologies and hyperammonemia, who received a hypoammonemic agent (LOLA) as part of complex therapy; the comparator group included patients with liver cirrhosis, hyperammonemia and sarcopenia, who did not receive LOLA. All patients underwent measurements of muscle mass (shoulder muscle volume, skeletal muscle mass indices (SMI) measured by dual-energy X-ray absorptiometry), strength (dynamometry, chair stand test) and function (short physical performance battery).
Results. An analysis of clinical outcomes included 42 patients: 30 from the treatment group and 12 from the comparator group. In the treatment group, the proportion of patients with reduced muscle mass decreased from 76.67% to 73.33% (p = 0.012).
The average shoulder muscle volume in the treatment group was 20.86 cm, which reached 21.35 cm (p = 0.072) at 3 months of therapy. The growth in shoulder muscle values and changes in the skeletal muscle indices for the upper limbs showed an increase in muscle mass. In the treatment group, mean muscle mass values measured by handheld dynamometry (HHD) increased from 20.53 to 22.48 kg at 3 months of therapy (p = 0.011). The increase in dynamometry scores demonstrated an increase in muscle strength during LOLA therapy. The increase in balance test scores determining muscle function was reported (p < 0.001). The capillary blood ammonia levels did not change significantly in both groups.
Conclusion. The study showed a significant increase in muscle mass, strength and function in patients with liver cirrhosis and hyperammonemia, receiving LOLA as part of decompensated liver cirrhosis therapy.
Introduction. Neutrophils are important participants in the innate immune response, are the first to react to a pathogenic factor and quickly develop non-specific reactions. At the same time, there are no studies on the functional activity of neutrophils in patients with Opisthorchis felineus (O. felineus) invasion.
Aim. To study the clinical and laboratory manifestations of opisthorchiasis depending on the leukocyte indicators of the complete blood count.
Materials and methods. A total of 328 patients with O. felineus invasion (120 men and 208 women) and 51 practically healthy patients (28 men and 23 women) were examined. Opisthorchiasis was diagnosed using coproovoscopy and microscopy of duodenal contents. All patients with O. felineus invasion underwent complete and biochemical blood tests. Liver elastometry using Aixplorer (France) or Siemens Acuson S2000 (Germany) with determination of the liver fibrosis degree according to METAVIR, and blood neutrophils functional activity study were performed in 103 patients with chronic opisthorchiasis (58 men and 45 women).
Results. A tendency was found to increase the proportion of leukopenia by 3.5 times (p = 0.12) and neutropenia by 1.9 times (p = 0.15) in patients with liver fibrosis F2-F3 according to METAVIR compared to individuals with liver fibrosis F0 according to METAVIR. The absolute neutrophil content in patients with O. felineus invasion and liver fibrosis F2-F3 according to METAVIR was decreased in comparison with individuals with liver fibrosis F0 according to METAVIR (2.24 × 109/l versus 3.06 × 109/l, p = 0.04). A decrease in the functional activity of neutrophils in the blood was also registered in patients with liver fibrosis F2-F3 according to METAVIR in comparison with individuals with F0 according to METAVIR.
Conclusion. A decrease in the number and functional activity of neutrophils in the blood may be markers of an increased risk of liver fibrosis in patients with opisthorchiasis. It is advisable to study the possibilities of immunomodulatory drugs on the course of O. felineus invasion.
Metabolic-associated fatty liver disease or metabolic dysfunction-associated steatotic liver disease is a common chronic disease characterized by increased fat accumulation in the liver and underlying metabolic dysfunction. In the occurrence of this disease, cardiometabolic factors are important: dyslipidemia, impaired carbohydrate metabolism, insulin resistance, which increase as metabolic dysfunction- associated steatotic liver progresses and most often contribute to the development of cardiovascular pathology. Currently, metabolic dysfunction-associated steatotic liver is a multisystem disease associated with obesity, type 2 diabetes, cardiovascular diseases, chronic kidney disease, oncology, etc. Metabolic dysfunction- associated steatotic liver most often affects comorbid patients who take a considerable number of medications. Over the past decades, many drugs have been identified that have the potential to cause steatohepatitis in susceptible individuals. The range of drugs that have hepatotoxicity is quite large. More than 300 drugs are known to cause drug-induced liver injury. However, the true prevalence of drug-induced liver injury remains unknown, since it is not always possible to determine the true cause of liver damage or a specific drug. In this regard, the issue of management tactics for patients with metabolic dysfunction-associated steatotic liver and drug-induced liver injury remains relevant, especially when it comes to the need to take medications that are vital for the patient. The article provides a review of the literature on the etiopathogenetic, clinical and diagnostic aspects of both metabolic dysfunction-associated steatotic liver and in combination with drug-induced liver injury, features of the management of comorbid patients with metabolic dysfunction-associated steatotic liver and drug-induced liver injury. Therapeutic approaches are reviewed with an emphasis on comprehensive management (non-pharmacological and pharmacotherapy). Prescribing essential phospholipids may be effective in the treatment of such patients.
Introduction. Fatty liver disease is the largest contributor to the burden of chronic liver disease worldwide. Current approaches do not allow sufficient differentiation between alcoholic and non-alcoholic etiology of the process.
Aim. Create diagnostic panels including electrical and viscoelastic parameters of erythrocytes to differentiate fatty liver disease of alcoholic and non-alcoholic genesis.
Materials and methods. The study included 38 men (47.5 ± 2.9 years) with NAFLD; 31 men with alcoholic fatty liver disease (AFLD) (45.1 ± 3.1 years) according to ultrasound of the abdominal organs, the degree of fibrosis did not exceed F1 (FibroScan® 502). Electrical and viscoelastic parameters of erythrocytes were studied by dielectrophoresis using an electro-optical cell detection system. To determine the parameters of erythrocytes – biomarkers for distinguishing between AFLD and NAFLD, a system of machine learning methods – Random Forest was used.
Results. Electrical, viscoelastic parameters of erythrocytes, which are biomarkers for distinguishing between AFLD and NAFLD, were established: cell membrane capacity (p = 1.21E-11), the degree of change in the deformation amplitude at a frequency of 5 x 105 Hz (p = 2.38E-08), cell polarizability at a frequency of 106 Hz (p = 9.38E-08), the speed of erythrocyte movement to the electrodes (p = 4.32E-06), the magnitude of the dipole moment (p = 1.66E-05), relative polarizability (p = 2.35E-05), the index of erythrocyte destruction at a frequency of 5 x 105 Hz (p = 0.016), the position of the crossover frequency (p = 2.13E- 06). The diagnostic model, including five parameters – the position of the crossover frequency, cell polarizability at a frequency of 106 Hz, cell electrical conductivity, membrane capacity, the degree of change in the deformation amplitude at a frequency of 5 x 105 Hz, provided the highest diagnostic accuracy with an AUC of 0.975, a sensitivity of 96.3%, and a specificity of 91.8% in differentiating between AFLD and NAFLD.
Conclusion. Thus, systematic exposure to alcohol modifies the structure of erythrocyte membranes, leading to a decrease in the surface charge, the barrier function of membranes, reducing the resistance of cells, their ability to deform, which determines the key role of the identified electrical, viscoelastic parameters of erythrocytes in differentiating between AFLD and NAFLD.
Introduction. Gallstone disease is one of the most common diseases of the digestive system, its prevalence rate averaged to 10–15%, which is associated with high healthcare costs for patient management such as diagnosis, cholecystectomy with over 500 000 operations performed per year in the Russian Federation, and pharmacotherapy, which is increasingly used for the combined treatment.
Aim. To assess the clinical efficacy and safety of hymecromon, a domestic drug, in patients with dyspeptic form of GSD.
Materials and methods. A total of 30 patients (14 men and 16 women) with gallstones in their gallbladders were observed in the study. The patients were divided into 2 groups: Group 1 included 15 patients who received hymecromone at a dose of 600 mg/ day; Group 2 included 15 patients who received hymecromone at a dose of 1200 mg/day. The course of therapy was 21 days.
Results. Intensity of all GSD symptoms significantly decreased by the end of hymecromone therapy in patients of both groups. Almost all patients reported a stool normalization. The use of hymecromone at a dose of 400 mg three times a day did not result in loose stools, and in patients who had loose stools before initiation of treatment, hymecromone contributed to the normalization of its frequency and nature. Vomiting, urge to retch and loss of appetite were completely discontinued in patients who received hymecromone at a dose of 1200 mg/day, however, there were no significant differences between Groups 1 and 2 in the changes in symptoms. No adverse events or side effects were observed during therapy.
Conclusion. The therapy had a beneficial effect on upper gastrointestinal symptoms and bowel dysfunction (flatulence, diarrhoea, constipation). A significant improvement in the patients’ quality of life based on GSRS questionnaire scores was noted. The domestic drug Odecromon is considered to be effective in the treatment of dyspeptic GSD.
Introduction. The search for markers reflecting immune disorders and their contribution to the progression of liver cirrhosis (LC) is very relevant.
Aim. To study the possibility of using the “neutrophil to lymphocyte ratio” indicator as a predictor of the development of systemic inflammatory response syndrome and death.
Materials and methods. For a retrospective clinical study, 225 case histories of patients with cirrhosis were selected from 2008 to 2018. Three groups were formed from them: group 1: patients with cirrhosis class A according to Child – Pugh (n = 24); group 2: patients with cirrhosis class B and C according to Child – Pugh (n = 201) and group 3: healthy individuals (n = 50). The prognostic value of the neutrophil-to-lymphocyte ratio (NLR) indicator in the development of systemic inflammatory response syndrome (SIRS) and death in patients with cirrhosis was analyzed.
Results. Patients with LC had statistically significantly higher values of NLR compared to healthy individuals (p < 0.001). The NLR indicator is an independent risk factor and a statistically significant predictor of the development of SIRS in patients with LC. A NLR value > 3.59 had a sensitivity of 0.38 [95% CI: 0.28; 0.48] and specificity 0.93 [95% CI: 0.87; 0.97]. NLR served as a statistically significant predictor of death (p < 0.001). A NLR value > 4.5 had a sensitivity of 0.24 [95% CI: 0.15; 0.36] and specificity 0.97 [95% CI: 0.92; 0.99].
Conclusion. An NLR value of more than 3.59 increases the risk of developing SIRS in patients with cirrhosis, and an NLR value of more than 4.5 increases the risk of death.
At present obesity is a major public health challenge globally, which accounts for a significant portion of all healthcare costs. Obesity and its complications, insulin resistance and dyslipidemia, have been identified as independent risk factors for cholelithiasis. Cholelithiasis is mainly caused by four factors: bile cholesterol overload caused by excess cholesterol made in the liver due to genetic factors; systolic dysfunction of the gallbladder wall; bowel dysfunction with excess absorption of cholesterol or cholesterol overload caused by impaired hepatic bile circulation; and accelerated growth of cholesterol crystals and solid cholesterol crystals. Rapid weight loss (≥1.5 kg/week) due to low-calorie diets as the main treatment method, or after bariatric surgery is one of the risk factors for gallstone formation. Bariatric surgery is effective for the treatment of obesity and its complications, but bariatric surgery does not reduce the incidence of cholelithiasis. On the contrary, many studies showed that bariatric surgery may increase the incidence of cholelithiasis. The rapid weight loss causes fat mobilization and then increases serum cholesterol and triglyceride levels. On the other hand, bowel dysfunction due to bariatric surgery is accompanied by decreased cholecystokinin levels, causing impaired gallbladder contractility. Cholelithiasis requires close attention after bariatric surgery, with 10% of patients undergoing bariatric surgery having to undergo cholecystectomy postoperatively due to a high risk of cholelithiasis. UDCA is a natural bile acid that is prescribed to be taken orally (by mouth). UDCA inhibits the absorption of cholesterol in the bowel, enhances the biosynthesis of bile acids, and reduces biliary cholesterol secretion. UDCA is a choleretic agent, as all bile acids, but differs from other dihydroxy bile acids in being non-cytotoxic. The use of UDCA while following a low-calorie diet and after bariatric surgery significantly reduces the risk of gallstone formation and cholecystectomy with associated complications.
Introduction. The muscle mass in sarcopenia is assessed in patients with liver cirrhosis (LC) using skeletal muscle indices (SMI) measured by dual-energy X-ray absorptiometry (DXA), the results of which are distorted due to lower limb edema. This requires the development of upper limb SMI (UL SMI) to ensure more accurate assessment of muscle mass in patients with LC and ascitice-dematous syndrome.
Aim. To compare the diagnostic accuracy of standard MSI and UL SMI, and develop criteria for the reference range of UL SMI in patients with decompensated LC of various origin and sarcopenia, taking into account the lower limb edema in comparable age groups.
Materials and methods. A prospective cohort study was conducted. The treatment group included patients with decompensated LC and lower limb edema of various origin; the control group included healthy volunteers matched to patients by gender and age to determine the diagnostic accuracy of the technique and calculate the criteria for the reference ranges in UP SMI. All patients underwent measurements of muscle mass by DXA.
Results. A total of 59 patients were examined: 39 patients with LC and 20 healthy volunteers. Based on the results of the ROC analysis, it was determined that the cut-off values for UL SMI are 1.91 kg/m2 for men (sensitivity = 62.5%, specificity = 85.71%) and 1.47 kg/m2 for women (sensitivity = 86.96%, specificity = 69.23%) as compared to the cut-off values for the standard SMI of 7.78 kg/m2 for men (sensitivity = 75% and specificity = 57.14%), and SMI of 6.05 kg/m2 for women (sensitivity = 56.52% and specificity = 69.23%). UL SMI is a more accurate marker of sarcopenia in patients with LC and lower limb edema than the standard SMI.
Conclusion. The advantages of UL SMI over classical SMI for sarcopenia diagnosis in patients with cirrhosis and lower extremity edema were demonstrated. The UL SMI criteria for the reference range in patients with decompensated LC and sarcopenia were developed.
Introduction. MAIT cells are a new subpopulation of T cells that protect mucous barriers against penetration of foreign substances. There are practically no studies devoted to the participation of these cells in the pathogenesis of parasitic diseases.
Aim. To study the phenotype of blood MAIT cells in patients with Opisthorchis felineus (O. felineus) invasion depending on the severity of liver fibrosis.
Materials and methods. A total of 78 patients with O. felineus invasion (42 men and 36 women) and 26 control group individuals (14 men and 12 women) were examined. Opisthorchiasis was diagnosed using coproovoscopy and duodenal contents microscopy. All patients underwent liver elastometry using Aixplorer (France) or Siemens Acuson S2000 (Germany) systems with determination of the liver fibrosis degree according to METAVIR. The phenotype composition of lymphocytes was investigated using a Navios flow cytometer (Beckman Coulter, USA). T cells, T helpers, and T cytotoxic lymphocytes were isolated and the presence of NCR Va7.2 and CD161 on the surface of these cells was assessed.
Results. The content of MAIT T-helpers was decreased in patients with O. felineus invasion compared to healthy individuals (p < 0.001). In MAIT T-cytotoxic cells, a similar pattern was not detected (p = 0.5). In patients with liver fibrosis F2 according to METAVIR compared to individuals with F0 according to METAVIR, a decrease in the total number of T-cells, T-helpers and T-cytotoxic cells, as well as MAIT T-helpers and MAIT T-cytotoxic cells was observed. Thus, the content of CD161+ NCR Va7.2+ T-helpers was 0.020% [0.004–0.042%] in patients with opisthorchiasis with F0 according to METAVIR and 0.0% [0.0–0.003%] in individuals with liver fibrosis F2 according to METAVIR (p = 0.001). For CD161+ NCR Va7.2+ T-cytotoxic cells, these indicators were, respectively, 1.47% [0.41–2.49%] and 0.12% [0.07–0.31%] (p < 0.001).
Conclusion. Further study of MAIT cells in patients with liver pathology has undoubted prospects for the creation of new therapeutic and diagnostic technologies.
Introduction. Metabolic dysfunction-associated steatotic liver disease is one of the leading causes of cirrhosis, liver cancer and extrahepatic complications. The number and various combinations of cardiometabolic risk factors, as well as the severity of liver steatosis, can affect the aggressiveness and prognosis of the disease. The article presents the results of own studies aimed at determining the prognostic significance of risk factors (individual and in different combinations) and steatometry.
Objective. To determine the influence of individual cardiometabolic factors, their number and various combinations on the aggressiveness and prognosis of metabolic dysfunction-associated steatotic liver disease; to assess the prognostic value of steatometry for the disease.
Material and methods. The examination results (steatometry, blood biochemistry tests, abdominal ultrasound) of patients diagnosed with metabolic dysfunction-associated steatotic liver disease were retrospectively analyzed. Statistical analysis: Student's t-test, Pearson's χ2-test, odds ratio, relative risk, Fisher's φ-test, ROC-analysis.
Results. 146 patients were included. Cohort characteristics: average age 49.3 years, 84 men (57.5%). Aggressive forms (steatohepatitis, advanced steatosis) were associated with arterial hypertension, carbohydrate metabolism disorders (the most significant is insulin resistance), dyslipidemia, hyperuricemia. The severity of liver steatosis was less in patients who received therapy for lipid metabolism disorders comparing with those who didn’t. The presence of three or more cardiometabolic risk factors in a patient increased the risk of steatohepatitis and advanced steatosis. The combination of arterial hypertension and hyperuricemia significantly increased the risk of steatohepatitis. Advanced hepatic steatosis (≥310 dB/m2 by steatometry) was reliably associated with steatohepatitis.
Conclusion. Individual risk factors, their number and combinations, contribute differently to the development of aggressive forms of the disease. Hyperuricemia should be considered as an additional cardiometabolic risk factor. Steatometry is capable of identifying advanced hepatic steatosis, being a risk factor for the development of steatohepatitis, which allows us to recommend it for the early diagnosis of metabolic dysfunction-associated steatotic liver disease.
BOWEL DISEASES
Constipation is a disorder that affects a large number of people and has a negative impact on quality of life. Constipation is one of the common reasons for seeking medical help from an outpatient doctor. The problem of constipation can often be multifactorial, with important causes being low fiber in the diet, decreased fluid intake and physical inactivity. For some patients, constipation is not a chronic problem, but may occur at some point in their lives, usually lasts a limited period of time and is not a serious problem, the solution to which may be changes in diet and lifestyle, or a short course of laxatives. In everyday outpatient practice, so-called simple or functional constipation is more common. At the same time, long-term or chronic constipation is often a complex problem for both the doctor and the patient; it is often secondary in nature, affecting not only personal well-being and quality of life, but also causes considerable financial costs, since most patients do not immediately seeks medical help, trying to self-medicate, for a long time and not always successfully, transforming the problem into a chronic one, further complicating the diagnostic search and choice of treatment tactics. Chronic constipation is more often a problem for women and older people. Knowledge and understanding of the causes and possibilities for diagnosing constipation, approaches to therapy, as well as measures for its prevention will allow the outpatient doctor to choose the necessary tactics for managing the patient. The article provides a review of the literature on the etiopathogenetic, diagnostic aspects of constipation, as well as the possibility of an integrated approach in the treatment of patients. Algorithms for diagnostic search and choice of therapy for a patient with constipation are convenient for practical use, which is also presented in the article.
The article reviews data on the long-term effectiveness and survival of biological therapies for treating inflammatory bowel diseases, such as ulcerative colitis and Crohn’s disease. It highlights the shift in treatment goals, emphasizing not only induction and maintenance of remission but also long-term outcomes. The choice of therapy is becoming increasingly complex, as it must consider both clinical efficacy and endoscopic remission, which, serves as a predictor of long-term treatment effectiveness. Special attention is given to ustekinumab – antibodies targeting interleukins 12 and 23. This drug has shown high long-term effectiveness and safety in treating ulcerative colitis and Crohn’s disease. Studies indicate that ustekinumab effectively maintains clinical remission in patients, providing stable results and a low rate of serious adverse events. Long-term data also highlight its advantages over other biological agents, such as infliximab and adalimumab, in terms of therapy sustainability. The article includes data from clinical trials of ustekinumab extending up to 5 years, demonstrating good treatment sustainability, as well as various real-world practice studies confirming the prolonged effectiveness of ustekinumab in patients with ulcerative colitis and Crohn’s disease. The article evaluates and analyzes these data on long-term effectiveness and drug survival and also emphasizes the importance of an individualized approach in selecting therapy, taking into account prior treatment experience and inflammation activity.
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 indicates the specific niche and principles for choosing mesalazine formulations, and the selection of a dose for the treatment of mild to moderate extensive (left-sided and total) ulcerative colitis (UC). It doesn’t consider any approaches to the treatment of more severe UC or distal UC (proctitis). The current concepts on the use of 5-aminosalicylic acid (5-ASA) formulations to induce and maintain remission in mild to moderate active UC are discussed. The principles for drug administration and a comparative analysis of domestic and international mesalazine dosing recommendations are provided. The guidelines place special emphasis on the importance of high-dose mesalazine therapy (≥4 g/day), which allows to achieve the targets set by the Treat-to-target (T2T) strategy and to reach the clinical and endoscopic remission. The evidence from meta-analyses and comparative studies demonstrating the same efficacy of different forms of mesalazine in the treatment of UC are presented. Attention is drawn to the choice of the optimal drug with enteric coating that consists of two types of Eudragit (Eudragit L and Eudragit S) in contrast to mesalazine formulations with one and the same type of coating (only L or only S). The double Eudragit (L + S) pH-dependent coating of mesalazine tablets dissolves in the terminal ileum, cecum and partially in the right half of the colon at pH 6–7.5, while formulations coated with only L or S dissolve at a narrower pH range. The clinical efficacy of mesalazine directly depends on its intraluminal concentration that is determined by the amount of the released drug according to the pH level in the intestinal lumen. The double Eudragit coating allows to cover the entire pH range in the ileum and colon. The paper presents evidence from the domestic clinical practice that confirms the Cochrane meta-analysis statements on the comparable efficacy of different mesalazine formulations concerning the targets to reach remission and reduce the level of fecal calprotectin. In addition, a high incidence of clinical remissions (more than 80% at 48 weeks of treatment) on double coated (L + S) mesalazine is demonstrated.
Short bowel syndrome is a gastrointestinal disorder resulting from massive resection of the small intestine. The most common causes of resection are acute mesenteric ischemia, Crohn’s disease, abdominal trauma, adhesive intestinal obstruction, intestinal malignancies, and radiation enteritis. Short bowel syndrome with intestinal failure is characterized by severe malabsorption-m aldigestion accompanied by abdominal pain, diarrhea, dehydration, and progression of protein-energy malnutrition. Many patients with SBS develop long-term clinical complications over time due to altered bowel anatomy and physiology or various therapeutic interventions such as parenteral nutrition and central venous catheterization. This review focuses on the most important aspects of diagnosis, treatment, and prevention of several complications that can occur in this patient population, including macronutrient and micronutrient imbalances, diarrhea, fluid and electrolyte imbalances, metabolic bone disease, biliary disorders, bacterial overgrowth in the small intestine, and complications related to venous access. The main therapeutic strategies for SBS with intestinal failure are: special diet, enteral nutritional support with semi-elemental mixtures, parenteral nutrition, oral rehydration, antimicrobal and antidiarrheal drugs, enzymes. Administration of glucagon-like peptide 2 analog, teduglutide, is clinically effective in reducing dependence on parenteral nutrition and improving quality of life. Management of patients with SBS with intestinal failure is a complex long-term process which requires dynamic clinical and laboratory monitoring.
Ulcerative colitis is an immune-inflammatory disease characterized by ulcerative-destructive processes in the colon mucosa. Cytokines, proteins secreted by activated immune cells that affect the activity, differentiation, or proliferation of other cells, play a key role in pathogenesis. Improving the effectiveness of drug therapy for ulcerative colitis is currently associated with the addition of genetically engineered biological drugs (GEBD) and targeted immunosuppressants, Janus kinase inhibitors (tofacitinib), to traditional therapy. Compared with GEBD, tofacitinib has a number of advantages, including its oral administration, rapid onset of action, rapid elimination, and lack of immunogenicity. Tofacitinib was approved by the FDA in 2012 for the treatment of rheumatoid arthritis and in 2017 for the treatment of psoriatic arthritis, and in May 2018 for the treatment of ulcerative colitis. Currently, tofacitinib occupies an important place in the Federal Clinical Guidelines for Ulcerative Colitis of 2024. The Pubmed and Scopus databases were searched for articles on the use of tofacitinib in ulcerative colitis published in the current decade, with an emphasis on publications of the last year and publications not included in previously published domestic reviews. The studies found confirm the effectiveness of tofacitinib in the treatment of moderate to severe ulcerative colitis in patients in various geographic regions. A number of studies have noted the pharmacoeconomic effectiveness of tofacitinib compared to GEBD. Tofacitinib is not presented in the current clinical guidelines for ulcerative colitis for children, but a number of studies indicate the prospects for its integration into pediatric protocols.
COMORBID PATIENT
Introduction. More than half of post-reproductive age women are overweight and obese, which puts them at high risk of developing non-alcoholic fatty liver disease (NAFLD). In the abdominal type of obesity, adipose tissue dysfunction and impaired leptin secretion develop.
Aim. To evaluate the possibilities and diagnostic characteristics of leptin for the determination of liver steatosis in pre-obese and obese women in the early postmenopausal period.
Materials and methods. 76 women in the early postmenopausal period were examined, including 63 patients with NAFLD and overweight and obesity with an average age of 50.50 ± 2.16 years and 13 practically healthy women with an average age of 49.29 ± 2.64 years, who underwent an ultrasound examination of the liver, calculation of the HSI index (Hepatic Steatosis Index) and determination of the level of leptin in the blood.
Results. Abdominal type of obesity was detected in 84% of patients, the gynoid type was 16%, and the body mass index averaged 33.5 ± 1.3 kg/m2. According to the ultrasound examination and the HSI index, all patients had liver steatosis. Their leptin levels significantly exceeded the control data (p < 0.001) and directly correlated with the severity of steatosis according to the HSI index (r = 0.321; p = 0.010). The threshold value of the serum leptin level in patients with NAFLD was 13 ng/ml with sensitivity and specificity of 90.5% and 92.3%, respectively.
Conclusion. Leptin is a highly informative marker of NAFLD in women with pre-obesity and obesity in the early postmenopausal period, the value of which is higher or equal to 13 ng/ml allows to verify steatosis, less than this value – to exclude it in this category of persons with high diagnostic effectiveness.
Inflammatory bowel diseases, which include Crohn’s disease and ulcerative colitis, are a global disease of the 21st century. Periodontitis is the sixth most common disease in the world (second among dental pathologies after caries) and the leading cause of tooth loss in adults. At the beginning of the 21st century, the concept of “periodontal medicine” was formed, within the framework of which the bidirectional connection of periodontal pathology with systemic diseases of the body is considered. Extraintestinal manifestations of inflammatory bowel disease are associated with the generalized nature of the inflammatory response. In clinical guidelines, only aphthous stomatitis is described as a systemic manifestation of Crohn’s disease and ulcerative colitis from the oral cavity. Periodontitis is considered a less representative non-specific oral manifestation of inflammatory bowel disease. We searched the Pubmed and Scopus information databases for articles published before 02/15/2024 that examined the relationship between inflammatory bowel disease and periodontal pathology. The results of clinical studies, their synthesis in systematic reviews and meta-analyses, indicate a bidirectional relationship between Crohn’s disease and ulcerative colitis with periodontal pathology. The most likely mechanism is associated with a change in the microbiocenosis of the oral cavity and a further change in the intestinal microbiome due to oral intake of periodontal organisms, which leads to impaired intestinal permeability and the development of immune reactions that play a key role in the development of periodontal diseases and inflammatory bowel diseases.
Introduction. Mastocytosis is a heterogeneous group of diseases characterized by the abnormal accumulation of clonal mast cells (MCs) in various tissues and organs, including skin, bone marrow, liver, spleen and lymph nodes. The clinical picture of cutaneous and indolent systemic mastocytosis is formed by a wide range of symptoms associated with activation of mast cells. Single European studies have demonstrated wide variability in the frequency of gastrointestinal symptoms (GI-symptoms)) in children with mastocytosis (from 15 to 50%).
Aim. To analyze the frequency of mediator-related GI-symptoms in children with different subtypes and clinical forms of mastocytosis.
Materials and methods. A prospective observational study included data from 289 children aged 3 to 17 years who were under observation at the Moscow Scientific and Practical Center of Dermatovenereology and Cosmetology. Symptoms were assessed using the Pediatric grade scale of symptoms of mastocytosis. Clinical manifestations of reactions caused by mast cell degranulation were compared with data from clinical and laboratory studies. The concentrations of tryptase and histamine in the blood serum of patients were determined. The incidence of organomegaly and mesenteric lymphadenitis in children with mediating symptoms and without symptoms was determined using ultrasound.
Results. 67 (23.2%) patients had GI symptoms. More than half of the patients (51.6%) indicated abdominal pain, 32.3% reported diarrhea. The severity of pain symptoms correlated with the level of serum tryptase (ρ = 0.564, p < 0.01). The incidence of hepatomegaly and mesadenitis in children with GI- symptoms was 19.4% and 25.4%, respectively. In a comparative analysis in groups of children with and without GI symptoms, the differences in the number of identified cases of organomegaly and mesadenitis were statistically significant (p < 0.001). An increase in histamine levels in the blood was detected in half of the patients with complaints of heartburn and nausea.
Conclusion. Our results demonstrated that a study of the level of serum tryptase, ultrasound of the abdominal organs and lymph nodes should be carried out in all children with mediator-related GI-symptoms regardless of the clinical form of mastocytosis.
Metabolic syndrome is a pathological condition that includes obesity, elevated blood glucose levels, hypertension and dyslipidemia. This comorbid condition is a global problem of our time. According to the INTERHEART study, metabolic syndrome occurs in more than 26% of the world’s population. In the Russian Federation, 40% of residents have 2 components of the metabolic syndrome, 11% have 3 or more of its components. In addition to well-known risk factors for the development of metabolic syndrome, such as genetic predisposition, overeating, physical inactivity, hormonal disorders and others, in recent years, increasing attention has been paid to the study of the intestinal microbiota and its effect on the metabolic syndrome. For example, a comparison of the intestinal microbiota of people with normal BMI and obesity showed different species of microorganisms inhabiting our gastrointestinal tract. Analyzing patients diagnosed with type 2 diabetes mellitus we can note a decrease in butyrate-producing bacteria (Faecalibacterium prausnitzii and Roseburia) that modify insulin sensitivity to body tissues. Some species of Lactobacillus are able to normalize lipid metabolism, reduce the number of adipocytes, reduce the absorption of cholesterol by converting it into insoluble coprostanol. In patients with arterial hypertension there is dysbacteriosis of I and II degree, in arterial hypertension with metabolic syndrome – absence of dysbacteriosis of I degree and presence of dysbacteriosis of II and III degrees, with prevalence of opportunistic forms. Understanding the role of intestinal microbiota becomes a key element not only in diagnosis, but also in the development of effective treatment methods and their application in complex treatment of metabolic syndrome.
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