[Exocrine pancreas insufficiency: clinical significance and approaches to correction from evidence medicine].

Exocrine pancreatic insufficiency (EPI) is a common complication of both benign and malignant diseases of the pancreas, as well as a consequence of radical surgical operations on the pancreas and a whole range of other variable extra-pancreatic causes. In clinical practice in the adult population, most cases of EPI are associated with chronic pancreatitis, while in the pediatric population with cystic fibrosis. The regression of the production of digestive enzymes in EPI mediates the development of the syndrome of maldigestion and malabsorption, leading to the progressive development of malnutrition, the importance of which is often underestimated by practitioners. At the same time, the development of nutritional deficiency is not just a complication of EPI, but also has an important effect on the course of the underlying causative disease, worsening the prognosis and quality of life of the patient, and is also a proven risk factor for osteoporosis and sarcopenia. To date, compensation for the absolute deficiency of pancreatic enzymes using enzyme replacement therapy is the only possible way to correct the EPI and prevent nutritional deficiency.

[Obesity as a risk factor for diseases of the digestive system].

Currently, the global prevalence of obesity among the worlds adult population is about 650 million people, which makes it possible to consider this chronic metabolic disease as a non-infectious pandemic of the 21st century. It has been proven that obesity is associated with several gastroenterological diseases, while the mechanisms of these associations are extremely heterogeneous and multifactorial. Hypertrophy and hyperplasia of adipocytes in obesity lead to a change in the profile of adipokine production (a decrease in adiponectin, an increase in leptin), an increase in the production of pro-inflammatory cytokines (interleukin-1, 6, 8, tumor necrosis factor ), C-reactive protein, free fatty acids, as well as active forms of oxygen (superoxide radicals, H2O2). All the above induces the development of chronic slowly progressive inflammation, oxidative stress, and insulin resistance. In addition, peptides secreted by adipocytes (adiponectin, leptin, nesfatin-1 and apelin) can modulate gastrointestinal motility, acting both centrally and peripherally. The qualitative and quantitative changes in the intestinal microbiota observed in obese patients (increased Firmicutes and decreased Bacteroidetes) lead to a decrease in the production of short-chain fatty acids and an increase in the intestinal permeability due to disruption of intercellular tight junctions, which leads to increased translocation of bacteria and endotoxins into the systemic circulation. Numerous studies have demonstrated the association of obesity with diseases of the esophagus (gastroesophageal reflux disease, Barretts esophagus, esophageal adenocarcinoma, esophageal motility disorders), stomach (functional dyspepsia, stomach cancer), gallbladder (cholelithiasis, gallbladder cancer), pancreas (acute pancreatitis, pancreatic cancer), liver (non-alcoholic fatty liver disease, hepatocellular carcinoma), intestine (diverticular disease, irritable bowel syndrome, colorectal cancer).

[Efficacy of butyric acid inclusion in eradication regimens for Helicobacter pylori infection: a meta-analysis of controlled trials].

AIM: Systematization of data on the efficacy and safety of butyric acid inclusion in eradication therapy (ET) regimens for Helicobacter pylori infection. METHODS: Research searches were carried out in the electronic databases MEDLINE/PubMed, EMBASE, Cochrane, Google Scholar, the Russian Science Citation Index (RSCI) until November 2020. All controlled studies comparing the efficacy and/or safety of including butyric acid in ET regimens for H. pylori infection were included in the final analysis. RESULTS: The meta-analysis included 6 controlled studies (1 Italy, 5 Russia) involving 736 patients (381 in the ET groups with butyric acid; 355 in the comparison groups). The pooled eradication efficiency in the butyric acid groups was 90.23% (95% confidence interval CI 86.73493.069), while in the comparison groups it was 65.69% (95% CI 60.44170.669). Meta-analysis showed that the addition of butyric acid to ET regimens significantly increased the eradication efficiency (odds ratio OR 5.355, 95% CI 3.5048.184; p0.001). There was no significant heterogeneity between results (p=0.1408; I2=42.1%). The addition of butyric acid to ET regimens significantly reduces the risk of diarrhea (OR 0.225, 95% CI 0.09230.549; p=0.001; I2=34.21%) and abdominal distention (OR 0.357, 95% CI 0.1550.818; p=0.015; I2=80.13%) by the end of the 1st week of treatment. CONCLUSION: The present meta-analysis demonstrated that the inclusion of butyric acid in ET regimens for H. pylori infection significantly increases the effectiveness of treatment and reduce the incidence of side effects. Apparently, the increase in the effectiveness of eradication is due to an increase in patient compliance with treatment due to an improvement in the safety profile of therapy.

[Development of the Russian version of quality of life questionnaire in patients with GERD - GERD-HRQL].

Gastroesophageal reflux disease (GERD) is a common chronic disease of the upper gastrointestinal tract with long course of the disease and followed by different symptoms significantly reducing quality of life (QoL) in pts. Assessment of QoL in pts with GERD may be of value for comprehensive evaluation of treatment effect as well as for monitoring of pts during treatment course in a real clinical practice. AIM: Development of the Russian version of GERD-HRQL questionnaire to assess symptomatic outcomes of GERD in research and real clinical practice. MATERIALS AND METHODS: GERD-HRQL questionnaire (V. Velanovich, USA) consists of 11 items: 10 items for assessment of the most frequent symptoms/problems related with QoL in pts with GERD and 1 item for assessment of patient-reported global satisfaction with health condition. RESULTS: In accordance with international guidelines, the new language version of the tool may be used in research and clinical practice after cross cultural adaptation, linguistic validation and psychometric testing. This paper presents the results of cross-cultural adaptation and linguistic validation of the Russian version of GERD-HRQL. The following steps of linguistic and cultural adaptation of GERD-HRQL for Russia were conducted after the permission from the author of GERD-HRQL was obtained: forward translation with creation of two forward translations of GERD-HRQL in Russian, reconciliation and expert evaluation of translations of GERD-HRQL in Russian and creation of the preliminary version of GERD-HRQL in Russian, back translation, harmonization, creation of the first test-version of GERD-HRQL in Russian, cognitive debriefing and decentering, creation of the second test-version of GERD-HRQL in Russian, final expert evaluation and development of the final test-version of GERD-HRQL in Russian. Satisfactory face validity of the Russian test-version of GERD-HRQL was shown: face validity indices were 0.98, 0.95, 0.92, and 0.97. CONCLUSION: As the result of translation, cross cultural adaptation and linguistic validation, the Russian version of GERD-HRQL for the use in pts with GERD in Russia was developed. The Russian version of GERD-HRQL may be used in research studies and clinical practice after testing its psychometric properties.

[Antibiotic resistance of Helicobacter pylori in the European part of the Russian Federation: first results].

AIM: Determine the primary antibiotic resistance of Helicobacter pylori (H. pylori) strains isolated from patients living in the European part of the Russian Federation. MATERIALS AND METHODS: As part of a clinical laboratory study, from 2015 to 2018, 27 gastrobiopsy samples obtained from H. pylori-infected patients were analyzed. H. pylori infection was verified using a rapid urease test or a 13C-urea breath test. The values of the minimum inhibitory concentration (MIC) of antibiotics were determined by the diffusion method using E-test strips (BioMerieux, France) according to the recommendations of the manufacturer. The sensitivity of the isolates was determined for 6 antibacterial drugs (amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline, rifampicin). RESULTS: According to the data obtained, resistance to amoxicillin was 0%, clarithromycin 11.1%, metronidazole 59.3%, levofloxacin 3.7%, tetracycline 0%, and rifampicin 14.8%. Dual resistance to clarithromycin and metronidazole was recorded in two isolates (7.4%). CONCLUSION: Thus, the first results of the evaluation of H. pylori antibiotic resistance in the European part of the Russian Federation indicate a low resistance of the microorganism to clarithromycin and quite high to metronidazole.

[The effectiveness of pancreatic enzyme replacement therapy using microencapsulated pancreatin preparations in the correction of nutritional status in patients with chronic pancreatitis: a prospective observational study].

AIM: The goal is to evaluate the effectiveness of pancreatic enzyme replacement therapy (PERT) using microencapsulated pancreatin preparations for the correction of nutritional status in patients with chronic pancreatitis (CP) and associated exocrine pancreatic insufficiency (EPI). MATERIALS AND METHODS: The study included 58 patients with CP who were divided into two groups depending on the results of a laboratory assessment of indicators of nutritional status: group I (n=30) consisted of patients with CP and signs of EPI (according to low elastase test values) without deviations in nutritional status; Group II (n=28) consisted of patients with CP with a EPI and an abnormal nutritional status. In both groups, patients during the entire observation period (8-12 months) received PERT using microencapsulated pancreatin preparations at a dose adjusted for the severity of permanent residence permit. Before and after the PERT course, the dynamics of anthropometric [body weight, body mass index (BMI)] and laboratory indicators of nutritional status (total protein, albumin, vitamins D and B12, transferrin, iron and magnesium) were evaluated. RESULTS: After the completion of PERT, a significant tendency towards an increase in BMI in patients was noted in both groups. In group I, this indicator increased from 21.45 [95% confidence interval (CI) 19.80-23.92] kg/m2 to 22.15 (95% CI 20.31-23.86) kg/m2, and in II group - from 19.22 (95% CI 18.33-21.99) kg/m2 to 22.0 (95% CI 19.97-24.08) kg/m2. At the same time, the duration of PERT (months) significantly correlated with the dynamics of the patient's body weight (r=0.4679; 95% CI 0.2384-0.6479, p=0.0002). When assessing laboratory markers of nutritional status after PERT, a general tendency was found to increase the levels of total protein, albumin, vitamin D, magnesium, transferrin, and iron in both groups, however, statistically significant differences in the dynamics were observed mainly in group II patients. So, the level of total protein in group II increased from 69.05 (95% CI 65.6717-70.9000) g/l to 72.8 (95% CI 71.1358-74.9000) g/l, vitamin D - from 10.6 (95% CI 32.8397-38.9603) ng/ml to 17.1 (95% CI 12.0166-23.6232) ng/ml, magnesium - from 0.72 ( 95% CI 0.6892-0.7825) mmol/L to 0.795 (95% CI 0.7692-0.8800) mmol/L, and transferrin from 2.91 (95% CI 2.1800-3.3656 ) g/l to 2.92 (95% CI 2.4000-3.5200) g/l. CONCLUSION: A prospective observational study demonstrated the effectiveness of PERT using microencapsulated pancreatin preparations in the correction of nutritional status in patients with CP.

[The prevalence of sarcopenia in patients with chronic pancreatitis: a meta-analysis].

AIM: Systematization of data on the prevalence of sarcopenia in patients with chronic pancreatitis (CP). MATERIALS AND METHODS: MEDLINE/PubMed, EMBASE, Cochrane, the Russian Science Citation Index (RSCI) through June 2020 were searched to identify studies evaluating the prevalence of sarcopenia in CP. Additionally, a search for relevant abstracts was carried out in the electronic databases of the conferences of the European Pancreatic Club (EPC), the International Association of Pancreatology (IAP) and the European Congress of Radiology (ECR). For the final analysis, publications were selected that used validated muscle mass assessment tests with detailed descriptive statistics to enable the resulting data to be included in the meta-analysis. RESULTS: The final analysis included 7 studies involving 604 patients with CP. The pooled prevalence of sarcopenia in patients with CP was 42.09% (95% confidence interval CI 27.84557.055). There was significant heterogeneity between the results (p0.0001; I2=90.81%). When studies with a total sample of less than 50 patients were excluded from the meta-analysis, the overall prevalence of sarcopenia in patients with CP was 22.24% (95% CI 15.47529.847). CONCLUSION: The present meta-analysis demonstrated that sarcopenia is a common complication of CP and is observed in about 2 out of 5 patients with this inflammatory disease of the pancreas. Given the high incidence of adverse outcomes associated with sarcopenia, it is necessary to promptly diagnose this pathological condition in patients with CP.

[Testing and validation of the Russian version of quality of life questionnaire in patients with GERD - GERD-HRQL].

AIM: This study aimed to test the Russian version of GERD-HRQL in the focus group of patients with GERD, as well as to evaluate its psychometric properties reliability, validity and sensitivity. MATERIALS AND METHODS: The total of 57 patients with GERD (mean age 45.812.4 years, 72% women, 68% patients with not erosive reflux disease, 84% had esophageal manifestations of GERD) were enrolled into the study. All the patients filled out the Russian version of GERD-HRQL and generic quality of life questionnaire RAND SF-36 during the routine visit to the gastroenterologist. According to the results of testing of GERD-HRQL, it was clear and easy to complete for patients and reflected the main concerns specific for GERD patients. The most frequent and bothersome symptoms/problems which interfered with quality of life in GERD patients were heartburn (100% of patients) and bloating (84% of patients). During the validation procedure, the high reliability and validity of the Russian version of GERD-HRQL were demonstrated. It was shown that the tool was sensitive both to changes over time and to clinically determined differences in patients status. RESULTS: The Total GERD-HRQL Score was significantly higher (worse quality of life) in the following groups: a) patients who had esophageal manifestations of GERB vs those without esophageal manifestations of GERB; b) patients with GERD complications vs those without GERD complications, c) patients with comorbidities of upper gastrointestinal tract vs without those comorbidities; d) patients with erosive esophagitis vs with non-erosive reflux disease (p0.05). CONCLUSION: The developed Russian version of the GERD-HRQL questionnaire proved to have high psychometric properties and may be used in the Russian population of GERD patients both in research studies and in a real clinical practice.

[Prevalence of small bowel bacterial overgrowth in patients with functional dyspepsia: a meta-analysis].

AIM: Systematization of data on the frequency of detection of the syndrome of bacterial overgrowth in the small intestine (SIBO) in patients with functional dyspepsia (FD). MATERIALS AND METHODS: MEDLINE/PubMed, EMBASE, Cochrane, Google Scholar, the Russian Science Citation Index (RSCI) through July 2020 were searched to identify studies evaluating the prevalence of SIBO in FD. In addition, a search for relevant abstracts was carried out in the electronic databases of the United European Gastroenterology Week (UEG), American College of Gastroenterology (ACG), International Conference on Nutrition and Food (ICNF). For the final analysis, publications were selected that used validated tests for the assessment of SIBO (hydrogen breath test using glucose or lactulose) with detailed descriptive statistics, allowing the resulting data to be included in the meta-analysis. RESULTS: The final analysis included 7 studies with 1248 patients with FD. Overall pooled prevalence of SIBO in patients with FD was 34.73% (95% CI 24.80745.383). There was significant heterogeneity between the results (p0.0001; I2=89.91%). When excluded from the meta-analysis of a study in which the incidence of SIBO was studied in patients with refractory FD, the pooled prevalence was 38.98% (95% CI 28.96449.490). CONCLUSION: This meta-analysis has demonstrated that SIBO is often associated with FD and is observed in about every third patient with this functional gastrointestinal tract disease.

[Recommendations for the Protocol of functional examination of the anorectal zone and disorders classification: the International Anorectal Physiology Working Group consensus and Russian real-world practice].

This manuscript summarizes consensus reached by the International Anorectal Physiology Working Group (IAPWG) for the performance, terminology used, and interpretation of anorectal function testing including anorectal manometry (focused on high-resolution manometry), the rectal sensory test, and the balloon expulsion test. Based on these measurements, a classification system for disorders of anorectal function is proposed. Aim to provide information about methods of diagnosis and new classification of functional anorectal disorders to a wide range of specialists general practitioners, therapists, gastroenterologists, coloproctologists all who face the manifestations of these diseases in everyday practice and determine the diagnostic and therapeutic algorithm. Current paper provides agreed statements of IAPWG Consensus and comments (in italics) of Russian experts on real-world practice, mainly on methodology of examination. These comments in no way intended to detract from the provisions agreed by the international group of experts. We hope that these comments will help to improve the quality of examination based on the systematization of local experience with the use of the methods discussed and the results obtained. Key recommendations: the International Anorectal Physiology Working Group protocol for the performance of anorectal function testing recommends a standardized sequence of maneuvers to test rectoanal reflexes, anal tone and contractility, rectoanal coordination, and rectal sensation. Major findings not seen in healthy controls defined by the classification are as follows: rectoanal areflexia, anal hypotension and hypocontractility, rectal hyposensitivity, and hypersensitivity. Minor and inconclusive findings that can be present in health and require additional information prior to diagnosis include anal hypertension and dyssynergia.

[Helicobacter pylori resistance in the Russian Federation: a meta-analysis of studies over the past 10 years].

AIM: Systematization of data on antibiotic resistance of Helicobacter pylori in Russia over the past 10 years. METHODS: A search for studies were carried out in electronic databases MEDLINE/PubMed, EMBASE, Cochrane, Russian Science Citation Index. We analyzed the papers published over the past 10 years (2011 to 2020). In the final analysis, publications were selected from periodical peer-reviewed foreign and Russian publications, in which validated tests for assessing the microorganism resistance were used with detailed descriptive statistics, which allows the obtained data to be included in the meta-analysis. RESULTS: The final analysis included 11 studies (808 isolates). H. pylori resistance to clarithromycin was 10.39% (95% confidence interval CI 7.10314.219), metronidazole 33.95% (95% CI 15.32955.639), amoxicillin 1.35% (95% CI 0.281 3.202), levofloxacin 20.0% (95% CI 12.63728.574), tetracycline 0.98% (95% CI 0.3532.163). Double clarithromycin-metronidazole resistance was reported in 2.7% (95% CI 1.1364.345). CONCLUSION: This meta-analysis is the first analytical work that allows objectifying the current structure of H. pylori antibiotic resistance in the Russian Federation. The data obtained in the analysis of publications over the past 10 years indicate a low resistance of the microorganism to clarithromycin (less than the regulated threshold of 15%), which allows us to consider the triple regimen of eradication therapy as a first-line therapy in our country.

[Current advances in the treatment of gastroesophageal reflux disease: a focus on esophageal protection].

Gastroesophageal reflux disease (GERD) is characterized by high morbidity and a significant decrease in the quality of life of patients, and is a major risk factor for esophageal adenocarcinoma. Nowadays, antisecretory therapy with proton pump inhibitors (PPI) is the "gold standard" of conservative treatment of GERD, but in some cases this therapy is unsuccessful. According to various studies, the prevalence of refractory GERD can reach 30-40%. The latest scientific data in the field of genetics and pathophysiology of GERD demonstrate that a disruption of the barrier function of the esophageal mucosa and an increase of its permeability can be the leading causes of refractoriness. Thus, the optimal therapy for patients with GERD should not only suppress the secretion of hydrochloric acid, but also restore the barrier function of the mucous membrane, providing an esophagoprotective effect. To achieve these goals, Alfasoxx was developed, which consists of a mixture of low molecular weight hyaluronic acid and low molecular weight chondroitin sulfate dissolved in a bioadhesive carrier (poloxamer 407). The clinical efficacy of this product has been confirmed by three prospective, randomized, placebo - controlled trials. Alfasoxx has a healing and restorative effect towards the esophageal epithelium and due to high ability for bioadhesion provides long - term protection of the mucous membrane of the esophagus. Combination therapy for GERD with the use of PPI and an esophagoprotector offers new perspectives for the treatment of patients with GERD.