Changes in the Intestinal Microbiota in Patients with Chronic Pancreatitis: Systematizing Literature Data

The purpose of the review. To systematize literature data on changes in the structure of the intestinal microbiota in patients with chronic pancreatitis (CP).Key findings. The human intestinal microbiota is a dynamically changing system that is constantly undergoing qualitative and quantitative changes, especially in several pathological conditions of the digestive system. At present, the differences in the intestinal microbiota in pancreatic diseases are poorly understood. The severe CP is associated with impaired synthesis of antimicrobial peptides, bicarbonates, and digestive enzymes by the pancreas, which is a risk factor for dysbiotic changes in the intestinal microbiota, consisting in the development of small intestinal bacterial overgrowth (SIBO) and gut dysbiosis. The results of two large meta-analyses show that about a third of CP patients have SIBO. The colonic microbiota in patients with CP is also characterized by dysbiotic disorders, primarily in the reduction of alpha-diversity. Some studies have shown that these patients have an increase in Firmicutes, while Bacteroides and Faecalibacterium are reduced. In addition, as a rule, in patients with CP, the growth of Escherichia, Shigella and Streptococcus is recorded.Conclusion. In general, scientific papers have revealed significant heterogeneity in the profiles of the intestinal microbiota in patients with CP. Thus, several questions remain open, prioritizing the further study of the intestinal microbiota in patients with CP for identifying the specifics of its structure that can personalize the selection of enzyme replacement therapy and restrict the unreasonable prescription of additional pharmacotherapy (the use of proton pump inhibitors and / or antibacterial drugs)

The cardiovascular system in patients with functional and inflammatory bowel diseases

Aim. Identification of subclinical and metamanifests state changes of cardiovascular system in patients with functional and inflammatory bowel diseases (IBD) without a background of cardiac pathology. Materials and methods. Was examined 79 patients with colon diseases, 20 patients were diagnosed with irritable bowel syndrome (IBS) with diarrhea, 37 - with undifferentiated colitis (UdC) and 22 patients with ulcerative colitis (UC). As a control group were examined in 50 healthy subjects. All patients received treatment in accordance with international and national guidelines. Prescribed medications had effect on the function of the cardiovascular system. Patients with contacting the hospital and against the onset of remission was performed ultrasound of the heart. Determines the size of the left atrium, heart rate, end-diastolic volume, end-systolic volume, ejection fraction (EF), cardiac index (CI), total peripheral vascular resistance, the presence of right heart failure, blood flow, the area of the right atrium and right ventricle in systole and diastole, and calculated the proportion of contractility of the right atrium and right ventricle. Determined systolic pressure in PA (SPPA), the average pressure in PA (APPA). Results. Clinical manifestations of cardiac syndrome was identified in 75,0% of patients with IBS, 54,1% of patients NK and 68,2% patients with UC. When performing correlation analysis in the patients with UdC and UC was noted the relationship of hemodynamic parameters and disease severity was more pronounced in UC. So, when comparing the duration of the disease and levels of the MLC - r=0,52 and r=0,73 (

A high-pressure hydrogen time projection chamber for the MuCap experiment

The MuCap experiment at the Paul Scherrer Institute performed a high-precision measurement of the rate of the basic electroweak process of nuclear muon capture by the proton, $\mu^- + p \rightarrow n + \nu_\mu$. The experimental approach was based on the use of a time projection chamber (TPC) that operated in pure hydrogen gas at a pressure of 10 bar and functioned as an active muon stopping target. The TPC detected the tracks of individual muon arrivals in three dimensions, while the trajectories of outgoing decay (Michel) electrons were measured by two surrounding wire chambers and a plastic scintillation hodoscope. The muon and electron detectors together enabled a precise measurement of the $\mu p$ atom's lifetime, from which the nuclear muon capture rate was deduced. The TPC was also used to monitor the purity of the hydrogen gas by detecting the nuclear recoils that follow muon capture by elemental impurities. This paper describes the TPC design and performance in detail.Comment: 15 pages, 13 figures, to be submitted to Eur. Phys. J. A; clarified section 3.1.2 and made minor stylistic corrections for Eur. Phys. J. A requirement

Inflammatory bowel diseases: Transformation of representations. A review

The global burden of inflammatory bowel disease (IBD) is currently significant and continues to grow due to the increasing prevalence of ulcerative colitis (UC) and Crohn's disease (CD), the increasing costs of diagnosis and treatment, and the high level of disability in patients with this disease. Categories, which leads to the search for risk factors and predictors of aggressive course and extraintestinal manifestations. According to the latest data, the prevalence of UC in Russia is 16.6 per 100 000 population, the annual registered increase is 11.3%; the prevalence of CD is 5.6 per 100 000 population, and the increase is 13.7%. In the Russian population of patients with IBD, the average age of disease onset is 35.3 years for UC and 31.2 years for CD. Moreover, in 89.3% of patients with UC, it took at least 2 years to verify the diagnosis, and in CD, within 2 years from the onset of clinical symptoms, the diagnosis was established in only 72.6% of patients. One of the dominant characteristics of IBD is its multisystem nature, which leads to the development of extraintestinal manifestations (ECM), which can be observed in 50–60% of patients, while up to 25% of patients with IBD have several EMC and the most common variants are joint lesions. A higher frequency of extraintestinal manifestations is observed in CD (up to 45% of patients), in female patients, in smokers and with a longer duration of the disease. To predict clinical remission, the level of fecal calprotectin and CRP, the need for glucocorticosteroids are important, to predict endoscopic remission – the level of fecal calprotectin, and to predict histological remission, an endoscopic Schroeder index value of ≤1 is important. The absolute risk of developing colorectal cancer in IBD remains relatively low, ranging from 1.1 to 5.4% after 20 years of disease. The main risk factors for IBD are total intestinal damage, high inflammatory activity, the stricturing phenotype of CD and the presence of primary sclerosing cholangitis

Functional gastrointestinal diseases: mechanisms of development and principles of multitarget therapy

Currently, functional dyspepsia (FD) and irritable bowel syndrome (IBS) are among the most common nosological  units in the structure of functional gastrointestinal  diseases in adults. An important problem of treatment of these diseases at the current stage of medicine is low efficiency of monotarget drugs, which is determined by multicomponent pathogenesis. Indeed, the currently available  methods of drug treatment of FD and IBS have suboptimal  efficacy, as illustrated  by recent meta-analyses demonstrating high rates of NNT (the average number of patients who need to be treated to achieve a certain favorable outcome). In addition, the frequent “overlap” of these diseases forces clinicians to prescribe several drugs with different pharmacological actions to the patient, which inevitably leads to a decrease in compliance. The optimal strategy for managing patients with FD and IBS is the tactics of multitarget drugs that act on several links in the pathogenesis of these pathologies and have a significant evidence base in the effectiveness and safety of use. STW 5 (Iberogast®), included  in the clinical  guidelines  of the Russian Gastroenterological Association on the diagnosis and treatment of patients with FD, published in 2017, has the above-mentioned characteristics, as well as the clinical guidelines of the Russian Gastroenterological Association in collaboration with the Russian Association of Coloproctologists on the diagnosis and treatment of IBS, published in 2021. The clinical effectiveness of Iberogast in the treatment of FD and IBS has been demonstrated in a number of randomized trials, the results of which showed high efficacy of the drug and its good tolerability

Gastroesophageal reflux disease: risk factors, current possibilities of diagnosis and treatment optimisation

Gastroesophageal reflux disease (GERD) is one of the most common causes of health care seeking at the primary care level in many countries. At an epidemiological level, GERD has been shown to be associated with a number of risk factors: obesity, tobacco smoking, alcohol abuse, certain patterns of eating behaviour, and the use of several medications. GERD is now regarded as a heterogeneous disease and includes different phenotypes (erosive reflux disease, non-erosive reflux disease, hypersensitive oesophagus, functional heartburn), the proper diagnosis of which improves the effectiveness of therapy in patients with heartburn symptoms. Daily impedance–pH monitoring is known to be an integral part of the diagnostic algorithm for GERD and is a functional diagnostic method to record all types of refluxes entering the oesophagus regardless of pH, to assess their association with symptoms, and to determine whether patients with heartburn symptoms belong to a particular phenotype. Esophageal manometry plays a key role in the evaluation of patients with heartburn symptoms, as it helps to rule out other conditions that may mimic GERD: achalasia cardia and scleroderma esophagus. This technique is used to assess thoracic esophageal motility and sphincter function and in the assessment of patients prior to antireflux surgery or in the refractory course of GERD. The article describes in detail GERD risk factors (triggers of heartburn), as well as diagnostic aspects, taking into account a differentiated approach to patients with heartburn based on daily impedance–pH monitoring data in accordance with the current guidelines and recommendations

Features of the functional activity of macrophage link of immunity with gastroesophageal reflux disease depending on the type of reluctate: in vitro model

Aim. A generalized analysis of changes in functional activity of macrophages on the basis of phagocytic activity, cytokine profile, changes in the level of expression of surface markers characteristic of pro - or anti-inflammatory phenotype of the cells when exposed to reluctate. Materials and methods. Developed in vitro model of co-peritoneal macrophages of mice With57/BL6 (n=65) and reluctate patients with gastroesophageal reflux disease (GERD; n=65) having different pH values (three group comparison). Took into account the standard criteria phagocytic ability (absorption Staphylococcus aureus 9198, light microscopy), secretory activity (cytokine profile Th1/Th2, flow cytometry) and receptor characterization of macrophages (expression of CD25/80/163/206, flow cytometry). Results. The phagocytic activity of macrophages, calculated on the basis of the average number of bacteria ingested by one phagocyte, is not associated with the pH value of the added reluctate. It is established that the alkalinisation of reluctate leads to significant alteration in the expression of CD receptors - decrease M1 and increase M2. The index of total production of Th1/Тһ2 in groups progressively decreased with increasing pH of reluctate and amounted to 3.6 units in the group pH from 4.6 to 6.6; 2.8 units group a pH of 6.7-7.2 and 1.6 units in the group pH of 7.3 to 8.1, due to increased production of Th2 cytokines at offset reluctate pH to slightly alkaline side. The data obtained indicate the increase of expression and secretion of anti-inflammatory markers at an alkaline pH shift of reluctate. Analysis of the studied characteristics of the activity profile of macrophages in the proposed in vitro model justifies the need for considering the peculiarities of the functional activity of macrophages under the influence of reluctate different nature. The special importance of studying the cytokine profile and characteristics of the functional activity of macrophages in patients with GERD, given the nature of reluctate

Technologically-Treated Polyclonal Affinity-Purified Antibodies to the Tumor Necrosis Factor-α, Brain Specific S-100 Protein and Histamine in Treatment of Functional Dyspepsia: Results of the Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

The aim of the study was to evaluate the efficacy and safety of Kolofort® (a complex medicine containing technologically processed forms of antibodies to S-100 protein, tumor necrosis factor-α and histamine) in the management of functional dyspepsia (FD) in outpatient clinical practice.Methods: Outpatients (N = 309) at the age of 18–45 in whom FD was diagnosed according to the Rome IV criteria were enrolled in a multicenter, double-blind, placebo-controlled, randomized clinical trial. Patients were randomized in two groups receiving Kolofort® or placebo 2 tablets tid for 8 weeks. The primary endpoint of the study was a change in the FD symptoms severity score according to the Gastrointestinal symptom score (GIS) at week 8. ITT and [PP] analysis were performed.Results: at week 8 the reduction in GIS sum score was observed in Kolofort® group and placebo group (by 7.2 ± 3.3 [7.2 ± 3.4] and 6.3 ± 4.6 [6.2 ± 4.5], respectively, p = 0.041 [0.039]). The proportion of cases with GIS score reduction by ≥4 was 88,1 % [88.6 %] and 79.1 % [79.6 %] in Kolofort® group and placebo group, respectively (p = 0.046 [p = 0.051]). None of the patients in Kolofort® group had progression of FD symptoms or required additional therapy. There were 29 adverse events (AEs) recorded in 25 patients including 16 cases in 13 (8.6 %) patients in Kolofort® group and 13 AEs in 12 (7.6 %) patients in placebo group.Conclusion: the clinical trial demonstrates the positive effect of Kolofort® in FD with a favorable safety profile

Differences in In Vitro Properties of Pancreatin Preparations for Pancreatic Exocrine Insufficiency as Marketed in Russia and CIS

BACKGROUND: Pancreatic enzyme-replacement therapy (PERT), provided as pancreatin to patients with pancreatic exocrine insufficiency (PEI), is considered an essential substitute for the pivotal physiological function the pancreas fulfills in digestion. PEI involves a reduction in the synthesis and secretion of pancreatic enzymes (lipase, protease, amylase), which leads to an inadequate enzymatic response to a meal and consequently to maldigestion and malabsorption of nutrients. The efficacy of PERT is strongly dependent on enzyme activity, dissolution, and pancreatin particle size. OBJECTIVE: The physiological properties of eight pancreatin preparations (nine batches; five different brands) available in Russia and CIS (Commonwealth of Independent States: Armenia, Azerbaijan, Belarus, Kazakhstan, Kyrgyzstan, Moldova, Russia, Tajikistan, Uzbekistan) were investigated. METHODS: The lipase activity, dissolution, and particle size distribution of samples from multiple batches of pancreatin of different strengths were measured. RESULTS: Regarding lipase activities, all pancreatin preparations except Micrazim(R) matched the labeled content. Considerable differences were observed in particle size and dissolution. CONCLUSION: Pancreatin preparations available in Russia and CIS demonstrate product-to-product and batch-to-batch variability regarding the measured properties of lipase activity, dissolution, and particle size. This may impact the efficacy of PERT and therefore clinical outcomes