Successful Experience of Fecal Transplantation in a Patient with Severe Pseudomembranous Colitis

Introduction. At the present time there is increase the number of patients diagnosed with pseudomembranous colitis due to Clostridiodes difficile, respectively it significantly increases the frequency of hospitalizations, the length of hospital stay and the cost of treatment. Approved drug methods for correcting a  pathological condition are not always able to lead to recovery after the first use, repeated and prolonged courses of therapy are often required, especially with recurrent Clostridiodes difficile. An alternative way of treatment is fecal microbiota transplantation from a donor. Nowadays, fecal microbiota transplantation is included in national clinical guidelines in several countries in Europe, the USA and Australia. In Russia this method has not been registered, however, there are some publications about its successful application in gastrointestinal diseases, oncohematology, and some autoimmune diseases. Aim. To show the result of successful treatment of severe pseudomembranous colitis after a single fecal microbiota transplantation.Material and methods. Outpatient treatment of an acute respiratory infection with a broad-spectrum antibacterial drug caused the development of severe pseudomembranous colitis in a young patient. Standard courses of metronidazole and vancomycin were unsuccessful. Transplantation of fecal microbiota from a donor was performed via ileocolonoscopy.Results. A single fecal microbiota transplantation contributed to the patient’s complete recovery, short term  rehabilitation and the absence of recurrence of Clostridiodes difficile within two years. Conclusions. Evidence-based medicine has shown the high efficiency of fecal microbiota transplantation. In Russia a legislative basis is needed for including fecal microbiota transplantation in clinical guidelines for the treatment of severe Clostridiodes difficile resistant to standard therapy

Protracted fever after infliximab induction therapy in a patient with ulcerative colitis (clinical case)

Inflammatory bowel diseases (ulcerative colitis and Crohn’s disease) tend to increase in frequency and prevalence worldwide and lead to a significant reduction in quality of life with a complicated course. Intravenous administration of corticosteroids in acute severe ulcerative colitis is effective in 60–70 % of cases. Rescue therapy for patients with steroid‐refractory and steroid-dependence attacks is effective for reducing colectomy or colproctectomy and improves long-term treatment outcomes. Despite the proven efficacy of infliximab, limitations to the use of monoclonal antibodies are adverse reactions to the administration of genetically engineered biologic therapy (GEBT), both well-known and studied, and rare.The aim of the study. To analyze a case of an extremely rare and paradoxical incurable hyperergic reaction that occurred after using genetically engineered biological therapy with tumor necrosis factor alpha blockers in a patient suffering from ulcerative colitis.Materials and methods. We carried out the search in the PubMed, Embase, Scopus and Medline databases until November 1, 2022 using the following keywords: inflammatory bowel disease, ulcerative colitis (UC), anti-tumor necrosis factor α (antiTNFα), infliximab, fever, adverse events. In the scientific electronic library eLIBRARY, a search was made for Russian-language publications using similar queries in Russian. We analyzed the patient’s medical records from 03.06.2013 up to the present day; the patient signed an informed consent for the publication and discussion of the presented data.Conclusion. The widespread use of GEBT in the treatment of autoimmune and autoinflammatory diseases leads to the accumulation of both positive and negative experience of clinicians in real clinical practice. The officially described adverse events in the appointment of any drug suggest options for their prevention and treatment. Atypical manifestations or casuistic cases must be systematized for further fundamental pathophysiological studies

Assessment of the State of Cell Membranes against the Background of Prolonged Use of Anticytokine Therapy in Patients with Ulcerative Colitis

Biological therapy in the treatment of immune-mediated conditions has changed their course, the quality of life of patients and the prognosis of diseases. The accumulated by mankind 20 years of experience with the use of genetically engineered drugs has led to a number of questions regarding, among other issues, safety in the long-term administration of biological therapy. Patients suffering from ulcerative colitis revealed changes in cell membranes, reflecting their structural and energy characteristics. Long-term administration of Infliximab leads to the stabilization of energy processes in the erythrocyte membrane and improves homeostatic function of the kidneys.The aim of the study was to evaluate the effect of long-term use of TNF-α blockers (Infliximab) on the structural and functional characteristics of cell membranes and the functional state of the kidneys in patients with moderate to severe ulcerative colitis.Materials and methods. We examined 103 patients with moderate to severe ulcerative colitis during the period of acute attack and remission, of which 28 patients received basic therapy using the drug Infliximab (IFX) for 10 years, 75 patients received standard basic treatment. The patients of the biological therapy group took the original drug Infliximab – Remicade. The comparison group consisted of 30 healthy volunteers, comparable by sex and age. The analysis of the state of erythrocyte membranes was carried out using a set of physicochemical methods: UV spectroscopy (SF-46m spectrophotometer), high-performance thin-layer reaction paper chromatography, membrane ultrafiltration, erythrocyte NMR spectroscopy on phosphoric (31P) and proton (1H) nuclei. The functional state of the kidneys was evaluated using a dynamic scintigraphic study (with the technemage –Tc-99m).Results. Prolonged use of anticytokine therapy with Infliximab for 10 years in patients with ulcerative colitis, upon reaching deep remission, improves endogenous intoxication, restores the structural and functional characteristics of cell membranes, normalizes cell energy metabolism and does not negatively affect the functional state of the kidneys

Association of Interleukin-10 Gene Polymorphisms with Ulcerative Colitis

This literature review is devoted to the study of the role of polymorphic variants of the anti-inflammatory interleukin-10 gene (Interleukin-10, IL10) in the etiology and pathogenesis of ulcerative colitis in patients of various ethnic groups.Aim. To generalize the results obtained from electronic databases on the study of the characteristics of the course of ulcerative colitis in patients of different ethnic groups, taking into account the carriage of IL10 gene polymorphisms.Materials and methods. Twenty-five studies were selected, including four meta-analyzes devoted to the  study of associative relationships of single nucleotide polymorphisms (SNPs) of the IL10 gene isolated from  blood samples at positions -592AA/CA, -819CT, -1082АА/GA, and rs3024505 in the development and course of ulcerative colitis.Results. A number of researchers from Europe, Saudi Arabia report an increased incidence of ulcerative colitis among carriers of the IL10-1082AA SNP and a low incidence among carriers of -592AA. Positive associations of IL10-819CT with the prevalence of ulcerative colitis are presented in single reports from Europe, the Middle East and in a number of studies from Asian countries. However, the identified associations, even within the  same population, are often contradictory. Perhaps the discrepancies are due to the ethnic heterogeneity of the groups in the considered cohorts, and therefore it is necessary to continue epidemiological studies with a large sample size in specific geographic areas

Результаты оценки микробиоты в условиях экспериментального язвенного поражения толстой кишки

 Background. The increased incidence of inflammatory bowel disease (IBD) in the world and the lack of consensus on the causes and development mechanisms of IBD are the key elements that determine the relevance of the study. According to some authors, in the pathogenesis of the development and occurrence of ulcerative colitis, one of the leading causes is a change in the composition of the colon microflora and the impact of the products of their metabolism on the enteric system and intestinal motility.The aim was to study the qualitative and quantitative changes in the colon microbiota in rats when modeling ulcerative lesions by the original method.Materials and methods. The experimental study was carried out using male Wistar rats (n = 24). Ulcerative colitis was modeled in an original way. The quantitative and qualitative composition of the parietal microflora of the distal colon was determined.Results. When modeling ulcerative lesions of the colon using the original method, changes in the qualitative and quantitative composition of the parietal microflora of the colon were revealed. On the 3rd day there was a decrease in Lactobacillus ssp. and Escherichia coli, as well as the growth of  fungal microflora and the appearance of representatives of opportunistic microflora. The changes were progressive in nature, and by the 7th day of the study revealed a marked reduction of the total parietal concentration of the normal flora bacteria and an increased percentage and absolute number of representatives of conditionally pathogenic microflora. By the 10th day of the experiment, with a small increase in the total number of parietal bacteria, the  predominant microorganisms were Bacteroides ssp. (26.8%) and Peptococcus ssp. (27.6%).  Введение. Язвенный колит – хроническое  рецидивирующее системное воспалительное заболевание с преимущественным поражением слизистой оболочки  толстой кишки. Каждый год регистрируется до 20 новых случаев заболевания на 100 тыс. населения, в основном среди лиц трудоспособного возраста. По мнению ряда авторов, в патогенезе развития и возникновения  заболевания одну из ведущих причин играет изменение в составе микрофлоры толстой кишки, а также продукты их метаболизма, воздействующие на энтериновую систему и моторику кишечника.Цель. Изучить показатели микробиоты толстой кишки у самцов крыс линии Вистар при моделировании язвенного поражения.Материалы и методы. Экспериментальное исследование выполнено с использованием самцов крыс линии Вистар (n = 24). Предложен оригинальный способ модели язвенного колита. Определен количественный и качественный состав пристеночной микрофлоры дистального отдела толстой кишки.Результаты. Выявлены изменения качественного и количественного состава пристеночной микрофлоры толстой кишки: на 3-и сут отмечали снижение концентрации Lactobacillus ssp. и Escherichia coli, а также рост грибковой микрофлоры, появление представителей условно-патогенной микрофлоры. Изменения носили прогрессирующий характер, и уже к 7-м сут выявляли  выраженное снижение общей пристеночной концентрации бактерий нормофлоры и повышение процентного и абсолютного числа представителей условно-патогенной микрофлоры. К 10-м сут эксперимента при малом увеличении общей численности пристеночных бактерий преобладающей микрофлорой являются Bacteroides ssp. (26,8%) и Peptococcus ssp. (27,6%).

Diagnosis and Treatment of Irritable Bowel Syndrome: Clinical Recommendations of the Russian Gastroenterological Association and Association of Coloproctologists of Russia

Aim. Current clinical recommendations accentuate current methods for the diagnosis and treatment of irritable bowel syndrome (IBS).Key points. IBS is a functional bowel disorder manifested with recurrent, at least weekly, abdominal pain with the following attributes (any two leastwise): link to defecation, its frequency or stool shape. The symptoms are expected to persist for at minimum three months in a total six-month follow-up. Similar to other functional gastrointestinal (GI) disorders, IBS can be diagnosed basing on the patient symptoms compliance with Rome IV criteria, provided the absence of potentially symptom-causative organic GI diseases. Due to challenging differential diagnosis, IBS can be appropriately established per exclusionem, with pre-examination as follows: general and biochemical blood tests; tissue transglutaminase IgA/IgG antibody tests; thyroid hormones test; faecal occult blood test; hydrogen glucose/ lactulose breath test for bacterial overgrowth; stool test for enteric bacterial pathogens and Clostridium difficile A/B toxins; stool calprotectin test; abdominal ultrasound; OGDS, with biopsy as appropriate; colonoscopy with biopsy. The IBS sequence is typically wavelike, with alternating remissions and exacerbations often triggered by psychoemotional stress. Treatment of IBS patients includes dietary and lifestyle adjustments, various-class drug agents prescription and psychotherapeutic measures.Conclusion. Adherence to clinical recommendations can facilitate timely diagnosis and improve medical aid quality in patients with different clinical IBS variants

Diagnosis and Treatment of Irritable Bowel Syndrome: Clinical Recommendations of the Russian Gastroenterological Association and Association of Coloproctologists of Russia

Aim. Current clinical recommendations accentuate current methods for the diagnosis and treatment of irritable bowel syndrome (IBS).Key points. IBS is a functional bowel disorder manifested with recurrent, at least weekly, abdominal pain with the following attributes (any two leastwise): link to defecation, its frequency or stool shape. The symptoms are expected to persist for at minimum three months in a total six-month follow-up. Similar to other functional gastrointestinal (GI) disorders, IBS can be diagnosed basing on the patient symptoms compliance with Rome IV criteria, provided the absence of potentially symptom-causative organic GI diseases. Due to challenging differential diagnosis, IBS can be appropriately established per exclusionem, with pre-examination as follows: general and biochemical blood tests; tissue transglutaminase IgA/IgG antibody tests; thyroid hormones test; faecal occult blood test; hydrogen glucose/ lactulose breath test for bacterial overgrowth; stool test for enteric bacterial pathogens and Clostridium difficile A/B toxins; stool calprotectin test; abdominal ultrasound; OGDS, with biopsy as appropriate; colonoscopy with biopsy. The IBS sequence is typically wavelike, with alternating remissions and exacerbations often triggered by psychoemotional stress. Treatment of IBS patients includes dietary and lifestyle adjustments, various-class drug agents prescription and psychotherapeutic measures.Conclusion. Adherence to clinical recommendations can facilitate timely diagnosis and improve medical aid quality in patients with different clinical IBS variants

The hardware method of biomaterial preparation for fecal transplantation

Background: Nowadays fecal transplantation (FT) is considered as a  component of the treatment for a  wide range of disorders, including autoimmune diseases (ulcerative colitis, Crohn's disease, type 1 diabetes mellitus and insulin resistance, multiple sclerosis, psoriasis). High-quality preparation of the biomaterial is a necessary procedure that allows for long-time storage of the prepared fecal transplant at ultralow temperature conditions and it use as needed.Aim: To optimize the method of preparation of the biomaterial for fecal transplantation and to evaluate its "survival" at different time points under cryopreservation conditions.Materials and methods: A device for the preparation of donor fecal material for transplantation has been developed and proposed (the Russian Federation patent No. 2659417 from July 2, 2018). Donor fecal material (collected in a  sterile container on the same day of preparation in the morning), the solvent, and glycerol are homogenized automatically in the closed loop device and passed through a disposable filter with attached sterile hemocon container. Freezing at ultralow temperature (cryopreservation at -80 °C) allows for long time storage of this fecal graft. We studied the microbial composition of the obtained native substrate and samples that were cryopreserved at different time points (7 to 365 days).Results: The proposed original method makes it possible to prepare the biomaterial for storage at a low temperature mode without any contact, in a  closed loop, for subsequent fecal transplantation within 6–12 months. The analysis of the fecal transplant at different time points has shown no qualitative and quantitative differences in the microbial composition between the native donor material and the freshly prepared filtrate. The biomaterial prepared according to the original method is stable for 12 months.Conclusion: The proposed hardware method for preparing the biomaterial for fecal transplantation is easy to use and allows for the preparation of a  graft with minimal external microbial contamination, in contrast to the conventional method of donor material preparation by filtering fecal matter through gauze or coffee filters with manual assistance

The role of TNF-alpha gene (-238G/A and -308G/A) polymorphisms in the etiology and pathogenesis of inflammatory bowel diseases in various ethnic groups

This literature review deals with specifics of the natural course of inflammatory bowel disease (IBD) in patients from various ethnic groups and -308G/A and -238G/A promoter polymorphisms in tumor necrosis factor-alpha (TNF-α) gene. The search in PubMed, Medline, Еlibrary.ru databases has led to identify in total 20 studies, including 2 meta-analyses, on the role of TNF-α-308G/A and -238G/A gene polymorphism in the etiology and pathophysiology of IBD. The TNF-α-308G/A polymorphism is associated with increased secretion of this proinflammatory cytokine, whereas the TNF-α-238G/A genotype is characterized by reduced TNF-α secretion. A  number of studies have shown an association between TNF-α-308G/A gene polymorphism and severe course of IBD, requiring more active treatment of patients (cytostatics, corticosteroids, biological agents). Some investigators have found that the patients carriers of TNF-α-308G/A had a  higher probability of surgical interventions. The association between TNF-α-308G/A and the phenotypic characteristics of IBD has been identified in studies performed in Europe, Asia, and Russia. The association of this polymorphism with the prevalence of ulcerative colitis has been proven in some studies, in particular, in the Asian population. Similar associations have been noted in few publications originating from Europe and North America, while some studies have found no links between TNF-α-308G/A, -238G/A, and the course of IBD. TNF-α-238G/A gene polymorphism has not shown any significance for the prevalence and course of ulcerative colitis and Crohn's disease. One can assume that the differences in the study results arising from one and the same geographical area are related to genetic heterogeneity of the study groups, phenotypic variances between the study subjects, as well as relatively small sample sizes. Currently, the search for genetic, biochemical and other prognostic criteria for IBD course is in progress. There are studies in progress to investigate the mechanisms of transformation of the genetic information into the particulars of ulcerative colitis and Crohn's disease manifestations, with consideration of ethnicity

Social and demographic characteristics, features of disease course and treatment options of inflammatory bowel disease in Russia: results of two multicenter studies

Background: Epidemiological studies  performed in different countries  have identified a number  of trends  that  allow to predict  the problems  related to the  prevalence  of inflammatory  bowel  diseases  (IBD),  their  severity  and  healthcare resources utilization. Aim:  To  present   comparative   results of two large epidemiological  studies of IBD in the Russian Federation (RF), i.e. ESCApe and ESCApe-2. Materials     and     methods:     Two    multicenter cross-sectional cohort studies with a similar design were performed  at three-year interval. The studies had the common aim: to identify social and demographic and clinical particulars of ulcerative colitis (UC) and Crohn’s disease (CD) in RF, as well as treatment options. Twenty (20) centers of gastroenterology from 17 RF regions participated in the ESCApe (2010–2011) and 8 centers from 7 RF regions in the ESCApe-2 study (2013–2014). Results: The ESCApe study included 1797 patients (1254 UC and 543 CD), whereas   the   ESCApe-2  included   1000  patients (667 UC and 333 CD). Patient demographic and social characteristics: In both  studies, female: male ratio was similar in UC and CD. Patients’ age was almost identical: in UC, median  age was 38 years and 40 years in ESCApe and ESCApe-2, respectively; in CD the  corresponding  values were  36 and 35 years. In ESCApe, the peak UC onset was at the age of 21 to 40 years, whereas in CD it was shifted towards younger age (22.5% of the patients  manifested before 20 years) and the peak incidence was in three age groups (below 20 years, 21 to 30 and 31 to 40 years).  A statistically significant difference between CD and  UC was found  only in the  age group  of 11 to 20 years (22.5% vs. 13.6%, respectively, p < 0.01). In ESCApe-2, median age of disease onset in UC and CD was approximately 30 years. In both  studies, urban:rural ratio for UC and CD was 4:1. In ESCApe, the proportion of current  smokers among  CD patients  was almost  two-fold  higher than  among  those  with  UC (15.6  and  8.8%,  respectively, p < 0.001); the same trend was found in ESCApe-2 (15 and 7.3%, p < 0.001). Socioeconomic characteristics of patients in both studies were similar: 50 to 60% were at work (professional occupation and income levels were not studied); in ESCApe 30.9% of UC patients and 40.9% of CD patients had legal disability due  to various reasons  (including that related to UC and CD in 12,6 and 14.9%, respectively), whereas in ESCApe-2 the respective proportions  were  35.7 and  51.1%.  Clinical characteristics of patients: The time from the  first UC symptoms to diagnosis  was similar in both  studies  (median, 5 months  in ESCApe and 4 months  in ESCApe-2); in CD patients  these parameters were significantly different in both studies (12 vs. 1 month). As for the severity of the disease, the UC patients  in ESCApe had  mild disease  in 16%, moderate in 53%, and severe in 31%, whereas the respective proportions among  the  CD patients  were 21, 44, and  35%. In ESCApe-2, there were no patients  with severe disease;  mild and  moderate UC were  diagnosed  in 51.3 and  46.6% of the  patients, respectively, and mild and moderate CD, in 52.3 and 47.3%. The frequency of left-side UC was similar: 38% in ESCApе and 34% in ESCApе-2. Proctitis was more frequent in the  first study  (33 vs. 11%, p < 0.01), and  total UC was more frequent  in the second  study (29 vs. 55%, p < 0.02). There were no significant differences between ESCApe and ESCApe-2 in the main CD localizations: terminal ileitis was seen  in 31.3 and 35.4% of the  patients,  respectively,  ileocolitis in 33.4 and 37.8%, colitis in 25.6 and 32.1%. The upper gastrointestinal involvement In ESCApе was found 4.4%, and mixed involvement  in 5.3%. In both studies, extra-intestinal  manifestations were more frequent  in CD, than  in UC: in ESCApe, 33.1% and 23% (р < 0.05), and in ESCApe-2 in 41.7 and 29.4%, respectively   (р < 0.05).   Peripheral   arthropathies were  most  frequent. Ankylosing spondylitis  was found in CD only, and primary sclerosing cholangitis, only in UC. Aphthous  stomatitis  was significantly more prevalent in CD in both studies. There were no significant differences in all other extra-intestinal symptoms  (eye and skin involvement). Treatment characteristics: Treatment options before the  study entry, as well as at the  study inclusion visit were analyzed. In ESCApe, the majority of the patients  had not been given any treatment before the study entry (49.1% with UC and 40.5% with CD). Three years later  the  situation  was changing: in ESCApe-2, the  proportion of treatment-naïve patients was 2.5 to 3-fold lower (15.3% with UC and 14.4% with CD), which was most probably related to increasing  awareness  of physicians. Before the study entry, most  patients  (40 to 70%) had  been treated with 5-aminosalicylic acid (5-ASA). Before the  second  study,  the  patients   were  more  frequently  treated with  glucocorticosteroids (GCS), immunosuppressors and  genetically  engineered biological agents  (GEBA),  but  with no significant differences  from the  first study. 5-ASA prevailed also  among  the  agents  that  were  administered during  the  inclusion visits in both  studies  (80 to 90% UC patients  and  about  70% of CD patients). Compared   to  ESCApe,  in  ESCApe-2  there   was a trend  towards  lower rate of GCS administration in UC and CD, but the differences did not reach the significance level. It may be explained  by the absence of severe IBD types in ESCApe-2. In ESCApe, immunosuppressors were rarely used (in 14.4% of the UC patients  and in 26.8% of the CD patients); however, in ESCApe-2 there were administered more  frequently: up to 35.9% of the  UC patients and 55.1% of the CD patients  (р < 0.01 for both cases). It was unknown  if immunosuppressors were used as monotherapy or in combination with GCS. Three years later, the rate of GEBA administration was also higher, but  this increase  was significant only in CD: 28.3%  in ESCApe-2 vs. 9.2% in ESCApe (р < 0.01). According to the results of ESCApe, in the UC patients steroid resistance was seen in 23% and steroid dependency in 21%, whereas in the CD patients these values were 24 and 27%, respectively. In ESCApe-2 these  parameters were not assessed. Conclusion:  Both studies  showed  a  number   of patterns coinciding  with  the  world  trends,  such as age and gender  distribution  of UC and CD patients, age at manifestation, the proportion of urban to rural residents, smoking status, prevalence and types of extra-intestinal  symptoms. Unlike in European countries, moderate and severe forms of UC with extensive involvement are prevalent in RF. Low prevalence  of mild and limited types of IBD is to be explained by underdiagnosis. Of note is the high proportion of patients  with UC and CD treated with 5-ASA, although in CD these  agents  have demonstrated low efficacy. The rates of immunosuppressors  and GEBA administration significantly increased  in the second  study, most likely, due to the  implementation of a  system  of educational measures. Nevertheless, the rate of GEBA use in IBD remains low, which is to be related to their insufficient availability. In total, steroid resistance / steroid dependency rate amount  to almost half of UC and CD cases. In general, some positive changes  in the patient  management are  obvious  in the  second study. However, monitoring  these  changes  over time could only be possible if similar studies would be performed at regular intervals