[Clinical cases of microscopic colitis: Diagnosis and treatment issues. Case report].

Currently, there is an increase in the incidence of microscopic colitis. There are difficulties in diagnosing this disease due to the variability of histological signs, variability of morphological changes in the mucous membrane of the colon in different parts of the colon, and the combination in one patient of not only various forms of microscopic colitis, but also other intestinal diseases. The article describes the differential diagnosis, an example of its staging and successful treatment of various forms of microscopic colitis with budesonide (two clinical cases presented).

[The role of a combined probiotic in the treatment of lactase deficiency].

AIM: To study the effectiveness of the combined probiotic Bifiform and the enzyme lactase in the treatment of secondary lactase deficiency (SLD). MATERIALS AND METHODS: We examined 79 patients with SLD, isolated from the group of patients with post-infectious irritable bowel syndrome (IBS) with a predominance of diarrhea. The age of patients reached 273.5 years, women predominated by gender 62%. Diagnosis of SLD was carried out in biopsies of the small intestine mucosa using a color rapid test. To diagnose small intestinal bacterial overgrowth (SIBO) all patients underwent lactulose breath test (LBT) during 2 hours by gas analyzer. All patients with lactase deficiency (LD) were divided into 2 groups: group 1 included 54/79 patients who received the combined probiotic Bifiform (1 capsule per day), group 2 was treated with the enzyme lactase [1 capsule (3450 ME) 3 times a day]. The effectiveness of therapy was evaluated by the dynamics of clinical symptoms, indicators of LBT and the detection of hypolactasia in biopsies of the small intestine mucosa twice, before and 2 weeks after treatment. RESULTS: In the group of patients with LD, as a result of 14-day therapy with the combined probiotic Bifiform, 85.2% showed positive clinical dynamics, the values of SIBO in the small intestine decreased from 5814 to 219 ppm, p0.05, and the activity of the lactase enzyme was completely restored. In 14.8% of patients, LD was preserved against the background of persistent SIBO. In the second group of 25 patients, 84% of patients did not achieve a positive dynamics of the disease as a result of taking the lactase enzyme, and hypolactasia and changes in the lumen microflora of the small intestine were preserved after repeated examination of small intestine biopsies. Recovery of the activity of the lactase enzyme was observed in a small percentage of patients, which was 16%. CONCLUSION: In 85.2% of patients, as a result of therapy with the combined probiotic Bifiform, the activity of the lactase enzyme was restored, due to the suppression of bacterial contamination in the lumen of the small intestine. Replacement therapy with the enzyme lactase only led to remission of LN in 14.2%, while in the majority 85.8% hypolactasia and SIBO remained. Pathogenetic therapy of LN in the adult population includes the appointment of a combined probiotic Bifiform 1 capsule 3 times a day, a course of at least 14 days. As a symptomatic therapy for LN, replacement therapy with the enzyme lactase can be prescribed.

Personalized medicine in the treatment of inflammatory bowel diseases.

Personalized medicine (personalized medicine, individualized medicine) represents the totality of methods of prevention of a pathological condition, diagnosis and treatment in the event of its occurrence, based on individual patient characteristics. Such individual characteristics include genetic, epigenetic, and transcript, proteome, metabolomic and metagenomic markers, as well as a set of variable phenotypic traits - both of the patient's body and its separate tissues or cells. For example, treatment of inflammatory bowel diseases (IBD) can most clearly show the importance of applying personalized approaches. Currently in the treatment of patients with IBD paid great attention to genetic studies, monitoring of the concentration of the biological drugs and the level of antibodies to them, the role of microbiota as a predictor of effectiveness of therapy of IBD. Used clinical, laboratory, instru- mental methods, as well as new biomarkers to assess the forecasting efficiency of conservative therapy in IBD patient. In the future treatment of patients with IBD will include a number of personalized data in order to better predict outcomes of the disease in each patient and more ac- curately select the appropriate treatment regimen.

Mesenchymal stromal cells of bone marrow and azathioprine in Crohn's disease therapy.

AIM: To evaluate the effectiveness of MSCs therapy in patients with CD receiving azathioprine (AZA). MATERIALS AND METHODS: The study included 34 patients with inflammatory (luminal) form of CD. The 1st group of patients (n=15) received an- ti-inflammatory therapy using MSCs culture in combination with AZA. The 2nd group (n=19) received MSCs without AZA. The severity of the attack was assessed in points in accordance with the of Crohn's disease activity index (CDAI). Immunoglobulins (IgA, IgG, IgM), interleukins (IL) 1ß, 4, 10, tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ), transforming growth factor-1ß (TGF-1ß), C-reactive protein (CRP), platelets and erythrocyte sedimentation rate (ESR) at 2, 6 and 12 months from the beginning of MSCs therapy. RESULTS: The initial mean CDAI in the 1st group was 337.6±17.1 points, in the 2nd group - 332.7±11.0 points (p=0.3). In both groups of pa- tients there was a significant decrease in CDAI after 2 months. From the beginning of therapy MSCs: in the 1st group to 118.9±12.4 points, in the 2nd - 120.3±14.1 points (p=0.7), after 6 months - 110.3±11.1 and 114.3±11.8 points (p=0.8), respectively. After 12 months CDAI in the 1st group was 99.9±10.8 points, in the 2nd group it was 100.6±12.1 points (p=0.8). The level of IgA, IgG, IgM was significantly lower in the group of patients with a longer history of the disease and long-term ASA. After the introduction of MSC in both groups of patients with BC, there was a tendency for the growth of pro- and anti-inflammatory cytokines, with a significantly lower level of pro-inflammatory cytokines - INF-γ, TNF-α, IL-1ß - in the 1st group, indicating potentiation of the immunosuppressive effect of MSCs and AZA, which provides a more pro- nounced anti-inflammatory effect. CONCLUSION: Transplantation of MSCs promotes an increase in the serum of patients with CD initially reduced concentration of IG, cytokines and restoring their balance as the onset of clinical remission. The combination with AZA has a more pronounced anti-inflammatory effect.

Biomarkers of inflammatory bowel disease activity.

The review presents data on calprotectin, lactoferrin, leukocytes labeled with isotope indium 111In, calgranulin C and pyruvate kinase type M2 - highly sensitive biomarkers to assess the severity of intestinal inflammation. Their importance in diagnostics, determination of treatment efficiency, including as predictors of recurrence of ulcerative colitis and Crohn's disease is shown.

Stem Cell Therapy for Perianal Crohn's Disease.

AIM: To compare the effectiveness of the effect of combination therapy (local and systemic administration) with bone marrow mesenchymal stromal cells (MSC), anticlitokine therapy with infliximab (IFX), and antibiotic (AB)/immunosuppressive (IS) therapy on the frequency of healing of simple perianal fistulas in Crohn's disease. MATERIALS AND METHODS: In our study, the 1-st group of patients aged 19 to 58 years (Me-29) (n = 12) received MSCs culture systemically according to the scheme and locally. The 2-nd group of patients with CD (n = 10) from 20 to 68 years old (Me-36) received anticytokine therapy with infliximab (IFX) according to the scheme. The 3-d group of patients with CD (n=14) from 20 to 62 years old (Me-28) received antibiotics (AB) and immunosuppressors (IS). Efficacy was assessed by the index of perianal activity of Crohn's disease (PCDAI) and the frequency of relapses. RESULTS: After 12 weeks among patients of the 1-st group, healing of simple fistulas was noted in 8/12 patients (66.6%), in the 2-nd group in 6/10 (60.0%) In the 3-d group, in 1/14 patients (7.14%). After 6 months in the 1-st group of patients, healing of simple fistulas was preserved in 8/12 (66.6%), in the 2-nd group - in 6/10 (60.0%). In the 3-d group - in 1/14 patients (7.14%). After 12 months in the 1-st group, healing of simple fistulas was preserved in 7/12 (58.3%), in the second group - in 6/10 (60.0%). In the 3-d group - in 2/14 patients (14.3%). After 24 months, among the patients of the 1-st group, fistula closure was maintained in 5/12 patients (41.6%), in the 2-nd group - in 4/10 (40.0%). In the 3-d group - in 0/14 patients (0.0%). CONCLUSION: Combined cellular and anticytokine therapy of CD with perianal lesions significantly contributes to the more frequent and prolonged closure of simple fistulas, as compared to antibiotics/immunosuppressors, and to a decrease in the frequency of recurrence of the disease.

[Efficacy of adalimumab for Crohn's disease in real clinical practice]. / Effektivnost' adalimumaba pri bolezni Krona v real'noi klinicheskoi praktike.

AIM: To evaluate the efficacy and safety of adalimumab (ADA) in patients with Crohn's disease (CD) treated at the Department of Inflammatory Bowel Diseases, Moscow Clinical Research and Practical Center, and to determine the predictors of a therapy response. SUBJECTS AND METHODS: All the patients with CD treated with ADA were followed up for at least 6 months or until the drug was discontinued. Therapeutic effectiveness was evaluated at 4 weeks and 6 months after the initiation of treatment and at the end of a follow-up. Complete intestinal mucosal healing was assessed at 3 and 12 months following treatment initiation. Univariate and multivariate analyses were used to determine the predictors of treatment response. RESULTS: A clinical analysis covered 70 patients (57.1% male); the follow-up period averaged 112 weeks. Perianal fistulas were at baseline established in 22 (31.4%) patients with CD. 12 (17.4%) patients had been previously treated with infliximab (INF), 7 of them discontinued the drug for secondary loss of response and 5 for adverse reactions. 68 (97.1%) patients responded to an induction course of ADA. At 4 weeks, 6 months, and at the end of the follow-up, clinical remission occurred in 66.7, 80.4 and 67.4 % of patients with luminal CD and in 45.4, 36.5, and 36.4% of those with perianal CD, respectively. At 3 and 12 months and at the end of the follow-up, there was complete healing of the intestinal mucosa in 23.5, and 41.2 and 29.5% of cases, respectively. Six (8.8%) patients responding to the induction course needed to be optimized with ADA to 40 mg weekly. The time interval between treatment initiation and dose optimization averaged 30 weeks (range 12-120 months). There were 15 (21,4%) adverse events that were responsible for ADA discontinuation in 3 (4,2%) patients. CONCLUSION: The findings demonstrate the efficacy and safety of ADA used in clinical practice.

[Common variable hypogammaglobulinemia: the author's observation].

The paper gives a case history of a patient with common variable hypogammaglobulinemia (CVHGG). Its clinical picture was characterized by frequent inflammatory airway diseases, pansinusitis, and periodic rises in temperature up to febrile ones. The diagnosis was established on the basis of the decreased serum concentrations of immunoglobulins (IG) A, M, and G, the unusual small intestinal (SI) wall relief created by large lymphoid follicles, as well as the characteristic sign of CVHGG, namely, the lack of plasma cells in the lamina propria of the SI mucosa. Antibacterial therapy was noted to have a good effect that confirmed the leading role of excessive bacterial growth in the pathogenesis of chronic diarrhea and fever, which are the major clinical manifestations of CVHGG in this patient.

[Small intestinal bacterial overgrowth as a cause of lactase deficiency].

AIM: To establish the rate of lactase deficiency (LD) in patients with post-infectious irritable bowel syndrome (PI-IBS), to define a role of enteric bacteria in the pathogenesis of hypolactasia, and to evaluate the efficiency of probiotic therapy. SUBJECTS AND METHODS: Examinations were made in 386 patients with PI-IBS, including 112 (79.4%) women; mean age 33.9 ± 9.1 years; disease duration 2.6 ± 1.4 years. Rapid tests of small intestinal mucosa (SIM) biopsy specimens obtained from the duodenal retrobulbar segment were used to diagnose LD. Bacterial growth was estimated by a hydrogen breath test using a H2 MICRO gas analyzer. RESULTS: The patients with PI-IBS were revealed to have moderate and severe LD in 25.6 and 10.9%, respectively. All the patients with LD were detected to have small intestinal (SI) bacterial overgrowth (BOG). An inverse correlation was found between LD and the degree of SI BOG (r = -0.53; p < 0.001). 73.7% of the patients with moderate LD showed a positive effect of probiotic therapy as regression of clinical symptoms of LD, a decrease of hydrogen levels in expired air from 72.4 ± 25.1 to 16.41 ± 3.2 ppm (p < 0.05), an increase of lactate activity in the SIM biopsy specimens and an improvement of quality of life from 2.69 ± 0.53 to 5.53 ± 0.64 scores according to the GCI scale. No improvement occurred in 73.8% of the patients with severe LD. CONCLUSION: LD was identified in 36.5% of the patients with PI-IBS. There was an inverse correlation between the degree of LD and SI BOG. The good therapeutic effect of probiotics in LD suggests that the symbiotic gut microflora positively affects the activity of lactase in the human SIM. No therapeutic effect of probiotics in patients with severe LN serves as the basis for a search for more active probiotic therapy.

[Safety of mesenchymal stromal cell therapy for inflammatory bowel diseases: results of a 5-year follow-up].

AIM: To compare the safety of therapy in patients with ulcerative colitis (UC) and Crohn's disease (CD) who have received combination anti-inflammatory therapy using bone marrow mesenchymal stromal cells (MSC) and standard therapy with 5-aminosalicylic acid, glucocorticosteroids, and immunosuppressive agents. SUBJECTS AND METHODS: Unfavorable consequences were analyzed in 103 patients (56 with UC and 47 with CD) with inflammatory bowel disease (IBD) after MSC administration. The findings were compared with data obtained in 208 patients with UC and CD on standard anti-inflammatory therapy. All the patients were similar in demographic parameters, the duration of disease, the extent of intestinal injury, the nature of a course, the type and degree of disease. The analyzed groups did not include patients who had received therapy with anti-TNF-α drugs. The safety of therapy was evaluated from the presence of complications occurring during the follow-up. RESULTS: By analyzing the unfavorable consequences in 103 patients with IBD and comparing them with treatment results in 208 patients with UC and CD on standard anti-inflammatory therapy, the authors revealed no differences in the development of acute posttransfusion reactions, infectious complications, exacerbations of chronic inflammatory diseases, severe infectious complications, malignant transformation, and fatal cases in patients with UC and CD, except for those with transient fever. CONCLUSION: The results of this study demonstrate that the innovative method of cell therapy is clinically safe.

[The role of small bowel microflora in the development of secondary lactase deficiency and the possibilities of its treatment with probiotics].

AIM: To estimate the incidence of secondary lactase deficiency (SLD) in patients with postinfectious irritable bowel syndrome (PIBS) and the value of the small bowel microflora in its development and to elaborate treatment options for SLD. SUBJECTS AND METHODS: One hundred and thirty-eight patients with PIBS, including 112 (81.2%) women and 26 (18.8%) men, were examined. The patients' mean age was 33.9 +/- 9.1 years. The duration of the disease was 2.6 +/- 1.4 years. Lactase deficiency (LD) was diagnosed using the color scale to test biopsy specimens from the duodenal retrobulbar region. The bacterial overgrowth syndrome (BOS) was identified by a 2-hour lactulose (20 ml) hydrogen breath test. Sixty patients with moderate SLD were randomized to 2 groups: 1) 41 patients received basic therapy (mesim forte as one tablet t.i.d., no-spa, 40 mg, t.i.d.) and combined probiotic bifiform (Ferrosan) containing Bifidobacterium longum 107, Enterococcus faecium 107 as one capsule t.i.d. for 14 days. Group 2 patients (n = 19) had basic therapy in combination with placebo. RESULTS: SLD was detected in 59.4% of the patients with PIBS, including 43.5 and 15.9% with moderate and severe forms, respectively. In all cases, SLD was accompanied by BOS in the small bowel lumen, as confirmed by the results of a hydrogen breath test [101 +/- 37 ppm (a normal value of < 20 ppm)]. After a 14-day course of therapy with the combined probiotic bifiform, restoration of eubiosis in the small bowel lumen was achieved in 70.8% of the patients, as shown by the lesser degree of BOS (86.9 +/- 40.9 and 17.4 +/- 6.6 ppm before and after treatment, respectively; p < 0.01) and by normalization of the lactase test (p < 0.01). In the comparative placebo group, 68.4% showed no clear positive changes, SLD and BOS remained. CONCLUSION: The changes in the small bowel intraluminal microflora, which developed after prior intestinal infection, played a great role in the development of SLD. Bifiform belongs to the currently available probiotics and may be recommended to correct SLD in patients with PIBS resulting from the impaired microbiota of the small bowel and to prevent BOS.

[Lactase deficiency in patients with postinfectious irritable bowel syndrome and the role of intestinal microflora in its development].

PURPOSE: to define the frequency of secondary lactase deficiency (SLD) in patients with postinfectious IBS and to develop therapy for the correction of mild SLD in adult patients. METHODS AND MATERIALS: In this study, 138 patients (the mean age - 33.9 +/- 9.09; F/M - 112/26) with postinfectious IBS were analyzed concerning lactase deficiency. All patients underwent intestinal endoscopy with biopsies from the mucosa of the descending duodenum in order to determine lactase deficiency twice before and after therapy. To diagnose small intestinal bacterial overgrowth (SIBO) all patients underwent lactulose breath test during 2 hours. RESULTS: SLD was detected in 59.4% of patients with postinfectious IBS. Mild SLD was determined in 43.5% of patients, and severe SLD - in 15.9% of patients. SLD in all cases was accompanied by SIBO (the mean level of lactulose breath test was 101 +/- 37 ppm, N<20 ppm). In group patients who took the probiotic during 14 days in 70.8% of patients recovering of lactose metabolism in the small intestine and decreasing of the intensity of clinical symptoms were registered. The decrease of the lactulose breath test level (86.9 +/- 40.9 ppm; 17.4 +/- 6.6 ppm; p<0.01) and negative LQT (p<0.01) were registered in the first group. In group patients who took placebo during 14 days there was no positive effect in 68.4% of cases. CONCLUSION: the probiotic Bifiform, composed of Bifidobacterium longum 10(7) and Enterococcus faecium 10(7), demonstrated efficiency in correction of mild SLD in patients with postinfectious IBS and can be used to prevent SIBO.