[Irritable bowel syndrome in the Russian Federation: results of the ROMERUS multicenter observational study].

BACKGROUND: Irritable bowel syndrome (IBS) is one of the most common functional disorders of the gastrointestinal tract. According to Russian guidelines, a standard examination using laboratory and instrumental evaluation methods, including colonoscopy, should be performed to establish the diagnosis of IBS. AIM: To characterize the Russian population of IBS patients. MATERIALS AND METHODS: A multicenter observational prospective study ROMERUS was conducted at 35 clinical centers in the Russian Federation. The study included male and female patients aged 18 to 50 with a diagnosis of IBS based on the Rome IV criteria, with no signs of structural gastrointestinal disease. The follow-up duration was 6 months and included three patients' visits to the study site. During the study, data were collected on patients' demographic and clinical characteristics, medical history, and drug therapy. The secondary parameters included the assessment of the proportion of patients with a diagnosis of IBS confirmed by a standard examination among all patients meeting the Rome IV criteria, the evaluation of the change over time of the IBS symptoms, quality of life (QoL), and adherence to therapy. Characterization of the population was performed using descriptive statistics methods. The standard examination results were presented as the percentage of patients with IBS confirmed by the standard examination among all patients meeting the Rome IV criteria, with a two-sided 95% confidence interval. RESULTS: The study included 1004 patients with a diagnosis of IBS according to the Rome IV criteria, with 790 (78.7%) patients included in the final analysis. The mean age of patients was 34.0±7.5 years; they were predominantly female (70.4%), Caucasian (99.4%), married (55.1%), urban residents (97.5%) with higher education (64.5%) and a permanent position (74.9%). Patients enrolled in the study have low physical activity and lack a healthy diet. The smoking rate was 26.3%. IBS symptoms with predominant constipation (IBS-C) were observed in 28.1% of patients; 28.9% had IBS with predominant diarrhea (IBS-D), 11.9% had mixed-type IBS, and 31.1% had non-classified IBS. The main IBS symptoms were pain (99.7%), abdominal distension (71.1%), and fullness (36.8%). Biliary tract dysfunction (18.9%) and gastritis (17.2%) were the most frequently reported comorbidities. Prior to enrollment, 28% of patients received drug therapy. The most commonly prescribed drug during the study was mebeverine (54.1%). At 6 months of follow-up, there was a significant reduction of abdominal pain, bloating, and distention, and a twofold reduction in the incidence of constipation and diarrhea in the subgroups of patients with IBS-C and IBS-D, respectively. The overall QoL score measured by the IBS-QoL questionnaire increased from 83.0 to 95.2 points (p<0.05) during the study. In the overall assessment of their condition, 69.6% of patients noted no symptoms and 25.3% reported marked improvement, 35% were asymptomatic according to the physician's overall assessment of the patient's condition, and 51.8% showed significant improvement. CONCLUSION: IBS patients in the Russian Federation were characterized. The diagnosis of IBS, established following the Rome IV criteria, is confirmed by the results of a standard examination in 96.3% of patients. The Rome IV criteria for the IBS diagnosis make it possible to establish a diagnosis with a probability of 94.7%. For 6 months of follow-up, there was a clinical improvement with a decrease in the severity of symptoms and a QoL improvement.

Certolizumab pegol in treatment of Crohn's disease with perianal lesions.

AIM: To assess the effectiveness of conservative treatment of Crohn's disease (CD) with perianal lesions. MATERIALS AND METHODS: The study included 20 patients with CD with perianal fistulae. Prior to the start of conservative therapy, 7 patients underwent fistulae drainage with setton placement. During the study, all patients received therapy with certolizumab pegol (CP) for a year. At the time of treatment initiation and after 12 months, the CD activity index, the quality of life according to IBDQ questionnaires and the perianal Crohn's disease activity index (PCDAI) were assessed. RESULTS: After a year of CP therapy, clinical remission was achieved in 8 (40%) patients, endoscopic remission in 7 (35%) patients, fistula closure in 6 (30%) patients. There was also a decrease in the PCDAI with the average score 3.6 points compared to 9.3 points (p˂0.05) prior to the treatment. An improvement in the quality of life of patients was also established, the average quality of life index was 182,2 points compared to 156,0 points (p˂0.05) prior to the treatment. CONCLUSION: This study showed that CP therapy is effective in treatment of CD with perianal lesions.

[All-Russian Consensus on Diagnosis and Treatment of Celiac Disease in Children and Adults]. / Vserossiiskii konsensus po diagnostike i lecheniyu tseliakii u detei i vzroslykh.

The paper presents the All-Russian consensus on the diagnosis and treatment of celiac disease in children and adults, which has been elaborated by leading experts, such as gastroenterologists and pediatricians of Russia on the basis of the existing Russian and international guidelines. The consensus approved at the 42nd Annual Scientific Session of the Central Research Institute of Gastroenterology on Principles of Evidence-Based Medicine into Clinical Practice (March 2-3, 2016). The consensus is intended for practitioners engaged in the management and treatment of patients with celiac disease. Evidence for the main provisions of the consensus was sought in electronic databases. In making recommendations, the main source was the publications included in the Cochrane Library, EMBASE, MEDLINE, and PubMed. The search depth was 10 years. Recommendations in the preliminary version were reviewed by independent experts. Voting was done by the Delphic polling system.

CANCERPREVENTIVE IN ULCERATIVE COLITIS.

Colorectal cancer (CRC) is an actual problem today And it occurs 6 times more frequently in patients with inflammatory bowel diseases (IBD) than in healthy population. CRC in IBD patients is more aggressive and needs total colectomy, which leads to permanent disability That is why canceroprevention is one of the key goals of IBD treatment. The aim of this review is to overview actual pathogenesis pathways of CRC in IBD and methods of chemoprevention. In this review we describe risk factors of CRC, which can be summarized as aggressive disease and chronic inflammation and are based on pathogenesis of CRC. That is the reason why methods of chemoprevention needs to influence on inflammation and other pathogenesis pathways. The role of such classes of medication as non-steroidal anti-inflammatory drugs, 5-aminosalicylic acid, immunomodulators, ursodeoxycholic acid in canceroprevention in RD patients are described in this review.

[Efficiency of tacrolimus therapy for perianal Crohn's disease].

AIM: To determine the efficacy of 0.1% tacrolimus ointment in patients with perianal Crohn's disease (CD). SUBJECTS AND METHODS: This prospective randomized trial enrolled 20 patients with perianal CD as anal fissures and rectal fistulas. The inclusion criteria were rectovaginal or extrasphincteric fistulas and purulent leakages. A study group comprised 11 patients, including 9 with anal fissures and 2 with fistulas. A control group included 9 patients, including 8 with fissures and 1 with fistulas. The study group received systemic therapy with azathioprine 2 mg/kg/day and tacrolimus ointment 2 mg/day; the control group had systemic therapy with azathioprine 2 mg/kg/day, hormone ointment 1 mg/day, and metronidazole suppositories 250 mg/day. Control examination and perianal CD activity index (PCDAI) determination were done 6 and 12 weeks after therapy initiation. RESULTS: At 6 weeks after beginning the study, local examination revealed the signs of anal fissure epithelialization in 5 (45.5%) of the 11 patients in the study group and in 3 (33.3%) of the 9 patients in the control one. At 12 weeks, fissure epithelialization and fistula obliteration were stated in 6 (54%) patients in the study group and in 3 (33%) of the 9 patients in the control group. At 12 weeks, PCDAI in the study and control groups was 2.00 and 4.44 scores (p = 0.01). CONCLUSION: The findings suggest that topical 0.1% tacrolimus ointment versus antibacterial suppositories and hormone ointments is effective in treating patients with perianal CD. Topical 0.1% tacrolimus ointment therapy caused a reduction in PCDAI.

[Long-term results of medical treatment in patients with a severe attack of ulcerative colitis].

AIM: To assess the long-term result of medical treatment in patients with a severe attack (SA) of ulcerative colitis (UC). SUBJECTS AND METHODS: The course of UC was analyzed in 56 patients who were accessible by telephone contact and consecutively recruited for a year after therapy for a SA of UC. All the patients were stated to have a SA of UC according to the Truelove-Witts' criteria; they received therapy with intravenous glucocorticosteroids (GCS) (prednisolone 2 mg/kg) along with anti-recurrence therapy with mesalasine (5-ASA) or azathioprine (AZA). Ten (17.9%) GCS-resistant patients were given infliximab (INF) (5 mg/ kg), followed by its maintenance infusions. Anti-recurrence therapy using 5-ASA, AZA, and INF was performed in 33 (58.9%), 13 (23.2%), and 10 (17.9%) patients, respectively. RESULTS: During one year, 14 (25%) patients continued to be in clinical remission on maintenance therapy or to have attacks stopped without using GCS, immunosuppressive agents, or INF (a satisfactory response group). Colectomy was carried out in 23 (41.1%) patients; due to recurrent UC when decreasing the dose of GCS, 5 (8.9%) patients continued to take the latter during a year. A GCS cycle was repeated in 3 patients who had received AZA (the basic therapy was not corrected) and 11 patients who had taken 5-ASA. The prognostic factors for a long-term result of medical therapy included the choice of AZA as an anti-recurrent drug (57.1 and 11.9% in the satisfactory and poor treatment outcome groups, respectively; p = 0.004) and patient age (34.4 and 42.8 years, respectively; p = 0.0357). CONCLUSION: During 1 year after a SA of UC, indications for colectomy and repeated GCS use occurred in 41 and 34% of the patients, respectively. The long-term efficiency of medical therapy for a SA of UC declines with advancing age. The use of AZA as an anti-recurrence agent after termination of GCS intake increases the probability of long-term clinical response.

[Role of rifaximin in correction of IBS-like symptoms in patients with inflammatory bowel disease].

One of the important problems in the treatment of patients with inflammatory bowel disease are the persistent complaints of pain, abdominal distention, frequent stools, excretion of mucus with faeces with the presence of endoscopic or roentgenologic remission in the damaged parts of gastrointestinal tract. In this review we describe possible causes of such complaints and some methods of their therapeutic correction.

[The clinicomorphological characterization of segmental lesion in ulcerous colitis].

The authors analyzed the clinical picture in 18 patients with distal lesion of the colon and an inflammatory focus in the cecum (segmentary lesion), and five patients with distal lesion of the colon revealed with endoscopy and pathomorphological signs of inflammation in visually intact cecum. The analysis shows that in a range of cases the extent of lesion in ulcerous colitis (UC) cannot be determined correctly with colonoscopy. An apparent segmentary character of lesion (inflammation in the distal colon and an inflammatory focus in the cecum) is an additional criterion of unfavorable prognosis of transformation into disseminated UC forms. Such patients need application of the same treatment regimens as in patients with disseminated UC forms.

Alterations in the colonic flora and intestinal permeability and evidence of immune activation in chronic constipation.

BACKGROUND: Disturbances in bowel function in chronic constipation could result in changes in the colonic flora and lead to disordered immunity and to decreased resistance to pathogenic flora. AIM: To investigate systemic immunity, the faecal flora and intestinal permeability in patients with chronic constipation, under basal conditions and following therapy with the laxative Bisacodyl. METHODS: Intestinal permeability, faecal flora analysis, T- and B-lymphocyte numbers, T-cell subpopulations, lymphocyte proliferation, phagocytosis, intracellular killing of Staphylococcus aureus by neutrophils, as well as circulating levels of immunoglobulins, immune complexes and antibacterial antibodies were assessed in 57 patients with functional constipation. In 12 patients with severely delayed transit, investigations were repeated following therapy with Bisacodyl. RESULTS: Ovalbumin concentrations, in serum, were higher in constipated patients (28.2+/-4.1 ng/ml versus 1.0+/-0.4 ng/ml, p < 0.05). Elevated counts of CD3+, CD4+, CD25+ cells, increased spontaneous proliferation of lymphocytes, elevated titres of antibodies to Escherichia coli and S. aureus, diminished counts of CD72+ B cells, diminished lymphocyte proliferation under phytohemagglutinin (PHA) stimulation and a diminished phagocytic index for both neutrophils and monocytes were found in the constipated patients. Concentrations of Bifidobacterium and Lactobacillus were significantly lower in constipated patients; potentially pathogenic bacteria and/or fungi were increased. Therapy with Bisacodyl resulted in normalisation of the faecal flora, a reduction in ovalbumin concentration and return towards normal for certain immunologic parameters. CONCLUSION: Constipation is associated with striking changes in the faecal flora, intestinal permeability and the systemic immune response. Relief of constipation tends to normalise these findings suggesting that these changes are secondary to, rather than a cause of, constipation.

[Use of the Gepon immunomodulator for ulcerative colitis treatment].

The efficacy of the Gepon immunomodulator was studied in 36 patients with ulcerative colitis (UC) having distal lesions in the resistant form. Taking into account the fact that immunological abnormalities play the main role in UC pathogenesis, the drug with immunomodulatory action was used for overcoming resistance to basic anti-inflammatory drugs. The clinical and immunological reaction to the used drugs was found to be ambiguous. Most of the patients (83.3%) had clinical and endoscopic amelioration after taking Gepon and managed to overcome the resistance to basic anti-inflammatory drugs.

[IgG, IgM, IgA, secretory IgA and the complement components C3, C4 and C9 in the large intestine in nonspecific ulcerative colitis and Crohn disease]. / IgG, IgM, IgA, sekretornyi IgA i komponenty komplementa C3, C4, C9 v tolstoi kishke pri nespetsificheskom iazvennom kolite i bolezni Krona.

The immunohistological study of the large intestines excised from 20 patients with ulcerous colitis and Crohn's disease was made with the use of the indirect immunofluorescence test. A considerable increase in the number of IgG immunocytes has been noted in the lamina propria of the mucous membrane, especially in infiltrations around ulcers. In cases of a highly active inflammatory process accompanied by the pronounced destruction of the epithelium, IgG and C3, C4, C9 were detected in the epithelium of crypts and in blood vessels of the mucous membrane and the submucosa. One-third of the patients showed a decrease in the number of crypts with secretory and serum IgA. The authors suggest that immune complexes take part in maintaining the chronic inflammatory process.

[Titers of antibodies against antigen O of E. coli O14 in patients with inflammatory diseases of the large intestine]. / Soderzhanie antitel protiv O-antigena E. coli O14 u bol'nykh Vospalitel'nymi zabolevaniiami tolstoi kishki.

The content of serum antibodies to E. coli O14 O-antigen in patients with inflammatory diseases of the large intestine was studied in the passive hemagglutination test. These antibodies were detected in 77% of patients with nonspecific ulcerous colitis and in all patients with Crohn's disease; of these, 93.5% had antibody titers of 1:32 and greater, while none of the patients with ulcerous colitis showed such titers. This study has led to the conclusion that the detection of these antibodies in high titers can be one of the criteria for the differential diagnosis of nonspecific ulcerous colitis and Crohn's disease.

[Effect of human immunoglobulins on microflora of the large intestine in nonspecific ulcerative colitis]. / Vliianie immunoglobulinov cheloveka na mikrofloru tolstogo kishechnika pri nespetsificheskom iazvennom kolite.

The use of commercial preparations of human immunoglobulin for the treatment of ulcerous colitis produces a positive effect on the microflora of the large intestine, contributing to the disappearance of Proteus, the lactose-negative forms of enterobacteria and the hemolytic variants of staphylococci, as well as to the increase of the amount of useful indigenous microflora (bifidobacteria and lactobacteria). The quantitative and qualitative improvement of the microflora leads, possibly, to the decrease of the intoxication of the body, improvement in the activity of the intestine and increased vitamin formation, thus giving a pronounced clinical effect and improvement in the endoscopic picture of the mucous membrane of the large intestine, peculiar for this disease.

[Use of immunoglobulin for treating patients with nonspecific ulcerative colitis]. / Primenenie immunoglobulina dlia lechenii bol'nykh nespetsificheskim iazvennym kolitom.

The therapeutic effect of human immunoglobulins was assessed in 29 patients with nonspecific ulcerative colitis, as was their influence on intestinal flora. A 5 to 15 ml dose of immunoglobulin was administered intramuscularly every other day, 3 injections altogether. The clinical and endoscopic effect of treatment was positive in 21 patients (72.4%). Large-intestinal mucosal imprints were studied histologically in 17 patients. Inflammation subsided in 11 patients (64.7%), and glandular epithelial proliferation declined in 4 (23.5%). In the course of treatment, lactobacilli, and bifidobacteria were considerably increased in number, while opportunity organisms were decreased, a possible cause of the positive clinical effect.

[Impact of the impaired intestinal microflora on the course of acne vulgaris]. / Vliiane disbakterioza kishechnika na techenie vul'garnykh ugrei.

The paper deals with studies of the intestinal microflora in 114 patients with acne vulgaris (94 and 20 with its papulopustular and nodulocystic forms). Sixty-one (54%) patients have either the first (21%) or second (78.7%) impaired bacterial microflora. At the same time, there are no great differences in the content of the intestinal microflora in different forms of acne. It is noted that adding intestinal microflora-correcting agents to combined therapy in patients with papulopustular acne vulgaris and verified dysbacteriosis reduces the duration of treatment by over twice and makes its duration the same as that in patients without dysbacteriosis.

[Status of the pituitary-adrenal system in patients with non- specific ulcerative colitis]. / Sostoianie gipofizarno-nadpochechnikovoi sistemy u bo'lnykh nespetsificheskim iazvennym kolitom.

The blood content of basal cortisol was studied in 54 patients with a total form of non-specific ulcerous colitis and in 23 of them that of ACTH. A low cortisol level was revealed in 71.4 per cent of the patients, while the level of ACTH remained unchanged. Treatment with prednisolone (1-2 mg/kg) for 6-9 weeks did not deteriorate the functional state of the hypophyseal-adrenal system. A single administration of the total daily dose of prednisolone in the morning protected the adrenal cortex from exhaustion and in some of the patients even caused increased in and normalization of the cortisol level. Rectal administration of hydrocortisone (125 mg), which was included in therapeutic scheme ensured normalization of the blood plasma cortisol level and did not cause decrease in the ACTH level.