Course Of Crohn Research Articles

Creeping Fat in the Pathogenesis of Crohn's Disease: An Orchestrator or a Silent Bystander?

Although the phenomenon of hypertrophied adipose tissue surrounding inflamed bowel segments in Crohn's disease has been described since 1932, the mechanisms mediating the creeping fat formation and its role in the pathogenesis of the disease have not been fully unraveled. Recent advances demonstrating the multiple actions of adipose tissue beyond energy storage have brought creeping fat to the forefront of scientific research. In Crohn's disease, dysbiosis and transmural injury compromise the integrity of the intestinal barrier, resulting in an excessive influx of intraluminal microbiota and xenobiotics. The gut and peri-intestinal fat are in close anatomic relationship, implying a direct reciprocal immunologic relationship, whereas adipocytes are equipped with an arsenal of innate immunity sensors that respond to invading stimuli. As a result, adipocytes and their progenitor cells undergo profound immunophenotypic changes, leading to adipose tissue remodeling and eventual formation of creeping fat. Indeed, creeping fat is an immunologically active organ that synthesizes various pro- and anti-inflammatory cytokines, profibrotic mediators, and adipokines that serve as paracrine/autocrine signals and regulate immune responses. Therefore, creeping fat appears to be involved in inflammatory signaling, which explains why it has been associated with a higher severity or complicated phenotype of Crohn's disease. Interestingly, there is growing evidence for an alternative immunomodulatory function of creeping fat as a second barrier that prevents an abnormal systemic inflammatory response at the expense of an increasingly proliferating profibrotic environment. Further studies are needed to clarify how this modified adipose tissue exerts its antithetic effect during the course of Crohn's disease.

Obesity and novel management of inflammatory bowel disease.

Obesity is prevalent within the inflammatory bowel disease (IBD) population, particularly in newly developed countries. Several epidemiological studies have suggested that 15%-40% of IBD patients are obese, and there is a potential role of obesity in the pathogenesis of IBD. The dysfunction of mesenteric fat worsens the inflammatory course of Crohn's disease and may induce formation of strictures or fistulas. Furthermore, obesity may affect the disease course or treatment response of IBD. Given the increasing data supporting the pathophysiologic and epidemiologic relationship between obesity and IBD, obesity control is being suggested as a novel management for IBD. Therefore, this review aimed to describe the influence of obesity on the outcomes of IBD treatment and to present the current status of pharmacologic or surgical anti-obesity treatments in IBD patients.

OP18 Disease course of Crohn’s disease during the first ten years following diagnosis in a prospective European population-based inception cohort – the Epi-IBD cohort

Abstract Background The Epi-IBD cohort is a prospective European population-based cohort of 1,390 patients diagnosed in 2010 and 2011 with inflammatory bowel disease (IBD) according to Copenhagen criteria in centres from Eastern and Western European countries. The study aims at describing differences in incidence, treatment strategies, disease course and prognosis of Crohn’s disease (CD) across Eastern and Western Europe. Methods CD patients were followed prospectively from the time of diagnosis until December 31st, 2020, death, emigration or loss of follow-up. Clinical data on surgery, hospitalizations, and medical treatment, were captured throughout the follow-up period and entered into a validated web-database, www.epi-ibd.org. Associations between surgery and covariates were analysed by multivariate Cox regression analyses. Results In total, 482 CD patients aged ≥15 years from 21 centres in 5 Eastern and 11 Western European countries were included. At 10-years follow-up, 101 (21%) patients underwent first intestinal resection and 11 out of these 101 patients (11%) underwent additional resections. Furthermore, 176 (37%) patients had at least one CD related hospitalization. Cancer was diagnosed in 21 (4%) patients, including 4 gastrointestinal cancers. The use of IBD medication was comparable between Eastern and Western European centres apart from 5-aminosalicylic acid agents (Table 1). During follow-up, 60 out of 360 patients (17%) progressed from non-stricturing-non-penetrating disease (B1) at diagnosis to stricturing or penetrating disease (B2 or B3) while 13 out of 83 patients (16%) with stricturing disease (B2) progressed to penetrating disease (B3). The median time to progression was 28 (IQR: 9-64) months from diagnosis. No patients from Eastern Europe were exposed to biological therapy prior to change in behaviour, compared to 23 out of 66 patients (35%) from Western Europe. Multivariate Cox regression analysis showed no difference in risk of surgery according to European region (Eastern vs. Western Europe, HR: 0.54, 95%CI: 0.24-1.21). Early intervention with biological therapy (within 6 months) did not influence the risk of surgery (HR:0.75, 95%CI: 0.31-1.83), however early introduction of immunomodulators reduced the risk significantly (HR:0.54, 95%CI: 0.30-0.98). Progression in behaviour from B1 was associated with higher risk of surgery (HR:7.62, 95%CI: 3.91-14.87). Conclusion After 10 years of follow-up, 21% underwent intestinal resection and 10% required additional resections. Despite the widespread use of immunomodulators and biological therapy, 16% of the patients had disease behavioural progression, which was associated with higher risk of surgery. Early introduction of immunomodulators was found to be beneficial.

P325 Proton pump inhibitors are associated with a disabling course of Crohn’s disease

Abstract Background The impact of proton pump inhibitors (PPIs) on the evolution of inflammatory bowel disease (IBD) remains debated with only sparse data available. The primary objective of this study was to analyze the impact of PPIs on the course of IBD. Methods This was a single-center, retrospective cohort study. We included consecutive adult patients diagnosed with Crohn disease (CD) or ulcerative colitis (UC) who were followed prospectively in our day hospital over a 4-month period (from May to August 2022). PPI exposure was defined as PPI use for a cumulative duration of more than seven days from the date of IBD diagnosis until the end of follow-up. We performed a time to event analysis to investigate the association of PPI exposure with treatment failure defined as an IBD-related surgery or hospitalization and/or failure for more than four biologic treatment (Anti TNF, Vedolizumab, Ustekinumab). Results Among the 281 patients identified, 244 patients were eligible for analysis of the primary objective (152 with CD, mean age 45 years, sex ratio 1:1). 113 (46%) patients had been previously exposed to a PPI. PPI-exposed patients were significantly older (p=0.013), more often women (p=0.029), with more frequent active smoking (p=0.001). A total of 152 patients (62%) had treatment failure. Using Cox regression analysis, (Table 1), PPI use identified as an independent factor associated with treatment failure (HR = 1.920; 95% CI [1.084-3.403]; p0.025). In a subgroup analysis by IBD type, this remained statistically significant only for CD (HR = 3.190; 95% CI (1.412-7.206); p 0.005) but not for UC (HR = 0.981; 95% CI (0.384-2.504); p0.968). Survival without treatment failure (Figure 1) was significantly higher in patients without PPI exposure compared to patients with PPI exposure, (325 months vs. 228 months, respectively, p=0.022 (Log-Rank). In a subgroup analysis of infliximab-treated patients, PPI use was not associated with risk of immunogenicity (HR = 1.071; 95% CI (0.515-2.226); p0.854). Conclusion This study demonstrates the negative impact of PPIs on the disease course in patients with CD. The use PPIs should better be discussed on a case-by-case basis.

P145 Phenotypic progression of Crohn’s disease : assessment of risk factors in a Tunisian population

Abstract Background Phenotype progression in patients with Crohn’s disease (CD) is common, but its risk factors vary between studies. The knowledge of these factors at diagnosis help to identify patients with high risk to progression. These patients should be given aggressive treatments given early in the disease course. The aim of our study was to evaluate the long-term behavioral course of Crohn's disease and to determine predictive factors for phenotypic progression. Methods We conducted a retrospective, descriptive study including patients with Crohn's disease that were managed at our department, over a 9-year period [January 2011 - January 2020]. Patients with less than 2 years of follow-up were excluded. We screened for factors associated with phenotypic progression during follow-up by a univariate study. By binary logistic regression, we sought for factors independently related to phenotypic progression, including variables that had a p <0.2 in univariate study. Results We included 341 patients with a sex ratio of 1.05. The median age at diagnosis of CD was 31 years. Smoking was observed in 36.4% of patients and 16.5% were alcohol users. Forty-four patients (12.9%) had a family history of Inflammatory Bowel Disease and 5.3% had associated autoimmune diseases. The mean BMI of the patients was 20.57 ± 4.5 kg/m². Seventy-six patients were at least overweighted at the time of diagnosis. The disease was classified as ileal, colonic and ileocolic in 150, 86 and 99 patients respectively. The involvement of the upper gastrointestinal (GI) tract was noted in 49 patients (14.36%) and 84 patients (24.6%) had perineal lesions mainly complex fistulas (17.3%). CD was initially classified as inflammatory, stricturing and fistulizing in 71%, 17% and 11% respectively. Phenotypic progression during follow-up was observed in 33 patients (9.6%), finally classifying the disease as inflammatory in 41%, stricturing in 22% and fistulizing in 35% of cases. In univariate study, the factors associated with phenotypic progression were represented by isolated ileal location (p=0.028, OR=2.28), the presence of perineal fistulas (p=0.006, OR=3.07) and hypoalbuminemia at diagnosis of less than 27.94g/L (p=0.035). Extensive ileal involvement and the presence of granuloma on histology were not associated with phenotypic progression. In multivariate study, only initial upper GI tract’s involvement was an independent predictor of phenotypic progression (p=0.024. OR=0.11, IC[0.18-0.75]). Conclusion Our study showed that upper GI tract’s involvement was the main predictor of phenotypic progression in CD.

P013 Role of IL-36RA mutations in Crohn’s disease

Abstract Background The interleukin 36 (IL-36) family consists of three agonists (IL-36α, IL-36β, IL-36γ), that activate the NF-κB pathway and lead to the production of pro-inflammatory cytokines and the natural antagonist (IL-36RA), which inhibits IL-36 signaling. While it is known that IL-36 signaling is important in the skin, it has been only recently reported that IL-36 might play an important role in maintaining gut homeostasis and in the development of fibrosis (Scheibe et al., 2019). Here, we aim to understand how IL-36RA mutations contribute to development and maintenance of intestinal inflammation in Crohn’s disease. Methods By whole-exome sequencing (WES) and subsequently targeted Sanger sequencing we identified a Crohn’s disease (CD) patient with a heterozygous missense mutation in IL-36RA (p.Ser113Leu). To understand how the mutation affects immune cells composition and function, we characterized peripheral blood mononuclear cells (PBMCs) of the patient by mass cytometry and measured cytokine levels in the serum by ELISA. In an available WES dataset of 177 CD patients, 47 ulcerative colitis (UC) patients and 34 healthy donors (HD), we searched for additional patients with IL-36RA mutations. Finally, we overexpressed the identified IL-36RA mutations in HEK cells and produced mutated recombinant proteins to study the effect of the mutations on protein expression and function. Results Our IL-36RA mutation-carrying patient presented with a severe course of Crohn’s disease and consecutive of fibrosis, which was resistant to all commonly used treatment options. In the patient, we detected increased levels of IL-36RA, IL-18 and IL-23 in the serum and an increased frequency of TH17 cells in the blood. These findings could hint towards an over-activation of the IL-36 signaling pathway in the IL-36RA mutated patient. In the available WES data, we identified two more CD patients with IL-36RA mutations (p.Leu133Ile, p.Pro76Leu), indicating that IL-36RA mutations are enriched in CD patients. By overexpressing the three identified mutations in HEK cells, we could demonstrate that two mutations (p.Ser113Leu and p.Pro76Leu) lead to a reduced protein expression. Also, our current data shows that the p.Ser113Leu mutant has a reduced capacity to antagonize IL-36 stimulation. However, further testing is required for the two other IL-36RA mutants. Conclusion Our data suggests that IL-36RA mutations are enriched in Crohn’s disease patients and should be considered as a possible cause for therapy-refractory and fibrotic Crohn’s disease.

P293 Correlation between clinical measures to capture disease burden and prediction of the initial course of Crohn’s disease - findings from a Copenhagen IBD Inception Cohort Study (IBD Prognosis Study)

Abstract Background The initial disease burden of Crohn’s disease (CD) is dissimilar across patients; however, the ability to capture and predict the disease burden at diagnosis is scarcely investigated. The aim of the current study was to describe the initial disease burden of Crohn’s disease. Methods IBD Prognosis Study is an ongoing prospective population-based inception cohort of newly diagnosed patients with CD between May 1st, 2021, and November 1st, 2022, according to the Copenhagen IBD Criteria.1 We defined an indolent disease presentation as no need for CD-related surgery, hospitalization, nor initiation of steroid, immunomodulatory, or biologic therapies within the first 30 days after diagnosis, while a complicated course was defined as the opposite. Results The study included 134 patients with adult-onset CD, of whom approximately one-third (44/134, 33%) had an early indolent course, with 26 patients (19%) not requiring any medication (Tables 1-2). In demographic factor adjusted analyses, a colonic phenotype (adjusted odds ratio (aOR) =4.5 (95% confidence interval (CI) 1.6-15) and a low symptom load measured with Harvey-Bradshaw Index (HBI) <5 (aOR = 3.1 (CI 1.0-10) were independently associated with an indolent course. In contrast, a C-reactive protein (CRP) level higher than 10 mg/L was the only parameter associated with a complicated onset of CD (aOR = 4.7 (CI 2.1-12)). Pearson’s correlation analyses demonstrated a significant, moderate correlation between fecal (F-) calprotectin, CRP, and endoscopic lesions, measured with Simple Endoscopic Score for CD (SES-CD) (Table 3). HBI and the International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) exhibited a significant but weak correlation with CRP. In a sensitivity analysis allowing exposure to anti-inflammatory therapy for only up to seven days, the platelet count, F-calprotectin, and bowel wall thickness measured in IBUS-SAS demonstrated a significant and moderate correlation with SES-CD. The total IBUS-SAS and CRP showed a significant but weak correlation, and other measures included in the IBUS-SAS did not yield significant correlations. Conclusion Preliminary data from the ongoing population-based cohort indicate that one-third of patients with newly diagnosed CD have an early indolent course. This study identified colonic disease location and CRP levels to be associated with the early course, while platelet count, bowel wall thickness, and CRP were correlated with endoscopic lesions at the onset of CD.

P187 Intestinal ultrasound is accurate for detecting intra-abdominal complications in Crohn’s disease: a meta-analysis

Abstract Background The clinical course of Crohn’s disease (CD) is associated with development of complications including strictures and penetrating lesions such as fistulas and abscesses. Close disease monitoring and optimizing therapy can prevent these complications. Intestinal ultrasound (IUS) is a non-invasive cross-sectional imaging method ideal for frequent assessment of disease activity and intra-abdominal complications. In this meta-analysis we provide an updated assessment of the diagnostic accuracy of IUS and its advanced modalities in the detection of intra-abdominal complications in CD compared to endoscopy, MRI/CT, surgery and pathology. Methods We conducted a literature search in Pubmed/MEDLINE and EMBASE databases from 01-01-1970 up to and including 17-10-2022 for studies describing diagnostic accuracy of IUS in adult patients with CD related intra-abdominal complications. Quality of the included studies was assessed with the QUADAS-2 tool. A univariate random-effects model was used to calculate the diagnostic test accuracy variables, including the log diagnostic odds ratio and area under the pooled ROC (AUC for SROC). All data were calculated with 95% confidence intervals (CIs). Chi-squared (χ²) test was used to assess study heterogeneity with p < 0.05 indicating significant heterogeneity. Funnel plots were created to assess publication bias. All meta-analysis were performed using the R-package mada. We calculated pooled sensitivity and specificity in Meta-DiSc. Results We identified 1506 studies of which 68 were used for the systematic review. Twenty-three studies with 3863 patients were included in this meta-analysis with an overall moderate to high risk of bias. In total 6 meta-analyses were performed, both for conventional IUS (B-mode) and oral contrast IUS (SICUS) for diagnosing CD-related complications. Pooled overall log diagnostic odds ratio for strictures, fistulas and inflammatory masses by B-mode IUS were 3.56 (2,90-4.21), 3.84 (3.28-4.41) and 3.97 (3.30-4.64) and the AUC were 0.926, 0.896 and 0.960 respectively. Pooled overall diagnostic odds ratio for the diagnosis of strictures, fistulas and inflammatory masses by SICUS were 4.51 (3.28-5.73), 4.80 (3.46-6.14) and 5.46 (3.61-7.30) and the AUC were 0.955, 0.982 and 0.985, respectively. Significant heterogeneity was seen between studies reporting data on diagnosing strictures by B-mode IUS. Conclusion These results indicate that IUS is an accurate tool for the diagnosis of intra-abdominal complications related to CD. IUS as a non-invasive, point-of-care modality is recommended as the first-line imaging tool if there is a suspicion of CD-related intra-abdominal complications.

Clinical case of atypical course of Crohn’s disease

Crohn’s disease (CD) is a chronic recurrent inflammatory bowel disease with a wide variety of clinical manifestations – from classical gastrointestinal phenotypes to predominance of extraintestinal symptoms. Atypical course of CD is observed relatively often and is manifested with a damage to almost all body systems, including hepatobiliary, immune, hematopoietic, cardiovascular, nervous, as well as eyes, skin, lungs and kidneys. Atypical manifestation often precedes intestinal, making diagnosis difficult. The presence of various clinical manifestations of CD, often an atypical course, as well as the absence of standardized diagnostic criteria can be an obstacle for physicians in the timely detection of the disease and effective treatment. Aim: to describe a clinical case of a diagnostically difficult patient of our clinic with an atypical course of CD and complications incompatible with life; highlight the problem of monitoring and possible solutions. Results. In the presented clinical case the patient with an atypical course of CD, with the prevailing displays of defeat of nervous and vascular systems is described. During hospitalization, a full range of diagnostic tests was performed, consultations with related specialists were obtained, but no direct data of inflammatory bowel disease were found. At the same time, the impossibility of performing a colonoscopy with a biopsy, due to the severity of the patient’s condition, delayed the timely diagnosis of CD and contributed to the development of complications incompatible with life. The diagnosis was made posthumously. The patient died as a result of intoxication due to the development of complications of CD – perforation of the intestine, intestinal abscess, development of peritonitis, septicemia. Conclusions. In the described clinical case CD is considered as a complex interdisciplinary problem, and emphasizes the importance of doctor’s awareness of the variants of atypical manifestations and course of inflammatory bowel disease, methods for their assessment and ways of effective management. This case also presents the latest epidemiological data on the prevalence of atypical manifestations of CD, identifies key areas of diagnostic search in case of a difficult patient.

TREATMENT PATTERNS OF PEDIATRIC AND ADULT PATIENTS WITH CROHN’S DISEASE

Abstract OBJECTIVE Crohn’s Disease (CD) is a chronic disease characterized by transmural inflammation and may involve any portion of the gastrointestinal tract. Children with CD are more likely to present with extensive disease and have more rapid clinical progression than adults.1 This study aimed to compare the treatment patterns between pediatric and adult patients with CD. METHODS This is a retrospective claims-based study using the Merative L.P Marketscan® Research database (January 1, 2014 through December 31, 2021). Pediatric (≤ 17 years) and adult (≥ 18 years) patients with a CD diagnosis code and ≥12 months continuous enrollment with medical and pharmacy benefits before and after the first diagnosis of CD (index date) were included. Descriptive statistics described treatment patterns for pediatric and adult CD cohorts. RESULTS There were 2810 pediatric and 25,934 adult patients with CD included in the analysis. The mean (SD) ages in years for pediatric and adult patients were 13.5 (3.1) and 46.0 (15.9), respectively (Table 1). While females (53.6%) were slightly predominant in the adult cohort, there was a numerically higher proportion of males (59.5%) in the pediatric cohort. The most common monotherapy in children was corticosteroids (22.9%) or biologics (34.9%), while adult monotherapy was primarily corticosteroids (29.6%) or aminosalicylates (32.9%). The time from diagnosis to initiation of corticosteroids and immunomodulators was numerically shorter in children than adults (median days between index and corticosteroids or immunomodulators initiations: 14 vs. 54 and 26 vs 34, respectively). Combination therapies, including biologics and/or immunomodulators with corticosteroids, were numerically more often used in children than in adults (32.4% vs 15.0%). Among all biologic users, adalimumab (18.1%) was numerically more commonly prescribed for adults while infliximab (38.2%) was numerically more common in children. Pediatric patients showed numerically higher 6-month persistence from initiation of a biologic when compared with adult patients (persistence rate: 94.6% vs 87.2%; Table 2). Notably, a small proportion of pediatric patients were on either ustekinumab or vedolizumab (0.1% and 0.2%, respectively) as add-on therapy despite those medications not being currently approved in this population. CONCLUSION The study suggests that children with newly diagnosed CD receive combination therapies more frequently than adults. This may be related to greater disease severity in children. Children treated with biologics had numerically greater persistence, suggesting similar efficacy compared to adults. REFERENCE 1. Freeman H.J., Natural history and long-term clinical course of Crohn’s disease. World J Gastroenterol. 2014 Jan 7;20(1):31-6.

Latent course of Crohn’s disease: the role of tomographic imaging in diagnosis

Crohns disease with localization in the upper gastrointestinal tract, terminal ileum, or colon is diagnosed based on visualization of the lesion area using endoscopic methods and histological examination. In cases of damage to the small intestine, when endoscopy methods are not informative enough and the use of videocapsular endoscopy has a number of contraindications, it is advised to use radiation diagnostic methods, such as multispiral computed tomography and/or magnetic resonance enterography, to make a diagnosis.
 We present a clinical case of ambiguous clinical manifestations of Crohns disease with small intestine and rectal involvement. Tomographic imaging was used to confirm the diagnosis. A 44-year-old patient presented with complaints of non-pronounced abdominal pain, dyspepsia. The lab panel showed indirect signs of malabsorption, an increase in fecal calprotectin. An endoscopic examination with histological verification revealed a picture of proctitis. After performing computed tomography and/or magnetic resonance enterography multiple lesions of the small intestine were revealed. This clinical case demonstrates an atypical clinical picture of Crohns disease with jejunal, iliac, and rectal lesions.
 The patient had no characteristic complaints; the results of endoscopic and morphological studies were not informative. Imaging by means of computed and magnetic resonance tomography has played a crucial role in the diagnosis and successful treatment.

Immunohistochemical features lymphoid tissue colonic mucosa of children with different phenotypic variants of Crohn’s disease

The aim of the study was to determine the immunohistochemical features of the lymphoid tissue of the mucous membrane (MM) of the colon in children with different course of Crohn’s disease. Methods: the results of IHC and morphometric analyzes of colonic colony of children with Crohn’s disease of uncomplicated and complicated course are presented. Results: An important role of the ratio and distribution of subpopulations of T-lymphocytes of CO and lymphoid clusters in children with Crohn’s disease is shown, depending on the phenotypic variant of the course of the disease. In children with a favorable prognosis of Crohn’s disease, the immunoregulatory index (IRI) was close to normal with a predominance of the CD4 + T-lymphocyte population against the background of a moderately increased number of CD8 + cells and B-lymphocytes. IRI of children of the II group was significantly increased due to a sharp increase in CD4 +, CD8 + T-lymphocytes and CD19 + B-lymphocyte link. Conclusion: A high level of IRI with a pronounced disproportion of intrapopulation T-lymphocytes is combined with an unfavorable course of the disease. For children with uncomplicated course of the disease, a minimal mismatch in the intrapopulation T-lymphocyte system is characteristic against the background of increased IRI.

Relationships of circulating CD4+ T cell subsets and cytokines with the risk of relapse in patients with Crohn's disease.

We aimed to analyze circulating CD4+ T cell subsets and cytokines during the course of Crohn's disease (CD). CD4+ T cell subsets, ultrasensitive C-reactive protein (usCRP), and various serum cytokines (IL-6, IL-8, IL-10, IL-13, IL-17A, IL-23, TNFα, IFNγ, and TGFβ) were prospectively monitored every 3 months for 1 year, using multicolor flow cytometry and an ultrasensitive Erenna method in CD patients in remission at inclusion. Relapse occurred in 35 out of the 113 consecutive patients (31%). For patients in remission within 4 months prior to relapse and at the time of relapse, there was no significant difference in Th1, Th17, Treg, and double-positive CD4+ T cell subsets co-expressing either IFNγ and FOXP3, IL-17A and FOXP3, or IFNγ and IL-17A. On the contrary, in patients who remained in remission, the mean frequency and number of double-positive IL-17A+FOXP3+ CD4+ T cells and the level of usCRP were significantly higher (p ≤ 0.01) 1 to 4 months prior to relapse. At the time of relapse, only the IL-6 and usCRP levels were significantly higher (p ≤ 0.001) compared with those patients in remission. On multivariate analysis, a high number of double-positive IL-17A+FOXP3+ CD4+ T cells (≥1.4 cells/mm3) and elevated serum usCRP (≥3.44 mg/L) were two independent factors associated with risk of relapse. Detection of circulating double-positive FOXP3+IL-17A+ CD4+ T cell subsets supports that T cell plasticity may reflect the inflammatory context of Crohn's disease. Whether this subset contributes to the pathogenesis of CD relapse needs further studies.

Evaluation of Fecal Calprotectin, Serum C-Reactive Protein, Erythrocyte Sedimentation Rate, Seromucoid and Procalcitonin in the Diagnostics and Monitoring of Crohn's Disease in Children.

Background: The development of diagnostic and monitoring algorithms for Crohn’s disease based on non-invasive methods is of particular importance in children and is the subject of many studies. Objectives: Evaluate the usefulness of fecal calprotectin, serum C-reactive protein, erythrocyte sedimentation rate, seromucoid and procalcitonin in the differential diagnosis of non-inflammatory gastrointestinal tract diseases and Crohn’s disease in children and their usefulness in determining the phenotype of Crohn’s disease. Material and methods: Forty-seven children with non-inflammatory gastrointestinal tract diseases and fifty-four with Crohn’s disease were enrolled. Clinical and endoscopic activity was evaluated based on the Pediatric Crohn’s Disease Activity Index (PCDAI) and the Simple Endoscopic Score for Crohn’s Disease (SES-CD). Results: Fecal calprotectin, C-reactive protein, erythrocyte sedimentation rate and seromucoid were significantly higher in children with Crohn’s disease than in controls (p < 0.001). Fecal calprotectin correlated with clinical and endoscopic activity according to the Pediatric Crohn’s Disease Activity Index (r = 0.338; p = 0.012) and the Simple Endoscopic Score for Crohn’s Disease (r = 0.428; p = 0.001). Non-invasive biomarkers did not correlate with the location and clinical manifestation of Crohn’s disease. Conclusions: Fecal calprotectin, C-reactive protein, erythrocyte sedimentation rate and seromucoid are useful in the differentiation of Crohn’s disease from non-inflammatory gastrointestinal tract diseases in children and in monitoring the clinical course of Crohn’s disease, but not in evaluating activity and phenotype of the disease.

Clinical case of a new coronavirus infection in a patient with severe Crohn’s disease

The article discusses clinical case of a new coronavirus infection in a patient with a severe course of Crohn’s disease (CD) in a long anamnesis. The issues of the complexity of diagnosing Crohn’s disease in an atypical course (gastroduodenal form), the algorithm for selecting basic therapy for a severe course of the disease are considered. The second problem in the article is the tactics of managing patients with COVID-19 against the background of combined basic immunosuppressive therapy for autoimmune diseases.

S952 The Effect of Commonly Prescribed Renin-Angiotensin-Aldosterone System Blocking Agents on the 5- and 10-year Disease Course of Crohn’s Disease Patients With Hypertension

S952 The Effect of Commonly Prescribed Renin-Angiotensin-Aldosterone System Blocking Agents on the 5- and 10-year Disease Course of Crohn’s Disease Patients With Hypertension

КЛИНИЧЕСКОЕ НАБЛЮДЕНИЕ СПОНТАННОЙ ЭМФИЗЕМЫ МНОЖЕСТВЕННОЙ ЛОКАЛИЗАЦИИ У РЕБЕНКА С ТЯЖЕЛЫМ ТЕЧЕНИЕМ БОЛЕЗНИ КРОНА

The authors present a clinical case of asymptomatic spontaneous emphysema in a child with a severe course of Crohn's disease, which is a type of inflammatory bowel disease (IBD). The emphysema was diagnosed on the occasion, during the CT scan prior to the start of the immunobiological (Anti-TNF-α) therapy. The etiopathogenetic causes for this condition, its diagnosis and relationship with the severity of the underlying disease are discussed in the paper. A retrospective analysis of the prevalence of this pathology is also given. Conclusion: in the absence of an obvious cause (perforation), the pneumomediastinum can be explained by retroperitoneal air leak through microperforations in severe colitis, which is an unfavorable prognostic criterion for a severe course of the Crohn's disease and increases the risk of surgical treatment, colectomy as usual.

Residential treatment exclusively for smoking cessation in patients with Crohn’s disease: Results from a pilot study

INTRODUCTIONCigarette smoking is a risk factor for the induction and severity of the course of Crohn’s disease (CD). Hospital admission may be required for treatment of the disease but is generally not available solely for smoking cessation. Outpatient group therapy is readily available, however long-term quit rates are limited. Residential treatment for smoking cessation may offer a more intense contact between patient and therapist, and may result in higher abstinence rates in a sensitive group of patients. The objective of this pilot study is to evaluate the feasibility of implementing a residential program with hospital admission, exclusively for smoking cessation for patients suffering from CD.METHODSTwelve eligible smokers suffering from CD were recruited for a 9-day inpatient smoking cessation treatment. Treatment consisted of single and group behavioral therapy together with supportive measures such as exercise therapy, relaxation techniques or nutritional counselling. Nicotine replacement therapy or prescription medication was offered according to the Fagerström test for nicotine dependence (FTND) score and treatment guidelines. Quit rates were assessed by CO-testing during hospital treatment and by follow-up calls 6 months after discharge.RESULTSAll recruited participants arrived on time for treatment and collectively stopped smoking on the 2nd day after admission. All participants completed the therapy process without relapse and left the hospital smoke-free (100% quit rate on discharge, CO monitored). Self-reported abstinence rates after 6 months were 72.7% for continuous abstinence and 81.8% for 7-day point prevalence abstinence.CONCLUSIONSResidential treatment exclusively for smoking cessation is feasible and efficient and may be a valuable treatment option for patients suffering from CD.

Mediterranean diet diminishes the effects of Crohn's disease and improves its parameters: A systematic review.

The pathogenesis and clinical course of Crohn's disease (CD) is influenced by diet. Mediterranean Diet (MD) helps Crohn's patients through many mechanisms. This study aimed to evaluate the effect of the MD on CD patients and to evaluate such effect on body parameters. PubMed, Science Direct, Web of Science, MEDLINE and Cochrane central library were searched for MD and CD from 2010 to 2020. Included studies met the following criteria: (1) male and female adults (18-75 years) with a confirmed diagnosis of CD; (2) MD as an intervention; (3) original interventional Trial, Cross-Sectional Analysis, or Prospective Cohort Studies. Five studies were included, involving 83,564 participants. A small number of patients with CD fulfilled the P-MDS criteria, the overall scores were low, 4.7 and 4.5 for females and males respectively. Patients with an inactive disease whose adherence to MD was greater, the MD score was negatively correlated with disease activity (p <0.001) and positively with IBDQ (p = 0.008). Twenty-seven percent had a prevalence of impaired adherence to a MD (mMED score = 0-2), giving such a population a risk attributed to 12% for the later CD. Seventy-point reduction in CDAI + decreased fecal CRP / calprotectin, calprotectin <250 mcg/gm or >50% decrease from baseline and hsCRP < 5 mg/L or >50% from baseline. MD showed anti-inflammatory properties. Adherence to MD was associated with improvement in CD patients and negatively correlated with the disease activity, in addition to a lower risk of developing CD later in life.

Трудности дифференциальной диагностики воспалительных заболеваний кишечника

The clinical case of a complicated course of Crohn's disease (CD) in an elderly patient is presented. The article reflects thefeatures of the diagnosis, tactics of conservative and surgical treatment of CD. Timely diagnosis of colorectal cancer (CRC) in an elderly patient with CD also demonstrated.