Inflammatory bowel disease evolution in the past two decades: a chronological multinational study.

Background: The multifactorial nature of inflammatory bowel disease (IBD), which manifests differently in individuals creates a need for a better understanding of the behaviour and pattern of the disease due to environmental factors. The current study aimed to study the changes in IBD behaviour, presentation, and characteristics in patients over the past two decades with a goal of improving patients' diagnosis, management and outcomes. Methods: During a 6-month period (1/02/2022-30/07/2022), the information of patients with IBD who attended IBD outpatient clinics of 11 referral centre's in six countries was collected, and based on the first time of diagnosis with IBD, they were allocated as group A (those who were diagnosed more than 15 years ago), group B (those who were diagnosed with IBD between 5 and 15 years ago) and group C (IBD cases who diagnosed in recent 5 years). Then the most prevalent subtypes and characters of the disease are evaluated and compared to make clear if the presenting pattern and behaviour of the disease has changed in the last 2 decades. Findings: Overall 1430 patients with IBD including 1207 patients with ulcerative colitis (UC) (84.5%) and 205 patients with Crohn's disease (CD; 14.3%) included. Mean age of participants at the first time of diagnosis with IBD was 30 years. The extra-intestinal involvement of IBD in groups A and B was more prevalent in comparison with group C. Most of those in groups A & B had academic education but in group C, the most prevalent educational status was high school or diploma (P = 0.012). In contrast to groups A and B, the relative prevalence of medium socioeconomic level in group C had decreased (65%). Relative prevalence of UC subtypes was similar among groups A and B (extensive colitis as most prevalent) but in group C, the most prevalent subtype is left side colitis (38.17%). The most prevalent subtype of CD in groups A and B was ileocolic involvement while in group C, upper GI involvement is significantly increased. The rate of food sensitivity among groups A and B was more than group C (P = 0.00001). The relative prevalence of patients with no flare has increased with a steady slope (P < 0.00001). Relative prevalence of presenting symptoms among patients with UC in group C differs and nowadays the rate abdominal pain (70.7%) and bloating (43.9%) have increased and frequency of diarrhoea (67.4%) has decreased. Interpretation: In the recent 5 years, the pattern of UC presentation has changed. The rate of upper GI involvement in CD and relative prevalence of patients with no disease flare increased and the rate of extra intestinal involvement decreased. Funding: None.

The effect of selenium supplementation on disease activity and immune-inflammatory biomarkers in patients with mild-to-moderate ulcerative colitis: a randomized, double-blind, placebo-controlled clinical trial.

PURPOSE: Selenium (Se) supplementation may help reduce inflammation and disease activity in ulcerative colitis (UC) patients. We investigated the therapeutic effects of Se administration in cases with mild-to-moderate active UC. METHODS: A multicenter, double-blind, randomized clinical trial (RCT) was conducted on 100 cases with active mild-to-moderate UC. The patients were randomly allocated to be given an oral selenomethionine capsule (200 mcg/day, n = 50) or a placebo capsule (n = 50) for 10 weeks. The primary outcome was defined as disease activity via the Simple Clinical Colitis Activity Index (SCCAI), and secondary outcomes were measured at the end of the study. RESULTS: After 10 weeks, the SCCAI score's mean was reduced in the Se group (P < 0.001). At the end of the intervention, clinical improvement (decline of 3 ≥ score from baseline score) was observed in 19 patients (38%) of the Se group and 3 patients (6%) of the placebo group. The patients with clinical remission (defined as SCCAI ≤ 2) were assigned in the Se group (P = 0.014). The Se group's quality of life and Se serum levels were enhanced at the end of the study (P < 0/001). In the Se group, the mean concentration of interleukin-17 decreased (P < 0/001). However, the levels of interleukin-10 showed no considerable change between the two groups in the 10th week (P = 0.23). CONCLUSION: Se supplementation as add-on therapy with medical management induced remission and improved the quality of life in patients with active mild-to-moderate UC. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: IRCT20091114002709N51; 2020-04-13.

IS DAIRY FOODS RESTRICTION MANDATORY FOR INFLAMMATORY BOWEL DISEASE PATIENTS: A MULTINATIONAL CROSS-SECTIONAL STUDY.

BACKGROUND: The role of dairy foods in inflammatory bowel disease (IBD) has been controversial and it is debatable if patients with IBD should avoid milk and dairy products or not, as well as the relationship between these foods and symptoms among those population. OBJECTIVE: This multi centric cross-sectional study designed to evaluate if it is really necessary to deprive IBD patients from consumption of dairy foods. METHODS: A multicenter study with 12 gastroenterology referral centers in four countries was designed to evaluate gastrointestinal (GI) symptoms after consumption of dairy foods from all outpatients with IBD during 6 months and to compare patients treated at the same centers without IBD (non IBD cases). RESULTS: Overall 1888 cases included (872 IBD patients and 1016 non IBD cases). 56.6% of participants were female with average age of 40.1 years. Racially 79.8% participants were Caucasians and originally they were citizens of 10 countries. Relative prevalence of IBD was higher in Africans and Indians and the most frequent prevalence of dairy foods intolerance was seen in Asians. Among IBD patients, 571 cases diagnosed as ulcerative colitis and 189 participants as Crohn's disease. Average duration of diagnosis as IBD was 6.8 years (from 2 months to 35 years). The most prevalent GI symptoms after consumption of all the dairy foods were bloating and abdominal pain. Totally, intolerance of dairy foods and lactase deficiency was more prevalent among IBD patients in comparison with non IBD cases (65.5% vs 46.1%, P=0.0001). But the rate of GI complains among IBD patients who had not any family history of lactase deficiency, history of food sensitivity or both were 59.91%, 52.87% & 50.33% respectively and similar to non IBD cases (P=0.68, 0.98 & 0.99 respectively). CONCLUSION: The rate of dairy foods intolerance among IBD patients without family history of lactase deficiency or history of food sensitivity is similar to non IBD cases and probably there is no reason to deprive them from this important source of dietary calcium, vitamin D and other nutrients.

A restrição de alimentos lácteos é obrigatória para pacientes com doença inflamatória intestinal? Estudo transversal multinacional / Is dairy foods restriction mandatory for inflammatory bowel disease patients: a multinational cross-sectional study

ABSTRACT Background: The role of dairy foods in inflammatory bowel disease (IBD) has been controversial and it is debatable if patients with IBD should avoid milk and dairy products or not, as well as the relationship between these foods and symptoms among those population. Objective: This multi centric cross-sectional study designed to evaluate if it is really necessary to deprive IBD patients from consumption of dairy foods. Methods: A multicenter study with 12 gastroenterology referral centers in four countries was designed to evaluate gastrointestinal (GI) symptoms after consumption of dairy foods from all outpatients with IBD during 6 months and to compare patients treated at the same centers without IBD (non IBD cases). Results: Overall 1888 cases included (872 IBD patients and 1016 non IBD cases). 56.6% of participants were female with average age of 40.1 years. Racially 79.8% participants were Caucasians and originally they were citizens of 10 countries. Relative prevalence of IBD was higher in Africans and Indians and the most frequent prevalence of dairy foods intolerance was seen in Asians. Among IBD patients, 571 cases diagnosed as ulcerative colitis and 189 participants as Crohn's disease. Average duration of diagnosis as IBD was 6.8 years (from 2 months to 35 years). The most prevalent GI symptoms after consumption of all the dairy foods were bloating and abdominal pain. Totally, intolerance of dairy foods and lactase deficiency was more prevalent among IBD patients in comparison with non IBD cases (65.5% vs 46.1%, P=0.0001). But the rate of GI complains among IBD patients who had not any family history of lactase deficiency, history of food sensitivity or both were 59.91%, 52.87% & 50.33% respectively and similar to non IBD cases (P=0.68, 0.98 & 0.99 respectively). Conclusion: The rate of dairy foods intolerance among IBD patients without family history of lactase deficiency or history of food sensitivity is similar to non IBD cases and probably there is no reason to deprive them from this important source of dietary calcium, vitamin D and other nutrients.

RESUMO Contexto: O papel dos alimentos lácteos na doença inflamatória intestinal (DII) tem sido controverso e é discutível se os pacientes com DII devem ou não evitar leite e laticínios, bem como a relação entre esses alimentos e sintomas nesta população. Objetivo: Estudo transversal multicêntrico foi projetado para avaliar se é realmente necessário privar os pacientes com DII do consumo desta classe de alimentos. Métodos: Um estudo multicêntrico com 12 centros de referência em gastroenterologia de quatro países foi projetado para avaliar sintomas gastrointestinais após o consumo de alimentos lácteos em todos os ambulatórios de DII durante seis meses e comparar pacientes tratados nos mesmos centros sem DII. Resultados: No total, foram incluídos 1888 casos (872 pacientes com DII e 1016 casos sem DII. 56,6% dos participantes eram do sexo feminino com idade média de 40,1 anos. 79,8% dos participantes eram caucasianos e originalmente eram cidadãos de 10 países. A prevalência relativa de DII foi maior em africanos e indianos e a prevalência mais frequente de intolerância a alimentos lácteos observada nos asiáticos. Entre os pacientes com DII, 571 casos foram diagnosticados como colite ulcerativa e 189 participantes como doença de Crohn. A duração média do diagnóstico como DII foi de 6,8 anos (de 2 meses a 35 anos). Os sintomas de gastrointestinais mais prevalentes após o consumo de todos os alimentos lácteos foram inchaço e dor abdominal. No total, a intolerância aos alimentos lácteos e a deficiência de lactase foi mais prevalente entre os pacientes com DII em comparação com os casos sem DII (65,5% vs 46,1%, P=0,0001). A taxa de queixas gastrointestinais entre os pacientes com DII que não tinham histórico familiar de deficiência de lactase, histórico de sensibilidade alimentar ou ambos foram de 59,91%, 52,87% e 50,33% respectivamente e semelhantes aos casos sem DII (P=0,68, 0,98 e 0,99, respectivamente). Conclusão: A taxa de intolerância de alimentos lácteos entre pacientes com DII sem histórico familiar de deficiência de lactase ou histórico de sensibilidade alimentar é semelhante aos casos sem DII e provavelmente não há razão para privá-los dessa importante fonte de cálcio dietético, vitamina D e outros nutrientes.

Effect of Selenium Supplementation on Expression of SIRT1 and PGC-1α Genes in Ulcerative Colitis Patients: a Double Blind Randomized Clinical Trial.

Selenium (Se) supplementation may decrease the severity of ulcerative colitis (UC) through the activation of genes responsible for immune modulation. The present research was aimed to assess the effect of Se supplementation on the expression of silent information regulator 1 (SIRT1) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) in UC patients. In a double-blind randomized parallel clinical trial, 100 patients with mild-to-moderate active UC met inclusion criteria and divided into 2 groups of treatment (50 patients received selenomethionine [200 µg daily]) and placebo (50 patients received placebo [1 capsule daily]) for 10 weeks. The expression rates of SIRT1 and PGC-1α were examined in the peripheral blood mononuclear cell (PBMC) using the real-time polymerase chain reaction. There was no considerable difference in the mean of baseline demographic and clinical characteristics between groups. Also, there were no significant differences in total energy intake, macronutrients, and micronutrients between groups. The SIRT1 gene expression in the Se group was significantly increased compared to the placebo (p < 0.001). An increase in the expression of the PGC-1α gene in the Se group was not statistically significant. It seems that Se supplementation caused a significant decrease in the inflammatory response of the colon by a significant increase in the expression of the SIRT1 gene.

Does the inflammatory potential of diet affect disease activity in patients with inflammatory bowel disease?

BACKGROUND: Diet is an important modulator of inflammation, which is associated with inflammatory bowel disease (IBD). In this study, we examined whether the inflammatory properties of diets are associated with disease activity in patients with IBD. METHODS: A cross-sectional study was conducted on 143 IBD patients, including 32 patients with Crohn's disease (CD) and 111 patients with ulcerative colitis (UC). Dietary intakes were assessed by a valid 168-item food frequency questionnaire (FFQ). The inflammatory potential of the diet was assessed by calculating the two scores of Dietary Inflammatory Index (DII®), and the Empirical Dietary Inflammatory Pattern (EDIP), and CD and UC disease activity were determined by the Crohn's disease activity index (CDAI) and the Mayo score, respectively. Associations of the inflammatory indices as median and as tertiles with disease activity were analyzed using logistic regression in a univariate model and after adjusting for total energy intake (continuous), type of disease (CD and UC) and drug consumption (no drugs, single drug, and multiple drugs). RESULTS: Sixty-four IBD patients (44.8%) in this study had active disease.The DII® score and the EDIP did not differ significantly between active and inactive patients (- 1.45 ± 1.04 vs.- 1.20 ± 1.24; 0.56 ± 0.22 vs. 0.53 ± 0.28, respectively). After adjusting for energy intake, drug use, and IBD type, the odds (95%CIs) of active disease among patients in tertile 3 compared to those in tertile 1 were 0.84 (0.32-2.17) for DII and 1.50 (0.61-3.72) for EDIP; neither of which were statistically significantly different from the rates in tertile 1. CONCLUSIONS: Although point estimates were in the expected direction of increased risk, the inflammatory potential of diet, assessed using DII or EDIP, was not associated with severity of disease in IBD patients. Whether diet-related inflammation affects disease activity in patients with IBD deserves further investigations.

Resveratrol Supplementation and Oxidative/Anti-Oxidative Status in Patients with Ulcerative Colitis: A Randomized, Double-Blind, Placebo-controlled Pilot Study.

BACKGROUND AND AIMS: Oxidative stress is involved in both pathogenesis and exacerbation of ulcerative colitis (UC). This study was designed to evaluate whether resveratrol, an excellent anti-oxidant agent, can help in treatment of UC and its related oxidative stress. METHODS AND RESULTS: Fifty six patients with active mild to moderate disease were randomized to receive either 500 mg/day resveratrol capsules or the same amount of placebo for 6 weeks. Before and after the intervention, disease activity, quality of life, and oxidative stress were assessed using the Simple Clinical Colitis Activity Index Questionnaire (SCCAIQ), Inflammatory Bowel Disease Questionnaire-9 (IBDQ-9), and serum level of malondialdehyde (MDA), superoxide dismutase (SOD), and total anti-oxidant capacity (TAC), respectively. Serum SOD (122.28 ± 11.55 to 125.77 ± 10.97) and TAC (9.87 ± 1.51-11.97 ± 1.61) increased, whereas serum MDA (5.62 ± 1.18-3.42 ± 1.01) decreased significantly in resveratrol group (p <0.001). Moreover, resveratrol supplementation significantly decreased disease activity and increased the quality of life (p <0.001). CONCLUSION: Our data indicate that 500 mg/day resveratrol supplementation can improve the disease activity and quality of life in patients with UC at least partially through reduction of oxidative stress. Further studies are needed to determine the optimal dosage of supplementation for these patients.

Anti-Inflammatory Effects of Resveratrol in Patients with Ulcerative Colitis: A Randomized, Double-Blind, Placebo-controlled Pilot Study.

BACKGROUND AND AIMS: Ulcerative colitis (UC) is a chronic idiopathic inflammatory disease in which reducing pro-inflammatory and/or increasing anti-inflammatory molecules is the mainstay of treatment. The aim of this study was to evaluate the effects of supplementation with resveratrol as an antiinflammatory and antioxidant agent on inflammation and quality of life in patients with active UC. METHODS AND RESULTS: In this randomized, double-blind, placebo-controlled study, 50 eligible patients with active mild to moderate UC were supplemented with either a 500-mg resveratrol or placebo capsule for 6 weeks. Serum inflammatory markers, activity of NF-κB in peripheral blood mononuclear cells (PBMC) and quality of life were assessed at baseline and at the end of the study. Resveratrol supplementation led to a significant reduction in plasma levels of TNF-α (19.70 ± 12.80 to 17.20 ± 10.09 pg/mL) and hs-CRP (4764.25 ± 2260.48 to 2584.50 ± 1792.80 ng/mL) and activity of NF-κB in PBMCs (0.19 ± 0.05 to 0.10 ± 0.04 OD) (p <0.001), whereas there were no significant changes of these factors in placebo group. Also, the score of inflammatory bowel disease questionnaire -9 (IBDQ-9) increased, whereas the clinical colitis activity index score decreased significantly in the resveratrol group (32.72 ± 7.52 to 47.64 ± 8.59) (p <0.001) and when compared with the placebo group (35.54 ± 9.50 to 41.08 ± 6.59) (p <0.001). CONCLUSION: Our results indicate that 6 weeks supplementation with 500 mg resveratrol can improve quality of life and disease clinical colitis activity at least partially through inflammation reduction in patients with UC. Whether these effects will be continued in longer duration of treatment remains to be determined.

Assessing the role of the RND efflux pump in metronidazole resistance of Helicobacter pylori by RT-PCR assay.

INTRODUCTION: Metronidazole is a significant antibiotic used for eradication of Helicobacter pylori infections and it is of notice that metronidazole-resistant clinical isolates have been found in high rates worldwide. While the RND family of efflux pumps plays a central role in drug resistance among Gram-negative bacteria, this is questionable for H. pylori. METHODOLOGY: To understand whether TolC homologues of RND pumps contribute to metronidazole resistance in H. pylori isolates, expression of four TolC homologous genes of five resistant clinical isolates exposed to varying concentrations of metronidazole were evaluated by RT-PCR and transcriptional analysis. RESULTS: The results indicate that excess amounts of metronidazole are able to increase the expression level of these genes at the transcriptional stage. CONCLUSIONS: Therefore, it may be hypothesized that use of metronidazole in H. pyori infection can induce metronidazole resistance. Furthermore, the RND family of efflux pumps may contribute to metronidazole resistance in clinical isolates of H. pylori.

Evaluation of a new antigen for diagnosis of Helicobacter pylori infection in stool of adult and children.

BACKGROUND: Nowadays, there is an increasing interest in noninvasive methods to diagnose Helicobacter pylori infection. Indeed, they can profitably replace endoscopy in predicting the diagnosis. The stool antigen test for H. pylori is a noninvasive immunoassay to diagnose active infection with this bacterium in human fecal samples. The aim of this study was detection of alkyl hydroperoxide reductase protein (AhpC) antigen by immunoblotting in stool samples for diagnosis of H. pylori. MATERIALS AND METHODS: Chromosomal DNA from H. pylori was isolated. AhpC gene was amplified by PCR, These amplicons were cloned into pTZ57R/T cloning vector then subcloned into pQE30 expression vector and overexpressed using isopropyl-beta-D-thiogalactopyranoside in E. coli M15. AhpC protein was purified by affinity chromatography. Rabbits were immunized with the purified AhpC protein for the production of antibodies. To determine the accuracy of the test for diagnosing H. pylori infection from stool, we evaluated 84 patients (6-81 years old) using Western blot analysis by rabbit anti-AhpC antibody. Positive rapid urease test on biopsy samples was considered as the gold standard. RESULTS: AhpC gene was overexpressed, and AhpC protein was purified. Rabbit anti-AhpC antibody produced after immunization with the purified AhpC protein. By immunoblotting, we detected AhpC protein in the positive stool samples. The test showed a 83.3% sensitivity (95% CI: 69.8-92.5%) and a 91.7% specificity (95% CI: 77.5-98.2). Among the children, the sensitivity was 88.2% (95% CI: 63.6-98.5) and the specificity was 100% (95% CI: 69.2-100); in adults, the sensitivity and specificity were 80.6% (95% CI: 62.5-92.5) and 88.5% (95% CI: 69.8-97.6), respectively. CONCLUSIONS: Using of AhpC antigen for diagnosis of H. pylori infection is a useful noninvasive method, accurate in adolescents and children, and can be used for the development of a stool antigen detection kit for H. pylori.

A decision tree-based approach for determining low bone mineral density in inflammatory bowel disease using WEKA software.

BACKGROUND: Decision tree classification is a standard machine learning technique that has been used for a wide range of applications. Patients with inflammatory bowel disease (IBD) are at increased risk of developing low bone mineral density (BMD). This study aimed at developing a new approach to select truly affected IBD patients who are indicated for densitometry, hence, subjecting fewer patients for bone densitometry and reducing expenses. MATERIALS AND METHODS: Simple decision trees have been developed by means of WEKA (Waikato Environment for Knowledge Analysis) package of machine learning algorithms to predict factors influencing the bone density among IBD patients. The BMD status was the outcome variable whereas age, sex, duration of disease, smoking status, corticosteroid use, oral contraceptive use, calcium or vitamin D supplementation, menstruation, milk abstinence, BMI, and levels of calcium, phosphorous, alkaline phosphatase, and 25-OH vitamin D were all attributes. RESULTS: Testing showed the decision trees to have sensitivities of 65.7-82.8%, specificities of 95.2-96.3%, accuracies of 86.2-89.8%, and Matthews correlation coefficients of 0.68-0.79. Smoking status was the most significant node (root) for ulcerative colitis and IBD-associated trees whereas calcium status was the root of Crohn's disease patients' decision tree. CONCLUSION: BD specialists could use such decision trees to reduce substantially the number of patients referred for bone densitometry and potentially save resources.

Immunogenicity of recombinant hepatitis B virus vaccine in patients with and without chronic hepatitis C virus infection: a case-control study.

AIM: To compare the response of standard hepatitis B virus (HBV) vaccination between patients with chronic hepatitis C virus (HCV) infection and healthy individuals. METHODS: This is a prospective case-control study. A total of 38 patients with chronic HCV infection and 40 healthy controls were included. Vaccination was performed by injection of 20 microg recombinant HBsAg into the deltoid muscle at mo 0, 1 and 6. Anti-HBs concentration was determined 3 mo after the last dose and compared between the two groups. The response pattern was characterized as (1) high-response when the anti-HBs antibody titer was > 100 IU/L, (2) low-response when the titer was 10-100 IU/L and (3) no-response when the titer was < 10 IU/L. RESULTS: In the patient group, there were 10/38 (26.3%) non-responders, 8/38 (21.1%) low-responders and 20/38 (52.6%) high-responders. The corresponding values in the control group were 2/40 (5.0%), 7/40 (17.5%) and 31/40 (77.5%), respectively. The response pattern was statistically different between the two groups. In multivariate analysis, smoking was a significant confounder, while HCV infection lost its significant correlation with lower antibody response. CONCLUSION: Patients with chronic HCV infection tend to respond weakly to HBV vaccination compared to healthy individuals, though this correlation is not independent according to multivariate analysis.

Clinical course of ulcerative colitis in patients with and without primary sclerosing cholangitis.

BACKGROUND AND AIM: We noticed in our practice that patients with ulcerative colitis (UC) who have developed primary sclerosing cholangitis (PSC) experience a milder course of colonic disease. Our objective in this study was to define whether or not there is any difference between UC activity and its course in patients with and without PSC. METHODS: Nineteen patients with UC and PSC (eight male, mean age 25 years) were enrolled. To every patient with UC and PSC, three patients with UC alone (total of 57 patients, 28 male, mean age 24 years) matched for age at onset, duration of the disease and extension of colonic disease were selected as the control group. We used number of hospitalizations due to activity of UC and number of short corticosteroid administrations in various years of follow-up as variables indicating course and severity of the colonic disease in this period. For comparing trends of UC activity between two groups, we used repeated measures two-way analysis of variances. RESULTS: Mean duration of follow up in case and control groups was 12.2 +/- 5.7 and 11.4 +/- 4.9 years, respectively. Two groups had no significant difference in use of sulfasalzine or aminosalicylates. Number of hospitalizations and courses of steroid therapy because of UC activity decreased significantly over time (P < 0.000) in both groups, and it was significantly higher in controls than in cases (P = 0.045 and 0.032, respectively). CONCLUSIONS: Development of PSC in patients with UC might have a positive effect on colonic disease. Further investigations to evaluate the basis of this improvement are warranted.