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Context: Patients with inflammatory bowel disease (IBD) were found to have the higher intestinal expression of Angiotensin-Converting Enzyme2 (ACE2) that could consequently increase susceptibility to COVID-19 infection. Objective: This study reports the outcomes of COVID-19 infection in a large cohort of IBD patients. We compare levels of serum ACE and IFN-α between COVID19 patients with and without IBD. We performed a cross-sectional retrospective multicenter study. Methods: We enrolled patients with IBD screened for SARS-COV-2 in six medical centres in Iran from June to November 2020. The blood samples were drawn to measure COVID-19 IgM and IgG, and serum levels of sACE2, sACE1, and interferon-α, regardless of suspicious symptoms have done the molecular test. Results: A total of 534 IBD patients were included in the study. Of these, 109 (20.0%) cases had detectable IgG and IgM against SARS-CoV-2. sACE2 levels were higher in IBD patients than controls, whereas ACE1and IFN-α levels were similar among groups. [ABSTRACT FROM AUTHOR]

Aim: Description of the inflammatory bowel disease natural history in Tehran province. Background: Inflammatory bowel disease (IBD) is a non-homogeneous disorder with an unpredictable natural history that impairs a patient's quality of life over the course of their life. As a result, providing evidence for efficient patient management is critical. Methods: In this case series study, 198 IBD patients who were visited in our clinic at least three times routinely from Oct 2015 to May 2020 were included. Then, two panel-based approaches, the Multi-State Model (MSM) and random-effect ordered logistic, were used to deduce the clinical course of IBD, which included remission, mild, moderate to severe, and surgical states. Results For ulcerative colitis (UC), women had a slightly poorer condition for remission but better for moderate to severe and a faster transition from moderate to severe to mild (HR=1.490, 95% CI: 1.02-2.16) compared to men. For Crohn's disease (CD), they had a better condition for remission but a slightly poorer condition for the severe state and higher transition from mild to moderate to severe (HR=1.221, 95% CI: 0.4713.22) than men. Oral 5-ASA had better efficacy in people with remission and/or mild states but not for those with moderate to severe states, especially in CD (mild to moderate to serve, HR=1.526, 95% CI: 0.59-3.89). Immunosuppressive drugs were better for patients with lower disease severity, especially with UC (mild to remission, HR=1.258, 95% CI: 0.75-2.09). Conclusion: Panel approaches have the potential efficacy to tackle the unpredictable clinical course of IBD (UC/CD). Hence, we highly recommend that our findings be included into the Iranian routine clinical environment of IBD and/or that related studies be conducted in Iran and other regions to gain a better understanding of the natural history of IBD. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is characterized by recurring episodes of inflammation limited to the mucosal layer of the colon. The exact etiology of UC is unknown, but the role of autoimmunity and activated inflammatory cascade is quite clear. Melatonin possesses anti-inflammatory and immune-modulative properties in animal and clinical trials. The aim of the present study was to evaluate the efficacy and safety of oral melatonin as an adjudicative therapy in clinical, biochemical, and quality of life in UC patients. Thirty patients diagnosed with mild to moderate UC, were randomly allocated to either receive melatonin (3 mg/d) or the placebo group for three months. Simple clinical colitis activity index (SCCAI), fecal calprotectin (FC), C-reactive protein (CRP), Erythrocyte Sedimentation Rate (ESR), and Sf-36 questionnaire have been used for assessment at the baseline and the end of the trial. Melatonin significantly improve SCCAI score, FC, role-emotional, energy and general health relative to placebo (p = 0.03, 0.05, 0.002, 0.032, 0.004 respectively). Regarding CRP, ESR, and the other components of SF-36 there is not any significant difference between melatonin and placebo group. Melatonin supplementation over a three-month period is effective and safe in improving clinical index, FC, and some quality of life in patients with mild to moderate UC. [ABSTRACT FROM AUTHOR]

Aim: We conducted this study to estimate the direct medical cost of Iranian IBD patients. Background: In the economic evaluation setting, descriptive epidemiological studies can provide substantial information for health system policymakers in taking accountable decisions for diseases such as Inflammatory Bowel Disease (IBD). Methods: To do so, we used a self-designed checklist to collect demographic and medical cost information for IBD patients. We also tried to have a national estimation of IBD costs. Results: The mean annual medical cost of IBD was 18354.52 PPP$. Crohn's disease (CD) vs. ulcerative colitis (UC) and UC township patients vs. Tehran resident patients had higher medical costs (31160.79 PPP$; P<0.001) and (20840.23 PPP$, P<0.025). The largest medical cost spent in both IBD subtypes (CD/UC) was attributed to biological agents, especially in UC patients. We estimated that the mean annual cost of IBD in Iran for 2017 was 746315864 (95% CI: 602964172, 964685749) PPP$ (constant incidence) and 862776811 (95% CI: 697055402, 1115222835) PPP$ (increment incidence) respectively. Conclusion: Our results suggest that for management of IBD patients, policymakers should address shifting the medical costs to biological agents, the higher cost of CD, and the impact of underlying factors on the distribution of these medical costs. [ABSTRACT FROM AUTHOR]

Aim: In the present study, two main variants of ATG16L1 gene, rs2241880 T300A and rs2241879 C/T, were evaluated in IBD patients as well as in remission and flareup phase across an Iranian population for the first time. Background: Inflammatory bowel disease (IBD) has found increasing global incidence and prevalence in recent years especially among pediatrics. ATG16L1 is the major gene that regulates autophagy pathway. The autophagy pathway also affects dysbiosis. Methods: Genomic DNA was isolated from peripheral blood samples following salting out extraction method. The genotypes of ATG16L1 polymorphisms rs2241880 T300A and rs2241879 C/T were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: In this case control study, a total of 101 IBD patients (75 ulcerative colitis (UC) and 26 Crohn's disease (CD)) and 99 healthy controls were evaluated. In the present study, a significant association was found between rs2241879 single nucleotide polymorphism on ATG16L1 gene and increased risk of IBD among an Iranian population (P=0.01). There was no statistically significant relationship between rs2241880 and IBD risk (P= 0.42). The effect on these two variants was investigated in relapse and flareup phase which was not significant either, but in CD, rs2241879 and rs2241880 were difference in the relapse phase. Conclusion: The results showed that ATG16L1 gene rs2241879 has a significant relationship with increased risk of IBD among an Iranian population. Individuals with C allele showed a significant relationship with 1.68-fold increased risk of IBD (P=0.01; adjusted OR=1.68; 95% CI=1.13-2.50). [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to explore the quality of life (QoL) in a group of patients who had an intractable disease on medical therapy including biologics and underwent surgery. Background: Quality of life of patients with ulcerative colitis (UC) has been measured with a series of multiple questionnaires Methods: An observational cross sectional study was carried out on 68 patients with documented UC referring to an IBD clinic in a tertiary hospital. Patients with UC who had a colectomy because of intractable disease and were in remission for a year were eligible for enrollment Patients were instructed to fill the SF-36 Questionnaire (interviewer-administered) regarding quality of life. Side effects were evaluated with another questionnaire. Results were compared with the normal population of the community. Results: In comparison with normal population, patients having colectomy have better general QoL. Impotency and incontinency were most common adverse events after colectomy while the adverse events that decreased the QoL significantly were anal secretions and number of bowel movements per day without using antidiarrheal- drugs. Conclusion: In conclusion, our study showed a significant improvement of general QoL in a selected group of UC patients, who were in clinical remission following IPAA and only number of bowel movements per day and anal secretions significantly impaired their QoL. We suggest that a disease-specific questionnaire should be designed, making changes in health-related QOL more detectable over time, since it is more sensitive to these changes in IBD patients than a general questionnaire. [ABSTRACT FROM AUTHOR]

Aim: In this study, we determined the gene expression analysis of IL-17 gene family for early detection of subclinical inflammation among IBD patients. Background: Cytokines have a vital role in the pathogenesis of inflammatory bowel disease (IBD). Interleukin-17 is the signature cytokine of the recently identified T helper 17 (Th17) cell subset. IL-17F is mainly involved in mucosal host defense mechanisms whereas the functions of IL-17B remain largely elusive. Methods: In this cross-sectional study, IBD patients divided into two active and inactive groups. Peripheral blood mononuclear cells (PBMCs) from 38 IBD patients which 20 inactive samples and 18 active individuals were collected. Changes of IL-17 F and IL-17B mRNA expression level evaluated by quantitative-real time-PCR. Results: mRNA expression level of IL-17B and IL-17F in CD, UC, active and inactive groups have been assessed and there were no significant differences (P>0.05). Patients were classified into five different categories as follows: i) 5-ASA; ii) 5-ASA + Pred; iii) 5-ASA + AZA; iv) 5-ASA + Pred + AZA; v) 5-ASA + Pred + AZA + IFX according to medication usage, expression of IL-17F and IL-17B had no differences (p>0.05). Conclusion: Evaluation of IL-17B and IL-17F mRNA expression level illustrate no difference among active and inactive patients. Therefore, IL-17B and IL-17F are not biomarkers in an Iranian IBD patients. [ABSTRACT FROM AUTHOR]

Aberrant immune response in a genetically susceptible host is acknowledged in the pathogenesis of Inflammatory Bowel Diseases (IBD) including Crohn's disease (CD) and Ulcerative colitis (UC). Here we aimed to evaluate IL-16 mRNA level, as the immune component and rs1131445 polymorphism of IL-16 gene, as the genetic susceptibility component of IBD development in PBMC sample. A total of 97 IBD patients (13 CD and 84 UC) and 100 healthy controls were included. Peripheral Blood Mononuclear Cells (PBMCs) were extracted. Polymorphism evaluation was performed by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) and the results were confirmed by sequencing method. Comparative Real- time PCR method was used for IL-16 mRNA assessment. A 3.92-fold increase was observed in the expression level of IL-16 in PBMC of IBD patients compared to the controls (p<0.0001). IL-16 expression was not significantly different in different IBD forms and pathological phases. Distribution of rs1131445 polymorphism was not significantly different between controls and patients (P=0.825). Distribution of CC genotype was significantly higher in CD patients (P=0.016). Although IL-16 mRNA level was considerably lower in CC genotype, this difference was not statistically significant (p=0.537). Lower IL-16 mRNA level was observed in CC genotype of rs1131445 SNP which was not in accordance with the expectations and needs to be further investigated. These data suggest that IL-16 level could be considered as a prognostic marker in Iranian IBD patients. [ABSTRACT FROM AUTHOR]

Aim: The present study evaluated the association between G241R and K469E polymorphisms of intercellular adhesion molecule 1 gene and inflammatory bowel disease in Iranian population. Background: Inflammatory bowel disease including ulcerative colitis and Crohn's disease, is a chronic idiopathic inflammatory disease of the gastrointestinal tract. There are two single base polymorphisms of intercellular adhesion molecule 1gene, G241R and K469E, reported to be associated with inflammatory disorders. Patients and methods: In this case-control study, 156 inflammatory bowel disease patients (110 ulcerative colitis and 46 Crohn's disease patients) and 131 healthy controls were enrolled. Two polymorphisms of intercellular adhesion molecule 1 gene, including G241R and K469E, were assessed by polymerase chain reaction followed by restriction fragment length polymorphism. Results: The E469 allele of K469E polymorphism was significantly more frequent in Crohn's disease patients compared to controls (P< 0.05, OR= 1.83; 95% CI: 1.13 to 2.96). The mutant homozygote genotype of K469E polymorphism (E/E) was also significantly more frequent in Crohn's disease patients compared to controls (P< 0.05, OR= 4.23; 95% CI: 1.42 to 12.59). No difference was observed in the frequency of K469E polymorphism among ulcerative colitis patients compared to controls. There were no significant differences in genotype and allele frequencies of G241R polymorphism among ulcerative colitis and Crohn's disease patients compared to control subjects. Conclusion: According to our findings, K469E polymorphism of intercellular adhesion molecule 1 gene may probably participate in the pathogenesis of Crohn's disease in Iran. [ABSTRACT FROM AUTHOR]

Aim: This retrospective study is aimed to review demographic and clinical characteristics of IBD to elucidate the probable factors associating with IBD development in Taleghani Hospital in Iran since 2001 during a 12-year-period. Background: Ulcerative colitis (UC) and Crohn's disease (CD) are two major idiopathic entities of inflammatory bowel disease (IBD). Previous studies have reported an increased incidence of IBD in Middle East countries. Patients and methods: In the present study 1914 patients with UC, 318 patients with CD and 25 with indeterminate colitis (IC) were included. Demographic information, clinical features, extraintestinal manifestations, complications and extension of disease were collected and interpreted for all participants. According to the time of registration, patients were divided into seven groups. Statistical analysis was performed using the chi-square test. Results: In seven groups of IBD patients, disease registry was estimated for UC, CD, and total IBD during a 12-year-period. From 2001 to 2005, a relative increased registry was observed among UC patients. However, in the years 2006 and 2007 a significant reduction in the number of patients was reported. Then an increasing trend was observed in UC patients. UC presented mostly with diarrhea, hematochezia and bloody diarrhea, while most of CD patients complained of abdominal pain. Conclusion: Evaluation of data related to registered IBD patients in Iran shows that probable incidence and prevalence of IBD (UC and CD) is increasing compared to previous decades. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) manifests as chronic inflammation within the gastrointestinal tract. The study focuses on a long noncoding RNA (lncRNA) known as Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). MALAT1's misregulation has been linked with various autoimmune diseases and regulates proinflammatory cytokines. The role of IL6 in immune-triggered conditions, including IBD, is another focal point. In this research, the expression of MALAT1 and IL6 in IBD patients was meticulously analyzed to uncover potential interactions. The study involved 33 IBD patients (13 with Crohn's disease and 20 with ulcerative colitis) and 20 healthy counterparts. Quantitative real-time polymerase chain reaction determined the MALAT1 and IL6 gene expression levels. The competitive endogenous RNA (ceRNA) regulatory network was constructed using several tools, including LncRRIsearch and Cytoscape. A deep dive into the Inflammatory Bowel Disease database was undertaken to understand IL6's role in IBD. Drugs potentially targeting these genes were also pinpointed using DGIdb. Results indicated a notable elevation in the expression levels of MALAT1 and IL6 in IBD patients versus healthy controls. MALAT1 and IL6 did not show a direct linear correlation, but IL6 could serve as MALAT1's target. Analyses unveiled interactions between MALAT1 and IL6, regulated by hsa-miR-202-3p, hsa-miR-1-3p, and has-miR-9-5p. IL6's pivotal role in IBD-associated inflammation, likely interacting with other cytokines, was accentuated. Moreover, potential drugs like CILOBRADINE for MALAT1 and SILTUXIMAB for IL6 were identified. This research underscored MALAT1 and IL6's potential value as targets in diagnosis and treatment for IBD patients.

Background/aim: Inflammatory bowel disease (IBD) is a multifactorial disorder. Single nucleotide polymorphisms (SNPs) in the IL-12 gene, which are the main factors to regulate the immune reaction, play an important role in the production of IL-12 molecules. The aim of this study was to evaluate the correlation between the SNP on position +1188 of the 3 ′ UTR region of the IL-12 p40 subunit gene and expression of the IL-12 p40 gene., Materials and Methods: This case-control study was performed with 102 patients with IBD and 107 healthy people. PCR-RFLP and comparative real-time PCR were performed to assess the association between genotype and IL-12 gene expression., Results: The frequency of AA, CA, and CC genotypes of this gene at position +1188 was calculated to be 58.8%, 32.4%, and 8.8% in patients and 61.7%, 26.2%, and 12.1% in the control group, respectively, with no significant difference between the two groups (IL- 12B rs3212227: AA (Reference 1), CA (P = 0.407); OR (95% CI) 0.771 (0.418–1.424), CC (P = 0.561); OR (95% CI) 1.313 (0.524–3.292)). Also, the IL-12B mRNA expression level was compared between IBD patients and healthy controls and demonstrated a significant association (R 2 0.136, 95% CI 1.892–3.872, P < 0.0001)., Conclusion: Our results show that IL-12B expression in IBD may be associated with altered immune and inflammatory responses., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Aim: Since the inflammatory bowel disease (IBD) is a disorder which requires continuous drug intake to induce and maintain the remission phase, finding the barriers for low adherent group, may improve the disease phase and quality of life in those patients., Background: IBD is defined as a chronic immune disorder with unpredictable flares. The common treatment of these diseases can be effective for inducing and maintaining remission courses. Therefore the use of long-term medication therapy is the crucial key to prevent surgery and complications in patients with IBD., Methods: Morisky Medication Adherence Scales (MMAS) is used for detecting level of adherence to the medicines for 137 patients with IBD. Demographic and clinical data are recorded for all patients and quality of life has been evaluated by Short-Form 36 questionnaire in 55 patients., Results: Demographic and clinical features showed no correlation with the degree of adherence. The MMAS-8 score in the low adherent group significantly different than that in the medium and high adherer group. No relation was found statistically between level of adherence and mental or physical sates ( p value=0.17, 1.2) and total quality of life ( p value=0.22) in patients with IBD., Conclusion: Designing smart reminder and the physician's explain about adverse effects and beneficial of medicines may be effective to confront with forgetfulness and feeling comfort with treatment. Improve a strategy in order to regular measurement of adherence to medication, provides enough information about stop taking medication.

Aim: Here we aimed at evaluating whether the apoptosis status of circulating leukocytes of inflammatory bowel diseases (IBD) patients is attributed to the diseases clinical status., Background: Defects in the programmed cell death of inflammatory cells is known as to play a major role in the pathogenesis of IBD, and has been associated with the clinical efficacy of therapeutic agents., Methods: A total of 50 IBD patients, 25 with remission and 25 with flare-up phase of the disease, who their disease was confirmed by colonoscopy, were included in this cross-sectional study. Pro-apoptotic Bax and anti-apoptotic Bcl-2 mRNA expression, along with Bax/Bcl-2 ratio, as measures of apoptotic status, were assessed in the Peripheral blood mononuclear cell (PBMC) of the patients using semi-quantitative Real-time PCR method., Results: The mean Bax mRNA expression level was 0.54±0.12 in flare-up group and 0.53±0.13 in remission group (p=0.8). The mean Bcl-2 mRNA expression level was 0.63±0.13 in flare-up group and 0.55±0.12 in remission group (p=0.03). The mean Bax/Bcl-2 ratio was 0.88±0.17 in flare-up group and 1±21 in remission group (p=0.05). The mean Bax/Bcl-2 ratio was not statistically significant between different disease types (p=0.54) or therapeutic agents (p=0.7)., Conclusion: According to our results, alteration in markers of apoptosis could be traced in the circulating leukocytes of IBD patients, which suggest a potential for clinical application of apoptosis markers in disease monitoring and prediction of relapse.

Background: Inflammatory bowel diseases (IBDs), which include ulcerative colitis (UC) and Crohn's disease (CD), are inflammatory disorders that affect the gastrointestinal tract. A combination of inflammatory cytokines has an important role in IBD development. Genome-wide association studies have shown that polymorphisms in the interleukin-23R gene ( IL-23R ) increase susceptibility to IBD. The aim of this study was to investigate the IL-23R 3' UTR SNP to determine a potential association between genotype distribution and IBD., Methods: The case group included 102 IBD patients and the control group included 107 healthy individuals. IL-23R polymorphisms rs10889677 were genotyped using PCR-RFLP analysis. RFLP results were confirmed by direct sequencing., Results: The allele and genotype frequencies in patients and controls were evaluated and compared, and no significant association between this functional rs10889677 polymorphism and risk of IBD was observed (P=0.587; adjusted OR: 0.89; 95% CI: 0.597-1.339). We also found no significant association between CD (14.71%) and UC (85.29%) patients in allele or genotype levels (P>0.05)., Conclusion: Our results suggest that the rs10889677 A>C polymorphism is not a potential prognostic marker in Iranian patients with IBD.

Aim: The aim of this study was to explore the quality of life (QoL) in a group of patients who had an intractable disease on medical therapy including biologics and underwent surgery., Background: Quality of life of patients with ulcerative colitis (UC) has been measured with a series of multiple questionnaires., Methods: An observational cross sectional study was carried out on 68 patients with documented UC referring to an IBD clinic in a tertiary hospital. Patients with UC who had a colectomy because of intractable disease and were in remission for a year were eligible for enrollment Patients were instructed to fill the SF-36 Questionnaire (interviewer-administered) regarding quality of life. Side effects were evaluated with another questionnaire. Results were compared with the normal population of the community., Results: In comparison with normal population, patients having colectomy have better general QoL. Impotency and incontinency were most common adverse events after colectomy while the adverse events that decreased the QoL significantly were anal secretions and number of bowel movements per day without using antidiarrheal- drugs., Conclusion: In conclusion, our study showed a significant improvement of general QoL in a selected group of UC patients, who were in clinical remission following IPAA and only number of bowel movements per day and anal secretions significantly impaired their QoL. We suggest that a disease-specific questionnaire should be designed, making changes in health-related QOL more detectable over time, since it is more sensitive to these changes in IBD patients than a general questionnaire., Competing Interests: The authors declare that they have no conflict of interest.

This corrects the article DOI: 10.1038/ctg.2017.44.

Objectives: Anti-tumor necrosis factor (TNF)-α agents like Infliximab (IFX) are effective in the treatment of inflammatory bowel diseases (IBDs) and are widely used. However, a considerable number of patients do not respond or lose response to this therapy. Preliminary evidence suggests that transmembrane TNF-α (tmTNF-α) might be linked to response to IFX by promoting reverse signaling-induced apoptosis in inflammatory cells. The main aim of this study was the evaluation of this hypothesis in primary IFX non-responders., Methods: A total of 47 IFX naive IBD patients were included in the study. Blood samples were taken before the start of IFX therapy (at week 0) and after induction therapy (at week 14). Endoscopic disease activity and markers of inflammation at baseline and at week 14 were used to evaluate response. Baseline soluble TNF-α (sTNF-α), percentage of circulating TNF-α positive cells, mean fluorescence intensity (MFI) of tmTNF-α, and apoptosis rate at week 14 in the peripheral blood mononuclear cells (PBMCs) were evaluated in IFX responders and non-responders., Results: Mean sTNF-α was not significantly different in responders compared to non-responders (P=0.13). Mean percentage of tmTNF-α bearing lymphocytes and monocytes was higher in the PBMCs of responders (P=0.05 and P=0.014, respectively). Mean MFI of tmTNF-α in circulating lymphocytes and monocytes was greater in responders (P=0.002 and P<0.001, respectively). Moreover, the mean percentage of apoptosis in PBMCs was significantly greater in responders compared to non-responders (P=0.002)., Conclusions: The percentage of tmTNF-α bearing lymphocytes and monocytes and the intensity of tmTNF-α in the circulating leukocyte population of IBD patients was directly related to primary response to IFX. This was likely due-as assessed by the apoptosis rate-to promotion of inflammatory cell death. Thus, our data suggest that peripheral leukocytes could in principle be used for predicting primary response to IFX in IBD patients.

Background: The CARD15/NOD2 gene, located on the pericentromeric region of chromosome 16 (IBD1) has been reported to have an association with IBD, especially Crohn's disease. Three common mutations of CARD15 are variably associated with Crohn's disease in different ethnic groups. We evaluated the frequency of these mutations (R702W, G908R and 1007fsinsC) in Iranian IBD patients and compared it with the healthy control population., Methods: One hundred patients with ulcerative colitis, 40 patients with Crohn's disease, and 100 sex- and age-matched controls were enrolled from a tertiary center during a one-year period (2005-2006). The three mutations were assessed in DNA of leukocytes by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP)., Results: The frequency of R702W mutation was significantly higher in Iranian patients with Crohn's disease (p< 0.001; OR 19.21; 95% CI 4.23-87.32) compared to healthy controls. No association was observed between the other mutations and Crohn's disease and none of these mutations was associated with ulcerative colitis., Conclusion: The R702W mutation of CARD15 gene was associated with Crohn's disease in the Iranian population.