Colitis In Remission Research Articles

Serum biomarkers confirming stable remission in inflammatory bowel disease

Crohn's disease (CD) and ulcerative colitis (UC) have a chronic-remittent course. Optimal management of inflammatory bowel diseases (IBD) relies on early intervention, treat-to-target strategies and a tight disease control. However, it is challenging to assess the risk of relapses in individual patients. We investigated blood-based biomarkers for the confirmation of disease remission in patients with IBD. We retrospectively analyzed samples of 40 IBD patients (30 UC, 10 CD) enrolled in a tight-control follow-up study. Half of the patients had a flare during follow up. Serum was analyzed for S100A12 as well as S100A8/A9 and for 50 further biomarkers in a bead-based multiplex assay. The concentrations of 9 cytokines/chemokines and S100A8/A9 significantly differed in IBD patients with unstable remission (before flares) when compared to IBD patients with stable remission. Although the number of patients was small, ROC curve analyses revealed a number of biomarkers (IL-1β, IL-1RA, IL-8, IL13, IL-15, IL-21, IL-25, IFN-β, CXCL9, CXCL10, CXCL11, Galectin-1, G-CSF and S100A8/A9) that were elevated in patients with later occurring relapses. While earlier studies on peripheral biomarkers in IBD are limited to only few analytes, our study using a broad screening approach identified serum biomarkers with the potential to indicate unstable disease control in IBD, which may help to steer individual therapies to maintain remission.

Washed microbiota transplantation for the treatment of recurrent fungal infection in a patient with ulcerative colitis.

Washed microbiota transplantation for the treatment of recurrent fungal infection in a patient with ulcerative colitis.

Proactive therapeutic drug monitoring is more effective than conventional management in inducing fecal calprotectin remission in inflammatory bowel disease.

Proactive therapeutic drug monitoring (pTDM) may improve treatment outcomes in inflammatory bowel disease. We compared 135 patients following a prospective pTDM protocol aiming at an infliximab trough level (IFXTL) between 5 and 10 μg/ml with sequential measurements of Fc, with 108 patients from a retrospective group under conventional management. We evaluated the rates of Fc remission (<250 μg/g) and other clinical outcomes at 2-year of follow-up. pTDM associated with higher rates of Fc remission (69.6% vs. 50.0%; P = 0.002), and steroid-free clinical remission (78.4% vs. 55.2%, P = 0.028) with a trend for clinical remission (79.3% vs. 68.5%, P = 0.075). There was no difference in treatment discontinuation (P = 0.195), hospitalization (P = 0.156), and surgery (P = 0.110). Higher IFXTL associated with Fc remission at week 14 (6.59 vs. 2.96 μg/ml, P < 0.001), and at the end of follow-up (8.10 vs. 5.03 μg/ml, P = 0.001). In patients reaching Fc remission after week 14, IFXTL increased from week 14 to the end of follow-up (2.71 vs. 8.54 μg/ml, P < 0.001). Fc remission associated with higher rates of clinical (85.8% vs. 56.8% P < 0.001) and steroid-free clinical remission (86.9% vs. 50.0% P < 0.001), lower IFX discontinuation (8.8% vs. 36.8%, P < 0.001), and hospitalization (13.5% vs. 33.7%, P < 0.001), without significance for surgery (6.1% vs. 12.6%, P = 0.101). pTDM was more effective than conventional management in inducing Fc remission which was associated with improved outcomes.

A150 INFLIXIMAB INDUCED EOSINOPHILIC PNEUMONITIS IN AN ADOLESCENT

Abstract Background Infliximab is used to induce and maintain remission of inflammatory bowel disease (IBD). Pulmonary abnormalities in IBD are rare, but comprise airway, parenchymal and interstitial lung complications. Pulmonary adverse effects reported after Infliximab include tuberculosis reactivation, invasive aspergillosis, interstitial pneumonitis, pulmonary oedema and alveolar hemorrhage. Aims Four cases previously reported associate Infliximab to eosinophilic pneumonitis. However, this is the first in pediatrics. Methods Case report of an adolescent female with IBD and a rare adverse reaction to Infliximab Results Our patient was diagnosed with ulcerative pancolitis, Mayo 2, initially treated with 5-ASA. Five months into therapy she was switched to azathioprine and Infliximab (10mg/kg every 8 weeks) due to worsening disease. She attained and maintained clinical and biochemical remission for the next 1.5 years. Azathioprine was stopped at the patient’s request. One month later, she presented with cough and nasal congestion but was afebrile. Peripheral eosinophilia was noted. Salbutamol and steroid inhalers were started, without improvement. She was admitted to hospital due to progressive cough, shortness of breath, and wheezing. Physical examination was otherwise unremarkable. Pulmonary function test showed FVC of 69%, FEV1 of 45% with bronchodilator effect of 12% and a FEV1/FVC of 59. Her blood work showed eosinophilia (4.42 x109/L) and an elevated IgE (4596 ug/L). Serum-specific IgE for Aspergillus was positive; but skin testing was negative. An X-ray showed marked bilateral interstitial thickening in the mid and lower zones. Chest CT showed extensive bronchiectasis with bronchial mucous plugging. A bronchoscopy with bronchoalveolar lavage (BAL) reported marked eosinophilia, negative for mycobacterium, bacterial and fungal growth. Other infectious and autoimmune etiologies were ruled out. She responded successfully to high-dose prednisone (50 mg/day). At discharge, symptoms had improved, and her pulmonary function tests were normal (FEV1 of 95% predicted and FEV1/FVC 84). Upon steroid taper, she relapsed in pulmonary symptoms, eosinophilia, as well as a flare of her IBD. Reinduction with steroids resolved her symptoms and eosinophilia. Due to her loss of response to Infliximab and pulmonary, she was switched to Vedolizumab with good response. After stopping Infliximab her lung function improved significantly (FVC of 96% predicted and FEV1 of 98% predicted) and has remained so. Peripheral eosinophilia dropped to 0.2 x109/L. Her IBD is currently in remission without any respiratory symptoms. Conclusions Eosinophilic pneumonitis can be a complication of Infliximab. Our patient had a delayed presentation of respiratory symptoms, 16 months after a satisfactory response to Infliximab. Although responsive to steroids, she ultimately needed to be switched to another immunosuppressive agent. Funding Agencies None

Steroids in inflammatory bowel disease: a clinical review

Corticosteroids are effective at inducing remission in inflammatory bowel disease (IBD). Acute severe ulcerative colitis and Crohn's disease are managed with intravenous steroids. In mild-to-moderate disease, corticosteroids can be given orally or topically. Long-term use should be limited to prevent commonly associated adverse effects. Corticosteroids should not be used to maintain remission. Blood pressure, body mass index and blood glucose monitoring are crucial while on steroids. Acid suppression along with calcium and vitamin D supplementation should be co-prescribed to all patients on long-term corticosteroids. Bridging these patients to a steroid-sparing agent early prevents steroid-refractory and steroid-dependent disease. GP education, IBD helplines, IBD clinics, multidisciplinary team meetings and regular auditing should be encouraged to prevent corticosteroid overprescribing.

Repeated Fecal Microbial Transplantations and Antibiotic Pre-Treatment Are Linked to Improved Clinical Response and Remission in Inflammatory Bowel Disease: A Systematic Review and Pooled Proportion Meta-Analysis.

The response of patients with inflammatory bowel disease (IBD) to fecal microbial transplantation (FMT) has been inconsistent possibly due to variable engraftment of donor microbiota. This failure to engraft has resulted in the use of several different strategies to attempt optimization of the recipient microbiota following FMT. The purpose of our study was to evaluate the effects of two distinct microbial strategies—antibiotic pre-treatment and repeated FMT dosing—on IBD outcomes. A systematic literature review was designed and implemented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A medical librarian conducted comprehensive searches in MEDLINE, Embase, Scopus, Web of Science Core Collection, and Cochrane Library on 25 November 2019 and updated on 29 January 2021. Primary outcomes of interest included comparing relapse and remission rates in patients with IBD for a single FMT dose, repeated FMT dosages, and antibiotic pre-treatment groups. Twenty-eight articles (six randomized trials, 20 cohort trials, two case series) containing 976 patients were identified. Meta-analysis revealed that both repeated FMT and antibiotic pre-treatment strategies demonstrated improvements in pooled response and remission rates. These clinical improvements were associated with increases in fecal microbiota richness and α-diversity, as well as the enrichment of several short-chain fatty acid (SCFA)-producing anaerobes including Bifidobacterium, Roseburia, Lachnospiraceae, Prevotella, Ruminococcus, and Clostridium related species.

Fusobacterium nucleatum impedes remission of colitis in a mouse model.

The role of Fusobacterium nucleatum, often associated with intestinal diseases, in the remission of dextran sulfate sodium (DSS)-induced colitis was investigated. Female mice were divided into groups DC (DSS control) and DF (DSS+F. nucleatum). F. nucleatum (1.0×1010 cfu/mouse/day) in phosphate-buffered saline (PBS) was orally given to DF, while DC had PBS only. All mice had DSS in drinking water. In Experiment 1, mice underwent 2 inflammation phases, an in-between recovery phase and had their disease activity indices (DAI) calculated. Experiment 2 was similarly conducted, except that mice were dissected 3 days postrecovery, and had blood and colonic mucosal samples collected. In Experiment 1, DF had significantly (P<.05) higher DAI than DC, during the recovery and 2nd inflammation phases. In Experiment 2, genus Bacteroides was significantly (P<.05) higher and family Lachnospiraceae significantly lower in cecal mucosa-associated microbiota of DF than in that of DC. We concluded that F. nucleatum can impede colitis remission.

Clinical Practice Survey of Repeat Endoscopy in Pediatric Inflammatory Bowel Disease in North America.

Endoscopic remission has become a standard treatment target in inflammatory bowel disease (IBD). It is unclear how widely this practice has been adopted amongst pediatric gastroenterology providers. This study determines the frequency of repeat endoscopy in pediatric IBD and evaluates for predictive baseline characteristics of providers. We developed a cross-sectional survey, which was distributed via 3 national email listservs to pediatric gastroenterology providers. We obtained baseline characteristics of respondents and assessed motivations and barriers for the practice of repeat endoscopy compared with none. Two hundred and thirty-eight unique respondents completed the online survey. Response rate was 11% (238 of 2300 possible participants). The majority practice in an academic setting (77%) and reported participation in ImproveCareNow (63%). Overall, 65% of respondents perform repeat endoscopy to assess for endoscopic remission in pediatric IBD as part of routine clinical practice. Fifty-six percent reported repeat endoscopy as individuals in the absence of a departmental protocol. "Symptoms are not sufficient to follow IBD patients" was reported by 82% of those who repeat endoscopy; conversely, "I perform endoscopy based on clinical, biomarker, and/or imaging trends" was reported by 81% of those who do not repeat endoscopy. The establishment of a pediatric-specific guideline was most commonly reported to change current practice, based on rank-order scoring. A majority of representative providers repeat endoscopy to assess for endoscopic remission in pediatric IBD. Fewer years in practice favored repeating endoscopy. The need for North American pediatric guidelines with pediatric-specific evidence to support the long-term benefits of endoscopic remission are highlighted in this study.

High infliximab trough concentrations are associated with sustained histologic remission in inflammatory bowel disease: a prospective cohort study

BackgroundThe threshold concentration of infliximab during maintenance therapy has not been well-defined in relation to histologic remission. The aim of the study is to dentify the maintenance-phase infliximab concentration associated with histologic remission in inflammatory bowel disease patients (IBD).MethodsA prospective cohort study was carried out in 104 IBD patients seen at a tertiary care centre in London, Canada. Infliximab trough concentrations were collected during the maintenance phase of treatment and compared between participants with and without evidence of histologic remission. Participants were additionally evaluated for sustained histologic remission, and relapse to active disease.ResultsParticipants in histologic remission attained higher mean concentrations of infliximab during the maintenance phase (10.34 ± 0.69 μg/ml) compared to those with persistent disease activity (6.23 ± 0.67 μg/ml, p-value < 0.0001). Additionally, during the maintenance phase, sustained histologic remission was also associated with a higher mean concentration of infliximab (10.81 ± 5.46 μg/ml) compared to those who relapsed to active disease (5.68 ± 3.70, p < 0.001). Overall, participants with a mean infliximab trough concentration greater than 8ug/ml were more likely to have histologic remission (area under the receiver operating characteristic curve, AUROC = 0.72, 95%CI = 0.65–0.84, p < 0.0001) and sustained histologic remission (AUC = 0.77, 95%CI = 0.63–0.91, p = 0.002).ConclusionMaintenance-phase infliximab trough concentrations greater than 8 μg/ml, which is higher than the currently recommended target concentration, are highly associated with histologic remission and sustained histologic remission.

ПРИМЕНЕНИЕ ОПРОСНИКА ДЛЯ СКРИНИНГА СКРЫТЫХ ФОРМ АЛЛЕРГИИ НА БЕЛКИ КОРОВЬЕГО МОЛОКА У ДЕТЕЙ С ВОСПАЛИТЕЛЬНЫМИ ЗАБОЛЕВАНИЯМИ КИШЕЧНИКА

The role of food allergy (FA) in the development of clinical reactions to food in patients with inflammatory bowel disease (IBD) is being studied and remains highly controversial. However, it is obvious that for personalized therapy of this category of patients, it is necessary to consider all possible forms of food hypersensitivity. Objective of the research: to develop a questionnaire to identify latent forms of cow's milk protein allergy (CMPA) in children with IBD and to evaluate the effectiveness of its use. Materials and methods: 376 children were questioned: 176 children with IBD in remission and/or with a low degree of disease activity (1st group); 100 with confirmed CMPA (2nd group); 100 without FA manifestations (3rd group). Statistical analysis was performed using the SPSS (Statistical Package for the Social Sciences Inc., USA) version 26.0. Data analysis included standard descriptive and analytical statistics. Results: using a structured questionnaire for collecting anamnesis, it was found that the frequency of allergic reactions to food in the family history of children with IBD and in the group of patients with CMPA did not differ significantly. The introduction of dairy products into complementary foods earlier than at the age of 6 months in IBD patients was noted statistically significantly more often than in children with CMPA and children in the comparison group; the most significant difference was noted in patients with Crohn's disease (CD). In the early history, among children with IBD 83 (47,1%) had skin rashes, 121 (68,7%) regurgitation, 138 (78,4%) colic, 68 (38,6%) constipation. %), blood in stool – 53 (30,1%), mucus (in significant amounts) in stool – 70 (39,7%), loose stool – 77 (43,7%), delayed weight gain was noted in 25 (14,2%) children. At the same time, regurgitation and colic in children with IBD in the first year of life were noted statistically significantly more often than in children with CMPA and children in the comparison group. The frequency of symptoms such as blood and mucus in the stool, diarrhea and delayed weight gain in the first year of life did not statistically significantly differ in children with IBD and in the group of children with CMPA, but was significantly more frequent than in group 3. The median of the indicator according to the results of the questionnaire survey in children with CD was 57 points [52; 62], with ulcerative colitis (UC) – 54 points [50; 57], with PA – 61 points [58; 64], in the 3rd group – 10 points [8; 14]. At a threshold value (cutoff point) of 55 points, the sensitivity and specificity of the method were 79% and 74%, respectively. The area under the ROC curve, corresponding to the relationship between the presence of a subclinical form of allergy and the scores of the questionnaire, was 0,819±0,022 with 95% CI: 0,776–0,862. The resulting model was statistically significant (p&lt;0,001). Conclusion: the questionnaire survey of children with IBD using a questionnaire aimed at identifying latent forms of FA allowed to reveal history peculiarities of children with IBD. The obtained indicators of questionnaire sensitivity and specificity allowed to use it in clinical practice as an additional screening method for detecting latent forms of CMPA in IBD patients with subsequent correction of nutritional support.

Human Intestinal Macrophages Are Involved in the Pathology of Both Ulcerative Colitis and Crohn Disease.

BackgroundIntestinal macrophages are key immune cells in the maintenance of intestinal immune homeostasis and have a role in the pathogenesis of inflammatory bowel disease (IBD). However, the mechanisms by which macrophages exert a pathological influence in both ulcerative colitis (UC) and Crohn disease (CD) are not yet well understood.MethodsWe purified intestinal macrophages from gastrointestinal mucosal biopsies (patients with UC, patients with CD, and healthy donors) and analyzed their transcriptome by RNA sequencing and bioinformatics, confirming results with quantitative polymerase chain reaction and immunohistochemistry.ResultsCompared with those of healthy donors, intestinal macrophages in patients with UC and with CD showed cellular reprograming of 1287 and 840 dysregulated genes, respectively (false discovery rate ≤ 0.1). The UC and CD intestinal macrophages showed an activated M1 inflammatory phenotype and the downregulation of genes engaged in drug/xenobiotic metabolism. Only macrophages from CD showed, concomitant to an M1 phenotype, a significant enrichment in the expression of M2 and fibrotic and granuloma-related genes. For the first time, we showed (and validated by quantitative polymerase chain reaction and immunohistochemistry) that intestinal macrophages in patients with IBD present both M1 and M2 features, as recently described for tumor-associated macrophages, that affect key pathways for IBD pathology, represented by key markers such as MMP12 (fibrosis), CXCL9 (T-cell attraction), and CD40 (T-cell activation).ConclusionsOur data support the therapeutic targeting of macrophages to maintain remission in IBD but also indicate that a shift toward an M2 program—as proposed by some reports—may not limit the recruitment and activation of T cells because M2 features do not preclude M1 activation in patients with UC or CD and could exacerbate M2-related CD-specific features such as fibrosis and the formation of granulomas.

Clinical effects and gut microbiota changes of using probiotics, prebiotics or synbiotics in inflammatory bowel disease: a systematic review and meta-analysis.

Probiotics have been reported to be beneficial for inflammatory bowel disease (IBD), but the types, number of strains, dosage, and intervention time of probiotics used remain controversial. Furthermore, the changes of gut microbiota in IBD's patients are also intriguing. Thus, this meta-analysis was to explore the clinical effects and gut microbiota changes of using probiotics, prebiotics and synbiotics in IBD. The search was performed in PubMed, Web of Science and the Cochrane library from inception to April 2020. Qualified randomized controlled trials were included. IBD's remission rate, disease activity index and recurrence rate were extracted and analyzed. Changes in the gut microbiota of patients with IBD are comprehensively described. Thirty-eight articles were included. Probiotics, prebiotics and synbiotics can induce/maintain IBD's remission and reduce ulcerative colitis (UC) disease activity index (RR = 1.13, 95% CI 1.02, 1.26, P < 0.05; SMD = 1.00, 95% CI 0.27, 1.73, P < 0.05). In subgroup analyses of IBD remission rate and UC disease activity index, we obtained some statistically significant results in some subgroup (P < 0.05). To some extent, probiotic supplements can increase the number of beneficial bacteria (especially Bifidobacteria) in the intestinal tract of patients with IBD. Our results support the treatment of IBD (especially UC) with pro/pre/synbiotics, and synbiotics are more effective. Probiotic supplements that are based on Lactobacillus and Bifidobacterium or more than one strain are more likely to be beneficial for IBD remission. The dose of 1010-1012CFU/day may be a reference range for using probiotics to relieve IBD.

Anti-inflammatory diet and inflammatory bowel disease: what clinicians and patients should know?

Current treatment for inflammatory bowel disease (IBD) includes the application of anti-inflammatory agents for the induction and remission of IBD. However, prolonged use of anti-inflammatory agents can exert adverse effects on patients. Recently, formulated dietary approach in treating IBD patients is utilized to improve clinical activity scores. An alteration of gastrointestinal microbiota through dietary therapy was found to reduce IBD and is recognized as a promising therapeutic strategy for IBD. One of the recommended formulated diets is an anti-inflammatory diet (AID) that restricts the intake of carbohydrates with modified fatty acids. This diet also contains probiotics and prebiotics that can promote balanced intestinal microbiota composition. However, scientific evidences are limited to support this specific dietary regime in maintaining the remission and prevention relapse of IBD. Therefore, this review aimed to summarize available data from various studies to evaluate the AID diet effectiveness which will be useful for clinicians to manage their IBD patients by application of improved dietary therapy.

Steroids in inflammatory bowel disease: a clinical review

Corticosteroids are effective at inducing remission in inflammatory bowel disease (IBD). Acute severe ulcerative colitis and Crohn's disease are managed with intravenous steroids. In mild-to-moderate disease, corticosteroids can be given orally or topically. Long-term use should be limited to prevent commonly associated adverse effects. Corticosteroids should not be used to maintain remission. Blood pressure, body mass index and blood glucose monitoring are crucial while on steroids. Acid suppression along with calcium and vitamin D supplementation should be co-prescribed to all patients on long-term corticosteroids. Bridging these patients to a steroid-sparing agent early prevents steroid-refractory and steroid-dependent disease. GP education, IBD helplines, IBD clinics, multidisciplinary team meetings and regular auditing should be encouraged to prevent corticosteroid overprescribing.

Discontinuation of Infliximab Increases the 1-Year Relapse Rate of Ulcerative Colitis in Remission - A Prospective, Multicentre, Randomised Controlled Trial

Background and Aims: Anti-tumour necrosis factor (TNF)- a agents are the mainstay of long-term treatment for refractory ulcerative colitis (UC). However, there has been no prospective randomised controlled trial evaluating whether anti-TNFa agents can be discontinued in UC patients in remission. Methods: This prospective, multicentre, randomised controlled trial enrolled UC patients from 23 specialist centres treated with infliximab (IFX) who were in remission. Patients who were confirmed to be: 1) in remission for > 6 months, 2) steroid-free, and 3) with a Mayo endoscopic subscore (MES) of 0 or 1, were randomised into two groups (continued IFX or discontinued IFX) in a 1:1 ratio stratified according to the use of immunomodulators and MES, using computer-generated stratified randomisation. The remission rate at week 48 in the full analysis set (FAS) was the primary endpoint in this trial. As secondary objectives, risk factors for relapse, and efficacy of re-treatment with IFX after relapse were also evaluated. Findings: A total of 95 patients were randomised, and 92 were included in the FAS. The remission rate at week 48 was 80.4% (n = 37/46; 95% CI: 66.1% to 90.6%) and 54.3% (n = 25/46; 95% CI: 39.0% to 69.1%) in the IFX-continued and IFX-discontinued groups, respectively (between-group difference: 26.1% [7.7% to 44.5%], p = 0.008). C-reactive protein and histological severity index were associated with future non-remission. Neither clinical nor endoscopic remission was predictive of remission. Retreatment with IFX upon relapse was safe, and two-thirds of patients achieved remission in 8 weeks. Interpretation: Discontinuing IFX resulted in a significantly increased relapse rate at 1 year. Residual subtle inflammation, as estimated based on CRP and histological inflammation seemed to be predictive of future relapse. Trial Registration:This study was registered at the University Hospital Medical Information Network Center Trials Registry (UMI12092). Funding Statement: This study was supported in part by a Grant-in-Aid for the Intractable Disease Project of the Ministry of Health, Labour and Welfare of Japan, and Mitsubishi- Tanabe Pharmaceuticals. Co. Declaration of Interests: Dr. Nakamura reports grants and personal fees from Mitsubishi Tanabe Pharma Corporation, grants and personal fees from EA Pharamaceutical Co Ltd, grants and personal fees from AbbVie Inc, personal fees from Janssen Pharmaceutical Co Ltd, grants and personal fees from Mochida Pharamaceutical Co Ltd, personal fees from Takeda Pharmaceutical Co Ltd, grants from Kyorin Holdings Inc, grants from JIMRO Co Ltd, grants from ZERIA Pharmaceutical Co Ltd, outside the submitted work. Dr. Motoya reports grants from Takeda pharmaceutical Co. Ltd, grants from Mitsubishi Tanabe Pharma Coporation, grants from Janssen Pharma coporation, during the conduct of the study. Dr. Hisamatsu reports grants and personal fees from EA pharma Co. Ltd., grants and personal fees from AbbVie GK, personal fees from Celgene K.K., personal fees from Janssen Pharmaceutical K.K., grants and personal fees from Pfizer Inc., grants and personal fees from Mitsubishi Tanabe Pharma Corporation, grants and personal fees from Kyorin Pharmaceutical Co. Ltd., grants and personal fees from JIMRO Co.Ltd, grants and personal fees from Mochida Pharmaceutical Co., Ltd, personal fees from Nichi-lko Pharmaceutical Co., Ltd., grants from Daiichi-Sankyo, grants and personal fees from Takeda Pharmaceutical Co. Ltd., outside the submitted work. Dr. Abe reports personal fees from EA Pharma Co.,LTD., personal fees from Kissei Pharmaceutical Co.,LTD., personal fees from Mochida Pharmaceutical Co.,LTD., personal fees from Mitsubishi Tanabe Pharma Corporation, outside the submitted work. Dr. Hibi reports personal fees from Aspen Japan K.K, grants and personal fees from Abbvie GK, personal fees from Ferring, personal fees from Gilead Sciences, personal fees from Janssen, grants and personal fees from JIMRO, personal fees from Kisse Pharmaceutical, grants and personal fees from Mitsubishi-Tanabe Pharma, grants and personal fees from Mochida Pharmaceutical, personal fees from Nippon Kayaku, personal fees from Pfizer, grants and personal fees from Takeda Pharmaceutical, grants and personal fees from Zeria Pharmaceutical, personal fees from Bristol-Myaers Squibb, personal fees from Celltrion, personal fees from EA Pharma, personal fees from Eli Lilly, grants and personal fees from kyorin, personal fees from Nichi-Iko Pharmaceutical, grants from Otuska Holdings, outside the submitted work. Ethics Approval Statement: The protocol was approved by the institutional review board of each participating institution. Written informed consent was obtained from all patients included in the study.

Long-term and continuous administration of Bacillus subtilis during remission effectively maintains the remission of inflammatory bowel disease by protecting intestinal integrity, regulating epithelial proliferation, and reshaping microbial structure and function.

Gut microbiota takes part in the pathogenesis of inflammatory bowel disease (IBD). Clinical research has found that probiotics have a beneficial effect on active ulcerative colitis, but to date, significant efficacy has rarely been found in the use of probiotics in the remission phase of ulcerative colitis and Crohn's disease. More studies are needed to assess the utilization of probiotics in IBD remission. In this study, we assessed the administration of Bacillus subtilis in remission and its possible mechanism in mice with IBD. Oral administration of B. subtilis was implemented for 6 weeks (dextran sulfate sodium (DSS)-P6w group), 2 weeks (DSS-P2w group) or 0 weeks (DSS-control(CT) group) in the remission phase in rodents with (DSS)-induced IBD. The body weight, colon length and disease activity index (DAI) were recorded, and colon H&E staining was performed. The expression of tight junction proteins (ZO-1 and occludin) mRNA and epithelium proliferation-related Ki67 was detected. Gut microbiota were tested by 16S rRNA sequencing. Administration of B. subtilis in remission effectively increased the body weight and colon length and decreased DAI in the DSS-P6w group compared with the DSS-CT group, but there is no significant difference between the DSS-P2w and DSS-CT groups. The epithelial integrity was improved, and the expression of ZO-1 and occludin increased due to administration of B. subtilis in remission, which was more evident in the DSS-P6w group. The expression of Ki67 increased in the DSS-CT group compared with that in the CT group. The administration of B. subtilis effectively down-regulated the expression of Ki67 in the DSS-P6w and DSS-P2w groups compared with the DSS-CT group. Furthermore, gut microbial structure was improved, with significantly decreased Escherichia/Shigella and Enterococcus, and increased Akkermansia and corresponding microbial function in the DSS-P6w group. Short-term administration of B. subtilis in the remission phase showed no significant improvement in mice with IBD. Long-term and continuous supplementation of B. subtilis in remission could effectively maintain the remission by protecting epithelial integrity, regulating proliferation of intestinal epithelial cells, and improving gut microbiota and the corresponding microbial function.

Cathelicidin - A Novel Potential Marker of Pediatric Inflammatory Bowel Disease.

IntroductionCathelicidin is a multifunctional host defense peptide which may also exert pro-inflammatory signals and contribute to the development of autoimmune disorders. We aimed to assess serum concentration of cathelicidin in children with inflammatory bowel disease (IBD) compared to healthy controls and to evaluate its relationship with disease activity and phenotype.Patients and MethodsThe study group included 68 children with IBD. The control group comprised 20 children with functional abdominal pain. All patients and controls were tested for complete blood count, C-reactive protein, erythrocyte sedimentation rate and cathelicidin. Stool samples were collected to assess calprotectin.ResultsCathelicidin was significantly increased in patients with ulcerative colitis (1073.39±214.52 ng/mL) and Crohn’s disease (1057.63±176.03 ng/mL) patients compared to controls (890.56±129.37 ng/mL) (H=16.28; p=0.0003). Cathelicidin was significantly elevated in children with active IBD (1044.90±176.17 ng/mL) and IBD remission (1098.10±227.87 ng/mL) compared to controls (Z=3.21; p=0.001; Z=−4.12; p<0.0001, respectively). Negative correlation between cathelicidin and calprotectin in children with ulcerative colitis was found (R=−0.39; p=0.02). Cathelicidin exhibited AUC of 0.815 for differentiation children with ulcerative colitis from the control group.ConclusionSerum cathelicidin is increased in children with Crohn’s disease and ulcerative colitis regardless of clinical activity of the disease suggesting that it may be a potential biomarker of IBD. Inverse correlation between cathelicidin and fecal calprotectin may imply a disparate role of these molecules in the pathophysiology of pediatric ulcerative colitis.

Anti-tumor necrosis factor-induced lupus in patients with inflammatory bowel disease: a hospital-based cohort study from Korea.

Background:Anti-tumor necrosis factor (TNF) agents are increasingly used for rheumatic diseases and inflammatory bowel disease (IBD), but are associated with the development of anti-TNF-induced lupus (ATIL). Nonetheless, few ATIL studies on non-Caucasian IBD patients exist. Here, we investigated the incidence, clinical features, and risk factors of ATIL in Korea.Methods:We retrospectively reviewed the medical records of IBD patients undergoing anti-TNF therapy at our tertiary IBD center between 2008 and 2020. ATIL was diagnosed as a temporal association between symptoms and anti-TNF agents, and the presence of at least one serologic and non-serologic American College of Rheumatology criterion. The risk factors for ATIL occurrence were assessed using multivariate Cox regression analysis.Results:Of 1362 IBD patients treated with anti-TNF agents, 50 (3.7%) ATIL cases were suspected, of which 14 (1.0%) received a definitive diagnosis. Arthritis and mucocutaneous symptoms were observed in 13 and 4 patients, respectively. All ATIL cases were positive for anti-nuclear and anti-dsDNA antibodies. Four patients (30.8%) improved while continuing anti-TNF therapy. At the final follow up, the ATIL group (n = 14) had a lower IBD remission rate (30.8% versus 68.8%, p = 0.019) than the non-ATIL group (n = 36). Ulcerative colitis and longer disease duration were associated with ATIL occurrence, with hazard ratios of 7.017 (p = 0.005) and 1.118 (p = 0.002), respectively.Conclusion:Although rare, ATIL is associated with poor treatment response to IBD in Korean patients. ATIL should be considered if arthritis and mucocutaneous symptoms develop during anti-TNF therapy for IBD.

Sarcoidosis development during ulcerative colitis remission in a patient with a susceptible human leukocyte antigen serotype.

The combination of sarcoidosis and ulcerative colitis (UC) is very rare, and its pathogenesis remains unknown. Hereditary factors as well as environmental factors have been speculated, including an association with the human leucocyte antigen (HLA) genotype. A 62-year-old Japanese woman with UC presented with complaint of a cough. Abnormal shadows were evident on the chest X-ray during mesalazine therapy. Multiple indolent subcutaneous nodules were also detected. Transbronchial lung and skin biopsies showed non-caseous epithelioid granulomas, which were pathologically compatible with sarcoidosis. After steroid therapy, she became asymptomatic and the abnormal shadows and subcutaneous nodules disappeared. HLA serological typing revealed that she harbored the sarcoidosis-related HLA-DR14 allele, as well as UC-related HLA-B52 and HLA-DR15 alleles. This case suggests that a susceptible HLA genotype may influence the onset of the combination of sarcoidosis and UC.

Correlation of Biomarkers with Endoscopic Score: Ulcerative Colitis Endoscopic Index of Severity (UCEIS) in Patients with Ulcerative Colitis in Remission.

Background and Objectives: Ulcerative colitis is a disease with an unpredictable evolution, often highlighted endoscopically, that is associated with persistent inflammation affecting the patient’s quality of life. An attempt was made to discover surrogate markers to evaluate the endoscopic remission of the disease in order to increase the patient’s quality of life and also their adherence to the treatment and monitoring plan. One such marker is fecal calprotectin (FC). To confirm the correlation between biomarkers and endoscopic disease activity and to define the optimal cut off value to detect clinical and endoscopic remission in a center of Romania. Materials and Methods: This was a prospective study that included 59 patients diagnosed with ulcerative colitis at the Department of Internal Medicine III, University Emergency Hospital of Bucharest. Patients had fecal calprotectin measurements and colonoscopy/rectosigmoidoscopy performed during baseline, 6 and 12 months. For endoscopic activity the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) was used. Results: During the study, relapses have occurred in 35.6% of patients, the median age was 47 years (21–77). During the study, the FC measurement was significantly increased at 3 months (median, range µg/g; 715, 14–4000) and at 6 months (median, range µg/g; 650, 4.5–3000) (p ≤ 0.05). Another inflammatory biomarker studied was CRP, which showed increased values at 3 months (median, range, mg/dL; 1.86, 0.14–58.9), at 6 months (median, range, mg/dL; 2.36, 0.12–45.8) and at 9 months (median, range, mg/dL; 2, 0.12–25.9) compared to the baseline (p = 0.01). Patients with recurrence of the disease also associated an increase in the values of clinical evaluation scores (SCCAI; p = 0.00001), but also endoscopic (UCEIS; p = 0.0006) Conclusion: A relapse is associated independently with younger age, the extension of the disease (E2-E3), increased FC level, C reactive protein, hemoglobin concentration, SCCAI index and UCEIS score.