Ulcerative Colitis In Clinical Remission Research Articles

Absence of Paneth Cell Metaplasia to Predict Clinical Relapse in Ulcerative Colitis with Endoscopically Quiescent Mucosa.

Paneth cells play multiple roles in maintaining intestinal homeostasis. However, the clinical role of Paneth cell metaplasia (PCM) in ulcerative colitis (UC) remains unclear. We aimed to investigate the relationship between PCM and relapse in patients with UC and compare the usefulness of PCM with other histological indexes, including mucin depletion (MD) and basal plasmacytosis (BP). Patients with UC in clinical remission (CR) who underwent colonoscopy to confirm a Mayo endoscopic subscore (MES) ≦1 with biopsies from the distal colon were enrolled into this retrospective cohort study. Biopsy samples were evaluated for histological findings of PCM, MD, and BP. Clinical relapse was defined as partial Mayo score ≧3 or medication escalation. Multivariate analysis was performed to determine independent predictors of relapse among the three histological findings, MES, and patient background, and relapse prediction models were generated. Eighty-three patients were enrolled in this study (MES 0, n = 47; MES 1, n = 36). The number of PCM cases was significantly higher in patients with prolonged CR than that in those with relapse (p = 0.01). Multivariate analysis showed that the absence of PCM and MD were related to relapse in all the patients. In patients with MES 1, the absence of PCM was the only risk factor significantly and independently associated with relapse (hazard ratio, 4.51 [1.15-17.7]; p = 0.03). The absence of PCM was a histological risk factor for relapse in patients with MES 1, implying a protective role for PCM in remission and a new index for mucosal healing.

Efficacy and safety of probiotics in IBD: An overview of systematic reviews and updated meta-analysis of randomized controlled trials.

Probiotics show promise in inflammatory bowel disease (IBD), yet knowledge gaps persist. We performed an overview of systematic reviews and an updated metanalysis of randomized controlled trials (RCT) assessing the effect of probiotics on Crohn's disease (CD) and ulcerative colitis (UC). MEDLINE, Web of Science, and the Cochrane Central Register of Controlled Trials were searched up to September 2023. Primary outcomes were clinical remission and recurrence; secondary outcomes included endoscopic response and remission, and adverse events. We calculated odds ratios (OR) using a random-effects model in R. The quality of systematic reviews was assessed using the AMSTAR-2; the trials' risk of bias was evaluated using the Cochrane Collaboration tool. Evidence certainty was rated using the GRADE framework. Out of 2613 results, 67 studies (22 systematic reviews and 45 RCTs) met the eligibility criteria. In the updated meta-analysis, the OR for clinical remission in UC and CD was 2.00 (95% CI 1.28-3.11) and 1.61 (95% CI 0.21-12.50), respectively. The subgroup analysis suggested that combining 5-ASA and probiotics may be beneficial for inducing remission in mild-to-moderate UC (OR 2.35, 95% CI 1.29-4.28). Probiotics decreased the odds of recurrence in relapsing pouchitis (OR 0.03, 95% CI 0.00-0.25) and trended toward reducing clinical recurrence in inactive UC (OR 0.65, 95% CI 0.42-1.01). No protective effect against recurrence was identified for CD. Multi-strain formulations appear superior in achieving remission and preventing recurrence in UC. The use of probiotics was not associated with better endoscopic outcomes. Adverse events were similar to control. However, the overall certainty of evidence was low. Probiotics, particularly multi-strain formulations, appear efficacious for the induction of clinical remission and the prevention of relapse in UC patients as well as for relapsing pouchitis. Notwithstanding, no significant effect was identified for CD. The favorable safety profile of probiotics was also highlighted.

Artificial intelligence-assisted video colonoscopy for disease monitoring of ulcerative colitis: A prospective study.

The Mayo endoscopic subscore (MES) is the most popular endoscopic disease activity measure of ulcerative colitis (UC). Artificial intelligence (AI)-assisted colonoscopy is expected to reduce diagnostic variability among endoscopists. However, no study has been conducted to ascertain whether AI-based MES assignments can help predict clinical relapse, nor has AI been verified to improve the diagnostic performance of non-specialists. This open-label, prospective cohort study enrolled 110 patients with UC in clinical remission. The AI algorithm was developed using 74713 images from 898 patients who underwent colonoscopy at three centers. Patients were followed up after colonoscopy for 12 months, and clinical relapse was defined as a partial Mayo score >2. A multi-video, multi-reader analysis involving 124 videos was conducted to determine whether the AI system reduced the diagnostic variability among six non-specialists. The clinical relapse rate for patients with AI-based MES = 1 (24.5% [12/49]) was significantly higher (log-rank test, P = 0.01) than that for patients with AI-based MES = 0 (3.2% [1/31]). Relapse occurred during the 12-month follow-up period in 16.2% (13/80) of patients with AI-based MES = 0 or 1 and 50.0% (10/20) of those with AI-based MES = 2 or 3 (log-rank test, P = 0.03). Using AI resulted in better inter- and intra-observer reproducibility than endoscopists alone. Colonoscopy using the AI-based MES system can stratify the risk of clinical relapse in patients with UC and improve the diagnostic performance of non-specialists.

Prebiotics for Induction and Maintenance of Remission in Inflammatory Bowel Disease: Systematic Review and Meta-Analysis.

Prebiotics are nondigestible carbohydrates fermented by gut bacteria into metabolites that confer health benefits. However, evidence on their role for inflammatory bowel disease (IBD) is unclear. This study systematically evaluated the research on prebiotics for treatment of IBD. A search was performed in PubMed, Embase, Cochrane, and Web of Science. Eligible articles included randomized controlled trials or prospective observational studies that compared a prebiotic with a placebo or lower-dose control in patients with IBD. Meta-analyses were performed using random-effects models for the outcomes of clinical remission, clinical relapse, and adverse events. Seventeen studies were included. For induction of clinical remission in ulcerative colitis (UC), the fructooligosaccharide (FOS) kestose was effective (relative risk, 2.75, 95% confidence interval, 1.05-7.20; n = 40), but oligofructose-enriched inulin (OF-IN) and lactulose were not. For maintenance of remission in UC, germinated barley foodstuff trended toward preventing clinical relapse (relative risk, 0.40; 95% confidence interval, 0.15-1.03; n = 59), but OF-IN, oat bran, and Plantago ovata did not. For Crohn's disease, OF-IN and lactulose were no different than controls for induction of remission, and FOS was no different than controls for maintenance of remission. Flatulence and bloating were more common with OF-IN; reported adverse events were otherwise similar to controls for other prebiotics. Prebiotics, particularly FOS and germinated barley foodstuff, show potential as effective and safe dietary supplements for induction and maintenance of remission in UC, respectively. The overall certainty of evidence was very low. There would be benefit in further investigation on the role of prebiotics as treatment adjuncts for IBD.

C-reactive protein-to-albumin ratio and neutrophil-to-albumin ratio for predicting response and prognosis to infliximab in ulcerative colitis.

The C-reactive protein-to-albumin ratio (CAR) and neutrophil-to-albumin ratio (NAR) serve as established markers for inflammatory diseases. However, limited studies have investigated their potential in predicting response and prognosis following infliximab (IFX) treatment. The objective of this paper was to evaluate feasibility of CAR and NAR as biomarkers to assess response to IFX induction therapy. Additionally, we attempted to determine the capacity to predict clinical remission in ulcerative colitis (UC) after 54 weeks of IFX treatment. We enrolled a total of 157 UC patients diagnosed via endoscopic mucosal biopsy at our hospital between October 2018 and June 2023. Additionally, 199 patients presenting with gastrointestinal symptoms, who underwent physical examinations, constituted the control group. Comprehensive clinical data, laboratory indicators, and endoscopic findings were systematically collected. CAR and NAR values were computed before treatment, post-induction, and subsequently at 8-week intervals. Comparisons between two groups were analyzed using the Wilcoxon rank-sum test or the independent samples t-test, and comparisons between multiple groups were analyzed using the one-way ANOVA (analysis of variance) or the Kruskal-Wallis rank sum test. We found CAR and NAR emerged as sensitive biomarkers for assessing disease activity. Notably, our findings indicated their dual predictive capability: foreseeing response post-IFX induction therapy and prognosticating the likelihood of UC patients achieving clinical remission following 54 weeks on IFX therapy.

P1210 Gut microbiota profiling and disease course in patients with ulcerative colitis in clinical remission

Abstract Background The inflammatory bowel diseases, encompassing ulcerative colitis (UC) and Crohn’s disease (CD) are characterized by a relapsing-remitting disease course. Despite achieving remission, approximately one-third of the patients relapse annually and yet the microbiota associated with relapse remains elusive. We hypothesized that distinctions in gut microbial composition among patients in clinical remission could potentially influence the disease course. We aimed to discern a distinctive microbial signature in patients with UC in clinical remission, which could serve as a predictive marker for the sustained clinical remission. Methods This was a prospective observational cohort study conducted as a collaborative work between Dayanand Medical College and Hospital (DMCH), Ludhiana, and Institute of Microbial Technology (IMTECH), Chandigarh. Adult (≥18 years age) patients with an established diagnosis of mild UC (defined as no previous requirement of immune-modulators or biologics to induce or maintain remission) and in clinical remission, were included between January 2019 and December 2020 and followed for one year. The clinical remission was defined as partial Mayo score <2 for at least 6 months, with endoscopic Mayo score 0 and fecal calprotectin <100 µg/g within 4 weeks of enrolment. Utilizing using 16S rRNA metabarcoding based metagenome analysis, the bacterial composition of the collected stool samples were determined. Results During the study period, 34 patients (mean age 41.41±13.89 years, 20 [58.82%] males) meeting the eligibility criteria were included for analysis and followed up for one year. (Figure 1) The majority of the patients (21, 61.76%) had left sided colitis. On follow-up, 14 patients (41.17%) experienced a disease relapse (median time to relapse 6 [3-8.25] months). The phyla Firmicutes, Actinobacteria, Bacteroidetes and Proteobacteria were abundant in both the groups [sustained remission (n=20) and disease relapse (n=14)], but specific phyla were enriched in each cohort, Actinobacteria in remission and Proteobacteria in relapse groups. The genera Escherichia, Klebsiella, Enterobacter, Enterococcus, Streptococcus were enriched in relapse group. Interestingly the genus Clostridium was enriched in relapsed cohort whereas genera like Bifidobacterium, Prevotella, Bacteroides, Alistipes, Faecalibacterium were abundant in the remission cohorts. Conclusion There are inter-individual differences in the gut microbiota profile of patients with UC in clinical remission. These microbial differences can serve as determinants of the disease course.

P514 Beyond the First Attempt: A Multi-Centre UK Analysis of Second JAK Inhibitor Use in Ulcerative Colitis

Abstract Background Tofacitinib, filgotinib, and upadacitinib are Janus Kinase inhibitors (JAKi) effective in inducing and maintaining remission in moderate-to-severe ulcerative colitis (UC). Limited data exists regarding outcomes in patients on a second JAKi after prior JAKi treatment failure. Here we describe the effectiveness of induction with a second JAKi in a cohort of UC patients. Methods In this retrospective cohort study, UC patients from 20 UK hospitals treated with a second JAKi were included. Clinical endpoints, as defined in Table 1, were assessed at week 8. Corticosteroid use, prior advanced therapies, and reason for cessation of first JAKi were documented. Results 99 patients commenced induction therapy with a second JAKi, 87% of whom had active disease by disease activity index, endoscopy or biomarkers. First JAKi was stopped due to failure or intolerance in 95% of cases. Tofacitinib was the most commonly used first JAKi (72%). Second JAKi was upadacitnib in 77% and filgotinib in 23%. There was no significant difference in the SCCAI (p=0.834) or pMayo (p=0.074) at baseline in those given either drug. Exposure to at least one other advanced therapy was seen in 78 patients, and 49 patients required steroids during induction. Both the median SCCAI and pMayo scores improved from 7 (SCCAI 5-9, pMayo 5-8) at baseline to 2 (SCCAI 0-3) and 1 (pMayo 0-3) at 8 weeks (p<0.001). Paired endoscopy results were available in 27 patients, showing an overall improvement from a median UCEIS 5 (5-6) and MES 2 (2-3) to 1.5 (0-5) and 1 (1-2.5) respectively (UCEIS p<0.001, MES p=0.019). Median faecal calprotectin reduced from 650 (331-1500) to 62 (31-173) in 45 patients (p<0.001) (figure 1B). Of the 82 patients with paired disease activity index at baseline and 8 weeks, 52% achieved clinical remission (figure 1A) of whom 93% (40/43) were in steroid-free remission, 64% (9/14) in endoscopic remission and 88% (22/25) in biochemical remission. There was no significant difference in remission rates depending on disease extent, number of previous advanced therapies, first or second JAKi, or reason for cessation of first JAKi including primary non-response (p=0.99). Serious adverse events were admission for IV steroids, colectomy and VTE (1 each), withdrawal due to adverse event n=1, zoster infections n=3. Conclusion on Our results suggest that treatment with filgotinib or upadacitinib following exposure to another JAKi can be effective in inducing clinical remission in UC. Efficacy was similar in our cohort regardless of mechanism of failure of the first JAKi or whether upadacitinib or filgotinib was used as a second JAKi. The observed safety profile was as expected especially with considerable risk of zoster infections.

P1164 Early monitoring of ustekinumab concentration after induction is related to clinical remission in ulcerative colitis & Crohn`s disease - STOCUSTE study

Abstract Background Ustekinumab (UST), an anti-interleukin-12/23 antibody, is used to treat moderate to severe inflammatory bowel disease (IBD). The STOCUSTE study includes IBD patients treated with UST at four teaching hospitals in Stockholm to provide long-term follow-up data. We investigated in a real-world setting the utility of therapeutic drug monitoring (TDM) to optimize treatment and correlated the serum concentrationof UST to clinical outcomes. Methods This retrospective study includes patients diagnosed with Crohn’s disease (CD) and ulcerative colitis (UC) treated with UST and followed until withdrawal of treatment for any reason, or until end of study,July 31, 2021. Concentration data and dosing interval were collected at each follow-up (3, 6, 9, 12, 24,36, 48, 60 months) in relation to presence of remission defined as Physician Global Assessment (PGA)= 0. Results In total, 418 patients were included, 322 (48% females) with CD and 96 (46% females) with UC. In 229 patients the UST concentration was analyzed at least once and never in the remaining 188 patients. In general, the UST serum concentrations were above 1 μg/ml. At 3 months follow-up, patients in remission had a significant higher concentration of UST compared to non-remitting patients. (Table 1) in the total cohort, as well as when analyzed separately in UC ad CD. There was no significant difference in UST concentrations at 6 months or later between patients in remission versus non-remission for either IBD diagnosis. Further, TDM was related to higher rates of remission at 3 months of follow-up. Conclusion In this study, early measurement of serum UST (≤3 months) correlated to the clinical response. Serum concentrations at later time points were similar in patients in remission and in patients with active disease. These results from a real-world setting might partly be explained by that serum concentrations were not taken in a systematic manner.

P810 Fecal microbiota transplantation in Ulcerative rectocolitis

Abstract Background The objective of this work was to carry out a systematic review of the literature to evaluate interventional trials that compare fecal microbiofa transplantation (FMT) with a control group and evaluate the incidence of remission of ulcerative colitis as an outcome. Methods The search was conducted using the database from PubMed, from February 2021 to April 2023. In all, 303 articles were found. After reading the titles, 43 articles were selected for the abstract reading. After all the analysis with inclusion and exclusion criteria, 7 articles were fully analyzed in the present study. Of the 7 selected studies, 71% (5/7) performed clinical trials. Results In all the studies, a total of 352 patients were submitted to the FMT, with a average of 63 participants per study. The age of the participants vary from 18 to 75 years old, with all the studies having an average age in the third or fourth decade. All articles included patients with clinical disease activity, and 85.7% used the Mayo severity index. Regarding the stool administered, in 71.4% of the studies the participants received frozen stool and the preparation was carried out with saline solution. The infusion was performed with colonoscopy on 85% (6/7) of the studies, however there was no standardized approach to the transplant protocol or preparation of the patients before the FMT. The association between the FMT and the clinical remission has been positive in 85% (6/7) of the studies. 4 of the 5 articles that evaluated the clinical response pointed to an improvement of the patients submitted to the transplant over the placebo group. The endoscopic remission were analyzed in all the 7 studies showing positive results in 43% (3/7) of them. The laboratory were performed in just 1 of the studies and they reported substantial improvement of the evaluated parameters of the FMT group. There was no significant difference between the risk of developing adverse effects between the FMT and the placebo groups. Conclusion The FMT has been shown to be effective on the induction of clinical remission of Ulcerative Colitis, however, clinical studies with greater scientific impact are needed to implement this new therapeutic modality.

A novel artificial intelligence–assisted “vascular healing” diagnosis for prediction of future clinical relapse in patients with ulcerative colitis: a prospective cohort study (with video)

Background and AimsImage-enhanced endoscopy (IEE) has attracted attention as a method for detecting inflammation and predicting outcomes in patients with ulcerative colitis (UC); however, the procedure requires specialist endoscopists. Artificial intelligence (AI)-assisted IEE may help non-experts to provide objective accurate predictions using optical imaging. We aimed to develop a novel AI-based system using 8853 images from 167 patients with UC to diagnose “vascular-healing” and establish the role of AI-based vascular-healing for predicting the outcomes of patients with UC. MethodsThis open-label, prospective cohort study analyzed data for 104 patients with UC in clinical remission. Endoscopists performed colonoscopy using the AI system, which identified the target mucosa as AI-based vascular-active or vascular-healing. Mayo endoscopic subscore (MES), AI outputs, and histological assessment were recorded for six colorectal segments from each patient. Patients were followed-up for 12 months. Clinical relapse was defined as a partial Mayo score >2 ResultsThe clinical relapse rate was significantly higher in the AI-based vascular-active group [23.9% (16/67)] compared with the AI-based vascular-healing group [3.0% (1/33)] (P=0.01). In a sub-analysis predicting clinical relapse in patients with MES ≤1, the area under the curve for the combination of complete endoscopic remission and vascular-healing (0.70) was increased compared with that for complete endoscopic remission alone (0.65). ConclusionsAI-based vascular healing diagnosis system may potentially be used to provide more confidence to physicians to accurately identify patients in remission of UC who would likely relapse rather than remain stable.

Rapidly achieving clinical remission in ulcerative colitis indicates better endoscopic and histological outcomes.

Clinical remission (CR) is the principal short-term treatment target in patients with ulcerative colitis (UC). However, whether rapidly achieving CR indicates better outcomes remains unclear. We aimed to explore the associations between the timing of CR and therapeutic outcomes in UC. This study included UC patients from the UNIFI trial. Week-2 CR and time to CR were the major variables of interest. Endoscopic remission (ER) at week 52 was the primary outcome. Multivariate logistic regression was performed to evaluate the association between variables and outcomes. Week-2 CR was associated with ER (aOR: 2.37 [95% CI: 1.28, 4.37], p=0.006) and Histological remission (HR) (aOR: 2.87 [95% CI: 1.42, 5.72], p=0.003) at week 52. Moreover, C-reactive protein (CRP) remission could further stratify patients without CR and predict week-52 outcomes. Patients with clinical activity+CRP remission (aOR: 0.49 [95% CI: 0.26, 0.93], p=0.039) and clinical activity+CRP activity (aOR: 0.24 [95% CI: 0.11, 0.52], p<0.001) had gradually decreased likelihood of achieving ER, when compared to those with CR. For time to CR, we found that the earlier to CR, the better endoscopic and histological outcomes patients would attain. Patients achieving CR at weeks 2, 4/8, 12/16 and >16 had gradually reduced proportions of ER (51.9% vs. 40.8% vs. 31.6% vs. 8.8%, p<0.001) and HR (37.0% vs. 19.8% vs. 17.1% vs. 6.1%, p<0.001) at week 52. Compared with week 2, achieving CR at weeks 4/8, 12/16 and >16 had 39%, 55% and 92% lower likelihoods of week-52 ER, respectively. Week-2 CR indicates better outcomes in UC patients receiving ustekinumab. Moreover, achieving CR more rapidly is associated with higher probability of ER and HR.

Reduction of Fecal Calprotectin Levels Induced by a Short Course of Escherichia Coli Nissle is Associated with a Lower Likelihood of Disease Flares in Patients with Ulcerative Colitis in Clinical Remission.

Fecal calprotectin (FC) is a biomarker of gut inflammation, and Escherichia coli Nissle 1917 (EcN) is a probiotic strain able to reduce gut inflammation and maintain disease remission in patients with inflammatory bowel disease (IBD). The aim is to assess the effects of EcN administration in patients with IBD in clinical remission and altered FC values. We prospectively included 82 patients with ulcerative colitis (UC) (n=49) and Crohn's disease (CD) (n=33) in clinical remission and with FC values above 250 mcg/g (T0) who were treated with EcN alone for 2 months. FC values were assessed at the end of EcN treatment (T1) and clinical disease activity at 3 months (T2). At T1 median FC values were significantly lower compared to T0 both in patients with CD (312 mcg/g vs 626 mcg/g, p<0.0001) and UC (100 mcg/g vs 584 mcg/g; p<0.0001). Patients with UC who experienced disease relapse at T2 had lesser reduction in median FC values at T1 (-229 mcg/g, vs -397 mcg/g, p=0.049), while in patients with CD we observed no statistically significant difference (-358 mcg/g, vs -427; p=0.568). In patients with UC, a reduction of at least 532 mcg/g in FC had an accuracy of 69.7% and a positive predictive value of 65.7% in predicting maintenance of remission. A short course of EcN was associated with a reduction of FC values in patients with IBD in clinical remission and baseline altered FC values, and in patients with UC this decrease was associated with maintenance of clinical remission.

Comparison of fecal calprotectin levels and endoscopic scores for predicting relapse in patients with ulcerative colitis in remission.

Although the usefulness of endoscopic scores, such as the Mayo Endoscopic Subscore (MES), Ulcerative Colitis Endoscopic Index of Severity (UCEIS), and Ulcerative Colitis Colonoscopic Index of Severity (UCCIS), and biomarkers such as fecal calprotectin (FC) for predicting relapse in ulcerative colitis (UC) has been reported, few studies have included endoscopic scores for evaluating the entire colon. To compare the usefulness of FC value and MES, UCEIS, and UCCIS for predicting relapse in patients with UC in clinical remission. In total, 75 patients with UC in clinical and endoscopic remission who visited our institution between February 2019 and March 2022 were enrolled. The diagnosis of UC was confirmed based on the clinical presentation, endoscopic findings, and histology, according to the current established criteria for UC. Fecal samples were collected the day before or after the colonoscopy for measurement of FC. Endoscopic evaluations were performed using MES, UCEIS, and UCCIS. The primary outcome measure of this study was the assessment of the association between relapse within 12 mo and MES, UCEIS, UCCIS, and FC. The secondary outcome was the comparison between endoscopic scores and biomarkers in enrolled patients with UC with mucosal healing. FC and UCCIS showed a significant correlation with UCEIS (r = 0.537, P < 0.001 and r = 0.957, P < 0.001, respectively). Receiver-operating characteristic analysis for predicting MES 0 showed that the area under the curve of UCCIS was significantly higher than that of FC (P < 0.01). During the 1-year observation period, 18 (24%) patients experienced a relapse, and both the FC and UCCIS of the relapse group were significantly higher than that of the remission group. The cut-off values for predicting relapse were set at FC = 323 mg/kg and UCCIS = 10.2. The area under the curve of the receiver-operating characteristic analysis for predicting relapse did not show a significant difference between FC and UCCIS. The accuracy of the endoscopic scores and biomarkers in predicting relapse was 86.7% for UCCIS, 85.3% for UCEIS, 76.0% for FC, and 73.3% for MES. The three endoscopic scores and FC may predict UC relapse during clinical remission. Among these scores, UCEIS may be the most useful in terms of ease of evaluation and accuracy.

Serum Activin A Is a Novel Biomarker of Endoscopic Activity in Ulcerative Colitis.

Endoscopic healing (EH) is the long-term therapeutic goal for ulcerative colitis (UC). Since repeated colonoscopies are inconvenient and invasive, a surrogate biomarker for endoscopic activity is needed. Activin A is one of the transforming growth factor-β superfamily of proteins and has been shown to be associated with intestinal inflammation. This single-center observational study included 27 Japanese patients with UC in clinical remission who underwent colonoscopy and blood sampling. We investigated the correlations between laboratory parameters, including serum activin A levels, and endoscopic activity, classified by the Mayo endoscopic subscore (MES) in these patients. This study included 15 males and 12 females. The median age was 44.0 years. In terms of endoscopic activity, five patients were diagnosed with MES 0, 14 patients with MES 1, seven patients with MES 2, and one patient with MES 3. The median serum activin level was 134.8 pg/mL (interquartile range (IQR), 105.3 - 188.1). Serum activin A levels were significantly correlated with the MES (Spearman's rank correlation coefficient r = 0.591, P = 0.001), which was better than that of C-reactive protein (CRP) (r = 0.487, P = 0.010). In the comparison between the EH group (MES 0) and non-EH group (MES 1-3), patients without EH had significantly higher serum activin A levels (Mann-Whitney U test, P = 0.047). A cutoff value of 133.6 pg/mL indicated non-EH with a sensitivity and specificity of 0.682 and 1.000, respectively. The area under the curve (AUC) of serum activin A for detecting non-EH was 0.791 (95% confidence interval (CI), 0.618 - 0.964), while that of CRP was 0.723 (95% CI, 0.504 - 0.941). The serum activin A level is a potential novel biomarker of endoscopic activity in UC.

Modificación de la dosis de mesalazina en función de los niveles de calprotectina fecal en pacientes con colitis ulcerosa en remisión clínica

BackgroundFaecal calprotectin (FC) shows an excellent correlation with endoscopic and histological activity of ulcerative colitis (UC) and it is the best predictor of clinical relapse. Our aim was to evaluate the usefulness of modifying the dose of mesalazine based on FC levels, in clinical practice. MethodsRetrospective, single-centre study in UC patients in clinical remission while treated with mesalazine which dosage was decreased (DOWN) or increased (UP) according to FC levels. The main endpoint was the long-term maintenance of clinical remission. ResultsA total of 56 patients were included (39 DOWN, 17 UP). In the DOWN group, the median baseline dose of mesalazine was 3.6g/day and the median baseline FC was 36μg/g. After a median follow-up of 22 months, 28% required rescue therapy. The cumulative relapse-free survival after tapering was 91% and 82% at 12 and 24 months, respectively. In the UP group, the median baseline dose of mesalazine was 2.4g/day, with a median baseline FC of 524μg/g. After a median follow-up of 12 months, 29% required rescue therapy. The cumulative relapse-free survival after dose increase was 86% and 72% at 12 and 24 months, respectively. ConclusionsMesalazine dose modification based on FC monitoring seems to be a safe strategy in patients with UC in clinical remission, with a probability of clinical relapse around 20% at two years.

Long-term follow-up of the red density pilot trial: a basis for long-term prediction of sustained clinical remission in ulcerative colitis?

Red density (RD) technology is an automated operator-independent endoscopic scoring system for disease activity in ulcerative colitis (UC). In this retrospective analysis we aimed to assess the predictive value of the RD sore for sustained clinical remission. All 39 patients from the RD pilot trial were evaluated for clinical outcome in a 5-year period. The highest RD score was considered for Receiver operating characteristic (ROC) analysis to determine the cut-off of the RD for the composite endpoint of treatment failure (defined as mortality, colectomy, hospitalizations, flares and UC therapy changes). Statistical significance was considered P < 0.05. Reassessment of the RD score was possible in 36 patients. The composite endpoint was reached in 17 of 39 patients. ROC analysis for clinical remission showed a RD cut-off of 65, area under the ROC was 0.68, sensitivity of 0.71, and a specificity of 0.63. A RD score of ≥ 65 demonstrated a statistically non-significant increase in composite endpoint (hazard ratio 0.49 (95% confidence interval 0.1871-1.280); P = 0.1453). In conclusion, the RD score may be an independent predictor of clinical remission in patients with UC for the disease course up to 5 years, but results of the ongoing PROCEED-UC trial are to awaited for definite conclusions.

Mirikizumab for inducing and maintaining clinical remission in ulcerative colitis.

Mirikizumab for inducing and maintaining clinical remission in ulcerative colitis.

Clinical and Endoscopic Outcomes After Upadacitinib Induction for Ulcerative Colitis: A Multicenter Retrospective Cohort Study.

In this retrospective cohort study, upadacitinib induction was effective in achieving steroid-free clinical remission of ulcerative colitis for the majority of patients. Adverse events leading to treatment discontinuation were rare and were consistent with the known safety profile of upadacitinib.

Mitochondrial remodeling and energy metabolism adaptations in colonic crypts during spontaneous epithelial repair after colitis induction in mice

Mucosal healing has emerged as a therapeutic goal to achieve lasting clinical remission in ulcerative colitis. Intestinal repair in response to inflammation presumably requires higher energy supplies for the restoration of intestinal barrier and physiological functions. However, epithelial energy metabolism during intestinal mucosal healing has been little studied, whereas inflammation-induced alterations have been reported in the main energy production site, the mitochondria. The aim of the present work was to assess the involvement of mitochondrial activity and the events influencing their function during spontaneous epithelial repair after colitis induction in mouse colonic crypts. The results obtained show adaptations of colonocyte metabolism during colitis to ensure maximal ATP production for supporting energetic demand by both oxidative phosphorylation and glycolysis in a context of decreased mitochondrial biogenesis and through mitochondrial function restoration during colon epithelial repair. In parallel, colitis-induced mitochondrial ROS production in colonic epithelial cells was rapidly associated with transient expression of GSH-related enzymes. Mitochondrial respiration in colonic crypts was markedly increased during both inflammatory and recovery phases despite decreased expression of several mitochondrial respiratory chain complex subunits after colitis induction. Rapid induction of mitochondrial fusion was associated with mitochondrial function restoration. Finally, in contrast with the kinetics expression of genes involved in mitochondrial oxidative metabolism and in glycolysis, the expression of glutaminase was markedly reduced in the colonic crypts both during colitis and repair phases. Overall, our data suggest that the epithelial repair after colitis induction is characterized by a rapid and transient increased capacity for mitochondrial ATP production in a context of apparent restoration of mitochondrial biogenesis and metabolic reorientation of energy production. The potential implication of energy production adaptations within colonic crypts to sustain mucosal healing in a context of altered fuel supply is discussed.

Prospects of using probiotics containing &lt;i&gt;Lactobacillus acidophilus&lt;/i&gt; in the prevention and treatment of gastrointestinal diseases

Aim theoretical analysis and systematization of the knowledge on using probiotics containingLactobacillus acidophilusin the prevention and treatment of diseases of the gastrointestinal tract.&#x0D; The bibliographic databases of the scientific libraries eLIBRARY.RU, Cochrane Library and CyberLeninka, the electronic resources of the Global Health platform, the sites of scientific publications ScienceDirect and Elsevier, MEDLINE and PubMed-NCBI were searched for the relevant information. Next, the full-text sources were analysed. We used structural-logical and analytical methods in this work.&#x0D; The probiotics containingLactobacillus acidophiluswere reported to enhance eradication therapy in the presence ofHelicobacter pyloriinfection, reduce pain and normalize bowel function in irritable bowel syndrome, normalize liver function, reduce liver enzymes, prevent the development of hepatic encephalopathy in non-alcoholic fatty liver disease, support clinical remission in ulcerative colitis. Also, they demonstrated the effectiveness for the prevention and treatment of antibiotic-associated diarrhea, including clostridial infection, and the improvement of intestinal microbiota. In many gastrointestinal diseases, the effect of probiotics had a high level of evidence. The beneficial properties of probiotics can be used in the development of functional food products for therapeutic and prophylactic purposes.