Disease Activity In Ulcerative Colitis Patients Research Articles

Microbial metabolite deoxycholic acid-mediated ferroptosis exacerbates high-fat diet-induced colonic inflammation

High-fat diet (HFD) has long been recognized as risk factors for the development and progression of ulcerative colitis (UC), but the exact mechanism remained elusive. Here, HFD increased intestinal deoxycholic acid (DCA) levels, and DCA further exacerbated colonic inflammation. Transcriptome analysis revealed that DCA triggered ferroptosis pathway in colitis mice. Mechanistically, DCA upregulated hypoxia-inducible factor-2α (HIF-2α) and divalent metal transporter-1 (DMT1) expression, causing the ferrous ions accumulation and ferroptosis in intestinal epithelial cells, which was reversed by ferroptosis inhibitor ferrostatin-1. DCA failed to promote colitis and ferroptosis in intestine-specific HIF-2α-null mice. Notably, byak-angelicin inhibited DCA-induced pro-inflammatory and pro-ferroptotic effects through blocking the up-regulation of HIF-2α by DCA. Moreover, fat intake was positively correlated with disease activity in UC patients consuming HFD, with ferroptosis being more pronounced. Collectively, our findings demonstrated that HFD exacerbated colonic inflammation by promoting DCA-mediated ferroptosis, providing new insights into diet-related bile acid dysregulation in UC.

Predictive Value of MHR and NLR for Ulcerative Colitis Disease Activity.

Numerous non-invasive serologic tests are available to diagnose and monitor ulcerative colitis (UC), but their accuracy levels are limited. Thus, there is a pressing need for a serologic biomarker with higher precision for clinical practice. This study aims to evaluate the predictive capacity of monocyte/HDL ratio (MHR) and neutrophil/lymphocyte ratio (NLR) for UC disease activity. We conducted a retrospective analysis of 81 UC patients and 77 age- and sex-matched healthy controls. UC patients were categorized into active and inactive groups based on the Mayo score. The Mayo endoscopic subscore classified them into mild-to-moderate and severe UC groups. The optimal cut-off values for diagnosing UC were 0.34 for MHR (85.7% sensitivity, 76.0% specificity, 88.9% positive predictive value, 70.4% negative predictive value) and 2.49 for NLR (66.1% sensitivity, 88.0% specificity, 92.5% positive predictive value, 53.7% negative predictive value). The optimal MHR and NLR cut-off values to differentiate between mild-to-moderate UC and severe UC were 0.38 (92.9% sensitivity, 56.6% specificity, 53.1% positive predictive value, 93.7% negative predictive value) and 3.46 (71.4% sensitivity, 88.7% specificity, 76.9% positive predictive value, 85.5% negative predictive value), respectively. NLR and MHR are simple yet effective biological predictors of disease activity in UC patients.

P177 C-reactive protein/albumin ratio: a novel biomarker for monitoring of the disease activity in Ulcerative Colitis patients

Abstract Background Fecal calprotectin (FC) is a reliable laboratory test for non-invasive assessment of disease activity in ulcerative colitis (UC) patients; it's high cost, absence of widespread availability and low patient adherence limits it's use as a potential surrogate for endoscopy. The association of higher C-reactive protein (CRP) and low albumin levels, both obtained from patient's sera, with disease acitivity in UC, is well established. C-reactive protein/albumin ratio (CAR) is suggested as a biomarker for evaluating disease activity in various inflammatory conditions. We aimed to evaluate association between CAR, FC, CRP and serum albumin values with disease activity in UC patients. Methods A single center, noninterventional retrospective chart review of adult UC patients treated with biologics at a tertiary center was performed. Routine clinical (stool frequency score – SFS, and rectal bleeding score – RBS), biochemical (CRP, serum albumin, FC), and endoscopic (Mayo Endoscopic Subscore – MES) findings were assessed prior to initiating biologics. Active UC was defined as SFS 2/3 + RBS 2/3 + MES 2/3. Differences between continuous variables were calculated using independent sample t-tests and Mann–Whitney U test. Sperman’s correlation and ROC curve analysis were carried out. The Z statistic was used to compare correlation coefficients and AUC. Results Total of 82 patients (52.2% females, mean age 40.3 ± 15.3 years, smokers 16.9%) with dominantly extensive UC (57.3%) were analysed. The CAR (0.175 vs 0.025; p=0.02) and FC (1363.5 vs 65.5; p=0.01) levels were significantly higher in active vs inactive UC patients. Positive correlation was observed between CAR (rs = 0.354, p = 0.01), FC (rs = 0.448, p = 0.001) and CRP (rs = 0.316, p = 0.005) with active UC. Although serum albumin (r's = - 0.093, p = 0.532) negatively correlated with disease activity it didn't reach statistical significance. There was no statistically significant difference between CAR and FC correlation coefficients. The area under the curve (AUC) for the diagnosis of active UC was 0.896 (SE: 0.058; 95% CI 0.73 - 0,983, p=0.015) and 0.994 (SE: 0.009; 95% CI 0.98 - 1, p=0.001) for CAR and FC, respectively. Although AUC for FC was higher compared to CAR it didn’t reach statistical significance (p = 0.1). The cut-off value associated with the active UC for CAR was 0.06 (sensitivity 77,2%, specificity 100%), and 120 mcg/g for FC (sensitivity 97.6%, specificity 100%). Conclusion There is good correlation between CAR and clinical as well as endoscopic disease activity in patients with UC, comparable to FC. CAR could be offered as a cheap and practical biomarker for detection of active UC disease.

Adherence to mediterranean diet in patients with inflammatory bowel disease.

Mediterranean diet may be beneficial for inflammatory bowel disease (IBD). The aim of this study was to evaluate the level of adherence to MD in Italian patients with IBD. Eighty consecutive outpatients with IBD, 62 with Crohn's Disease (CD) and 18 with Ulcerative Colitis (UC) were included in the study. Demographic and clinical data, previous and current medical history, nutritional status and Quality of Life (QoL) assessed with the Short Inflammatory Bowel Disease Questionnaire (SIBDQ) were assessed. Adherence to MD was studied with the Medi-Lite questionnaire. IBD patients reported a mean Medi-Lite score of 10.4 with no significant differences between CD and UC patients (p=0.543). Among CD patients, adherence to MD was higher in patients with inactive disease (p<0.001) than in patients during the active phase, while no significant difference was found regarding disease activity in UC patients. A significant negative correlation of the Medi-Lite score with SIBDQ score (r=-0.2; p=0.040) was found. MD adherence was lower in CD patients who had undergone ≥2 surgeries, whereas for patients with UC we found no significant differences in MD adherence in relation to pervious surgery. Adherence to MD in IBD is influenced by disease activity, QoL and patients' surgical history. A greater adherence to MD achieved with nutritional education may help improve quality of life and modulate disease activity.

P364 Patient reported outcomes, partial MAYO score and SCCAI are equally accurate in predicting mucosal healing in UC: final results form a prospective study

Abstract Background Optimal management of patients with ulcerative colitis (UC) requires the accurate assessment of disease activity. Endoscopic evaluation is considered the gold standard approach, but it is invasive. We aimed to determine how strong patient reported outcomes, clinical scores and symptoms correlate with endoscopy for assessment of disease activity in UC patients. Methods 171 patients were included prospectively and consecutively (age: 49 (IQR: 38-61) years, duration 12 (4-19)years, 79 females (46.2%), 57.3% extensive disease, 42.7% on biologicals) at the time of the colonoscopy. The 2 item patient reported outcome (PRO), partial MAYO, Simple Clinical Colitis Activity Index (SCCAI), Mayo endoscopic subscore (MES), Baron and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) scores were calculated. C reactive Protein (CRP) and fecal calprotectin (FCAL) was available in 83 and 45.6% of patients. 17.0% had clinical flare, treatment was escalated in 14.6% of patients. Sensitivity, specificity, PPV and NPV values were calculated, ROC analysis and K-statistics were performed. Results Rectal bleeding (RBS), stool frequency (SF) subscore of 0, or total PRO2 remission (RBS 0 and SF ≤1), partial MAYO (≤2) and SCCAI (≤2.5) remission were similarly associated to mucosal healing defined by MES (0 or ≤1) or Baron (0 or ≤1) scores (Table 1). PRO2 (AUCMES0/Baron0: 0.770/0.740, AUCMES0-1/Baron0-1: 0.868/0.858), SF (AUCMES0/Baron0:0.751/0.724, AUCMES0-1/Baron0-1:0842/0.820), RBS (AUCMES0/Baron0: 0.718/0.698, AUCMES0-1/Baron0-1: 0.814/0.845) partial Mayo (AUCMES0/Baron0: 0.823/0.788, AUCMES0-1/Baron0-1: 0.927/0.902) and SCCAI (AUCMES0/Baron0: 0.767/0.752, AUCMES0-1/Baron0-1:0.888/0.867) were similarly associated with mucosal healing in a ROC analysis. There was a strict association between MES 0 and Baron 0 (k=0.917) and UCEIS &amp;lt;4 and MES 0-1 (k=0.813), while moderate to fair agreement between UCEIS &amp;lt;4 and MES 0 (K=0.471) or Baron 0 (K=0.414)/Baron 0-1 (K=0.353), and between MES 0-1 and Baron 0-1 (K= 0.350) scores. Agreement between CRP and clinical remission or endoscopic healing (MES/Baron) was poor (K~0.2), while agreement between FCAL (&amp;gt;100 or &amp;gt;250) and RBS-PRO2 remission (K&amp;gt;100 or &amp;gt;250: 0.44-0.60) or pMAYO (K&amp;gt;100 or &amp;gt;250: 0.41-0.59) or MES/Baron 0 was moderate to good (K&amp;gt;100:0.53-0.52 and K&amp;gt;250:0.57-0.53). Conclusion We found no difference across accuracy of RBS, SF, PRO2, partial Mayo and SCCAI in predicting endoscopic healing. A strong association was found with high PPV for MES/Baron ≤1 and high NPV for MES/Baron 0. FCAL, but not CRP was associated to clinical and endoscopic remission.

DOP13 Artificial Intelligence (AI) in endoscopy - Deep learning for detection and scoring of Ulcerative Colitis (UC) disease activity under multiple scoring systems

Abstract Background Computer vision &amp; deep learning(DL)to assess &amp; help with tissue characterization of disease activity in Ulcerative Colitis(UC)through Mayo Endoscopic Subscore(MES)show good results in central reading for clinical trials.UCEIS(Ulcerative Colitis Endoscopic Index of Severity)being a granular index,may be more reflective of disease activity &amp; more primed for artificial intelligence(AI). We set out to create UC detection &amp; scoring,in a single tool &amp; graphic user interface(GUI),improving accuracy &amp; precision of MES &amp; UCEIS scores &amp; reducing the time elapsed between video collection,quality assurance &amp; final scoring.We apply DL models to detect &amp; filter scorable frames,assess quality of endoscopic recordings &amp; predict MES &amp; UCEIS scores in videos of patients with UC Methods We leveraged&amp;gt;375,000frames from endoscopy cases using Olympus scopes(190&amp;180Series).Experienced endoscopists &amp; 9 labellers tagged~22,000(6%)images showing normal, disease state(MES orUCEIS subscores)&amp; non-scorable frames.We separate total frames in 3 categories:training(60%),testing(20%)&amp;validation(20%).Using a Convolutional Neural Network(CNN)Inception V3,including a biopsy &amp; post-biopsy detector,an out-of-the-body framework &amp; blue light algorithm.Similar architecture for detection with multiple separate units &amp; corresponding dense layers taking CNN to provide continuous scores for 5 separate outputs:MES,aggregate UCEIS &amp; individual components Vascular Pattern,Bleeding &amp; Ulcers. Results Multiple metrics evaluate detection models.Overall performance has an accuracy of~88% &amp; a similar precision &amp; recall for all classes. MAE(distance from ground truth)&amp; mean bias(over/under-prediction tendency)are used to assess the performance of the scoring model.Our model performs well as predicted distributions are relatively close to the labelled,ground truth data &amp; MAE &amp; Bias for all frames are relatively low considering the magnitude of the scoring scale. To leverage all our models,we developed a practical tool that should be used to improve efficiency &amp; accuracy of reading &amp; scoring process for UC at different stages of the clinical journey. Conclusion We propose a DL approach based on labelled images to automate a workflow for improving &amp; accelerating UC disease detection &amp; scoring using MES &amp; UCEIS scores. Our deep learning model shows relevant feature identification for scoring disease activity in UC patients, well aligned with both scoring guidelines,performance of experts &amp; demonstrates strong promise for generalization.Going forward, we aim to continue developing our detection &amp; scoring tool. With our detailed workflow supported by deep learning models, we have a driving function to create a precise &amp; potentially superhuman level AI to score disease activity

Elevated systemic immune inflammation index level is associated with disease activity in ulcerative colitis patients

BackgroundIt has been confirmed that high Systemic immune-inflammation index (SII) levels usually indicate poor outcomes in various diseases, especially on malignancies. However, the clinical significance of the SII in ulcerative colitis (UC) patients is remain unclear. Therefore, the purpose of our paper is to analyze the levels of SII in UC patients and assess the relationship between the SII and disease activity. Materials and methodsWe studied 187 consecutive patients with UC and 185 age- and sex-matched healthy controls retrospectively. The Mayo scoring system was adopted to evaluate disease activity in UC patients. We collected clinical characteristics and laboratory parameters from hospital electronic medical records. ResultsThe SII levels were significantly higher in UC patients than those in healthy subjects (P < 0.001). Higher SII levels were observed in moderate and severe UC subgroups compared to mild or remission subgroups. Correlation analysis displayed that the SII levels were positively relatived with Mayo score (r = 0.469, P < 0.001), C reactive protein (CRP) (r = 0.480, P < 0.001), and erythrocyte sedimentation rate (ESR) (r = 0.336, P < 0.001), but negatively with haemoglobin (Hb) (r = −0.271, P < 0.001). A multiple linear regression analysis suggested that there was an independent correlation between Mayo score and SII (beta = 0.324, t = 4.241, P < 0.001). The receiver operating characteristic (ROC) curve revealed that the maximum area under the curve (AUC) was 0.711 (95% CI, 0.630–0.791, P < 0.001), and the cut-off value for diagnosing active UC was 485.95, the sensitivity was 0.641, and the specificity was 0.75. ConclusionsWe demonstrated that the SII was elevated significantly in UC patients and was closely related to the UC disease activity. In addition, the SII had a high discriminative capacity for active UC.

The Imbalance of Circulating Follicular Helper T Cells and Follicular Regulatory T Cells Is Associated With Disease Activity in Patients With Ulcerative Colitis

Ulcerative colitis (UC) is a chronic inflammatory bowel disease affecting the colon and rectum, in which the abnormality of B cells is involved in both its pathogenesis and progression. Follicular helper T cells (TFH) play an important role in assisting the immune function of human B cells in germinal centers, and follicular regulatory T cells (TFR) have the function of inhibiting TFH and germinal center B cell responses. The significance of circulating TFH and TFR in ulcerative colitis (UC) remains unclear. We analyzed peripheral blood of active and stable remission UC patients and found that circulating TFR was significantly decreased while TFH was increased in active UC patients. As to TFH subsets, TFH2 was elevated while TFH17 was decreased in active UC, with IL-4/IL-17A secretion enhanced. Helios+ and CD45RA−FoxP3high TFR cells were decreased while CD226+ and CD45RA+FoxP3int TFR cells were increased in active UC patients. The levels of new memory B cells, plasmablasts and serum IgG were significantly increased in active UC patients, and were positively correlated with TFH and TFH2, and negatively correlated with TFR. Serum CRP and Mayo Clinic scores were positively correlated with TFH and TFH2 but negatively correlated with TFR. Serum IL-12 and IL-21 were up-regulated while IL-10 was down-regulated in active UC. To conclude, an imbalance of circulating TFH and TFR cells is associated with disease activity in UC patients. Our results suggest a new mechanism for TFH and TFR imbalance in the pathogenesis of UC, providing a new perspective for theoretical research and therapeutic strategies for UC.

Sustained clinical benefit, improved quality of life, and reduced intestinal surgery from maintenance infliximab treatment in inflammatory bowel disease

Objectives: Anti-TNF treatment is established for patients with severe inflammatory bowel disease (IBD) refractory to conventional medication. However, long-term real-life observations are limited. We have monitored 200 patients with primary response to infliximab (Remicade®).Methods: Patients with either Crohn’s disease (CD) or ulcerative colitis (UC) who started IFX and had clinical response at 1 year were prospectively followed. C-reactive protein (CRP), albumin, fecal calprotectin (FCP), Harvey Bradshaw index (HBI) in CD cases, and Quality of Life index were monitored. Concomitant medications, surgery and hospitalisation were assessed.Results: Out of the 200 patients, 164 suffered from CD. Median disease duration was 5.0 (0.2–44.0) years and the observation time was 3.4 (1.0–13.9) years. Steroid use was reduced from 51% to 10%. HBI in CD patients decreased from 8.0 ± 0.40 to 2.7 ± 0.26. Disease activity in UC patients was only assessed by biochemical markers. CRP decreased from 29.0 ± 6.2 to 8.0 ± 7.1 mg/L. FCP showed a decrease from 1918 (1837) to 191 (646) mg/kg. Hospitalization showed similar tendency and quality of life was improved. Twenty-seven percent had been operated before IFX introduction compared to 11% during the observation period. Loss of response was seen in 42 patients, of which 20 patients needed intestinal surgery.Conclusion: Two-thirds of the patients demonstrated stable clinical benefit from maintenance IFX. The results show steroid-sparing efficacy as well as improved quality of life and reduced need for surgery.

P773 Patient reported outcomes, partial MAYO score and SCCAI are equally accurate in predicting mucosal healing in UC: Preliminary results from a prospective study

Abstract Background Optimal management of patients with ulcerative colitis (UC) requires the accurate assessment of disease activity. Endoscopic evaluation is considered the gold standard approach, but it is invasive. We aimed to determine how strong patient reported outcomes, clinical scores and symptoms correlate with endoscopy for assessment of disease activity in UC patients. Methods One hundred and thirty-six patients were included prospectively (age: 48 (IQR: 38–61) years, duration 12 (4–19) years, 63 females, 53.7% extensive disease, 40.4% on biologicals) at the time of the colonoscopy. The 2 item patient reported outcome (PRO), partial MAYO, Simple Clinical Colitis Activity Index (SCCAI), Mayo endoscopic subscore (MES), Baron and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) scores were calculated. C reactive Protein (CRP) and fecal calprotectin (FCAL) was available in 58.1 and 33.8% of patients. 20.7% had clinical flare, treatment was escalated in 17.8% of patients. Sensitivity, specificity, PPV and NPV values were calculated, ROC analysis and K-statistics were performed. Results Rectal bleeding(RBS), stool frequency(SF) subscore of 0, or total PRO2 remission(RBS0 and SF≤1), partial MAYO(≤2) and SCCAI(≤2.5) remission were similarly associated to mucosal healing defined by MES(0 or ≤1) or Baron (0 or ≤1) scores (Table 1). PRO2 remission (AUCMES0/Baron0:0.747/0.715, AUCMES0-1/Baron0-1:0.867/0.863), SF AUCMES0/Baron0:0.731/0.703, AUCMES0-1/Baron0-1:0851/0.839), RBS(AUCMES0/Baron0:0.708/0.685, AUCMES0-1/Baron0-1:0.828/0.835) partial Mayo (AUCMES0/Baron0:0.792/0.755, AUCMES0-1/Baron0-1:0.917/0.903) and SCCAI (AUCMES0/Baron0:0.738/0.724, AUCMES0-1/Baron0-1:0.908/0.880) were similarly associated with mucosal healing in a ROC analysis. There was a string association between MES and Baron (k=0.798), while moderate agreement between UCEIS and MES (K=0.451) or Baron (K=0.499) scores. Agreement between CRP and clinical remission or endoscopic healing (MES/Baron) was poor (K~0.2), while agreement between FCAL (&amp;gt;100 or &amp;gt;250) and RBS-PRO2 remission (K&amp;gt;250:0.56–0.61) or MES/Baron 0 was moderate to good(K&amp;gt;100:0.54-0.53 and K&amp;gt;250:0.50–0.54) Conclusion We found no difference across accuracy of RBS, SF, PRO2, partial Mayo and SCCAI in predicting endoscopic healing. A strong association was found with high PPV for MES/Baron ≤1 and high NPV for MES/Baron 0. FCAL, but not CRP was associated to clinical and endoscopic remission.

P087 Biomarkers of elastin degradation differentiate between clinically inactive and active disease in ulcerative colitis patients

Abstract Background In ulcerative colitis (UC), the state of chronic inflammation results in increased matrix metalloprotease (MMP) and serine protease activity, which effectively leads to a higher degree of intestinal tissue remodelling, including components of the extracellular matrix (ECM). One of these components is elastin a matrix protein of the interstitial matrix in the lamina propria and submucosa, providing tissue resilience and elasticity. As such, we investigated whether elastin degradation in UC patients was associated with disease activity and severity, potentially enabling patient differentiation based on elastin degradation. Methods Twenty-nine UC patients and 29 healthy donors were included in the study. Disease activity was determined according to the partial Mayo score (pMayo &amp;gt;1) and the Mayo Endoscopic Score (MES). Disease severity and extension was assessed using the Montreal classification. Disease severity was additionally assessed using the Trulove and Witt’s (TW) clinical score. The biomarkers of elastin degradation included: MMP-7 (ELM-7) cathepsin-G (EL-CG) and proteinase-3 (ELP-3), measured in serum by ELISA. One-way ANOVA (Kruskal–Wallis) correcting for the false discovery rate were applied for the statistical analysis. Results TW: ELP-3 levels in moderate-to-severe UC patients were significantly elevated in comparison with HD (p &amp;lt; 0.001). Partial Mayo: EL-CG levels in patients with active UC were significantly elevated in comparison with HD (p &amp;lt; 0.01), and UC patients in remission (p &amp;lt; 0.01). ELP-3 levels were likewise significantly elevated in active UC patients compared with HD (p &amp;lt; 0.001), and UC patients in remission (p &amp;lt; 0.01). Montreal classification: ELM-7 was significantly elevated in active UC compared with HD (p &amp;lt; 0.05), and UC patients in remission (p &amp;lt; 0.05). EL-CG were also significantly elevated in active UC compared with HD (p &amp;lt; 0.05), and UC patients in remission (p &amp;lt; 0.05). ELP-3 was significantly elevated in active UC compared with HD (p &amp;lt; 0.01). According to the MES score, ELP-3 levels in moderate-to-severe UC patients were significantly elevated in comparison to HD (p &amp;lt; 0.01). Conclusion The data presented in this study demonstrate an association between biomarkers of proteolytic elastin degradation and disease activity in UC patients especially the protease-3-derived biomarker, ELP-3, showed significant association with active UC in all the clinical scoring systems as well as the MES score. Utilising these minimally invasive elastin degradation biomarkers could serve as surrogate markers for monitoring of disease activity and potentially aid the differentiation of patients with an active disease from patients in remission or with a lower disease activity for UC.

P149 Ulcerative colitis patients with high calprotectin levels should undergo endoscopy within 7 days for therapeutic decision

Abstract Background Fecal calprotectin (FC) has considered as a useful surrogate marker to predict which patients with ulcerative colitis (UC) are in endoscopic activity. FC has to be collected at the time of endoscopy for more accurate correlation between FC and endoscopic disease activity. In real practice, however, both tests cannot be easy to perform at the same time. Therefore, the aim of this study was to evaluate the optimal time interval for the correlation between FC and endoscopic disease activity in UC patients. Methods We analysed retrospectively 103 cases (79 patients) that was performed FC measurement and endoscopy within 3 months. FC quantitative tests was defined as normal (&amp;lt;100 μg/g), mild (100–200, 100–250 or 100–300 μg/g), and moderate to severe activity (&amp;gt;200, &amp;gt; 250, or &amp;gt; 300 μg/g). Endoscopic activity was graded using the Mayo endoscopic subscore (MES). After assessing concordance between FC level and MES, we use the youden index method to estimate the optimal time interval between both tests using the receiver operator curves (ROCs). Results Among 79 UC patients, 64.5% (51/79) were male. The mean FC level was 673.6 ± 1054 μg/g. The mean interval between FC measurement and endoscopy was 13.8 ± 22.7 days. FC levels and MES were positively correlated (r = 0.473, p &amp;lt; 0.001). Using a ROC curve with a cut off value of FC 200 μg/g, the optimal cut-off of the time interval for separation of non-correlation and correlation between FC level and MES was 7 days with a sensitivity of 74.4% and a specificity of 50.0% (AUC 0.6032; 95% CI 0.4779–0.6896). Similarly, using ROC curves with a cut off value of FC 250 or 300 μg/g as a standard for dividing mild and moderate, the optimal cut-off of the time interval were all 5.5 days (FC 250, sensitivity 71.7%, specificity 49.1, AUC 0.5862, 95% CI 0.4728–0.6884; FC 300, sensitivity 69.6%, specificity 47.4, AUC 0.5549, 95% CI 0.4668–0.6513). Conclusion FC level within 7 days could reflect endoscopic disease activity in patients with UC. In patients with high-level FC more than 200 μg/g, endoscopic evaluation for therapeutic decision making should be performed within a maximum of 7 days.

Upregulated IL-17A secretion and CCR6 co-expression in Treg subsets are related to the imbalance of Treg/Th17 cells in active UC patients.

Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disease, which is characterized with overactive immune response. It is well established that the imbalance between Tregs and Th17 cells plays a pivotal role in pathogenesis of UC. In this study, we investigated the impact of functional changes in Treg subsets on Treg/Th17 ratio and further explored their clinical significance in the activity of UC. Treg subsets were comprehensively analysed using flow cytometry and in vitro cultured in both active and remission UC patients, of which nine active UC patients were further followed up. The correlation analyses were performed to explore the potential associations between Treg subsets and clinical indicators, as well as the impact of serum cytokines, detected by ELISA, on IL-17A secretion and CCR6 co-expression of Treg subsets. In active UC patients, we found CD45RA- FoxP3hi Tregs were obviously decreased and inversely correlated with disease activity, while CD45RA+ FoxP3lo Tregs were increased and positively correlated with disease activity. Meanwhile, IL-17A secretion and CCR6 co-expression levels in Tregs were significantly increased in active UC. Moreover, Tregs co-expressing CCR6 possesses higher level of IL-17A secretion. In nine followed up patients, we observed downregulated IL-17A secreting and CCR6 co-expression when achieving remission from active stage. In addition, IL-17A+ FoxP3+ and IL-17A+ FoxP3+ CCR6+ Tregs were positively correlated with serum IL-21 and disease activity, respectively. These findings suggested that upregulated IL-17A secretion and CCR6 co-expression in Treg subsets may be related to the imbalance between Tregs and Th17 cells and associated with the disease activity in UC patients.

Role of Fecal Calprotectin as a Noninvasive Indicator for Ulcerative Colitis Disease Activity.

It is essential in clinical management to determine the disease activity in ulcerative colitis (UC) patients. At present, the most accurate way of evaluating the UC severity is endoscopy with biopsy. Fecal calprotectin (FCP) is a non-invasive biomarker that is frequently used for monitoring of intestinal inflammation. The purpose of our study was to assess the role of FCP as a noninvasive indicator for UC disease activity. This prospective study enrolled 116 patients with UC (56 with quiescent UC and 60 with active UC) and 36 controls, referred for colonoscopy to our Center. Colonoscopy was performed in all the patients and the findings were graded according to Mayo endoscopic score (EMS) and UC endoscopic index of severity (UCEIS). FCP was analyzed in stool samples by means of point-of-care desk-top Quantum Blue® method. There was no significant difference between mean FCP levels in controls and UC patients in remission (р=0.205). Mean FCP in patients with active UC was significantly higher than that in controls (p<0.001) and in patients in remission (p<0.001). FCP significantly correlated with UCEIS (r = 0.869, p<0.001) and EMS (r = 0.814, p<0.001). The strong correlation with endoscopic disease activity suggests that FCP is a useful biomarker for noninvasive diagnosis and monitoring of disease activity in UC patients.

The effects of two vitamin D regimens on ulcerative colitis activity index, quality of life and oxidant/anti-oxidant status

BackgroundThe optimum dosage for vitamin D supplementation has not yet been elucidated in patients with Ulcerative colitis (UC). The aim of this study was to investigate the effects of two vitamin D regimens in UC patients with vitamin D deficiency.MethodsIn this double blind randomized clinical trial, 50 patients with mild to moderate UC, who met inclusion criteria, received either 1000 or 2000 IU/day of vitamin D (as low dose or high dose group, respectively) for 12 weeks. Serum 25-hydroxy vitamin D (25-OHD) level, total antioxidant capacity (TAC), and Total Oxidant Status (TOS), the inflammatory bowel disease questionnaire − 9 (IBDQ-9) score and the Simple Clinical Colitis Activity Index Questionnaire (SCCAI) score were assessed before and after intervention.ResultsAt the end of study, serum 25-OHD levels significantly increased in the high dose group (P < 0.001) and the increase was significantly more than low dose group (6.7 ± 3.8 ng/mL in the high dose group versus 0.2 ± 0.5 ng/mL in the low dose group) (P < 0.001). Serum TOS concentration decreased significantly (− 0.37 ± 0.26) only in the high dose group (P value = 0.023). There was no statistically significant change in serum TAC between two groups during the study. IBDQ-9 mean score significantly increased in high dose group compared to the low dose group (P value = 0.001) and SCCAI score in both groups reduced (− 2.58 ± 2.16 and − 0.9 ± 0.3 in high dose and low dose respectively), while this reduction was significant only in the high dose group (P value ≥0.001).ConclusionOur results indicate that 2000 IU daily dose of vitamin D can increase serum 25-OHD concentration, and quality of life, while it reduces disease activity in UC patients with vitamin D deficiency. We recommend assessment of the vitamin D status in all patients with UC because they may benefit from vitamin D therapy.

Skeletal muscle depletion correlates with disease activity in ulcerative colitis and is reversed after colectomy.

The body composition of patients with ulcerative colitis (UC) remains unclear. This study evaluated body composition in adult patients with UC and the associations of body composition with disease activity and surgical intervention. This study included 99 patients with UC, 105 with Crohn's disease (CD) and 60 controls. Skeletal muscle area (SMA), visceral fat area (VFA) and subcutaneous fat area (SFA) of the third lumbar vertebrae were evaluated by abdominal computed tomography. The effects of medical therapy and surgery on body composition in UC patients were determined. Sarcopenia was more frequent in UC patients (27.3%) than in controls (8.3%), but less frequent than in CD patients (59.0%). The prevalence of sarcopenia was significantly higher (33.8% vs. 4.5%, p<0.001), and SMA (144.26 vs. 182.32cm2, p<0.001), skeletal muscle index (SMI) (52.22 vs. 65.52cm2/m2, p<0.001) significantly lower, in UC patients with high (≥6) than low (<6) Mayo score, but SFA and VFA were similar. The prevalence of sarcopenia and alterations in body composition were reversed, along with UC disease activity, following medical treatment or surgery. SMA and SMI correlated significantly with disease activity in UC patients. Multivariate analysis showed that sarcopenia (odds ratio, 8.49; 95% confidence interval, 1.80-40.10; p=0.007) was a negative predictor of high Mayo score in UC patients. Sarcopenic patients with UC had high probability of need for colectomy in Kaplan-Meier survival curves. Sarcopenia is associated with high disease activity and poor clinical outcome in UC patients. Medical treatment and colectomy have positive effects on sarcopenia and skeletal muscle depletion.

MAIT cells are activated and accumulated in the inflamed mucosa of ulcerative colitis.

Ulcerative colitis (UC) is a chronic, relapsing and remitting, inflammatory disorder of the large intestine. Mucosal associated invariant T (MAIT) cells are a member of innate-like lymphocytes found abundantly in the mucosal tissue. The contribution of MAIT cells in the pathogenesis of UC is still unclear; therefore, this study aimed at investigating the role of these cells in patients with UC. The frequency of MAIT cells, as well as the production of cytokines and expression levels of activation markers by these cells in the peripheral blood of UC patients and healthy controls, was analyzed by flow cytometry. MAIT cells were also quantified in colon biopsies of UC patients using a confocal microscope. There was a significant reduction in MAIT cell frequency in the peripheral blood of UC patients compared with healthy controls (P < 0.0001). MAIT cells from UC patients secreted more interleukin (IL)-17 than healthy controls (P < 0.05). The expression levels of CD69 on these cells were correlated with disease activity and endoscopic scores and plasma levels of IL-18. Furthermore, MAIT cells increased in the inflamed mucosa, and their frequency was correlated with clinical and endoscopic disease activity in UC patients. The findings from this study indicate that MAIT cells could be associated with UC and may serve as potential biomarkers or therapeutic targets in UC.

Does serum 25 hydroxy vitamin D level predict disease activity in ulcerative colitis patients?

Background/Aim: There are controversial results regarding the relationship of serum 25 hydroxy vitamin D [25(OH)D] and ulcerative colitis (UC) activity. To address this issue, the current study was designed to evaluate the correlation of serum 25(OH)D level and disease activity in patients with UC.Method: All consecutively selected UC outpatients referred to a gastroenterology clinic were enrolled in 2014. UC was diagnosed based on clinical, colonoscopic and histologic findings by a gastroenterologist. The exclusion criteria consisted of the factors that might influence plasma 25(OH)D concentration including inadequate exposure or intake, reduced absorption and abnormal metabolism. Disease activity was assessed by ‘Truelove and Witts’ classification’.Results: Fifty UC patients with mean age of 36.98 (± 11.81) years were evaluated. Mean serum 25(OH)D concentrations were significantly higher in ‘mild disease activity’ group (27.06 ± 6.56 ng/ml) than ‘moderate disease activity’ group (11.14 ± 4.03 ng/ml). Lower serum 25(OH)D concentration was associated with an increased likelihood of exhibiting moderate disease activity [β = 0.37, 95% confidence interval (CI): 0.15–0.94, p value = 0.04].Conclusion: Lower serum 25(OH)D level might be associated with higher disease activity in UC patients with mild-to-moderate activity.

Comparison of energy metabolism and nutritional status of hospitalized patients with Crohn's disease and those with ulcerative colitis.

This study aimed to compare the nutritional status and energy expenditure of hospitalized patients with Crohn’s disease (CD) and those with ulcerative colitis (UC). Twenty-two hospitalized patients with CD and 18 patients with UC were enrolled in this study. We analyzed nutritional status upon admission by using nutritional screening tools including subjective global assessment, malnutrition universal screening tool, and laboratory tests. We measured resting energy expenditure (mREE) of the patients with indirect calorimetry and predicted resting energy expenditure (pREE) was calculated by using the Harris-Benedict equation. Results presented here indicate no significant difference in nutritional parameters and energy metabolism between CD and UC patients. In UC patients, a significant correlation was observed between mREE/body weight and disease activity detected by the Lichtiger and Seo indices. However, there was no correlation between mREE/body weight and Crohn’s disease activity index in CD patients. Inflammatory cytokine interleukin-6 levels correlated with mREE/pREE in CD and UC patients while tumor necrosis factor-α was not. In conclusion, energy expenditure significantly correlated with disease activity in UC patients but not in CD patients. These results indicate that establishing daily energy requirements based on disease activity of UC is imperative for improving the nutritional status of patients.

Fecal calprotectin and ulcerative colitis endoscopic activity index as indicators of mucosal healing in ulcerative colitis.

Ulcerative colitis (UC) is a chronic, idiopathic, inflammatory large bowel disease with recurrent variable periods of exacerbation. The aim of the current study is to evaluate the correlation of UCEIS with fecal calprotectin (FC) level to assess disease activity in UC patients in order to determine whether FC can prognosticate clinical outcome and disease activity of UC instead of colonoscopic evaluation. Our endoscopic investigations revealed the extension of UC as the following: proctitis (11.6%), procto-sigmoiditis (18.5%), left-sided colitis (15.8%), extensive colitis (11.7%), and normal endoscopy (42.4%). Conclusively, we suggest that FC can be used as a reliable tool to evaluate disease activity in ulcerative colitis patients. Moreover, our findings indicate a significant correlation between FC level and mucosal healing.