UC Activity Research Articles

Clinical Utility of Disease Activity Indices in Predicting Short-Term Response to Biologics in Patients with Ulcerative Colitis.

Background: The Mayo Score [MS], endoscopic Mayo Score [eMS] and the Ulcerative Colitis Index of Severity [UCEIS] are employed in the assessment of ulcerative colitis [UC] severity. This study compared the aforementioned indices in terms of predictory value for response to remission induction treatment with anti-TNF and anti-integrin biologics. Methods: A total of 38 patients were retrospectively evaluated in the study, 23 male and 15 female, aged 18-74 years old who had undergone a total of 53 biological therapy courses with either infliximab [IFX] or vedolizumab [VDZ] at the Department of Gastroenterology of the Medical University of Łódź. The clinical and endoscopic activity of UC was assessed at the outset of biological therapy and the 14th week remission induction assessment juncture. Results: The study analyzed 19 IFX and 34 VDZ treatment courses. The response rate of patients receiving IFX reached 73.67% and the response rate was 58.82% for VDZ. The mean MS, eMS and UCEIS improved among all patient groups: 8.316 ± 1.974 to 4.158 ± 2.218 (p < 0.05), 2.632 ± 0.597 to 1.790 ± 0.713 (p < 0.05) and 4.790 ± 1.745 to 3.000 ± 1.453 (p < 0.05) for IFX, 7.088 ± 2.234 to 3.618 ± 2.412 (p < 0.05), 2.706 ± 0.524 to 1.677 ± 1.065 (p < 0.05) and 4.235 ± 1.350 to 2.735 ± 1.880 (p < 0.05) for VDZ. Conclusions: The outcome assessment in induction treatment of UC includes clinical data and endoscopic evaluation. Severity of inflammatory lesion activity according to the eMS and UCEIS indices correlates with the overall disease presentation as evaluated with MS. The UCEIS provides an overall better predictor for biological induction treatment when compared with the eMS in both patient groups, particularly in those receiving VDZ. It provides a promising alternative to the eMS and can be employed for both initial disease severity assessment as well as for treatment response monitoring.

P146 Latent activation of the extrinsic coagulation pathway in patients with ulcerative colitis

Abstract Background Ulcerative colitis (UC) is associated with an increased risk of venous thromboembolism. We investigated the correlation of UC severity with latent activation of the extrinsic coagulation pathway and colonic stromal tissue factor (TF) expression. Methods Plasma exosomes, microparticles (EM), TF protein, activities of EM-bound TF (EM-TF) and FVIIa, as well as TF mRNA (F3) in primary colonic stromal cells in culture were measured. Disease extent by Montreal classification, medications, UC clinical activity by partial Mayo score (PMS), endoscopic severity by the MS endoscopic component (eMS; loss of response defines as ≥2), quality of life by the short IBD questionnaire- SIBDQ, complete blood count, CRP, ESR and albumin were retrieved. Statistical significance (p) was assessed with the following tests: Student’s t for 2 groups with normally distributed values, Mann-Whitney U if not, Wilcoxon test for paired data. Correlation of continuous against scale variables was assessed with Pearson’s or Spearman’s r and corresponding p values for linear or logarithmic continuous variables, respectively. Results Plasma was obtained from 38 UC patients (31 males, disease duration 151±25 months, 14 with extensive colitis, 5 current smokers) and 28 healthy blood donors (HBD; 20 males) who served as controls. TF mRNA (F3) was measured in primary colonic stromal cells in culture from 12 UC patients (11 males, disease duration 169±53 months, 8 with extensive colitis, 1 current smoker) and from 7 controls undergoing screening colonoscopy. UC patients had 4- and 3.7- times more exosomes and microparticles than controls, respectively (A). TF protein correlated with PMS (r 0.443), albumin (-0.362), ESR (0.353), PLT (0.575) and endoscopic UC severity (0.468; B). EM-TF activity was 1.6-times higher (C) and correlated to disease extent (E3: 1.9 x E2), albumin (-0.624), endoscopic severity (0.422; D) and SIBDQ (-0.64). Downstream, FVIIa activity was 2.2-times higher. Refractory-to-treatment patients had 5.8-, 1.5-, 2.1- times higher TF protein (E), MP-TF, FVIIa activity, respectively. Within responders, the need for steroids or biologics correlated with 2.2-times higher MP-TF activity. Colonic stromal cells from patients with UC maintained a 2.2-times higher F3 (F), which correlated to PMS (0.56), albumin (Spearman’s r -0.543), endoscopic severity (M3: 8.3 x M2). All the aforementioned were statistically significant with a &amp;lt; 0.05. Conclusion The extent of spontaneous activation of the extrinsic coagulation pathway is associated with clinical and endoscopic UC activity and response to treatment. TF in colonic stromal cells mirrors its systemic activity and indicates the possible contribution of such cells to increased TF plasma bioactivity.

Neutrophil Gelatinase-Associated Lipocalin as a Marker of Disease Activity in Patients with Ulcerative Colitis Disease

Abstract Background Inflammatory bowel disease (IBD) is an idiopathic disease caused by a dysregulated immune response to host intestinal microflora. Although the etiology of IBD remains largely unknown, it involves a complex interaction between the genetic, environmental, or microbial factors and the immune responses. Aim of the Work This study will assess the the role of neutrophil gelatinase-associated lipocalin (NGAL) as a marker of disease activity in patients with Inflammatory bowel disease. Patients and Methods A cohort prospective study. The study conducted at Ain Shams University Hospitals. The study will take place from August 2020 to February 2021. Our study conducted on 60 Egyptian person over 18 years old visiting the outpatient clinics or admitted in Ain Shams University Hospitals. The study conducted on 40 Egyptian patients with inflammatory bowel disease. Results The present study revealed a highly significant elevation of serum NGAL in active IBD patients with p-value &amp;lt;0.001 which show direct relationship between the activity and severity of UC and CD disease and serum NGAL was positively correlated with inflammatory markers (CRP and ESR) in UC and CD patients. And there is negative relation between serum hemoglobin and NGAL. Conclusion Serum NGAL is a valuable noninvasive marker in the assessment of activity in IBD patients correlated positively with inflammatory markers (CRP and ESR) and markers of disease activity (UCAI and UC histopathology grading in UC patients and clinical CDAI in CD patients). Other studies should be done on larger size of participants to determine the the role of neutrophil gelatinase-associated lipocalin (NGAL) as a marker of disease activity in patients with Inflammatory bowel disease.

Accuracy of Transperineal Ultrasonography for Assessing Rectal Lesions in Paediatric Ulcerative Colitis: A Prospective Study.

Transabdominal ultrasonography [TAUS] appears comparable to colonoscopy for evaluating ulcerative colitis [UC] activity, but it has low accuracy in rectal evaluation. In this study, the accuracy of transperineal ultrasonography [TPUS] for evaluating rectal activity was compared to that of colonoscopy in paediatric UC cases. Faecal calprotectin [FCP] values and TPUS and colonoscopic findings were compared prospectively in paediatric UC cases. Rectal wall thickening [RWT] and rectal wall flow [RWF] on power Doppler evaluated by TPUS were compared with the colonoscopy findings and were also measured on TAUS and assessed for the concordance rate of each finding. Thirty Mayo endoscopic sub-score [MES] 0-1 UC cases and 57 MES 2-3 UC cases were enrolled. FCP, RWT and RWF showed significant differences between the two groups [p < 0.05]. RWT and RWF were independent predictors of UC endoscopic activity, showing sensitivity of 95.8% and specificity of 100% with RWT ≥ 4.5 mm and positive RWF. The concordance rates between TPUS and TAUS findings in MES 2-3 were moderate to fair, whereas those in MES 0-1 were fair to poor. The concordance rates between ultrasonic examiners were good for both TAUS and TPUS. TPUS may evaluate rectal activity of UC with accuracy comparable to endoscopy. If accurate ultrasonic screening for the total colon can be performed by TPUS and TAUS, repeated evaluation of short-term treatment response may be possible.

Hocus Pocus: the Role of Hand-held Ultrasonography in Predicting Disease Extension and Endoscopic Activity in Ulcerative Colitis.

Ulcerative colitis [UC] assessment still requires ileocolonoscopy [IC]. Intestinal ultrasound [IUS] has emerged as a non-invasive assessment tool, and the Milan Ultrasound Criteria [MUC] score has been validated to estimate and grade UC disease activity. Recently, hand-held IUS [HHIUS] has been used in several clinical settings, but data about its use in UC are limited. We aimed to evaluate the diagnostic accuracy of HHIUS compared with conventional IUS in detecting UC extension and activity. From November 2021 to September 2022, we prospectively enrolled UC patients afferent to our third-level IBD Unit for IC evaluation. Patients underwent IC, HHIUS, and IUS. Ultrasound activity was defined by MUC >6.2, and endoscopic activity was defined by a Mayo endoscopic score [MES] >1. Cohen's k test was applied to test the concordance between IUS-MUC and HHIUS-MUC after MUC dichotomisation [MUC >6.2, yes/no]. In all, 86 patients with UC were enrolled. No significant difference was recorded between IUS and HHIUS at the per-segment extension [p = N.S.], and both procedures were comparable in terms of results of bowel wall thickness [BWT] and bowel wall stratification [BWS] assessment [p = N.S.]. IUS and HHIUS displayed excellent agreement when the MUC score system was applied [k = 0.86, p <0.01]. Hand-held intestinal ultrasound and IUS are comparable in UC extension definition and MUC evaluation. HHIUS could be reliable for detecting disease activity and estimating its extension, providing close monitoring. It also represents a non-invasive, easily practicable investigation, allowing immediate medical decisions with significant time and cost advantages.

P295 Hocus Pocus: The Role Of Hand-Held Ultrasonography In Predicting Disease Extension And Endoscopic Activity In Ulcerative Colitis

Abstract Background Ulcerative colitis (UC) diagnosis and monitoring still require ileo-colonoscopy (IC) as the reference standard. Bowel sonography (BS) has recently emerged as a non-invasive assessment tool, and Milan Ultrasound Criteria (MUC) score has been validated to estimate and predict UC disease activity. Recently, hand-held BS (HHBS) has been used effectively in several clinical settings (e.g. cardiology, orthopedy, gynaecology), while data about its use in UC are still limited. We aimed to evaluate the diagnostic accuracy of HHBS compared to conventional bowel sonography (BS) in predicting UC extension and activity compared to endoscopy. Methods From November 2021 to September 2022, we prospectively enrolled consecutive UC patients afferent to our third-level IBD Unit for IC evaluation. Patients underwent IC, HHBS, and BS, and the operators were blinded by the other procedure results. Endoscopy was considered the reference standard for UC extension. Cohen’s k test was applied after MUC dichotomization to test the concordance between BS-MUC and HHBS-MUC following Allocca et al. (MUC &amp;gt;6.2: yes/no). Results At the end of the study, 86 patients with UC were examined. No significant difference was recorded between BS and HHBS in terms of UC at the per-segment extension (p: N.S.) (table 1), and both procedures were comparable regarding colonic wall thickness (CWT) and colonic wall pattern (CWP) assessment (figure 1 and 2). Regarding the prediction of endoscopic activity, BS and HHBS displayed excellent agreement when applying the MUC score system (k = 0.86, p&amp;lt;0.01) (figure 3). Conclusion Hand-held bowel sonography and BS are comparable in defining UC extension and MUC evaluation in the UC setting. HHBS could be reliable for detecting disease activity and estimating its extension, providing close monitoring of the treat-to-target paradigm. It also represents a non-invasive, easily practicable investigation during a physical examination, allowing immediate medical decisions with significant time and cost advantages.

Epigenetic DNA methylation of Zbtb7b regulates the population of double-positive CD4+CD8+ T cells in ulcerative colitis

Background and aimsUlcerative colitis (UC) is a heterogeneous disorder with complex pathogenesis. Therefore, in the present study, we aimed to assess genome-wide DNA methylation changes associated explicitly with the pathogenesis of UC.MethodsDNA methylation changes were identified by comparing UC tissues with healthy controls (HCs) from the GEO databases. The candidate genes were obtained and verified in clinical samples. Moreover, the underlying molecular mechanism related to Zbtb7b in the pathogenesis of UC was explored using the dextran sodium sulfate (DSS)-induced colitis model.ResultsBioinformatic analysis from GEO databases confirmed that Zbtb7b, known as Th-inducing POZ-Kruppel factor (ThPOK), was demethylated in UC tissues. Then, we demonstrated that Zbtb7b was in a hypo-methylation pattern through the DSS-induced colitis model (P = 0.0357), whereas the expression of Zbtb7b at the mRNA and protein levels was significantly up-regulated in the inflamed colonic tissues of UC patients (qRT-PCR, WB, IHC: P < 0.0001, P = 0.0079, P < 0.0001) and DSS-induced colitis model (qRT-PCR, WB, IHC: P < 0.0001, P = 0.0045, P = 0.0004). Moreover, the expression of Zbtb7b was positively associated with the degree of UC activity. Mechanically, over-expression of Zbtb7b might activate the maturation of CD4+T cells (FCM, IF: P = 0.0240, P = 0.0003) and repress the differentiation of double-positive CD4+CD8+T (DP CD4+CD8+T) cells (FCM, IF: P = 0.0247, P = 0.0118), contributing to the production of inflammatory cytokines, such as TNF-α (P = 0.0005, P = 0.0005), IL-17 (P = 0.0014, P = 0.0381), and IFN-γ (P = 0.0016, P = 0.0042), in the serum and colonic tissue of DSS-induced colitis model.ConclusionsEpigenetic DNA hypo-methylation of Zbtb7b activated the maturation of CD4+T cells and repressed the differentiation of DP CD4+CD8+ T cells, resulting in the production of inflammatory cytokines and colonic inflammation in UC. Therefore, Zbtb7b might be a diagnostic and therapeutic biomarker for UC, and hypo-methylation might affect the biological function of Zbtb7b.

A57 ULCERATIVE COLITIS DISEASE ACTIVITY IS DOMINATED BY INNATE IMMUNITY AND FEATURES OF TISSUE REMODELING

BackgroundUlcerative colitis (UC) is a chronic inflammatory condition affecting the colonic epithelium, with potential roles for the inflammasome, complement activation, T cells, and the microbiome in pathogenesis. We applied an established method of microarray-based gene expression analysis to a set of 128 UC biopsies (from 113 patients), to elucidate the molecular changes associated with active UC.AimsOur aim was to describe the molecules most associated with UC disease activity (the endoscopic Mayo score) and to annotate these molecules into biological processes.Methods128 UC colonic biopsies were collected at the University of Alberta Hospital (Edmonton, Alberta) and Cedars-Sinai Hospital (Los Angeles, California) during standard of care colonoscopy. Biopsies were processed using Affymetrix microarrays. Gene expression data from the population was visualized using volcano plots (showing fold change and association between genes and endoscopic Mayo score), and heatmaps (showing expression of the top 30 genes in a previously established cell panel). Overexpression of top genes was analyzed using Gene Ontology and KEGG pathways.ResultsThe volcano plot (Figure 1A) showed strong associations between the endoscopic Mayo score and components of innate immunity, e.g. complement factor B (CFB), C1-inhibitor (also known as SERPING1), chitinase 3-like 1 (CHI3L1), and inflammasome genes (ZBP1 and PIM2). Moderate associations with calprotectin (S100A8 and S100A9), other inflammasome components (CASP1 and NLRP3), and T cell transcripts (i.e. CTLA4, PDL1) were observed. Targets of biologic therapy (TNFA, ITGA4/B7, IL12B) were weakly associated with the endoscopic Mayo score.Expression of the top genes in a cell panel (Figure 1B) showed primary expression in monocytes, macrophages, dendritic cells, and polymorphonucleocytes, with some expression in colon epithelial and endothelial cells. Minimal expression was found in CD4/CD8 T cells or NK cells.Pathway analysis represented extracellular matrix remodeling, complement regulation, and TNFA signaling, but revealed no pathways associated with adaptive immunity (Table 1).ConclusionsUC disease activity, as assessed by the endoscopic Mayo score, was strongly associated with tissue remodeling and molecules of innate immunity that were largely found in myeloid cells, colon epithelium, and endothelium. Cognate T cells were not dominant features of UC disease activity. These data suggest that the driver of ongoing UC activity is independent of the cognate T cell response. Funding AgenciesNone

Prostaglandin E-major urinary metabolite diagnoses mucosal healing in patients with ulcerative colitis in remission phase.

Background and AimUlcerative colitis (UC) is usually detected by clinical symptoms, such as bleeding and diarrhea; however, it is rather difficult to assess during asymptomatic clinical remission (CR). Hence, there is a need for a biomarker that can reliably detect UC during remission. We previously reported on the utility of the prostaglandin E‐major urinary metabolite (PGE‐MUM) as a biomarker reflecting UC activity. In this study, we evaluated the effectiveness of the PGE‐MUM in the diagnosis of endoscopic, histological, and histo‐endoscopic mucosal remission of UC, comparing with fecal tests.MethodsThis prospective study was conducted at the Jikei University Hospital between August 2017 and January 2021. Patients with UC in CR scheduled to undergo colonoscopy were included. The association between the PGE‐MUM with endoscopic remission (ER), histological remission (HR), and complete mucosal healing (CMH, defined as histo‐endoscopic remission) was analyzed. We also compared the area under the curve (AUC) for the receiver operating characteristic curves between PGE‐MUM, fecal calprotectin (FC), and fecal immunochemical test (FIT).ResultsIn total, 128 patients were analyzed. PGE‐MUM differed significantly in ER versus non‐ER (14.5 vs 16.7, P = 0.028), HR versus non‐HR (14.2 vs 17.4, P = 0.004), and CMH versus non‐CMH (14.3 vs 16.7, P = 0.021). There were no significant differences between the AUCs for PGE‐MUM, FC, and FIT for ER, HR, or CMH.ConclusionsThe PGE‐MUM can determine CMH in UC even during CR, regardless of the disease phenotype, indicating its clinical benefit for non‐invasive monitoring.

Ultrasonographic Evaluation of Bowel Wall Thickness and Intramural Blood Flow in Ulcerative Colitis

Abstract Background Ulcerative colitis, a type of inflammatory bowel disease that merely affects the mucosa and submucosa of colon in the form of inflammatory ulcers. Colonoscopy is the gold standard for its diagnosis. For optimal monitoring of disease activity in UC patients, colonoscopy should be performed on a regular basis. However, repeated colonoscopies represent a logistic and economic challenge, as well as significant burden for the patients. Objectives Our study aimed to provide an extensive overview of the main pathologic features of gut wall vessels and bowel wall thickness at US examination of UC. Patients and Methods This prospective case control study was done on 40 patients confirmed to have UC attending to Outpatient Clinics of Internal Medicine and Gastroenterology Department – Ain-Shams University from October 2018 to Augost 2019. They were divided into two groups: Relapse group: Include 20 patients with active UC disease. Remission group: Include 20 patients with inactive UC disease (in remission state). These two groups were matched with 20 healthy individuals, matched for age and gender and considered to be a control group. Disease activity was categorized according to the endoscopic Mayo score.Ultrasound and endoscopic findings were compared for each colon segment except for the rectum. Results The peak incidence of affected patients was 30–40 years of age. Female predominance compared to male with a ratio of 2.6:1. 20% of remission patients complaining from 1-2 bowel movement while 45% and 50% of relapsing patients suffer from 3-4 and 5 bowel movement respectively. 100%, 100%, 20% and 15% of relapsing patients suffer from bleeding per rectum, abdominal pain, tenesmus and urgency. Higher ESR and CRP and lower hemoglobin in relapsing compared to remission group. Furthermore, The last group has higher value of ESR and CRP and lower value of hemoglobin compared to control group. BWT was significantly thicker in relapse group (4.8±0.7 mm) than of remission (3.55±0.5 mm) compared to control group (1.6±0.5) (p value &amp;lt;0.001). BWT at a cut-offs &amp;gt; 4 mm discriminating between cases with relapse from those with remission and at a cut-offs &amp;gt;4 mm discriminating between mild endoscopic severity from moderate and severe UC. Furthermore, BWT at a cut-offs &amp;gt;4.6 mm discriminating between mild and moderate endoscopic severity from severe UC. Vascular signal number at a cut-offs &amp;gt;1 discriminating between cases with relapse from those with remission and at a cut-offs &amp;gt;2 discriminating between mild and moderate endoscopic severity of UC. Conclusion Abdominal ultrasound is a widely available non-invasive method for imaging of UC. It provides a high sensitivity, specificity and accuracy in diagnosis and monitoring of UC activity.

THE ROLE OF ENDOTHELIAL DYSFUNCTION IN INFLAMMATORY BOWEL DISEASES

The purpose of the study – to assess the disorders’ degree of endothelium dysfunction inpatients with nonspecific ulcerative colitis (NUC) and Crohn's disease (CD), dependingon the severity of inflammation.Material and methods. 34 patients with NUC and 18 people with CD with continuousrecurrent courses, 15 patients with NUC and 15 patients with CD in remission wereobserved. The control group included 30 healthy volunteers.Results. It has been established that patients with active NUC had a significantly higherlevel of markers characterizing changes of proliferative (VEGF-165) and adhesive(VCAM-1) endothelial functions vs. control (in 4.62 and 2.01 times) and patients whohad an inactive disease (at 3.95 and 4.62) (p&lt;0.05). In the active course of NUC, VEGF-165 level increased by 3.27 and 5.03 times, the level of VCAM by 1.83 and 2.09 times vs.inactive and control group (p&lt;0.05).In patients with severe and moderate degrees of NUC, we have set an increase in theconcentration of VEGF-165 compared with mild degree, p&lt;0.05. It has been proven thatin severe degree of CD, the concentration of VEGF-165 increased 21.5% vs. moderateactivity and 63.1% vs. mild activity, p&lt;0.05.It has been established that adhesive phenotype of endothelial dysfunction with severeactivity of NUC was associated with an elevated content of adhesion molecule, dependingof activity, p&lt;0.05. The adhesive phenotype of endothelial dysfunction is proved forpatients with severe activity of CD compared with moderate and mild activity, p&lt;0.05.We have revealed a reliable direct regression relationship between the concentration ofthe vascular endothelial growth factor and the activity of UC according to the TrueloveWitts scale (R=0.29, p&lt;0.05), between the CDAI index level in CD and the content ofVCAM-1 (R=0.29, p&lt;0.05).Conclusions. Inflammatory bowel diseases - NUC and CD are accompanied withendothelium dysfunction, proliferative and adhesive phenotypes, associated with theactivity of process.

Optimization of prediction of UC relapse and adjustment of adequate therapy in patient with ulcerative colitiss

Objective: to improve the assessment of activity of ulcerative colitis and the ability to predict the development of relapse of the disease, as well as the selection of adequate therapy.Materials and methods: the study included 90 people: 70 patients with ulcerative colitis and 20 healthy volunteers. The disease activity was evaluated using 7 disease activity indices. The expression of matrix metalloproteinase -9 (MMP-9) in the colon mucosa was evaluated by immunohistochemistry.Results: data were obtained on the activity of MMP-9 in colonobioptates in patients with ulcerative colitis with varying degrees of disease severity, which complements our knowledge of the pathogenetic mechanisms of UC and, based on the developed mathematical model, allows predicting the development of recurrence of UC. Based on the analysis of clinical indices of UC activity, an algorithm for evaluating the effectiveness of basic therapy has been developed.Conclusion: tools are provided to improve the prognosis of UC relapse, and a personalized approach to evaluating the effectiveness of the alternatives of drug therapy is developed.

Point-of-Care Ultrasound in Inflammatory Bowel Disease.

Inflammatory bowel diseases [IBD], including Crohn's disease [CD] and ulcerative colitis [UC], are chronic, relapsing and destructive inflammatory disorders of the gastrointestinal tract which can lead to organ damage and impair quality of life. A 'treat-to-target' strategy based on activity and severity of disease and response to treatment with close monitoring of intestinal inflammation is recommended. Ileocolonoscopy [CS] is considered the first-line procedure for the assessment of IBD, and magnetic resonance enterography [MRE] is the current standard for assessing the small bowel and complications in CD, and has been proposed as an alternative procedure to CS in the evaluation of both ileo-colonic CD and UC. As that both CS and MRE are invasive and expensive procedures and unappealing to patients, they are unfeasible as frequent and repetitive tools for the monitoring of disease activity. Bowel ultrasound [US] represents a well-tolerated, non-invasive and cost-effective modality to manage IBD patients in clinical practice. Compared to CS and MRE, bowel US has been shown to have the same level of accuracy in assessing and monitoring disease activity and severity of both CD and UC. It can be performed at the point-of-care and therefore allow for real-time clinical decision-making. Point-of-care ultrasound [POCUS] is suggested as the stethoscope of the future and is gaining interest and diffusion in the medical field because it can be used for the bedside examination of patients. The aim of this review is to discuss point-of-care bowel ultrasound [POCBUS] in the management of patients with IBD.

P291 Diagnostic utility of the neutrophil-platelet rate (NeuPla) as a marker of activity in patients with ulcerative colitis

Abstract Background Ulcerative colitis (UC) is a chronic disease characterised by periods of activity and remission. There are biomarkers such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and faecal calprotectin that are elevated in patients with active UC. The platelet, one of the main activators of neutrophils, contains IL-8, a potent neutrophil chemo-attractant and P-selectin that induces excretion of superoxide in the neutrophils, forming platelet-neutrophil aggregates that are increased in individuals with UC activity. No previous studies have evaluated the neutrophil-platelet (NeuPla) rate as a tool for evaluating disease activity. The aim of this study was to evaluate the clinical utility of NeuPla rate in patients with UC. Methods A total of 158 patients with a definitive diagnosis of UC were included and NeuPla index was calculated on the ratio between neutrophil differential count and platelets from complete blood count (CBC) at least 1 day after the colonoscopy and colon biopsies. The activity was classified according to Mayo endoscopic sub-score, Riley score, Truelove-Witts, Montreal, full Mayo, and Yamamoto-Furusho indexes. Results The correlation of the NeuPla index with all activity indexes was statistical significant (p &amp;lt;0.001) as well as faecal calprotectin (rho: 0.532, p = .0001). The ROC curve was used to determine the cut off level of NeuPla according to moderate activity (optimal cut off 14.63 with a sensibility of a 79.5% and specificity of 51.3% with an Area Under the Curve (AUC) of .635 and severe activity (optimal cut off 18.7 with a sensibility of 80% and specificity of 81.8% AUC of .749) considering as a gold standard the endoscopy findings as shown in Figure 1. Conclusion The NeuPla index has a good diagnostic utility in order to distinguish patients with clinical and endoscopic activity without the need to perform invasive studies such as colonoscopy. This index is a cheap and easy access monitoring tool and a better diagnostic performance in comparison with other serum biomarkers CPR, ESR and serum albumin.

P122 High correlation between faecal calprotectin and a Novel Integral Index for evaluating disease activity in ulcerative colitis patients

Abstract Background Ulcerative colitis (UC) is a chronic and incurable disease characterised by periods of activity and remission. There are several indexes that evaluate the UC activity from clinical, biochemical and endoscopic parameters. The faecal calprotectin is a non-invasive marker for detecting intestinal inflammation in UC patients. A new novel integral disease index (Yamamoto-Furusho index) includes clinical, biochemical, endoscopic and histological findings that evaluate the full spectrum of activity in UC patients. The aim is to correlate the Novel Index Activity index (Yamamoto-Furusho Index) with faecal calprotectin levels in UC patients and compare with other indexes. Methods A total of 158 patients with confirmed diagnosis of UC from the IBD Clinic were recruited in the period between July 2017 and June 2019. All demographic and clinical characteristics were collected from clinical charts. The faecal calprotectin was measured at least 1 week before the colonoscopy and biopsies. The Spearman’s Rho was used for the correlation. A p-value of &amp;lt;0.05 was considered as significant. Results We analysed 185 patients with UC, 85 patients (51.8%) were women and 73 (44.5%) men, with an average current age of 43.53 years (+14.35), an age at diagnosis of 36.6 + 15.1 years and disease duration of 11.27 ± 8.1 years. The extension was distributed on proctitis (E1) in 13.3%, left colitis (E2) in 19.6% and pancolitis (E3) in 31.6%. The treatment was based on mesalazine in 93.9%, steroids in 26.2% and azathioprine in 15.9%. The correlation between faecal calprotectin and the Yamamoto–Furusho index was high (rho = 0.730, p &amp;lt; 0.0001) compared with other indexes such as endoscopic Mayo sub-score (rho = 0.705, p = &amp;lt;0.001); Truelove–Witts (rho = 0.644, p = &amp;lt;0.001), Full Mayo score (rho = 0.708, p = &amp;lt;0.001) and Montreal (rho = 0.551, p = &amp;lt;0.001). Conclusion The novel integral index showed a high correlation with faecal calprotectin compared with other UC indexes for evaluating disease activity in UC patients.

Recovery of CD226-TIGIT+FoxP3+ and CD226-TIGIT-FoxP3+ regulatory T cells contributes to clinical remission from active stage in ulcerative colitis patients

PurposeUlcerative colitis (UC) is a chronic inflammatory immune-related disease. Imbalance between pathogenic cells and immunosuppressive cells is associated with disease activity of UC. Regulatory T cells (Tregs) are critical for this immune homeostasis. However, the clinical significance of CD226 and TIGIT expressions on FoxP3+Tregs in UC remains unclear. MethodsComprehensive analyses of CD226 and TIGIT expressions on FoxP3+Tregs were performed by flow cytometry in 72 UC patients and 35 healthy controls, and ten active UC patients achieving remission after treatment with 5-aminosalicylic acid were followed up. Expressions of β7, α4 and αE on FoxP3+Tregs were analyzed. Clinical indicators were retrospectively acquired and serum cytokines were detected using ELISA, and their correlations with FoxP3+Treg subsets were conducted. ResultsIn active UC, levels of FoxP3+Tregs and CD226−FoxP3+Tregs regardless of TIGIT expression were significantly decreased while percentages of CD226+TIGIT−FoxP3+Tregs and CD226+TIGIT+FoxP3+Tregs were obviously increased. The expressions of β7, α4β7 and αEβ7 in FoxP3+Tregs, CD226−TIGIT+FoxP3+Tregs and CD226−TIGIT−FoxP3+Tregs were significantly elevated in active UC. Furthermore, inverse correlations were found between FoxP3+Tregs, CD226−TIGIT+FoxP3+Tregs, CD226−TIGIT−FoxP3+Tregs and serum CRP, as well as Mayo scores. IL-10 was reduced and positively correlated with CD226−TIGIT+FoxP3+Tregs and CD226−TIGIT−FoxP3+Tregs while IL-12 was increased and negatively correlated with CD226−TIGIT+FoxP3+Tregs and CD226−TIGIT−FoxP3+Tregs in active UC. In follow-up patients, the levels of FoxP3+Tregs, CD226−TIGIT+FoxP3+Tregs and CD226−TIGIT−FoxP3+Tregs and serum IL-10 levels were significantly recovered when achieving remission after treatment. ConclusionsLack of CD226 expression on FoxP3+Tregs regardless of TIGIT expression may play an important role in exhibiting their suppressive function and preventing from disease activity in UC.

Enteropathic spondyloarthritis: Results from a large nationwide database analysis.

Spondyloarthrits (SpA) share clinical, genetic and immunological features with Inflammatory Bowel Diseases (IBD), and enteropathic SpA (eSpA) represent the clinical evidence of the association between gut and joint diseases. This cross-sectional study aimed to report data of eSpA patients collected from the first Italian database. A specific web-based interface has been created to insert and collect the main clinical, serologic and imaging data from patients with eSpA, as well as disease activity, comorbidities and treatment, in a real-life scenario. Data were collected in 14 Italian centers (7 rheumatology and 7 gastroenterology units). A total of 347 eSpA patients were enrolled in the study. Type 1 peripheral eSpA was the most frequent form. Crohn' Disease (CD) was the most represented IBD. CD activity was similar among eSpA, whereas UC activity was slightly higher in the axial and mixed form than in the peripheral eSpA. The disease was active in less than half of axial eSpA patients and in only 18% of patients with peripheral eSpA. Furthermore, most of the patients had an inactive IBD. Nineteen percent of the total eSpA patients were free of therapy at the time of the enrollment and 61% of the patients were receiving biotechnological agents. The multidisciplinary management of eSpA patients, favored by this ad hoc created web-based platform, allowed to obtain data from the largest eSpA cohort. The information coming of this database might advance knowledge of eSpA and improve their standard of care.

The Outcomes of Emergency Admissions With Ulcerative Colitis Between 2007 and 2017 in England.

Patients with ulcerative colitis [UC] may present as emergencies and require rapid escalation of therapy. This study aimed to assess the mortality, colectomy, and readmission risks, during and following a first emergency admission with UC. Using Hospital Episode Statistics, subjects aged between 18 and 60 years, coded with a first emergency admission with UC, were identified between 2007 and 2017. Influences of demographic factors, comorbidity, anti-tumour necrosis factor [TNF] therapy, and provider UC activity on mortality and colectomy were examined. A total of 10 051 subjects (46% female; median age 33 years [interquartile range [IQR] 25-44]) were identified. Mortality was 0.2% in hospital and 0.5% at 12 months and, following colectomy during acute admission, it was 1.4% in hospital and 2.1% at 12 months. Females had reduced risk of colectomy during admission: odds ratio [OR] 0.73 (95% confidence interval [CI] 0.62-0.85). Comparing the period 2007-2011 with 2012-2017, the rate of colectomy fell during acute admissions: OR 0.85 [0.72-0.99], p = 0.038 and at 12 months after admission: OR 0.73 [0.61-0.87]. Anti-TNF therapy increased 4-fold in acute UC admissions from 2007-2017. Those receiving anti-TNF therapy had a 70% increased risk of colectomy during index admission compared with those not receiving anti-TNF: OR 1.72 [1.29-2.31]. Increased time to colectomy during first admission was associated with female sex: hazard ratio [HR] 0.84 [0.72-0.98] and Asian ethnicity: HR 0.61 [0.44-0.85], whereas reduced time was associated with increased comorbidity, lower deprivation, and high provider volume of colectomies for UC: HR 1.59 [1.31-1.93]. Mortality following colectomy was 1.4% in hospital and 2.1% at 12 months, and no significant change over time was observed. Colectomy during emergency admission for UC was less common in females. Rates of anti-TNF therapy during emergency admission for UC have increased and overall colectomy rates have fallen. This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast.

Intensified Infliximab Induction is Associated with Improved Response and Decreased Colectomy in Steroid-Refractory Paediatric Ulcerative Colitis.

Infliximab pharmacokinetics in steroid-refractory [SR] ulcerative colitis [UC] suggest a need for higher dosing, but data concerning efficacy of intensification in this setting are lacking in children and inconsistent overall. Paediatric patients [N = 125] treated with infliximab for SR or steroid-dependent UC were retrospectively reviewed. Outcomes [clinical response and remission, colectomy, mucosal healing, safety] with standard vs intensified induction [mean induction dose ≥7 mg/kg or interval ≤5 weeks between doses 1 and 3] were compared. Among 125 patients [median age 14 years, median UC duration 0.7 years, 74 SR], 73 [58%] received standard induction and 52 [42%] received intensified induction. Overall, 73 [58%] achieved remission (judged by physician global assessment [PGA] and paediatric UC activity index [PUCAI]≤10]. Among patients in remission, 7 [10%] experienced secondary loss of response by a median of 0.7 [IQR 0.4-1.0] years. Of the 74 SR patients, 17 [23%] underwent colectomy, and of the 51 steroid-dependent patients, 12 [24%] underwent colectomy. Intensified induction in SR patients was associated with a higher chance of remission (hazard ratio [HR] 3.2, p = 0.02) and a lower chance of colectomy [HR 0.4, p = 0.05], but did not improve outcomes in steroid-dependent patients. During follow-up, 46/73 [63%] patients in remission had regimen individualization, with similar rates of return to standard dosing after 1 year between those with initial intensified or standard induction. Follow-up endoscopy, performed in 35/73 patients in remission, demonstrated mucosal healing for 66%. Adverse events were rare, despite use of intensified regimens. These data suggest a benefit from intensified infliximab induction specifically among children with steroid-refractory UC. Prospective studies comparing dosing regimens and incorporating therapeutic drug monitoring should be undertaken.

МОРФОЛОГІЧНІ ОСОБЛИВОСТІ СЛИЗОВОЇ ОБОЛОНКИ ТОВСТОЇ КИШКИ ХВОРИХ ІЗ РАННІМ ТА ПІЗНІМ ДЕБЮТОМ НЕСПЕЦИФІЧНОГО ВИРАЗКОВОГО КОЛІТУ

The purpose of the research was to determine the morphological features of the mucous membrane of the large intestine of patients with UC depending on the age of patients. A comparative analysis of the incidence and type of UC of patients with early onset and late debut of the disease was performed. It has been stated that for patients with a debilitating post-traumatic disorder, the left ventricular and total forms are characteristic; in patients with late debut, the distal form of UC predominates. The main trends in the activity of UC in patients with early onset and late debut have been determined. In the analysis of the degree of activity of UC revealed that in patients from 50 years of age and older, with the late debut of the disease, the first one is mostly found to be the least degree of activity, the second – the middle and the third – the high degree, they are found to be less likely. In turn, in patients under 50, the second and third stages of the disease are most often noted. Another component of the main characteristics of the UC was the histological changes of the mucous membrane of the large intestine. Thus, the conducted studies allowed to state that the number of PAS-positive substances in mucus is significantly higher in patients with distal and left-sided UC. In patients with UC there is a marked mucosal intestinal mucosa of qualitative and quantitative composition of mucus. These changes were characterized by a decrease in MUC2 as the disease progressed, as well as levels of MUC4 and TFF3. In patients with early onset of NSC, there is a more intense reduction in the number of mucins and TFF3 already with a minimal activity of UC associated with low levels of mucin from the intracellular mucus and indicates a more aggressive course of it. At the same time, patients with a late debut revealed a sharp decrease in the number of MUC2 and TFF3 with high activity of UC.