Ulcerative Colitis Activity Research Articles

P295 Early sonographic improvement predicts the middle-term efficacy of molecular-targeted medications for Ulcerative Colitis

Abstract Background Today molecular-targeted medications (MTMs) are widely used for ulcerative colitis (UC). Predicting the efficacy of MTMs early after induction remains a crucial clinical challenge. Intestinal ultrasound (IUS) is now considered a non-invasive, promising monitoring tool for UC. It can assess the disease activity of UC in the whole colon safely and repeatedly. Here, we hypothesized that over time IUS assessment can predict the MTM efficacy early, contribute to early clinical decision-making on whether to continue or switch MTMs, and reduce the burden of colonoscopy (CS) recommended to be scheduled at around 6 months after the induction. Methods We analyzed 44 patients who started an MTM for active UC, underwent IUS at baseline and 3 months, and took CS at 6 months after the induction. The clinical disease activity and endoscopic activity at 6 months were assessed with Lichtiger index (LI) and Mayo endoscopic subscore (MES), respectively. Clinical remission was defined as a LI ≤ 3. Endoscopic improvement (EI) was defined as a MES = 0 or 1. In addition to the assessment of sonographic findings, such as bowel wall thickness (BWT), bowel wall stratification including submucosa index (SMI), bowel wall flow with modified Limberg score (mLS), Milan Ultrasound Criteria (MUC), UC-IUS index (UII), Kyorin Ultrasound Criterion for UC (KUC-UC; BWT<3.8mm with SMI<50%) were evaluated. Results Patients who achieved steroid-free clinical remission (SFCR) showed better improvement in BWT, %BWT, and mLS in 3 months compared to those who did not achieve SFCR (p<0.01 for each). The improvement in MUC and UII was also observed in patients who achieved SFCR at 6 months (p<0.001 for both). In ROC analyses, the area under the curve for SFCR at 6 months was 0.80 with BWT, 0.80 with %BWT, 0.81 with mLS, 0.85 with MUC, and 0.85 with UII. Among the 44 patients, 7 patients achieved MUC≤ 6.2, estimating MES=0/1, at 3 months, and 6 out of 7 patients demonstrated EI at 6 months (positive predictive value [PPV]=87.5%). Meanwhile, 4 patients satisfied KUC-UC at 3 months and all of them achieved SFCR and EI at 6 months (PPV=100%). Conclusion Our study suggests that patients who achieved sonographic improvement in 3 months can continue an ongoing MTM therapy and that patients who demonstrated sonographic findings estimating EI at 3 months can postpone CS at 6 months.

P492 All intestinal ultrasound scores for ulcerative colitis (and IBUS-SAS) strongly correlate with endoscopic activity: a prospective study

Abstract Background Intestinal ultrasound (IUS) is gaining increasing acceptance as a reliable tool for tight monitoring of ulcerative colitis (UC). Although several IUS scores have been proposed, none has been formally implemented into official recommendations of international scientific societies. This study aims to compare the available IUS score for UC, in terms of correlation with endoscopic activity. Methods Patients with UC ≥ 18 years old undergoing partial or full colonoscopy between April and October 2023 were prospectively included. Endoscopic evaluation of at least the sigmoid colon was mandatory for inclusion, and patients with proctitis (Montreal E1) were excluded. Endoscopic activity was scored with both the Mayo Endoscopic Subscore (MES) and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS), and defined by MES ≥ 1 and UCEIS ≥ 2. IUS was performed within 4 weeks of endoscopy. The Milan Ultrasound Criteria (MUC, Allocca et al.), the UC-IUS score (Bots et al.), the US Score from Parente et al., and the score from Hata et al. were included in the analysis. Applicability of the US Score from Civitelli et al, an IUS score developed for paediatric patients, and the IBUS-SAS, an IUS score validated for Crohn’s disease, was also evaluated. The Spearman’s rank coefficient (rho = ρ) was used to perform correlations, while receiver operating characteristic (ROC) curves were compared with the Hanley & McNeil method. Results Fifty-nine patients were included, of which 59.3% and 50.8% showed any endoscopic activity using the MES and the UCEIS, respectively. Detailed information about the population is reported in Table. All the evaluated IUS scores showed a significant positive correlation with endoscopic activity (p < 0.001), with the UC-IUS score and the US Score from Civitelli et al. outperforming the others both with MES (ρ = 0.745, ρ = 0.762) and UCEIS (ρ = 0.751, ρ = 0.769). The same scores showed the highest Areas Under the Curve (AUC) for detecting a MES ≥ 2 (UC-IUS: 0.841, 95%CI 0.722-0.923, p < 0.001; Civitelli et al.: 0.842, 95%CI 0.724-0.924, p < 0.001) [Figure]. The optimal cut-offs for detecting a MES ≥ 2 with both the MUC and the Civitelli score were similar to that proposed by the Authors (> 5.04 vs > 6.20 and > 2 vs > 1, respectively). Conclusion All the included IUS scores showed good correlation with endoscopic activity. The UC-IUS and the US Score from Civitelli et al. performed better than the others in detecting a MES ≥ 2 and might be suggested to monitor disease activity of UC and intervene early during disease relapse.

P972 Short and long-term outcomes after acute severe ulcerative colitis in children: A Canadian single centre experience

Abstract Background The short and long-term course of ulcerative colitis (UC) following an episode of acute severe UC (ASUC) in children is insufficiently characterized. We aimed to assess contemporary outcomes in children hospitalized with ASUC. Methods This was a retrospective cohort study of children aged 2-17 years hospitalized with ASUC between 2010 and 2022 at a tertiary center in London, Ontario, Canada. All data were recorded using standardised Case Report Forms, de-identified, and entered into a central database registry using Research Electronic Data Capture (REDCap) Steroid non-response was defined as requirement of medical rescue therapy or colectomy. Results A total of 58 children hospitalized with ASUC were included (male: 55.2% [n =32], mean age at admission: 12.2 ± 3.5 years). The majority had extensive colitis (82.4% [n = 42]) at the time of diagnosis. 74% (n = 43) presented within one year of symptom onset and 31% (n = 18) had ASUC as their index presentation with UC. 15.5% (n = 9) of patients had prior purine analogues and 20.7% (n = 12) had received biologics prior to ASUC presentation. Median Pediatric Ulcerative Colitis Activity Index (PUCAI) score on admission was 65.0 (IQR: 60.0 – 75.0). After intravenous corticosteroid therapy 68.9% (n = 40) responded to steroids. Of the patients with steroid non-response (31% [n = 18]), 3.4% (2/58) underwent colectomy and 27.6% (16/58) patients received infliximab rescue therapy. Median PUCAI score was significantly lower on day 3 between steroid responders and steroid non-responders (37.5 vs 60, p <0.01). The short term (3 months following discharge) and long-term (3-12 months following discharge) colectomy rates following discharge were 7.4% (4/54) and 8% (4/50) respectively. Short term and long-term hospitalization rates for UC exacerbation following discharge was 25.9% (14/54) and 16% (8/50) respectively. Similar rates of long-term colectomy and hospitalizations were observed between steroid responders and non-responders. On univariate analysis, no statistically significant factors associated with steroid non-response were identified. Conclusion 17% of patients hospitalized for ASUC required colectomy within 12 months of presentation. Despite a high initial response to corticosteroids, long term colectomy rates and re-hospitalization rates are still high. Future research should focus on earlier identification and treatment of children at high risk of exacerbation to prevent complications.

P910 Salivary calprotectin as a prognostic biomarker in Early Onset Inflammatory Bowel Disease: a cohort study

Abstract Background Inflammatory Bowel Disease (IBD), including Ulcerative Colitis (UC) and Crohn’s Disease (CD) affects children in 25% of cases. In Early Onset IBD (EOIBD) oral involvement is common and oral manifestations (OM) are frequently the first presenting sign of disease. This study compared salivary calprotectin (SCp) between EOIBD and healthy controls (HC), differentiating patients based on their history of OM. Furthermore, this report correlated salivary and faecal calprotectin (FCp) in EOIBD and assessed the prognostic accuracy of SCp in predicting disease relapses. Methods A cohort study was conducted; 9 HC and 27 EOIBD (18 UC and 9 CD) were recruited at the University of Naples Federico II. EOIBD were divided in two subgroups based on the history of OM. A sample of stimulated whole saliva was collected by each participant by spitting. The samples were then processed by ELISA for determining SCp. For each patient clinical disease activity was measured through Paediatric Ulcerative Colitis Activity Index (PUCAI) and Paediatric Crohn’s Disease Activity Index (PCDAI), at baseline and during follow-up (4/8/12 weeks). At baseline, patients provided a stool specimen for FCp determination. SCp levels were compared between groups. In EOIBD SCp was correlated to clinical data and to FCp. Results At baseline all the patients were in treatment with immunosuppressive drugs; 19 were in clinical remission (PUCAI/PCDAI <10) and 8 had mild disease (PUCAI/PCDAI<35). 13 EOIBD had an history of OM: 12 suffered from aphthous-like manifestations while 3 reported granulomatous lesions; 10 experienced oral involvement before IBD diagnosis. OM were more prevalent in CD than in UC and were associated to ileocolic, perianal and upper gastrointestinal tract involvement. EOIBD with OM reported significantly higher SCp than EOIBD without OM and HC: 155,79±60,08 pg/mL in EOBD with OM vs 82,95±51,58 pg/mL in EOIBD without OM (P<0,01**) and 98,21±39,67 pg/mL in HC (P=0,21). Despite the systemic therapy and the clinical remission, in 7 EOIBD with OM oral lesions persisted. These patients had higher SCp compared to those who experienced OM remission (P<0,05*). In EOIBD with OM higher SCp was associated to higher FCp (P<0,05*) while in EOIBD without OM this correlation was not described. No correlation was found between SCp values and PUCAI/PCDAI at baseline. EOIBD with OM who reported higher SCp were found to have increased risk of relapse (P<0,05*) while no association was reported in EOIBD without OM. Conclusion In EOIBD with OM SCp is significantly higher, mirrors intestinal inflammation and predicts relapses. Our results suggest the use of SCp as a prognostic biomarker in EOIBD with OM although more studies are needed.

P066 Serum amyloid A – A Novel Biomarker of Ulcerative Colitis Disease Activity

Abstract Background Despite recent advancements in the treatment of ulcerative colitis (UC), a substantial number of patients fail to achieve long-term remission. Persistent histological activity has been linked with poorer treatment outcomes. Histological remission is now an accepted treatment target; however there remains significant variability in the interpretation of UC histology. As such, there is a need for novel biomarker identification to aid assessment and ultimately predict disease relapse. Serum amyloid A (SAA) is an acute-phase protein, of which serum levels have shown promise as a biomarker in IBD1. This study aims to explore the utility of SAA levels in UC colonic tissue as a diagnostic biomarker for disease activity and progression. Methods Two cohorts were prospectively recruited, including healthy controls and UC patients. Sigmoid biopsies were collected and tissue explants generated. Tissue-conditioned media from these explants was collected and secreted SAA quantified using 54 V-plex ELISA. Demographic information, disease characteristics, endoscopic Mayo scores and disease progression were documented. Endoscopic remission was defined as a Mayo endoscopic sub-score ≤1. Disease progression was defined as the requirement for corticosteroid therapy, UC-related hospitalisation, UC-related surgery or the introduction of a new immunomodulatory agent in follow-up period. P values <0.05 were considered significant in analyses. Results The two cohorts included 11 healthy controls and 16 UC patients (endoscopic remission n=6). Active UC patients demonstrated significantly higher SAA concentrations than healthy controls (p=0.0013) and those in endoscopic remission (p=0.02). There was no significant difference in SAA concentrations between healthy controls and UC patients in remission (p=NS). UC patients in the lowest SAA concentration quartile had a significantly longer time to disease progression (p=0.0462) (Figure 1). Conclusion Quantification of SAA secretion in IBD ex-plants has potential as a biomarker of UC activity and progression. Further investigation of SAA as a biomarker in IBD is warranted.

Clinical and epidemiological features of ulcerative colitis in children of the Rostov region

Russian data on the prevalence of inflammatory bowel diseases (IBD), including ulcerative colitis (UC), confirm the general global trend towards an increase in IBD, taking into account age-related as well as regional characteristics, which determined the purpose of this study. The purpose of the study. To evaluate the clinical and epidemiological features of the course of ulcerative colitis in children of Rostov-on-Don. Materials and methods. We observed 42 children aged from 1 to 14 years with a diagnosis of UC, which was made on the basis of anamnesis, clinical picture, laboratory test results, colonoscopy data, and morphological examination of the colon mucosa. UC activity was assessed taking into account the PUCAI index. Results. For the period from 2014 to 2023 On the basis of the pediatric somatic department of city hospital No. 20 in Rostov-on-Don, UC was diagnosed in 42 children aged 1 to 14 years, which amounted to 1.48% of the total number of patients with chronic intestinal diseases (2822 people). There was an increase in the incidence of ulcerative colitis from 2014 to 2023 (from 0.32% to 2.52%) with maximum values in 2021-2023. Conclusion. Clinical and epidemiological studies have shown an increase in the incidence of UC in children of Rostov-on-Don over the past 10 years. It has been established that ulcerative colitis is more often detected in the preschool group of children. The incidence of ulcerative colitis was higher in boys than in girls. A high degree of family history of children with UC was revealed for diseases of the digestive system, delivery by Caesarean section, artificial feeding in the first year of life, and acute intestinal infections. In the UC clinic, milder, erased forms of the disease dominated, which determined the later diagnosis of the disease at the prehospital stage.

Clinical usefulness of hypoxia imaging colonoscopy for the objective measurement of ulcerative colitis disease activity

Background and AimsColonic mucosal hypoxia is associated with mucosal inflammation in ulcerative colitis (UC). We aimed to assess the clinical usefulness of hypoxia imaging colonoscopy for the assessment of clinical, endoscopic, and histologic disease activities of UC. MethodsThis was a retrospective cohort study comprised of 100 consecutive UC patients who underwent hypoxia imaging colonoscopy between September 2022 and September 2023 at the University of Tsukuba Hospital. We measured colonic tissue oxygen saturation (StO2) at the biopsy sites and compared StO2 values between different disease activities. We used receiver operating characteristic (ROC) analysis to calculate the area under the ROC curve (AUROC). ResultsWe identified a significant correlation between rectal StO2 and the Simple Clinical Colitis Activity Index, with moderate accuracy to predict bowel urgency at a 40.5% cutoff (AUROC 0.74, 95% CI 0.62-0.87). Our analysis of 490 images showed median StO2 values for Mayo endoscopic subscores (MES) 0, 1, 2, and 3 as 52% (IQR 48%-56%), 47% (IQR 43%-52%), 42% (IQR 38.8%-47%), and 39.5% (IQR 37.3%-41.8%), respectively. Differences for all pairs were significant. Median StO2 was 49% (IQR 44%-54%) for Geboes scores 0-2, significantly higher than histologically active disease (Geboes score ≥ 3). At a colonic StO2 cutoff of 45.5%, AUROCs for endoscopically and histologically active diseases were 0.79 (95% CI 0.74-0.84) and 0.72 (95% CI 0.66-0.77), respectively. ConclusionsStO2 obtained by hypoxia imaging colonoscopy is useful for assessing clinical, endoscopic, and histologic activities of UC, suggesting StO2 may be a novel and objective endoscopic measurement.

Methanogenic Archaea in the Pediatric Inflammatory Bowel Disease in Relation to Disease Type and Activity.

The inflammatory bowel disease (IBD) is associated with gut microbiota dysbiosis; however, studies on methanogens-especially those focused on children-are extremely limited. The aim of this study was to determine the abundance of total methanogenic archaea and their three subgroups: Methanobrevibacter (Mb.) smithii, Methanosphaera (Ms.) stadtmanae, and Methanomassiliicoccales, in the feces of children with both active and inactive Crohn's disease (CD) and ulcerative colitis (UC). The results of a quantitative real-time PCR were cross-referenced with the disease type (CD vs. UC) and activity assessed with the use of Pediatric Crohn's Disease Activity Index (PCDAI) and Pediatric Ulcerative Colitis Activity Index (PUCAI) indices, and fecal calprotectin (FCP) concentration, and compared with controls. There was a significant decrease in the number of total methanogens in CD and UC compared to controls. The prevalence of total methanogens was also lower in UC compared to controls. Furthermore, patients from the inactive UC group were colonized by a lower number of Mb. smithii, and demonstrated the most pronounced positive correlation between the number of Ms. stadtmanae and the FCP concentration. Our results demonstrate that gut methanogens are related to the type and activity of pediatric IBD.

Treatment regimens and disease activity could alter salivary myeloperoxidase levels in patients with inflammatory bowel diseases.

Inflammatory bowel diseases (IBDs) present with alternating periods of exacerbation and remission; therefore, it is necessary to develop noninvasive diagnostic tools to control the disease activity and improve therapeutic effectiveness. Recently, we have found that patients with ulcerative colitis (UC) who qualified for biologic therapy had significantly lower salivary myeloperoxidase (MPO) levels. This cross‑sectional study aimed to assess the impact of IBD activity and applied treatment on salivary antioxidant system as reflected by the levels of catalase, total antioxidant status, and MPO. The study group comprised 99 patients diagnosed with Crohn disease (CD) and 61 patients with UC. The Crohn Disease Activity Index and modified Mayo scale were used to estimate the clinical activity of CD and UC, respectively. Unstimulated whole mixed saliva was collected. Salivary levels of selected markers were measured with enzyme‑linked immunosorbent assays and colorimetric assays. The patients with clinically active UC showed significantly decreased median (interquartile range) salivary MPO levels (79.4 [30.1-157.5] vs 94.8 [58.2-274.7] ng/ml) with significant correlations with the endoscopic stage on the Mayo scale (R = 0.423; P = 0.02). Receiver operating characteristic analysis confirmed a potential usefulness of MPO concentrations in predicting clinically active UC (area under the curve = 0.654; P = 0.03; cutoff <210.4 ng/ml). Moreover, in the patients treated with biologics and without steroid therapy, salivary MPO concentrations negatively correlated with neutrophil counts in the individuals with UC and positively with C‑reactive protein level in the patients with CD. Salivary MPO levels changed depending on the disease activity in the patients with UC. Decreased MPO concentration in the saliva could be a predictor of clinically active UC.

Predictive Value of Serum Inflammatory Markers on Activity of Ulcerative Colitis

Predictive Value of Serum Inflammatory Markers on Activity of Ulcerative Colitis

PHASE ANGLE AS A PREDICTOR OF MUSCLE MASS IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE.

Malnutrition/sarcopenia is frequent in patients with inflammatory bowel diseases (IBD), and results in muscle catabolism, impacting treatment response, postoperative complications, and quality of life. This study aims to assess whether the phase angle (PhA) is a parameter for predicting reduced muscle mass in patients with IBD. Adult patients with IBD were included in this cross-sectional study. For the estimation of muscle mass and the calculation of the PhA, we used bioelectrical impedance analysis (BIA). Crohn's disease (CD) and ulcerative colitis (UC) activity scores were defined using the Harvey-Bradshaw index and partial Mayo score, respectively. The area under the ROC curve was calculated to identify the PhA cut-off point for reduced muscle mass. The sample consisted of 145 patients, with 39 (26.9%) with IBD in the active phase. There was a correlation of the PhA with skeletal muscle mass (SMM) (rs 0.35, P<0.001) and with the skeletal muscle mass index (SMI) (rs 0.427, P<0.001), and the associations remained in the most active form (moderate or severe) of IBD. The ROC curve analysis indicated that the cut-offs points of the PhA ≤5.042 for female and PhA ≤6.079 for male can be used to predict muscle mass reduction. The PhA can be considered a predictor of muscle mass reduction in IBD patients, and we can use it for screening and monitoring the evolution of malnutrition. • This study aims to assess whether the phase angle is a parameter for predicting reduced muscle mass in patients with inflammatory bowel disease. • There was a correlation of the phase angle with skeletal muscle mass and the associations remained in disease activity. • The ROC curve analysis indicated that the cut-off point of the PhA ≤5.042° for women and PhA ≤6,079° for men can be used to predict muscle mass reduction. • The phase angle can be considered a predictor of muscle mass reduction in inflammatory bowel disease.

The synergy of dual faecal immunochemical and faecal calprotectin testing for accurate assessment of endoscopic and histological activity in inflammatory bowel disease.

Faecal biomarkers are increasingly utilized for disease assessment in inflammatory bowel disease (IBD). To characterize the relative and combined accuracy of faecal calprotectin (FC) and faecal immunochemical testing (FIT) for detecting endoscopic and histologically active disease in Crohn's disease (CD) and ulcerative colitis (UC), subdivided by disease location. A prospective cohort study. Patients with confirmed IBD undergoing routine ileocolonoscopy for activity assessment were prospectively recruited and performed both FC and FIT ±30 days of ileocolonoscopy. Endoscopic activity was assessed via the simplified endoscopic score for CD, Mayo endoscopic score for UC and histological activity graded as nil/mild/moderate. Receiver-operator curve analyses were utilized to assess the performance of FC and FIT per disease subtype and location. In all, 137 (79 CD, 57 UC) patients were recruited. FC was more sensitive than FIT in detecting active endoscopic (CD: 91% versus 69%, UC: 94% versus 82%) and histological (CD: 86% versus 55%, UC 88% versus 56%) disease. However, FIT was more specific than FC in detecting active endoscopic (CD: 94% versus 56%, UC: 85% versus 69%) and histological (CD: 93% versus 55%, UC: 96% versus 70%) diseases. FIT was more sensitive and specific than FC in detecting active colonic CD (endoscopic activity: 94% versus 93%, histological activity: 92% versus 77%, respectively); however, it was poorly sensitive for active ileal CD (43% versus 89%). FC demonstrated higher sensitivity and FIT higher specificity for active IBD. Hence, dual testing was synergistic, displaying excellent performance characteristics across most IBD locations and subtypes, holding promise for future clinical application. Not applicable.

Utility of abdominal ultrasonography in the management of ulcerative colitis:proposal of a new scoring system

In the management of ulcerative colitis (UC), colonoscopy (CS) is considered essential for diagnosis;however, its invasiveness poses a challenge. Conversely, recent advancements in ultrasound diagnostic devices have improved imaging quality for the digestive tract, rendering them valuable in UC management. Therefore, this study aimed to elucidate the correlation between abdominal ultrasonography (AUS) and CS in assessing UC activity. The indices adopted for UC evaluation using AUS were as follows:1) bowel wall stratification, 2) bowel wall thickness, 3) bowel wall flow at power Doppler, 4) presence of increased brightness of inflammatory fat, and 5) presence of mesenteric lymph node swelling greater than 5mm. Subsequently, we developed a new AUS index for UC, termed the UCUS score, which comprises the aforementioned five indices. Finally, we compared the UCUS score with representative endoscopic indices, the Mayo endoscopic sub-score, and the Ulcerative Colitis Endoscopic Index of Severity. The results demonstrated that our proposed UCUS score better reflected disease activity than individual items assessed separately. ROC curve analysis revealed a UCUS score cutoff of 3 points. Therefore, a UCUS score of ≥3 points indicates the need for further examination with CS. Conversely, a score below 3 points suggests low disease activity, and in situations when evaluating treatment effectiveness, AUS could potentially substitute for CS. We believe that the UCUS score is an important source of information to understand the patient's condition and to motivate the patient to undergo endoscopy.

MR Enterography in Ulcerative Colitis: Beyond Endoscopy.

Ulcerative colitis (UC) is a chronic idiopathic inflammatory bowel disease (IBD) that progressively affects mucosa and submuccosa of the colon and rectum in a continual pattern. In comparison, Crohn disease (CD), the other type of IBD, is a chronic transmural inflammatory disorder that can involve any part of the gastrointestinal tract. MR enterography (MRE) has emerged as an important imaging modality for the diagnosis and detection of disease activity and complications in CD, with comparable results to those of endoscopy. But MRE has been underused for assessment of UC in recent years, and clinicians heavily rely on endoscopic findings for management of UC. Despite UC being considered an endoscopically assessable disease, MRE can provide useful information beyond that obtained with endoscopy about mural or extramural abnormalities, inaccessible parts of the colonic lumen, associated extraintestinal diseases, and superimposed pathologic conditions. Moreover, endoscopy might be contraindicated in some clinical settings due to the risk of colonic perforation. In addition to depicting the features of UC activity in different phases, MRE demonstrates findings of disease chronicity that cannot be achieved with endoscopy, particularly in a patient with colitis of unknown cause. The valuable diagnostic role of MRE to exclude undiagnosed CD in patients with UC who have refractory disease or those with postproctocolectomy complications is also emphasized. Radiologists can play a crucial role in the management of UC with MRE by addressing what is beyond endoscopy. ©RSNA, 2023 Test Your Knowledge questions are available in the supplemental material.

Comparison of Fecal Calprotectin with Different Endoscopic Scores in the Assessment of Ulcerative Colitis (UC) Activity and Its Utility in Differentiating IBS from IBD.

Ulcerative colitis (UC), a chronic inflammatory disease of gastrointestinal tract, can have initial presentation which is clinically difficult to differentiate from functional bowel disorders [irritable bowel syndrome (IBS) and irritable bowel disease (IBD)]. Conventional laboratory tests, such as erythrocyte sedimentation rate (ESR), C-reactive protein, and albumin express systemic patient responses instead of intestinal inflammation. In the last decade, fecal calprotectin, a calcium-binding protein, has been suggested as a sensitive marker of intestinal inflammation. However, only few studies have investigated its role in relation with the extent of the disease. To evaluate the usefulness of fecal calprotectin as a biomarker for disease activity in UC, its correlation with disease extent and its utility in differentiating IBS from IBD. A total of 75 patients (50 cases with colonoscopic evidence of inflammation and 25 cases with normal colonoscopic examination) were included in the study. Fecal calprotectin test was done on the day of colonoscopy. Severity of the disease was assessed by modified Mayo's endoscopy score (MMES). Age and baseline parameters were comparable in both the groups (UC and IBS). Patients in the ulcerative group had tachycardia (95 vs 74), high ESR (26 vs 20), high leukocytes count (9198 vs 8852), high fecal calprotectin (594 vs 29), low albumin (3.00 vs 3.80) and low hemoglobin (11 vs 13.40). Minimum and maximum MMES were 2 and 13.2. A significant correlation was observed between fecal calprotectin and MMES (p-value < 0.001). Fecal calprotectin is a simple, noninvasive, cost-effective marker that is strongly associated with colorectal inflammation; moreover, it has better role in the differentiation of IBD (UC) from IBS. Acharya K, Bhardwaj V, Chuahan I, et al. Comparison of Fecal Calprotectin with Different Endoscopic Scores in the Assessment of Ulcerative Colitis (UC) Activity and Its Utility in Differentiating IBS from IBD. Euroasian J Hepato-Gastroenterol 2023;13(2):120-123.

Single-center Experience With Upadacitinib for Adolescents With Refractory Inflammatory Bowel Disease.

Upadacitinib (UPA) is a novel selective JAK inhibitor approved for adults with ulcerative colitis (UC) and with positive phase 3 data for Crohn's disease (CD). Pediatric off-label use is common due to delays in pediatric approvals; real-world data on UPA are needed to understand the safety and effectiveness in pediatric IBD. This is a single-center retrospective case series study of adolescents (12-17 years) with inflammatory bowel disease IBD on UPA. The primary outcome was postinduction steroid-free clinical remission (SF-CR) defined as Pediatric UC Activity Index (PUCAI) or Pediatric CD Activity Index (PCDAI) ≤10. Secondary outcomes include postinduction clinical response (decrease ≥12.5 in PUCAI/PCDAI), postinduction C-reactive protein (CRP) normalization, 6-month SF-CR, and intestinal ultrasound response and remission. Adverse events were recorded through last follow-up. Twenty patients (9 CD, 10 UC, 1 IBD-U; 55% female; median age 15 years, 90% ≥2 biologics) were treated with UPA for ≥12 weeks (median 51 [43-63] weeks). Upadacitinib was used as monotherapy in 55% and as combination with ustekinumab and vedolizumab in 35% and 10%, respectively. Week 12 SF-CR was achieved in 75% (15/20) and 80% (16/20) with CRP normalization. About 3/4 (14/19) achieved SF-CR at 6 months. Adverse event occurred in 2 patients (10%): Cytomegaloviruscolitis requiring hospitalization and hyperlipidemia requiring no treatment. In the 75% with ultrasound monitoring, response and remission were achieved in 77% and 60%, respectively. While awaiting pediatric registration trials, our data suggest that UPA is effective in inducing and maintaining SF-CR in adolescents with highly-refractory IBD with an acceptable safety profile.

Beneficial Effect of Faecal Microbiota Transplantation on Mild, Moderate and Severe Dextran Sodium Sulphate-Induced Ulcerative Colitis in a Pseudo Germ-Free Animal Model.

Transplantation of faecal microbiota (FMT) is generally considered a safe therapeutic procedure with few adverse effects. The main factors that limit the spread of the use of FMT therapy for idiopathic inflammatory bowel disease (IBD) are the necessity of minimising the risk of infection and transfer of another disease. Obtaining the animal model of UC (ulcerative colitis) by exposure to DSS (dextran sodium sulphate) depends on many factors that significantly affect the result. Per os intake of DSS with water is individual for each animal and results in the development of a range of various forms of induced UC. For this reason, the aim of our study was to evaluate the modulation and regenerative effects of FMT on the clinical and histopathological responses and the changes in the bowel microenvironment in pseudo germ-free (PGF) mice of the BALB/c line subjected to chemical induction of mild, moderate and serious forms of UC. The goal was to obtain new data related to the safety and effectiveness of FMT that can contribute to its improved and optimised use. The animals with mild and moderate forms of UC subjected to FMT treatment exhibited lower severity of the disease and markedly lower damage to the colon, including reduced clinical and histological disease index and decreased inflammatory response of colon mucosa. However, FMT treatment failed to achieve the expected therapeutic effect in animals with the serious form of UC activity. The results of our study indicated a potential safety risk involving development of bacteraemia and also translocation of non-pathogenic representatives of bowel microbiota associated with FMT treatment of animals with a diagnosed serious form of UC.

Calprotectin Is Associated with HETE and HODE Acids in Inflammatory Bowel Diseases.

Intestinal diseases are identified as autoimmune phenomena attributed to a specific virus that binds to the mucosal epithelium. The importance of precise diagnostic processes and identification is emphasized, but the multifaceted and complex etiological factors pose challenges for effective treatment. A recent supplementary study suggested a linkage between the secretion of calprotectin, a protein associated with inflammatory processes, and increased levels of hydroxyeicosatrienoic acids (HETE) and hydroxyoctadecadienoic (HODE) compounds. Sixty-two patients (average age: 14.06 ± 2.93 years) suffering from inflammatory bowel diseases were included in this study. Comparative analyses were performed to assess the concentrations of calprotectin against the levels of arachidonic acid derivatives. The calprotectin concentration was determined using the enzyme-linked immunosorbent assay (ELISA) method. The derivatives of HETE and HODE were identified through liquid chromatography. Patients with Crohn's disease (CD) displayed higher average concentrations of fatty acid metabolites; however, no correlation with calprotectin was observed. A dependency of 12S HETE concentration relative to age was noted in the CD group, and a similar trend was also identified in ulcerative colitis (UC), with the significant metabolites being 15 HETE and 5 oxoETE. In UC patients, a positive correlation was established between the calprotectin concentration and the acids 5-HETE and 12-HETE. These findings may be instrumental for monitoring the inflammatory states of patients and indicating a pathway for intervention. The metabolite 16RS HETE is associated with UC activity, and 15-HETE is related to the disease's duration. A relatively more significant role of HETE acids in the progression of the disease was observed in UC.

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.

Early Intestinal Ultrasound Predicts Clinical and Endoscopic Treatment Response and Demonstrates Drug-Specific Kinetics in Moderate-to-Severe Ulcerative Colitis.

Intestinal ultrasound (IUS) is an emerging modality in monitoring disease activity in ulcerative colitis (UC). Here, we aimed to identify early IUS predictors of treatment response as evaluated by endoscopy and assessed the kinetics of IUS changes. This prospective, longitudinal study included UC patients with endoscopic disease activity (endoscopic Mayo score [EMS] ≥2) starting anti-inflammatory treatment. Clinical scores, biochemical parameters and IUS were assessed at baseline (W0), at week 2 (W2), at W6(W6), and at the time of second endoscopy (W8-W26). Per colonic segment, endoscopic remission (EMS = 0), improvement (EMS ≤1), response (decrease in EMS ≥1), and clinical remission (Lichtiger score ≤3) were assessed and correlated with common IUS parameters. Additionally, drug-specific responsiveness of bowel wall thickness (BWT) was assessed. A total of 51 patients were included and followed, and 33 patients underwent second endoscopy. BWT was lower from W6 onward for patients reaching endoscopic improvement (3.0 ± 1.2 mm vs 4.1 ± 1.3 mm; P = .026), remission (2.5 ± 1.2 mm vs 4.1 ± 1.1 mm; P = .002), and clinical remission (3.01 ± 1.34 mm vs 3.85 ± 1.20 mm; P = .035). Decrease in BWT was more pronounced in endoscopic responders (-40 ± 25% vs -4 ± 28%; P = .001) at W8 to W26. At W6, BWT ≤3.0 mm (odds ratio [OR], 25.13; 95% confidence interval, 2.01-3.14; P = .012) and color Doppler signal (OR, 0.35; 95% confidence interval, 0.14-0.88; P = .026) predicted endoscopic remission and improvement, respectively. Submucosal layer thickness at W6 predicted endoscopic remission (OR, 0.09; P = .018) and improvement (OR, 0.14; P = .02). Furthermore, BWT decreased significantly at W2 for infliximab and tofacitinib and at W6 for vedolizumab. BWT and color Doppler signal predicted endoscopic targets already after 6 weeks of treatment and response was drug specific. IUS allows close monitoring of treatment in UC and is a surrogate marker of endoscopy.