Composite Assessment Using Intestinal Ultrasound and Calprotectin Is Accurate in Predicting Histological Activity in Ulcerative Colitis: A Cohort Study.

BACKGROUND: Beyond endoscopic remission, histological remission in ulcerative colitis (UC) is predictive of clinical outcomes. Intestinal ultrasound (IUS) may offer a noninvasive surrogate marker for histological activity; however, there are limited data correlating validated ultrasound and histological indices. AIM: Our aim was to determine the correlation of IUS activity in UC with a validated histological activity index. METHODS: Twenty-nine prospective, paired, same-day IUS/endoscopy/histology/fecal calprotectin (FC) cases were included. Intestinal ultrasound activity was determined using the Milan Ultrasound Criteria, histological activity using the Nancy Histological Index, endoscopic activity using Mayo endoscopic subscore and Ulcerative Colitis Endoscopic Index of Severity, and clinical activity using the Simple Clinical Colitis Activity Score. RESULTS: Histological activity demonstrated a significant linear association with overall IUS activity (coefficient 0.14; 95% CI, 0.03-0.25; P = .011). Intestinal ultrasound activity was also significantly associated with endoscopic activity (0.32; 95% CI, 0.14-0.49; P < 0.001), total Mayo score (0.31; 95% CI, 0.02-0.60; P = .036) but not FC (0.10; 95% CI, -0.01 to 0.21; P = .064) or clinical disease activity (0.04; 95% CI, -0.21 to 0.28; P = .768). A composite of IUS and FC showed the greatest association (1.31; 95% CI, 0.43-2.18; P = .003) and accurately predicted histological activity in 88% of cases (P = .007), with sensitivity of 88%, specificity 80%, positive predictive value 95%, and negative predictive value 57%. CONCLUSIONS: Intestinal ultrasound is an accurate noninvasive marker of histological disease activity in UC, the accuracy of which is further enhanced when used in composite with FC. This can reduce the need for colonoscopy in routine care by supporting accurate point-of-care decision-making in patients with UC.

Neutrophil-only Histological Assessment of Ulcerative Colitis Correlates with Endoscopic Activity and Predicts Long-term Outcomes in a Multicentre Study.

BACKGROUNDS AND AIMS: Absence of neutrophils is the minimum standard to consider histological remission of ulcerative colitis [UC]. The PICaSSO Histological Remission Index [PHRI] is a new simple index for UC, based only on the detection of neutrophils. We evaluate PHRI's correlation with endoscopy and its prognostic value compared with other established indices. METHODS: Consecutive patients with UC underwent colonoscopy at two referral centres [Birmingham, UK, and Milan, Italy,] and were followed up for 2 years. Correlation between histology (PHRI, Nancy [NHI], and Robarts [RHI] indexes) and endoscopy (Mayo Endoscopic Score [MES], Ulcerative Colitis Endoscopic Index of Severity [UCEIS], and PICaSSO index) was calculated as Spearman coefficients. Diagnostic performance of endoscopy was assessed with receiver operating characteristic [ROC] curves and outcome stratification with Kaplan-Meier curves. RESULTS: A total of 192 patients with UC was enrolled, representing all grades of endoscopic severity. Correlation between histology and endoscopy did not differ significantly when using PHRI instead of NHI or RHI. In particular, PHRI's correlation with MES, UCEIS, and PICaSSO was 0.745, 0.718, and 0.694, respectively. Endoscopically-assessed remission reflected the absence of neutrophils [PHRI = 0] with areas under the ROC curve of 0.905, 0.906, and 0.877 for MES, UCEIS, and PICaSSO, respectively. The hazard ratio for disease flare between patients in histological activity/remission was statistically similar [p >0.05] across indexes [2.752, 2.706, and 2.871 for RHI, NHI, and PHRI, respectively]. CONCLUSION: PHRI correlates with endoscopy and stratifies risk of relapse similarly to RHI and NHI. Neutrophil-only assessment of UC is a simple yet viable alternative to established histological scores.

Density of Biopsy Sampling Required to Ensure Accurate Histological Assessment of Inflammation in Active Ulcerative Colitis.

BACKGROUND: Histological response to treatment is an important outcome in patients with ulcerative colitis (UC). The accuracy of biopsy-based measurements of inflammation may be limited by error imposed by natural microscopic heterogeneity on the scale of individual biopsies. We determined the magnitude of this error, its histological correlates, and the density of biopsy sampling within mucosal regions of interest required to meet specified benchmarks for accuracy. METHODS: A total of 994 sequential 1-mm digital microscopic images (virtual biopsies) from consecutive colectomies from patients with clinically severe UC were scored by 2 pathologists. Agreement statistics for Geboes subscores and Nancy (NHI) and Robarts Histological Indices (RHI) between random samples from 1 to 10 biopsies and a reference mean score across a 2-cm region of mucosa were calculated using bootstrapping with 2500 iterations. RESULTS: The agreement statistics improved across all indices as the biopsy density increased, with the largest proportional gains occurring with addition of the second and third biopsies. One biopsy achieved moderate to good agreement with 95% confidence for NHI and RHI corresponding to scale-specific errors of 0.40 (0.25-0.66) and 3.02 (2.08-5.36), respectively; and 3 biopsies achieved good agreement with 95% confidence corresponding to scale-specific errors of 0.22 (0.14-0.39) and 1.87 (1.19-3.25), respectively. Of the individual histological features, erosions and ulcers had the greatest impact on the agreement statistics. CONCLUSIONS: In the setting of active colitis, up to 3 biopsy samples per region of interest may be required to overcome microscopic heterogeneity and ensure accurate histological grading.

Interobserver Reliability of the Nancy Index for Ulcerative Colitis: An Assessment of the Practicability and Ease of Use in a Single-Centre Real-World Setting.

BACKGROUND: Histological disease severity assessment in ulcerative colitis [UC] has become a mainstay in the definition of clinical endpoints ['histological remission'] in clinical trials of UC. Several scores have been established in the microscopic assessment of disease activity, but the Nancy index [NI] stands out as being the histological index with the fewest scoring items. To what extent histological assessment using the NI is affected by interobserver reliability in a real-word setting is poorly understood. We therefore performed a single-centre retrospective analysis of NI assessment in patients with UC. METHODS: We retrospectively evaluated the NI in two independent cohorts [total: 1085 biopsies, 547 UC patients] of clinically diagnosed UC patients, who underwent colonoscopy between 2007 and 2020. Cohort #1 consisted of 637 biopsies from 312 patients, while Cohort #2 consisted of 448 biopsies from 235 patients. Two blinded pathologists with different levels of expertise scored all biopsies from each cohort. A consensus conference was held for cases with discrepant scoring results. Finally, an overall consensus scoring was obtained from both cohorts. RESULTS: The interobserver agreement of the NI was substantial after the assessment of 1085 biopsy samples (κ = 0.796 [95% confidence interval, CI: 0.771-0.820]). An improvement of the interobserver agreement was found with increasing numbers of samples evaluated by both observers (Cohort #1: κ = 0.772 [95% CI: 0.739-0.805]; Cohort #2: κ = 0.829 [95% CI: 0.793-0.864]). Interobserver discordance was highest in NI grade 1 [observer 1: n = 128; observer 2: n = 236]. Interobserver discordance was lowest in NI grades 0 [observer 1: n = 504; observer 2: n = 479] and 3 [observer 1: n = 71; observer 2: n = 66]. CONCLUSION: The NI is an easy-to-use index with high interobserver reliability for assessment of the histological disease activity of UC patients in a real-world setting. While NI grades 0 and 3 had a high level of agreement between observers, NI grade 1 had a poorer level of agreement. This highlights the clinical need to specify histological characteristics leading to NI grade 1.

Positioning and Usefulness of Biomarkers in Inflammatory Bowel Disease.

BACKGROUND: Mucosal healing (MH) was proposed to be an ideal treatment goal for patients with inflammatory bowel disease (IBD). Instead of endoscopy to confirm MH, biomarkers are frequently used and have become an indispensable modality for the clinical examination of patients with IBD. SUMMARY: Common biomarkers of IBD include C-reactive protein (CRP), erythrocyte sedimentation rate, antineutrophil cytoplasmic antibodies, anti-Saccharomyces cerevisiae antibodies, leucine-rich α2 glycoprotein, fecal calprotectin (FCP), and the fecal immunochemical test. Biomarkers play five major roles in the management of IBD: (1) diagnosing and distinguishing between IBD and non-IBD or ulcerative colitis and Crohn's disease; (2) predicting treatment response, especially before administrating biologics; (3) monitoring and grasping endoscopic or histological disease activity; (4) replacing endoscopy for diagnosing MH, including endoscopic and histological remission; and (5) predicting recurrence before disease activity appears through symptoms. Many reports have demonstrated the usefulness of CRP and FCP for those five roles; however, they have limitations for diagnosing MH or predicting treatment response. In general, FCP has better ability in those positions than CRP; additionally, leucine-rich α2 glycoprotein can diagnose endoscopic disease activity better than CRP. The novel biomarker, prostaglandin E-major urinary metabolite, and anti-αvß6 antibody are expected to be noninvasive and reliable biomarkers; however, more evidence is required for future studies. Oncostatin M and microRNA are also prospects, in addition to other familiar and novel biomarkers. KEY MESSAGES: Each biomarker has a useful feature; therefore, we should consider their features and use appropriate biomarkers for the five roles to enable noninvasive and smooth management of IBD.

Histopathological assessment of the microscopic activity in inflammatory bowel diseases: What are we looking for?

Advances in diagnostics of inflammatory bowel diseases (IBD) and improved treatment strategies allowed the establishment of new therapeutic endpoints. Currently, it is desirable not only to cease clinical symptoms, but mainly to achieve endoscopic remission, a macroscopic normalization of the bowel mucosa. However, up to one-third of IBD patients in remission exhibit persisting microscopic activity of the disease. The evidence suggests a better predictive value of histology for the development of clinical complications such as clinical relapse, surgical intervention, need for therapy escalation, or development of colorectal cancer. The proper assessment of microscopic inflammatory activity thus became an important part of the overall histopathological evaluation of colonic biopsies and many histopathological scoring indices have been established. Nonetheless, a majority of them have not been validated and no scoring index became a part of the routine bioptic practice. This review summarizes a predictive value of microscopic disease activity assessment for the subsequent clinical course of IBD, describes the most commonly used scoring indices for Crohn's disease and ulcerative colitis, and comments on current limitations and unresolved issues.

Impact of adalimumab on disease burden in moderate-to-severe ulcerative colitis patients: The one-year, real-world UCanADA study.

BACKGROUND: A gap remains in documenting the impact of anti-tumor necrosis factor therapy on disease burden in ulcerative colitis (UC) patients treated in a real-world setting. The use of patient-reported outcomes (PROs) has been discussed as a primary endpoint in the context of the FDA PRO Guidance, for labelling purposes. Specifically, the efficacy and safety of adalimumab have been demonstrated in pivotal trials; however, data are needed to understand how clinical results translate into improvements in key aspects of the daily lives of UC patients, such as symptoms, health-related quality of life (HRQoL), and disability. AIM: To assess real-world effectiveness of adalimumab on PRO measures in patients with moderate-to-severe UC. METHODS: UCanADA was a single arm, prospective, 1-year multicenter Canadian post-marketing observational study in which multiple PRO questionnaires were completed-with psychologic distress/depression symptoms as the primary endpoint-by patients with moderate-to-severe UC. Assessments were performed during patients' routine care visit schedule, which was at the initiation of adalimumab (baseline), after induction (approximately 8 wk), and 52 wk after baseline. Additional optional assessments between weeks 8 and 52 were collected at least once but no more than two times during this period. Serious safety events and per-protocol adverse events were collected. RESULTS: From 23 Canadian centres, 100 patients were enrolled and 48 completed the study. Measured with the Patient Health Questionnaire-9 items at week 52, 61.5% (40/65) [95% confidence interval (CI): 49.7%-73.4%] of the patients improved in psychologic distress/depression symptoms, which was slightly higher in completers [65.9% (29/44); 95%CI: 51.9%-79.9%)]. At week 52, clinical response and clinical remission were achieved respectively by 65.7% (44/73) and 47.8% (32/73) of the patients. The odds of improving depressive symptoms for those achieving a clinical remission at week 52 was 7.94 higher compared with those not achieving a clinical remission (CI: 1.42, 44.41; P = 0.018). Significant changes from baseline to weeks 8 and 52 were observed in disability, HRQoL, and fatigue. Meaningful improvement was reported in work impairment. CONCLUSION: At week 52, over 60% of the UCanADA patients had depressive symptoms significantly reduced, as well as HRQoL, fatigue symptoms, and work impairment improved. No new safety signals were detected.

Ultrasound Elastography in Inflammatory Bowel Diseases: A Systematic Review of Accuracy Compared with Histopathological Assessment.

BACKGROUND AND AIMS: Ultrasound elastography [USE] is an innovative, non-invasive, promptly available, ancillary technique that has been proposed in the evaluation of intestinal fibrosis as a monitorable biomarker, in terms of stiffness. The non-invasive estimate of fibrosis by USE appears appealing for dedicated physicians, in order to optimise the treatments for inflammatory bowel disease [IBD] patients [surgical vs non-surgical]. We aimed to systematically review literature evidence on ultrasound elastography in IBD patients. METHODS: For this qualitative systematic review, we searched PubMed, EMBASE, and Scopus to identify all studies, published until October 2021, investigating the application of USE in IBD patients compared with histopathological assessment. RESULTS: Overall, 12 papers published between 2011 and 2019 were included. A total of 275 IBD patients were included: 272 Crohn's disease [CD] [98.9%] and three ulcerative colitis [UC] [1.1%]. Seven [58.3%] and four [41.6%] studies investigated strain elastography [SE] and shear wave elastography [SWE], respectively; in one study [0.1%] both techniques were addressed. The histological evaluation was largely conducted on surgical specimens and in two studies endoscopic biopsies were also included. The histological assessment was semi-quantitative in all the included studies, except for two where the fibrosis was evaluated only qualitatively. In 10/12 publications USE could accurately distinguish inflammation from fibrosis in the examined bowel tracts. CONCLUSIONS: From the preliminary available data, an overall moderate-to-good accuracy of USE in detecting histological fibrosis [10/12 studies] was found. Point-shear wave elastography has been shown to perform superiorly. Further studies are needed to confirm these evidences.

[Assessment of histologic activity in colitis]. / Otsenka gistologicheskoi aktivnosti kolitov.

The histological activity of the bowel inflammation is an extremely important morphological criterion that is encountered in the diagnosis of colitis. However, the determining of its degree is subjective and still does not have a generally accepted principle of gradation. The article describes the most common scale-schemes for assessing the severity of colitis, that include the degree of microscopic changes. The results of the analysis of the of histological activity degree on the material of colonobioptates in colitis of various etiologies (467 patients) are presented. It has been shown that the Geboes scale of ulcerative colitis can be used to assess histological activity in all forms of colitis. The histological features of inflammation should be reflected in the pathological diagnosis and are essential for clinical decision making. This index allows for a comparative analysis of clinical, endoscopic and morphological parameters and better control of the patient's condition during the treatment.

PICaSSO virtual electronic chromendoscopy accurately reflects combined endoscopic and histological assessment for prediction of clinical outcomes in ulcerative colitis.

BACKGROUND AND AIMS: A composite endoscopic-histologic remission is increasingly explored as an important endpoint in ulcerative colitis (UC). We investigated combined endoscopic-histologic remission for predicting clinical outcomes at 12 months compared with endoscopic remission alone using the high definition virtual chromoendoscopy (VCE) Paddington International virtual ChromoendoScopy ScOre (PICaSSO) and histology scores. METHODS: Ulcerative colitis patients, prospectively enrolled from 11 international centres, underwent VCE with targeted biopsies and followed up for 12 months. Endoscopic activity was assessed by Mayo Endoscopic Score (MES), Ulcerative Colitis Endoscopic Index Severity (UCEIS) followed by VCE-PICaSSO. Robarts Histopathological Index|Robarts Histological index≤3 without neutrophils in mucosa, and Nancy Histological index (NHI)≤ 1 were used to define histologic remission. Combined endoscopic-histologic remission was compared with endoscopic remission alone by Cox proportional hazards model and by two- and three-proportion analysis using pre-specified clinical outcomes. RESULTS: 307 patients were recruited and 302 analysed. There was no difference in survival without specified clinical outcomes between PICaSSO defined endoscopic remission alone and endoscopic plus histologic remission in the rectum (HR 0.42, 95%CI 0.16-1.11 and HR 1.03, 95%CI 0.42-2.52 for Robarts Histological index and NHI respectively) at 12 months. There was however a significant survival advantage without specified clinical outcome events for UCEIS combined with histology compared with UCEIS alone (HR 0.30, 95%CI 0.12-0.75, p = 0.02) at 12 months (but not combined with NHI). For MES there was no advantage for predicting specified clinical outcomes at 12 months for endoscopy alone versus endoscopy plus histology, but there were differences in two and three proportion analysis at 6 months. CONCLUSION: Endoscopic remission by VCE-PICaSSO alone was similar to combined endoscopic and histologic remission for predicting specified clinical outcomes at 12 months. Larger studies with specific therapeutic interventions are required to further confirm the findings.

Endoscopic and Histological Assessment, Correlation, and Relapse in Clinically Quiescent Ulcerative Colitis (MARQUEE).

OBJECTIVE: It is difficult to predict relapse in quiescent ulcerative colitis (UC), but newer endoscopic and histological indices could improve this. This study aimed to determine in UC patients in clinical remission (1) the prevalence of active endoscopic and histological disease; (2) the correlation between endoscopic and histological scores; and (3) the predictive power of these scores for clinical relapse. DESIGN: This multicenter prospective cohort study conducted by the Crohn's and Colitis Foundation Clinical Research Alliance included 100 adults with UC in clinical remission undergoing surveillance colonoscopy for dysplasia. Endoscopic activity was assessed using the Mayo endoscopic score (MES), ulcerative colitis endoscopic index of severity (UCEIS), and ulcerative colitis colonoscopic index of severity (UCCIS). Histology was assessed with the Riley index subcomponents, total Riley score, and basal plasmacytosis. RESULTS: Only 5% of patients had an MES of 0, whereas 38% had a score of 2 to 3; using the UCEIS, the majority of patients had at least mild activity, and 15% had more severe activity. Many patients also had evidence of histological disease activity. The correlations among endoscopic indices, histological subcomponents, and total score were low; the highest correlations occurred with the subcomponent architectural irregularity (ρ = 0.43-0.44), total Riley score (ρ = 0.35-0.37), and basal plasmacytosis (ρ = 0.35-0.36). Nineteen patients relapsed clinically over 1 year, with the subcomponent architectural irregularity being the most predictive factor (P = 0.0076). CONCLUSIONS: This multicenter prospective study found a high prevalence of both endoscopic and histological disease activity in clinically quiescent UC. The correlations between endoscopy and histology were low, and the power to predict clinical relapse was moderate.

Development of the symptoms and impacts questionnaire for Crohn's disease and ulcerative colitis.

BACKGROUND: Patient-reported outcome (PRO) measures historically used in inflammatory bowel disease have been considered inadequate to support future drug labelling claims by regulatory agencies. AIMS: To develop PRO tools for use in Crohn's disease (CD) and ulcerative colitis (UC) following guidance issued by the US FDA and the ISPOR (International Society for Pharmacoeconomics and Outcomes Research). METHODS: Concept elicitation and cognitive interviews were conducted in adult patients (≥18 years) across the United States and Canada. Semi-structured interview guides were used to collect data, and interview transcripts were coded and analysed. Concept elicitation results were considered alongside existing literature and clinical expert opinion to identify candidate PRO items. Cognitive interviews evaluated concept relevance, interpretability and structure, and facilitated instrument refinement. Concept elicitation participants, except those with an ostomy, underwent centrally read endoscopy to assess inflammatory status. RESULTS: In all, 54 participants (mean age: 46.2 years; 66.7% female) were included in the CD concept elicitation interviews. In total, 80 symptom concepts and 61 impact concepts were identified. After three waves of cognitive interviews, the 31-item Symptoms and Impacts Questionnaire for CD (SIQ-CD) was developed. In the UC concept elicitation phase, 53 participants were interviewed (mean age: 41.4 years; 49.1% female). In total, 79 symptoms concepts and 49 impact concepts were identified. Following two waves of cognitive interviews, the 29-item Symptoms and Impacts Questionnaire for UC (SIQ-UC) was developed. Both instruments include four symptom and six impact domains. CONCLUSIONS: We developed PROs to support CD and UC drug labelling claims. Psychometric validation studies to evaluate instrument reliability and responsiveness are ongoing.

Assessment of Endoscopic Healing by Using Advanced Technologies Reflects Histological Healing in Ulcerative Colitis.

BACKGROUND: Several studies have reported that ulcerative colitis [UC] patients with endoscopic mucosal healing may still have histological inflammation. We investigated the relationship between mucosal healing defined by modified PICaSSO [Paddington International Virtual ChromoendoScopy ScOre], Mayo Endoscopic Score [MES] and probe-based confocal laser endomicroscopy [pCLE] with histological indices in UC. METHODS: A prospective study enrolling 82 UC patients [male 66%] was conducted. High-definition colonoscopy was performed to evaluate the activity of the disease with MES assessed with High-Definition MES [HD-MES] and modified PICaSSO and targeted biopsies were taken; pCLE was then performed. Receiver operating characteristic [ROC] curves were plotted to determine the best thresholds for modified PICaSSO and pCLE scores that predicted histological healing according to the Robarts Histopathology Index [RHI] and ECAP 'Extension, Chronicity, Activity, Plus' histology score. RESULTS: A modified PICaSSO of ≤ 4 predicted histological healing at RHI ≤ 3, with sensitivity, specificity, accuracy and area under the ROC curve [AUROC] of 89.8%, 95.7%, 91.5% and 95.9% respectively. The sensitivity, specificity, accuracy and AUROC of HD-MES to predict histological healing by RHI were 81.4%, 95.7%, 85.4% and 92.1%, respectively. A pCLE ≤ 10 predicted histological healing with sensitivity of 94.9%, specificity of 91.3%, accuracy of 93.9% and AUROC of 96.5%. An ECAP of ≤ 10 was predicted by modified PICaSSO ≤ 4 with accuracy of 91.5% and AUROC of 95.9%. CONCLUSION: Histological healing by RHI and ECAP is accurately predicted by HD-MES and modified virtual electronic chromoendoscopy PICaSSO, endoscopic score; and the use of pCLE did not improve the accuracy any further.

Assessment of the Changes in Mitochondrial Gene Polymorphism in Ulcerative Colitis and the Etiology of Ulcerative Colitis-associated Colorectal Cancer.

BACKGROUND: Mitochondria are energy-producing organelles, and dysfunction in these organelles causes various types of disease. Although several studies have identified mutations in nuclear DNA that are associated with the etiology of ulcerative colitis (UC), information regarding mitochondrial DNA (mtDNA) in UC is limited. This study aimed to investigate the mitochondrial DNA polymorphism underlying the etiology of UC and UC-associated colorectal cancer. MATERIALS AND METHODS: Next-generation sequencing was performed to assess mitochondrial DNA mutations in 12 patients with UC-associated cancer. The mtDNA mutations in the non-neoplastic mucosa, tumor tissues, and healthy controls were compared. RESULTS: The incidence of mutations of nicotinamide adenine dinucleotide phosphate ubiquinone oxidase subunit, ATP synthetase, and tRNA was higher in non-neoplastic mucosa in those with UC compared with the healthy controls. However, no statistically significant differences were observed in mutations between the tumor tissues and non-neoplastic mucosa in UC. CONCLUSION: Significant mutations in mtDNA were observed in the non-neoplastic mucosa of patients with UC-associated cancer.

Factors associated with disability in patients with ulcerative colitis: A cross-sectional study.

OBJECTIVES: Ulcerative colitis (UC) can give rise to several restrictions of patients' working and social activities. We aimed to determine the association between disease chronicity and the state of disability in a large population with UC. METHODS: We recruited consecutive patients with UC attending the inflammatory bowel disease (IBD) unit of the Azienda Ospedaliera of Padua between July and December 2017. We collected patients' characteristics and clinical information, and all participants completed the IBD questionnaire (IBDQ) for quality of life assessment and the IBD disability index (IBD-DI) questionnaire. Using univariate logistic regression models we assessed whether the patients' characteristics and IBD-related variables were associated with an IBD-DI score ≤3.5. Statistically significant variables in the univariate analyses were then included in a multivariate regression model. Correlations between IBD-DI and all the above mentioned characteristics were investigated using the Spearman's rank correlation coefficient. RESULTS: We included 201 patients. A positive correlation was observed between IBD-DI and IBDQ (r = 0.82, P < 0.001). Multivariate regression modelling identified the following as independent factors related to disability: active disease (partial Mayo score ≥2) (odds ratio [OR] 6.54, 95% CI 3.21-13.22), the presence of extraintestinal manifestations (EIM) (OR 2.48, 95%, CI 1.11-5.54) and occasional alcohol consumption (OR 0.39, 95% CI 0.20-0.76). CONCLUSIONS: Impaired disability is mainly correlated with disease activity, the presence of EIM and no alcohol consumption. Moreover, there is a strong correlation with patients' quality of life. Therefore, in clinical practice, greater awareness of IBD-related disability is needed to better manage patients' outcomes.

The Ulcerative Colitis Response Index for Detection of Mucosal Healing in Patients Treated With Anti-tumour Necrosis Factor.

BACKGROUND: Surrogate markers that accurately detect mucosal healing [MH] in patients with ulcerative colitis [UC] are urgently needed. Several stool neutrophil-related proteins are currently used as biomarkers for MH. However, the sensitivity and specificity are not sufficient to avoid unnecessary endoscopic evaluations. METHODS: Novel serum neutrophil-related markers (neutrophil gelatinase B-associated lipocalin and matrix metalloproteinase-9 [NGAL-MMP-9 complex], cathelicidin LL-37 and chitinase 3-like 1 [CHI3L1]), together with C-reactive protein [CRP] and neutrophil counts were studied. Serum samples were obtained from 176 anti-tumour necrosis factor [anti-TNF]-treated UC patients (145 infliximab [IFX] and 31 adalimumab [ADM]) at baseline and after a median of 9.5 weeks. All patients had active disease prior to treatment (Mayo endoscopic subscore [MES] ≥ 2), and MH was defined as MES ≤ 1. Serum was also obtained from 75 healthy controls. Binary logistic regression analysis was used to generate the Ulcerative Colitis Response Index [UCRI]. The performance of individual markers and UCRI was tested with receiver operating characteristic analysis. RESULTS: All neutrophil-related markers were significantly higher in active UC patients compared to healthy controls. In the IFX cohort, CRP, NGAL-MMP-9, CHI3L1 and neutrophil count decreased significantly after treatment and all marker levels were significantly lower in healers compared to non-healers following IFX. In the ADM cohort, CRP, NGAL-MMP-9, CHI3L1 and neutrophil count decreased significantly only in healers. UCRI [including CRP, CHI3L1, neutrophil count and LL-37] accurately detected MH in both IFX-treated (area under the curve [AUC] = 0.83) and ADM-treated [AUC = 0.79] patients. CONCLUSIONS: The new UCRI index accurately detects MH after treatment with IFX and ADM. This panel is useful for monitoring MH in UC patients under anti-TNF treatment. PODCAST: This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast.

Endoscopic score vs blood cell indices for determining timing of immunomodulator withdrawal in quiescent ulcerative colitis.

While immunomodulators (IMs) are used as key drugs in remission maintenance treatment for ulcerative colitis (UC), there has been no evidence to date for determining monitoring methods and drug withdrawal. Therefore, we examined if a decrease in white blood cell count (WBC) and an elevation in mean cell volume (MCV) could be used as optimization indices and if mucosal healing (MH) could be a rationale for determining the time of IM withdrawal. Subjects were 89 UC patients who were using IMs and for whom clinical remission had been maintained. Those with a Rachmilewitz Clinical Activity Index score of 4 or lower and those with a Mayo endoscopic subscore (MES) of 0 or 1 were defined as MH. The remission maintenance rates of the following comparative groups were examined: an IM continuation group and an IM withdrawal group; an IM continuation group with a WBC of less than 3000 or a MCV of 100 or greater and an IM continuation group with a WBC of 3000 or greater and a MCV of 99 or lower; an IM continuation group of patients for whom MH had been achieved and an IM continuation group of patients for whom MH had not been achieved; and an IM withdrawal group with a MES of 0 and an IM withdrawal group with a MES of 1. A significantly higher remission maintenance rate was observed in the IM continuation group compared to the withdrawal group (p < 0.01). No significant difference was observed between the IM continuation group with a WBC of less than 3000 or a MCV of 100 or greater and the IM continuation group with a WBC of 3000 or greater and a MCV of 99 or lower (p = 0.08). Higher remission maintenance rates were observed in the IM continuation group of patients for whom MH had been achieved compared to the IM continuation group of patients for whom MH had not been achieved (p = 0.03). No significant difference was observed between the IM withdrawal group with MES 0 and the IM withdrawal group with MES 1. (p = 0.48). This retrospective study showed that remission maintenance could be firmly obtained by continuing IM administration in case of endoscopic MH; however, MH was not an indicator of IM withdrawal.

Simultaneous Assessment of Urinary and Fecal Volatile Organic Compound Analysis in De Novo Pediatric IBD.

Endoscopic evaluation is mandatory in establishing the diagnosis of pediatric inflammatory bowel disease (IBD), but unfortunately carries a high burden on patients. Volatile organic compounds (VOC) have been proposed as alternative, noninvasive diagnostic biomarkers for IBD. The current study aimed to assess and compare the potential of fecal and urinary VOC as diagnostic biomarkers for pediatric IBD in an intention-to-diagnose cohort. In this cohort study, patients aged 4-17 years, referred to the outpatient clinic of a tertiary referral center under suspicion of IBD, were eligible to participate. The diagnosis was established by endoscopic and histopathologic assessment, participants who did not meet the criteria of IBD were allocated to the control group. Participants were instructed to concurrently collect a fecal and urinary sample prior to bowel lavage. Samples were analyzed by means of gas chromatography-ion mobility spectrometry. In total, five ulcerative colitis patients, five Crohn's disease patients, and ten age and gender matched controls were included. A significant difference was demonstrated for both fecal (p-value, area under the curve; 0.038, 0.73) and urinary (0.028, 0.78) VOC profiles between IBD and controls. Analysis of both fecal and urinary VOC behold equal potential as noninvasive biomarkers for pediatric IBD diagnosis.