bluuebunny/crossref_metadata_2025 huggingface dataset:
P321 Development and validation of an Integrated Risk Score for future risk of Crohn’s disease in healthy first-degree relatives: The CCC-GEM Project, a multicentre prospective cohort study
Authors: Lee Dr. S H , Turpin W , Espin-Garcia O , Leibovitzh H , Xue M , Raygoza-Garay J A , Grana L , Smith M I , Goethel A , Madsen L. K , Avni-Biron I , Dotan I , Shomron B H , Griffiths A M , Steinhart A H , Silverberg M S , Turner D , Bernstein C N , Feagan B G , Moayeddi P , Paterson A , Guttman D , Xu W , Croitoru K
Published: January 2024

Background

Although the cause of Crohn’s disease (CD) is unknown, recent studies have identified a number of biomarkers associated with the risk of developing CD in healthy at-risk individuals. Establishing a combined prediction model that stratifies the future risk of CD in healthy at-risk individuals is the first step towards disease prevention and a better understanding of the preclinical phase of CD.

Methods

We recruited healthy first-degree relatives (FDRs) of persons with CD from 2008-2017 as part of the global multicenter prospective Crohn’s and Colitis Canada Genetic Environmental Microbial (CCC-GEM) Project. After collecting demographic information, blood, urine, and stool samples at recruitment, participants were followed for the development of CD. A GEM-integrative risk score (GEM-IRS), using random survival forest modeling that combined the baseline variables (demographics, measures of gut inflammation – fecal calprotectin, intestinal barrier function – urinary fractional excretion ratio of lactulose to mannitol, and fecal microbiome composition and predicted functional capacities – based upon 16S rDNA sequencing and PICRUSt2) to estimate time-to-CD onset, was derived and subsequently validated in two independent testing cohorts.

Results

Among 2,619 FDRs followed for a median of 6.8 years, 61 (2.3%) developed CD. The GEM-IRS, developed on the training cohort (n= 1,170), upon validation, showed a c-statistic of 0.789 in the pooled-testing cohorts (0.786 in the North American Testing cohort (n=1,141) and 0.804 in the Israeli Cohort (n=308)). The 4th quartile group compared to the rest had significantly increased risk of CD (hazard ratio [HR] 6.42, 95% confidence interval [CI], 3.10-13.30) in the pooled-testing cohorts (HR 5.89, 95% CI, 2.70-12.85 in North American Testing cohort; HR 10.7, 95% CI 1.24-92.65 in Israeli cohort). Furthermore, the GEM-IRS predicted CD in pre-specified subgroups of FDRs with minimal subclinical inflammation (fecal calprotectin<50 ug/g) or normal barrier function measures (lactulose/mannitol ratio<0.025), and up to 7 years before diagnosis in the pooled-testing cohort.

Conclusion

The GEM-IRS, which includes biomarkers of gut inflammation, intestinal barrier function, and the gut microbiome, is a valid risk stratification tool for predicting future development of CD in healthy first-degree relatives of persons with CD. The score may be used to guide preventative care for healthy first-degree relatives.
P324 Urine metabolite profile characterizes clinical activity and disease extent in patients with inflammatory bowel disease
Authors: Balderramo D C , Cuencas Barrientos M E , Tantucci L , Cabrera D , Fernandez M , Fochesato A , Delgado A , Correa S , Romagnoli P
Published: January 2024

Background

Inflammatory Bowel Disease (IBD), which comprises Crohn's Disease (CD) and Ulcerative Colitis (UC), is a disorder in which complex interactions between genetic, environmental, and microbial factors trigger alterations in the immune intestinal response. On the other hand, nutrient catabolism from the diet carried out by the microbiota results in the formation of metabolites that also impact immune responses on the intestinal mucosa. Considering that IBD patients have altered microbiota compared to healthy controls (HC) and that the urinary metabolic profile of an individual is the result of a combination of genetic, dietary, and microbial components, we propose the hypothesis that the urinary metabolic profile distinguishes IBD patients from HC. The aim of the study was to compare metabolomic analysis of urine samples from HC and IBD patients.

Methods

27 patients were included [HC (n=10), UC (n=10), and CD (n=7)]. Clinical IBD activity was evaluated with partial Mayo score (UC) and Harvey-Bradshaw index (CD). Metabolites in urine were measured using gas chromatography-mass spectrometry (GC-MS). Metabolomic analysis and machine learning were performed using the MetaboAnalyst software. PLS-DA was used for multivariate analysis, and clustering separation was performed using hierarchical clustering. To identify and interpret patterns of metabolite concentration changes in a biologically meaningful way we perform Over Representation Analysis.

Results

In total, 62 organic acids were detected. Comparing UC and HC revealed 11 significantly altered metabolites (9 increased and 2 decreased). Main increased metabolites comprised lactic acid (p=0.0015), pyroglutamic acid (p=0.0147), isocitric acid (p=0.0325), and phosphoric acid (p=0.0091). Interestingly, the value of adipic and suberic acids were higher in remission vs. active patients. Furthermore, adipic acid was higher in UC patients with proctitis compared to left-side colitis/extensive colitis. Comparing CD and HC revealed only 2 significantly altered metabolites, glycolic acid (p=0.0214), and lactic acid (p=0.0111). Oxalic acid was more concentrated in CD patient with perianal disease. Finally, propionic and phosphoric acid were able to discriminate UC from CD patients. The most affected metabolic pathways were related to energy metabolism and oxidative stress, including the Warburg effect (p=0.0016), gluconeogenesis (p=0.0106), pyruvate metabolism (p=0.0197) and glutathione metabolism (p=0.0039) (Fig.1).

Conclusion

We found that the urinary metabolic profile of IBD patients differs from the HC, particularly for UC patients. These metabolites profile could be used to improve diagnosis and monitoring in patients with IBD.
P327 Profiling serum metabolome and lipidome to differentiate primary sclerosing cholangitis from Inflammatory Bowel Disease and healthy controls
Authors: Fererberger T , Buechler C , Kandulski A , Elger T , Loibl J , Schmid S , Sommersberger S , Gunawan S , Zundler S , Bettenworth D , Kempa S , Weidlich S , Foeh B , Derer-Petersen S , Guenther U L , Marquardt J U , Kunst C , Guelow K , Mueller M , Sina C , Tews H C , Schmelter F
Published: January 2024

Background

Currently, the diagnosis of primary sclerosing cholangitis (PSC) is challenging due to a lack of specific biomarkers. Identification of a distinct metabolome and lipidome profile of PSC patients is crucial to facilitate diagnosis and contribute to a more accurate risk stratification. Therefore, our study aimed to assess the alterations in metabolites and lipoproteins in the serum of patients with PSC compared to patients with inflammatory bowel disease (IBD) and other extraintestinal manifestations (EIM) and healthy controls (HC).

Methods

Nuclear magnetic resonance (NMR) spectroscopy of serum samples from 33 patients with PSC (24 patients with IBD and 9 patients without IBD) was performed and compared with 64 patients with IBD and other EIM as well as with 40 sex-, age-, and BMI-matched HC. Univariate and multivariate analysis methods were used for data analysis.

Results

PSC patients exhibit a disease-specific amino acid and lipid profile in comparison to IBD and other EIM, as well as to HC. Intermediate density lipoproteins (IDL) and IDL apolipoprotein (Apo) B levels and free cholesterol content of very low density lipoprotein subfraction 4 were increased in PSC compared to the control groups. Several low density lipoprotein subfractions of PSC patients showed an increase in ApoB, cholesterol, free cholesterol, triglycerides, and phospholipids in comparison to IBD and other EIM. In addition, concentrations of the amino acids glycine, histidine, phenylalanine, and tyrosine were higher in PSC patients compared to IBD and other EIM.

Conclusion

NMR spectroscopy identified a specific metabolome and lipidome profile in PSC patients compared to IBD and other EIM, as well as to HC. Thus, in addition to the established image morphology, using NMR profiling can improve diagnosis of PSC and a differentiation of patients with PSC from HC and those with IBD and other EIM.
P332 The role of Handgrip Strength in Nutritional Status Assessment of Patients with Inflammatory Bowel Disease. A cross-sectional study
Authors: Vadarlis A , Maris T , Pramateftakis M G , Germanidis G , Chourdakis M
Published: January 2024

Background

Inflammatory bowel disease (IBD) has been extremely prevalent in recent years. Multiple factors such as chronic inflammation, insufficient nutrient intake, malabsorption and high energy requirements during disease flares increase the risk of malnutrition and impaired body composition leading to complications such as thromboembolism, prolonged hospital stay and surgery. Nutritional status assessment through screening tools, anthropometry and body composition analysis requires experienced personnel and is time consuming. The purpose of this single center cross-sectional study is to assess nutritional status of patients with IBD and investigate various methods for the early detection of malnutrition.

Methods

Eligible participants were patients diagnosed with Corhn’s disease (CD) or ulcerative colitis (UC) from August to October 2023. Exclusion criteria comprised corticosteroid or diuretic treatment and high output stoma or fistulas. Nutrition status was assessed with Subjective Global Assessment (SGA). Body composition analysis was performed with bioelectric impedance analysis (BIA, Bodystat Quadscan 4000). Handgrip strength (HGS) was measured to detect reduced muscle activity through Jamar dynamometer. BIA derived values were compared to reference values from epidemiological studies. Quality of life impairment evaluated through Inflammatory Bowel Disease Questionnaire (IBDQ). Data was analyzed with SPSS Statistics 29.0.1.

Results

104 patients were included (68 with CD, 36 with UC) with a mean age of 46 years (20-79). Based on body mass index (BMI) of the examined sample: 2% were underweight, 47% normal, 31% overweight and 18% obese. Body composition analysis revealed high level fat mass in 50% of females and in 48% of males. Fat free mass index (FFMI) was found low in 30% of females and in 17.5% of males, respectively. Not significant differences were observed between patients with CD and UC. Malnutrition assessment through SGA revealed 7 (6%) severely and 10 (7%) moderately malnourished patients. HGS was negatively strongly correlated with SGA (R2=0.52) and the percentage of fat mass (R2=0.51), whereas positively moderately correlated with FFMI (R2=0.48) and IBDQ score (R2=0.30).

Conclusion

A large percentage of patients with IBD appear to have disturbed body composition and higher levels of fat mass compared to healthy population. Handgrip strength measurement is a fast and cost-effective method of muscle function assessment that correlates well with nutritional status and quality of life. Further studies are needed to validate these findings and incorporate handgrip strength measurement in every day clinical practice to detect malnourished patients.
P343 Pancreato-biliary disorders in patients with inflammatory bowel diseases – a single-centre report
Authors: Topala M , Ionescu V , Ion A , Neamtu R , Dragan S , Gheorghe C
Published: January 2024

Background

Inflammatory bowel diseases (IBD) are regarded as multisystemic disorders due to the high prevalence of extraintestinal symptoms. Hepato-pancreato-biliary involvement can be present in up to 50% of patients, due to IBD extraintestinal manifestations and complications. Our aim was to evaluate the prevalence of the pancreato-biliary diseases in patients diagnosed with IBD.

Methods

We conducted a single-centre retrospective study which included patients diagnosed with Crohn’s disease (CD) and ulcerative colitis (UC), admitted between 1 January 2018 and 1 August 2023 in the Gastroenterology and Surgery Departments of the Fundeni Clinical Institute (Romania). We analysed the medical history (including abdominal imaging - ultrasound, computed tomography or magnetic resonance imaging) of patients during hospital follow-up and we screened for pancreato-biliary disorders.

Results

We analysed 1736 patients, of which 303 patients (17%) associated pancreato-biliary involvement and 756 patients (44%) had no pancreato-biliary disorders, with both subgroups having at least one abdominal imaging scan during follow-up; 677 patients (39%) had neither history of pancreato-biliary disorders, nor abdominal imaging. 30 patients (1.72% of total; 56.6% CD, 77% male) had acute pancreatitis (93.3% mild), 66.67% being drug-induced (13 cases - azathioprine, six cases - 5-amynosalicilates, one case - metronidazole). Three patients were diagnosed with idiopathic chronic pancreatitis and one with type 2 autoimmune pancreatitis. In the subgroup that underwent abdominal imaging (1059 patients) we identified 124 patients (11.70%) with pancreatic steatosis, 11 patients (1.03%) with pancreatic cysts (one case of intraductal papillary mucinous neoplasm) and three patients (0.28%) with congenital pancreatic anomalies (two annular pancreases, one pancreas divisum). There were no patients diagnosed with pancreatic adenocarcinoma. We identified 14 patients (0.8% from total; 64.28% UC, 57.14% male) with primary sclerosing cholangitis, of which five underwent liver transplantation, one case of primary biliary cholangitis and three cases of cholangiocarcinoma. The subgroup with abdominal imaging included 46 patients (4.34%) with prior cholecystectomy and 147 patients (13.88%) with gallbladder lithiasis or sludge (59.86% CD; 53.06% male; 39.45% intestinal resection).

Conclusion

Up to one third of patients with IBD that underwent abdominal imaging associated pancreato-biliary involvement. The high risk of drug-induced acute pancreatitis in IBD has to be taken into consideration. Screening for possible extraintestinal manifestations and early diagnosis of extraintestinal complications might improve the IBD management.
P344 Achieving Crohn's Disease treatment targets following the STRIDE-II recommendations in clinical practice
Authors: Aliu A , Janssen L , Rezazadeh Ardabili A , Mujagic Z , Pierik M
Published: January 2024

Background

The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) initiative proposes therapeutic targets for inflammatory bowel disease (IBD) to be used for a treat-to-target clinical management strategy. However, there is lack of information regarding how many patients actually achieve defined treatment targets as outlined in STRIDE-II after initiation of new therapies. The objective of this study was to investigate the treatment response of Crohn’s disease (CD) patients according to the STRIDE-II recommendations in the first year after starting a new pharmacological therapy in clinical practice.

Methods

CD patients included in a remote monitoring care-path using myIBDcoach, starting a new therapy between January 1st 2020 and December 31st 2021 were eligible for inclusion. The short-term (2-4 months) treatment target was defined as clinical response based on at least 50% decrease in the Monitor IBD at home (MIAH) questionnaire, a patient-reported outcome measure validated to predict endoscopic disease activity. Intermediate (5-9 months) targets were clinical remission (MIAH ≤3.6) and normalization of inflammatory parameters, i.e. faecal calprotectin (<150 ug/g) and C-reactive protein ([CRP] <10 mg/L). Long-term (10-12 months) targets were absence of disability (IBD-control questionnaire ≥13), and a combination of MIAH score ≤3.6 and calprotectin <150 ug/g as surrogate markers for endoscopic remission.

Results

39 CD patients were included in the current analysis, of which two started treatment with thiopurines and 37 with a biological. At baseline, median MIAH score was 3.0 (IQR 3.1) and median IBD-control score was 8.5 (IQR 9.0). After three months of therapy, 26% of patients showed clinical response and 64% of patients were in clinical remission (median MIAH 2.2 [IQR 1.8]). As for intermediate targets, clinical remission was seen in 62% (median MIAH 2.0 [IQR 2.3]), and CRP and calprotectin normalization in 79% and 59% of patients, respectively. At the end of follow-up, 41% had low surrogate marker scores indicative for endoscopic remission (median MIAH 1.9 [IQR 1.6] and median calprotectin 109.0 [IQR 241.0]). Resolution of disability was achieved in 65% (median IBD-control score 14.0 [IQR 6.0]). Three patients (9%) achieved all treatment targets within a year of follow-up (Table 1).

Conclusion

This study used an incident user real-world cohort to evaluate the STRIDE-II recommendations. While all patients achieved at least one treatment target, only 9% achieved all treatment targets according to the STRIDE-II recommendations. Using these recommendations provides good guidance in clinical settings. However, treatment approaches need to be improved to reach the optimal outcomes in daily clinical practice.
P353 Optimal Interval for Therapeutic Drug Monitoring in Patients with Inflammatory Bowel Disease Receiving Stable Infliximab Maintenance Treatment
Authors: Hong S N , Yujin L , Boram P , Ok Soon J , Young Ho K
Published: January 2024

Background

Recent studies suggest that proactive therapeutic drug monitoring (TDM) in patients with inflammatory bowel disease (IBD) receiving infliximab (IFX) improves clinical outcomes. However, as proactive TDM may lead to increased medical costs, we aimed to determine the optimal interval for TDM during infliximab maintenance therapy in IBD patients.

Methods

We conducted a retrospective analysis of a prospective cohort comprising 103 patients with IBD on IFX maintenance therapy who went through proactive TDM between February 2020 and May 2023. Following dose optimization till achieving a therapeutic trough level (TL) of 3 to 10 ug/mL, we applied the Kaplan-Meier (KM) method to calculate the time to subtherapeutic IFX TL (two consecutive IFX TLs below 3 ug/mL).

Results

90% of patients had a sustained therapeutic IFX TL for 10.3 months, whilst 80% had it for 14.3 months. In multivariable analysis, IFX TL at enrollment had a association with the risk of subtherapeutic IFX TL (P=0.025). Persistence rates for therapeutic IFX TL were significantly lower in patients with IFX TL from 3 to 5 µg/mL at recruitment than in those with IFX TL >5 µg/mL (P=0.017). For patients who had IFX TL between 3 to 5 µg/mL upon enrollment, the percentage of those who maintained therapeutic IFX TL was 80% after 12.0 months. The group with IFX TL greater than 5 µg/mL had a persistence rate of 90% after 12.3 months.

Conclusion

These results suggest that conducting annual measurement of IFX TL in patients with IBD who are on stable maintenance therapy with IFX, which may reduce the cost of proactive TDM.
P355 Correlation of Intestinal Ultrasound with histological activity in patients with Ulcerative Colitis
Authors: Katsaros M , Kalogirou M , Katsoula A , Paschos P , Katsiki E , Giouleme O
Published: January 2024

Background

Histological remission in ulcerative colitis (UC) is considered a therapeutic target predictive of favorable clinical outcomes. Intestinal ultrasound (IUS) represents an imaging tool that is well correlated with endoscopy and can accurately define disease activity in UC. There is a major gap in the international literature examining the potential link between activity indices on IUS and histological findings in UC1. We aimed to evaluate the correlation of the Milan Ultrasound Criteria (MUC) with Nancy Histological index (NIH) in patients with UC.

Methods

We performed a cross-sectional study that included consecutive patients with established diagnosis of UC. All patients underwent colonoscopy with biopsy samples, as well as IUS within 3 days of one another. Endoscopic activity was defined as an endoscopic mayo score (EMS) > 0, while histological activity was defined as NHI > 12. Active disease on IUS was calculated on the most affected bowel segment by MUC [MUC = 1.4 × Bowel wall thickness (BWT) in mm) + 2 × Bowel Wall Flow (BWF); BWF = 1 if present, or BWF = 0 if absent] 3. Activity on IUS was defined as a MUC score > 6.2. For maximum accuracy, the most affected bowel segments on endoscopy and IUS were matched. On the day of endoscopy, partial mayo score (PMS) was calculated (PMS >1 corresponded to clinical activity), and C-reactive protein (CRP) was recorded.

Results

A total of 45 patients were included (table 1). We observed a strong correlation between MUC and endoscopic activity [ρ: 0.802 (p< 0.001)], as well as between MUC, PMS and CRP [ρ: 0.743 (p< 0.001) and ρ: 0.798 (p< 0.001)] respectively. We revealed a strong correlation between MUC and NHI [ρ: 0.811 (p< 0.001)]. A MUC > 6.2 possessed 74.3% sensitivity, 90% specificity, 96.3% PPV and 50%, NPV (p<0.001) in predicting histological activity (Nancy>1). At the optimal cut-off value of 5.67, MUC displayed a sensitivity of 97.1% and a specificity of 90% [(AUC: 0.973, 95% CI: 0.918-1.000, (p<0.0001) – fig 1] in predicting histological activity (NHI>1), in patients with UC.

Conclusion

Intestinal ultrasound represents a promising non-invasive tool that can accurately define histological activity in patients with UC. Further studies are needed to confirm the aforementioned results.
P364 Faecal calprotectin testing in patients presenting with lower gastrointestinal symptoms; a retrospective primary care study in the United Kingdom
Authors: Umar N , Wambua S , Adderley N J , Haroon S , Trudgill N
Published: January 2024

Background

Faecal calprotectin (FC) is of value in differentiating Inflammatory Bowel Disease (IBD) from other causes of lower gastrointestinal (GI) symptoms and is recommended in national guidance. This study aims to examine the role of and factors associated with faecal calprotectin requesting in primary care.

Methods

Retrospective open cohort study using Clinical Practice Research Datalink (CPRD Aurum) of adults aged 18 years and above with lower GI symptoms between 2015 and 2019. FC requested 30 days before to 3 months after a lower GI symptom record in primary care were included. Logistic regression model was used to explore patient level factors associated with FC testing. Referral pathways and outcomes in terms of IBD diagnoses of patients with and without FC testing were also examined.

Results

Of 741,190 symptomatic patients, only 18,320 (2.5%) patients had a FC requested in primary care: median age 38.3 (IQR 28.9-50.7); 51.4% females. The percentage of FC requests in symptomatic patients increased from 0.02% in 2010 to 4.4% in 2019 (p=0.001).

FC value of <50 ug/g and 50-200 ug/g were predominantly seen in patients with abdominal pain (42.1% and 37.9% respectively) while FC > 200 ug/g was predominantly seen in patients with diarrhoea (45.3%). The only patients with a significant risk of IBD with a FC 50-200ug/g were patients with rectal bleeding (8%).

Factors associated with less FC requesting included: increasing age (>70 years aOR 0.16 ( 95% CI 0.15-0.18); female (0.89,0.86-0.92); Black (0.61, 0.56-0.66) or Asian (0.75, 0.70-0.80) ethnicity; obesity (0.89,0.85-0.93); lower socioeconomic status (0.91,0.86-0.98); comorbidity score >2 (0.73,0.68-0.79); and current smoking (0.89,0.85-0.92). Patients with change in bowel habit (7.31,6.90-7.75); rectal bleeding (2.04,1.95-2.13); diarrhoea (2.88,2.78-2.99) as a presenting symptom compared to abdominal pain and ex-smokers (1.06,1.03-1.11) had more FC requests.

Of patients referred with a FC >200 ug/g, 21.5% were diagnosed with IBD but only 2.9% of patients with a FC 50-200ug/g. 27.8% patients with a normal FC test result were still referred to secondary care, of which only 0.4% had IBD.

Conclusion

Despite an increase in FC requests in recent years, only 4.4% of patients with relevant lower GI symptoms had an FC requested in primary care as recommended. Despite a negative FC test, 27.8% of patients were still referred to secondary care with very few patients diagnosed with IBD (0.4%).
P374 Real-life effectiveness and safety of ustekinumab treatment in patients with ulcerative colitis: An Asan-Crohn’s and Colitis Association in Daegu-Gyeongbuk (CCAiD) multicenter cohort study
Authors: Baek J E , Kim E S , Kim K O , Jo H H , Hwang S W , Park S H , Jang B I , Kim E Y , Yang S K , Kim S K , Ye B D
Published: January 2024

Background

The real-life data on ustekinumab (UST) for Asian patients with ulcerative colitis (UC) are limited. We aimed to assess effectiveness and safety of UST for Korean patients with UC.

Methods

This was a multicenter retrospective study on patients with UC who received UST at 4 academic centers in Korea between January 2021 and April 2023. The primary endpoint was clinical remission defined as partial Mayo score (PMS) ≤2 and no subscore >1 at week (W) 8 of therapy. Secondary endpoints included clinical remission (W16–20 and W52–56), corticosteroid-free clinical remission (W8, W16–20 and W52–56), clinical response defined as reduction of PMS ≥3 and at least 30% from baseline with either a decrease in rectal bleeding subscore ≥1 or an absolute rectal bleeding subscore ≤1 (W8, W16–20 and W52–56), endoscopic remission defined as Mayo endoscopic subscore 0–1 (W16–20 and W52–56), durability of UST at W52–56 and adverse events.

Results

A total of 55 patients were included and 54 were analyzed excluding one in clinical remission at baseline (Male, 66.7%; Median age at UST initiation, 44.5 years; Disease duration at UST initiation, 7.5 years; Previous exposure to biologics/small molecules, 70.4%; Extensive colitis, 64.8%; Median baseline Mayo score, 8; Concomitant use of systemic corticosteroids, 48.1%; Concomitant use of immunomodulators, 38.9%). Out of 54 patients, 27 patients (50%) reached to W52–56 or stopped UST, while remained 27 patients still under maintenance UST therapy, not reaching W52–56. At W8, W16–20, and W52–56, 53.7% (29/54), 63% (34/54), and 44.4% (12/27) achieved clinical remission and 68.5% (37/54), 70.4% (38/54), and 51.9% (14/27) showed clinical response, respectively (Figure 1). Endoscopic remission rates at W16–20 and W52–56 were 57.4% (31/54) and 37% (10/27), respectively (Figure 1). The durability of UST at W52–56 was 74.1% (20/27). Multivariable analysis revealed that previous exposure to biologics/small molecules was negatively associated with clinical remission at W8 (OR: 0.10; 95% confidence interval [CI] 0.02–0.57; p=0.01) and W16–20 (OR: 0.18; 95% CI 0.04–0.91; p=0.04), whereas the concomitant use of immunomodulators showed a positive association with clinical remission at W8 (OR: 4.19; 95% CI 1.11–15.77; p=0.03). Adverse events occurred in 23 patients (42.6%) and serious adverse event in one patient (1.9%) (Table 1).

Conclusion

UST was effective with an acceptable safety profile for Korean patients with UC. Previous exposure to biologics/small molecules was negatively associated with clinical remission at both W8 and W16–20.

Financial Support

This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIT) (NRF-2021R1A2C2095096).
P382 The burden of anxiety, depression and perceived stress in patients with inflammatory bowel disease: a cohort study from north India
Authors: Bhardwaj A , Singh D.M. A , Midha V , Mahajan R , Bansal N , Sood A
Published: January 2024

Background

Patients with Inflammatory bowel disease (IBD) are susceptible to psychiatric co-morbidities. We aimed to ascertain the burden of anxiety, depression, and perceived stress in patients with IBD from north India.

Methods

Consenting adult patients with an established diagnosis of IBD were enrolled. The enrolled patients filled the Hospital Anxiety and Depression Scale (HADS) and Perceived Stress Scale (PSS) questionnaires. The patient and disease characteristics were analyzed to determine the correlations and predictors of psychiatric comorbidities. Spearman’s rho (ρ) was used for assessment of correlation between disease attributes and psychological disorders.

Results

A total of 318 patients (255 UC, 63 CD; mean age 40.13±12.06 years, 168 [52.8%] males; mean partial Mayo score 2.10±2.35; and mean HBI 2.77±2.13) were enrolled. The prevalence of anxiety, depression and moderate to high perceived stress was 14.15%, 12.57%, and 41% respectively. Females had higher mean perceived stress, anxiety and depression scores compared to males. The partial Mayo score (PMS) correlated poorly with anxiety (ρ=0.083, p=0.187), depression (ρ=0.123, p=0.49) and perceived stress (ρ=0.169; p=0.007). The Harvey Bradshaw index (HBI) correlated fairly with anxiety (ρ=0.336, p=0.007) and poorly with depression (ρ= 0.287, p=0.022) and perceived stress (ρ=0.20; p=0.117). Younger age (OR 0.93, 95% CI 0.90-0.97; p=0.001) and hand grip strength (OR 4.63, 95% CI 1.88-11.42; p=0.001) predicted anxiety in patients with UC while rural area of residence (OR 4.75, 95% CI 1.03-21.98; p=0.046) and HBI (OR 1.60, 95% CI 1.12-2.29; p=0.009) were significant predictors of anxiety in patients with CD.

Conclusion

Psychiatric comorbidities are common in patients with IBD, with higher prevalence in females. Young adults with UC and sarcopenia; and individuals with active CD living in rural areas are at an increased risk of anxiety.
P394 Unsuitability of the Oxidation-Reduction Potential measurement for the quantification of fecal redox status in Inflammatory Bowel Disease
Authors: Geertsema S , Jansen B H , van Goor H , Dijkstra G , Faber K N , Bourgonje A R
Published: January 2024

Background

Oxidative stress is a key pathophysiological process associated with the development and progression of inflammatory bowel disease (IBD). Biomarkers for oxidative stress, however, are scarce, as are diagnostic tools that can interrogate an individual’s gut redox status. Oxidation-Reduction Potential (ORP) measurements can provide insight into the redox (oxidation-reduction) status, which is relevant in understanding oxidative stress and associated pathophysiological processes. Until date, ORP analyses have not been explored in the context of IBD. This proof-of-concept study aimed to assess the potential utility of an ORP measurement probe in quantifying redox status in the fecal water of both IBD patients and healthy controls.

Methods

This proof-of-concept study recruited patients with Crohn's disease (CD), ulcerative colitis (UC), and healthy controls. Fecal samples were collected and analyzed for oxidation-reduction potential (ORP) using the PCE-228 redox probe at specific timepoints. Furthermore, the stability of ORP measurements was assessed across various test solutions with known ORPs by doing nine ORP measurements every 15 minutes.

Results

No significant differences in ORP measurement values were observed between patients with CD (n=5) (45 [30.0–62.0] mV), patients with UC (n=5) (48 [42.0–59.0] mV) and healthy controls (n=5) (25 [8.0–52.0] mV; p = 0.221) (Fig. 1A). Strikingly, ORP measurements exhibited high instability and rapidly fluctuated throughout time, presenting with values varying from +24 to +303 mV (Fig 1B). These fluctuations, potentially influenced by biological processes and limitations of the measuring equipment, precluded reliable measurements of ORP in fecal samples of patients with IBD.

Conclusion

ORP quantification may not be a reliable tool for assessing fecal redox status in patients with IBD or healthy controls. Our findings do not support further exploration of the specific ORP redox probe used in this study for determining fecal redox status. Future studies should focus on more sensitive methods to quantify fecal redox status and examine its biomarker potential in the context of IBD.

Funding

This study was supported by Janssen Research & Development LLC.
P395 The frequency of SARS-CoV-2 infection and the impact of vaccination on the disease morbidity in Polish pediatric patients with Inflammatory Bowel Disease treated with biologic therapies
Authors: Derda E , Szymanska E , Meglicka M , Wiernicka A , Osiecki M , Kierkus J
Published: January 2024

Background

Little is known about morbidity of Covid-19 infection in pediatric patients with inflammatory bowel diseases (IBD) treated with biologic medications. The aim of this study was to evaluate the frequency of SARS-CoV-2 infection in children with IBD who received biologic therapies.

Methods

A prospective, observational cohort study to evaluate coronavirus disease 2019 (COVID-19) vaccination state, and its effect on the disease course among pediatric patients with IBD. The questionnaire included information concerning numbers of vaccine doses, patients’ medication and disease activity. Disease flare was defined by worsening IBD symptoms and change in IBD medications. Outcomes were stratified by vaccine type and IBD medication classes.

Results

A total of 320 children with IBD, 169 with Crohn’s disease (CD)-52,8%, 150 with ulcerative colitis (UC) - 46,9%, 1 unclassified -0,3%, responded to the questionnaire concerning COVI-19 vaccination. In our cohort 141 (49,7%) patients received biologic therapy: 13 patients (9,2%) adalimumab (ADA), 54 (38,3%) infliximab (IFX), 27 (19,1%) vedolizumasb (vedo), 29 (20,6%) ustekinumab (ust), 6 - vedo + ADA (4,3%), 1 - IFX + vedo (0,7%), 11 - ust + ADA (7,8%). 32 (22,7%) patients had COVID-19 infection during biological therapy (ust 6- 4,3%, vedo 7- 5,0%, ada 2-1,4%, ifx 12- 8,5%, ust + ada 2- 1,4%, vedo + ada 3- 2,1%). Among the patients on biologic treatment suffering from COVID-19, 25 (78,1%) children had mild course of the infection, 4 moderate (12,5%), 2 severe (6,3%), and 1 unknown (3,1%). A total of 127 (39,7%) patients received at least 1 COVID-19 vaccine, and among them 8 (6,3%) patients who received 1 dose of COVID-19 vaccine got the infection during biologic therapy. In our group, 193 (60,3%) patients have not been vaccinated against COVI-19, and 24 (12,4%) suffered from the disease during biologic therapy.

Conclusion

Based on the outcomes from our questionnaire concerning COVID-19 vaccination state on the large cohort of pediatric patients with IBD, we conclude that unvaccinated patients get sick more often than vaccinated ones, and that the use of biological treatment has no impact the frequency of covid infections or their course.
P397 Distinct blood protein profiles associated with ileal and colonic ulcers in Crohn’s disease
Authors: Pierre N , Huynh-Thu V A , Baiwir D , Vieujean S , Bequet E , Reenaers C , Van Kemseke C , Salée C , Massot C , Fléron M , Mazzucchelli G , Trzpiot L , Eppe G , De Pauw E , Louis E , Meuwis M
Published: January 2024

Background

Ileal and colonic Crohn’s disease (CD) are nowadays considered as separate entities. Studies are needed to better characterise the biological specificities of these subphenotypes. In fine, this research should offer opportunities for the development of personalised medicine.

Methods

By combining different technologies (proximity extension assay, selected reaction monitoring and high-sensitivity turbidimetric immunoassay (hsCRP)), 207 serum proteins were measured in CD patients presenting no endoscopic lesions (endoscopic remission) (n=23), isolated ileal ulcers (n=17) or isolated colonic ulcers (n=16) (Table 1). To compare the endoscopic activity between the ileum and colon, and in order to obtain an assessment of the overall lesion burden, we used the Crohn’s disease endoscopic index (CDEIS) without dividing its total score (sum of each gut segment) by the number of inspected segments. The data analysis was conducted using Wilcoxon-Mann-Whitney test and area under the receiver operating characteristics curve (AUROC). The AUROC were compared using the bootstrap test (2000 replications).

Results

The median of the total CDEIS was higher in CD patients with isolated colonic ulcers than those with isolated ileal ulcers (23.1 vs 8.0) (Table 1). When compared to endoscopic remission, the presence of isolated ileal ulcers and isolated colonic ulcers were specifically associated with the level of 6 and 18 serum proteins, respectively: (high: JUN, CNTNAP2; low: FCRL6, LTA, CLEC4A, NTF4) (Figure 1A); (high: hsCRP, IL6, APCS, CFB, MBL2, IL7, IL17A, CCL19, CXCL10, CSF3, IL10, CLEC4G, MMP12, VEGFA; low: CLEC3B, GSN, TNFSF12, TPSAB1) (Figure 1B). No protein was associated with both isolated ileal ulcers and isolated colonic ulcers (Figure 1).

All CD patients in endoscopic remission showed a normal level of hsCRP (<5 mg.L-1). Compared to CD patients in endoscopic remission, CD patients with isolated colonic ulcers showed an increased median level of hsCRP (1.3 vs 5.9 mg.L-1, p-value=0.0045) and this was not the case for CD patients presenting isolated ileal ulcers (1.3 vs 2.2 mg.L-1, p-value=0.13). hsCRP detected ileal and colonic ulcers with an AUROC of 0.64 (p-value=0.07) and 0.77 (p-value=0.001), respectively. When compared to hsCRP (AUROC), the best marker pairs for detecting ileal or colonic ulcers were respectively CLEC4A×LTA (0.82 vs 0.64, p-value=0.06) or hsCRP×CSF3 (0.85 vs 0.77, p-value =0.02).

Conclusion

In CD patients, ileal and colonic ulcers were associated with distinct systemic responses. hsCRP showed a better capacity to detect patients with colonic than ileal ulcers. Some markers might help to detect ileal ulcers or to improve the ability of CRP for detecting colonic ulcers.
P404 Monocyte distribution width differentiates bacterial gastroenteritis from Acute Severe Ulcerative Colitis in patients presenting with diarrhoea
Authors: Li Wai Suen C , Kaul S , Tan E , Con D , Taylor M , Wiid J , Hogan C , Choy M , Visvanathan K , De Cruz P
Published: January 2024

Background

Monocyte distribution width (MDW) is a haematological parameter that can be generated by newer generation blood analysers on routine full blood examination. It reflects the variation in the size of monocytes and is elevated in the setting of infection, however its utility in inflammatory disorders in unknown.

We aimed to assess whether MDW can help differentiate bacterial gastroenteritis from Acute Severe Ulcerative Colitis (ASUC) among patients presenting to the Emergency Department (ED) with diarrhoea. We further aimed to assess whether MDW correlated with disease activity and clinical outcomes in ASUC.

Methods

We conducted a retrospective cohort study comprising three patient groups: (1) ASUC, (2) bacterial gastroenteritis and (3) a control group of patients without active inflammation. The control group consisted of outpatients with chronic hepatitis B in immune control phase with normal liver transaminases and suppressed viral load < 2000 IU/mL. Clinical outcomes, routine biomarkers and MDW were recorded.

Results

A total of 176 patients were identified (53 ASUC, 70 bacterial gastroenteritis and 53 controls).

At time of ED presentation, patients with bacterial gastroenteritis had the highest MDW (median 23.6, IQR 20.7-25.8) compared to ASUC (19.0, IQR 17.9-21.2) and controls (16.8, IQR 15.9-18.0; P<0.001). On receiver operator characteristic curve analysis, MDW discriminated bacterial gastroenteritis from ASUC with an area under the curve (AUC) of 0.78 (95% CI 0.70-0.87, P<0.001). Using Youden’s index, a MDW threshold > 22.3 had 64.3% sensitivity, 84.6% specificity, 63.8% negative predictive value and 84.9% positive predictive value for bacterial gastroenteritis.

Of the 53 patients with ASUC, 25 responded to intravenous hydrocortisone while 28 were steroid non-responders and required infliximab (IFX). 24 patients responded to IFX rescue, while the 4 IFX non-responders received tofacitinib sequential therapy. In ASUC, MDW correlated positively with established markers of disease activity including CRP (Spearman rank correlation, rho=0.54, P<0.001), platelet count (rho=0.36, P=0.009) and faecal calprotectin (rho=0.35, P=0.02). A lower MDW on the day of IFX administration appeared to predict IFX response (AUC 0.80, 95% CI 0.61-1.00, P=0.002). At follow-up (median 85 days), MDW was predictive of biochemical remission with a faecal calprotectin < 100 µg/g (AUC 0.80, 95% CI 0.64-0.95, P<0.001).

Conclusion

MDW is a novel biomarker that may help distinguish ASUC from bacterial gastroenteritis at time of ED presentation in patients with diarrhoea. In ASUC, MDW correlates with existing markers of activity and may help predict IFX response.
P416 Turning Point: Declining surgery rates and predictors for surgery in a three-year prospective inception cohort of Crohn's Disease in China
Authors: Hu W , Li S , Chen Z , Luo J , Yu Y , Liao X , Shen K , Luo J , Yan Z , Wang Q , Lu S , Xu D , Yu Q , Zhang H , Wang X , Li J , Chen Y
Published: January 2024

Background

Surgery in Crohn's disease is a critical management outcome. China currently faces a notable surge in CD incidence, making it an integral phase for improving diagnostic and therapeutic competencies. Analysing the rates of CD-related bowel surgeries in a prospective cohort offers significant insights for evaluating and optimizing disease management.

Methods

We conducted a single-centre, prospective inception cohort of CD patients since July 2019 at the Second Affiliated Hospital, Zhejiang University School of Medicine (ClinicalTrials.gov identifier NCT04135027). Annual follow-ups were performed. Survival analysis was used to identify predictors for bowel surgical outcomes. Bowel surgery encompassed gastrointestinal resections addressing complications such as obstruction, fistula, free perforation, and bleeding.

Results

A total of 438 newly diagnosed CD patients, predominantly male (73.5%), with a median age at diagnosis of 28.1 years were enrolled. Among them, 68 patients underwent surgery within three years. Surgery rates at one, two, and three years were 11.8%, 14.3%, and 15.4%, respectively. Specifically, patients enrolled in 2019-2020, 2020-2021, and 2021-2022 displayed surgery rates of 18.4%, 14.2%, and 5.3%, respectively during their first year in the study. Multivariate Cox regression demonstrated the enrolment timeframe (Hazard ratio 0.46, 95% Confidence Interval [CI] 0.22-0.96, P=0.039), smoke (Hazard ratio [HR] 3.98, 95% CI 2.02-7.87, P<0.001), and disease behaviour (stricturing, HR 29.75, 95% CI 10.34-85.56, P<0.001; penetrating, HR 39.13, 95% CI 13.18-116.17, P<0.001) and low albumin (HR 2.07, 95% CI 1.22-3.51, P=0.007) as significant predictors of surgery. Further analysis within the stricturing/penetrating subgroup maintained the enrolment timeframe (HR 0.45, 95% CI 0.21-0.95, P=0.035), smoke (HR 3.34, 95% CI 1.68-6.61, P<0.001), and low albumin (HR 2.03, 95% CI 1.19-3.48, P=0.01) as independent predictors. Propensity score matching confirmed smoke and low albumin as significant contributors to surgical risk.

Conclusion

A declining trend in the surgery rate among newly diagnosed patients was observed over the three years. Disease behaviour significantly stratified surgical outcomes. The enrolment timeframe, smoke, and low albumin emerged as independent predictors for surgeries in both the general cohort and the stricturing/penetrating subgroup.
P438 Histological scores are poor predictors of short-term response to therapy in acute severe ulcerative colitis
Authors: Jena A , Mishra S , Sekar A , Prasad K K , Sachan A , Singh A K , Shah J , Mandavdhare H S , Singh H , Dutta U , Sharma V
Published: January 2024

Background

Although all patients with acute severe ulcerative colitis (ASUC) undergo sigmoidoscopy and biopsy, the predictive value of various histological scores is unclear. We studied the association between histological scoring and the need for second-line rescue therapy and whether these scores predict the response to therapy in ASUC.

Methods

All consecutive patients of ASUC (as per Truelove and Witts criteria) admitted from 1st April 2019 to 31st January 2021 in North India were included. All patients, who underwent sigmoidoscopy and biopsy, underwent histological assessment by two independent pathologists [Simplified Geboes score (SGS), Robarts Histopathology Index (RHI) and Nancy histological index (NHI)]. The primary outcomes were to study the association between histological scores and the need for second-line rescue therapy in index admission and the accuracy of each score in predicting the need for second-line rescue therapy or colectomy at day 28. The secondary outcomes included an association between histological scores and endoscopic Mayo scores with response to corticosteroids on day three as per Oxford criteria.

Results

Eighty-two cases of ASUC (Mean age: 36 years, males 47.5%) were analyzed. Sixteen patients required second-line drug therapy and eight patients required colectomy in index admission. There was no significant association between the need for second-line therapy or colectomy and the baseline histological scores [NHI (p=0.61), SGS (p=0.116) and RHI (p=0.109)]. All three histopathological scores performed poorly to predict the need for second-line treatment or colectomy within 28 days of admission. No significant correlation was found between endoscopic Mayo score and histological scores. There was no significant association between the degree of inflammation on baseline histology and response to steroids (NHI (p=0.796), SGS (p=0.57) and RHI (p=0.941)]. There was a strong positive correlation among the three histological scores in patients of ASUC.

Conclusion

All three scores (SGS, RHI and NHI) performed poorly in predicting the need for second-line treatment or colectomy within 28 days of admission. There is a need for dedicated histopathology scores in the setting of acute severe ulcerative colitis.
P439 Mild Crohn’s disease is characterized by a unique serum metabolomic signature
Authors: Bourgonje A R , Ibing S , Argmann C , Sands B E , Dubinsky M , Jacobsen H A , Larsen L , Jess T , Suarez-Farinas M , Mehandru S , Colombel J F , Ungaro R C
Published: January 2024

Background

Approximately 20-30% of patients with Crohn's disease (CD) experience a mild disease course following initial diagnosis. Balancing the effectiveness and safety of medical treatments is crucial in the management of mild CD. However, the main clinical challenge currently lies in identifying patients likely to maintain this mild disease course, underscoring the urgent need for biomarkers of mild CD. In this study, we therefore aimed to identify potential circulating biomarkers for patients with mild CD leveraging a metabolomics approach.

Methods

Patients with mild CD were retrospectively identified from participants of the Mount Sinai Crohn's and Colitis Registry (MSSCR). Baseline screenings in MSSCR included assessments of the use of biologicals and immunomodulators, history of IBD-related surgeries, and the presence of disease complications (including stricturing, penetrating, and perianal CD). Mild CD was defined as the absence of all these variables at baseline as well as after a 5-year follow-up period. Untargeted serum metabolomic profiling was performed to measure the circulating metabolome of these patients. Multivariable logistic regression analyses, adjusting for age, sex, measurement batch, and smoking behavior, were conducted to identify metabolites associated with mild CD.

Results

In total, 114 patients with CD were characterized in which 1,456 different metabolites were profiled, with 32 patients (28.1%) meeting the criteria for mild CD. The remaining 82 patients (71.9%) partially met criteria for mild CD; these were all biologic-naïve and did not undergo IBD-related surgeries. Multivariable logistic regression revealed 45 distinct metabolites that were significantly associated with the mild CD group (nominal P<0.05). Sphingomyelin compounds and ceramides exhibited the most prominent associations with mild CD (odds ratios [OR] all >2.0), while tryptophan, pantothenate, and salicylate metabolites were also linked to mild CD. Conversely, primary and secondary bile acid metabolites and amino acid derivatives from lysine-, tyrosine-, and proline metabolism were all inversely associated with mild CD.

Conclusion

Mild CD is associated with distinct alterations in metabolic pathways compared to patients with moderate-to-severe CD. Future research should focus on longitudinal assessments of these metabolites for disease monitoring and determining optimal therapeutic strategies for this clinical subgroup.