bluuebunny/crossref_metadata_2025_split 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

Abstract

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&lt;50 ug/g) or normal barrier function measures (lactulose/mannitol ratio&lt;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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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 (&lt;150 ug/g) and C-reactive protein ([CRP] &lt;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 &lt;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

Abstract

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 &gt;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

Abstract

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) &gt; 0, while histological activity was defined as NHI &gt; 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 &gt; 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 &gt;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&lt; 0.001)], as well as between MUC, PMS and CRP [ρ: 0.743 (p&lt; 0.001) and ρ: 0.798 (p&lt; 0.001)] respectively. We revealed a strong correlation between MUC and NHI [ρ: 0.811 (p&lt; 0.001)]. A MUC &gt; 6.2 possessed 74.3% sensitivity, 90% specificity, 96.3% PPV and 50%, NPV (p&lt;0.001) in predicting histological activity (Nancy&gt;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&lt;0.0001) – fig 1] in predicting histological activity (NHI&gt;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.