bluuebunny/crossref_metadata_2025_split huggingface dataset:
A213 REDEFINING MILD-MODERATE ULCERATIVE COLITIS: PATIENTS WITH ENDOSCOPIC MAYO SCORE 1 AND ACTIVE HISTOLOGIC INFLAMMATION HAVE SIMILAR OUTCOMES TO PATIENTS WITH MAYO SCORE 2
Authors: Khan N , Wong E , Narula N 
Published: February 2025

Abstract

Background
Mild-to-moderate ulcerative colitis (UC) is conventionally defined as a total Mayo Clinic score of at least 4, with a Mayo Endoscopic Score (MES) of 2 and a Rectal Bleeding Score (RBS) of at least 1. Historically, endoscopic improvement with treatment has been defined as MES 0 or 1. However, studies have shown differences in prognosis between these two subsets of patients, with those who attain MES 1 reported to have higher rates of relapse. Patients with MES 1 and histologically active disease are currently excluded from contemporary clinical trials based on prevailing inclusion criteria. Consequently, insight into improving therapeutic outcomes for this patient population remains limited.

Aims
This study aims to explore whether UC patients with lower endoscopic burden but active histology have comparable outcomes to those with “conventional” mild-moderate UC.

Methods
This was a post-hoc analysis from the VARSITY study. Patients who completed induction (at week 14) with mild-moderate UC based on the conventional definition were compared to patients with histologically active MES 1 for achieving histo-endoscopic mucosal improvement (HEMI) at week 52, defined as Mayo endoscopic subscore ≤ 1 and Geboes highest grade &lt; 3.2. Secondary outcomes included endoscopic remission (ER) (Mayo endoscopic subscore of 0), histologic improvement (Geboes highest grade &lt; 3.2) and clinical remission (CR) (total Mayo score ≤ 2 and no subscore &gt;1 on any of the four subcomponents). Histologically active disease was defined as Geboes highest grade &gt; 3.2 (&gt;50% of neutrophil crypt involvement in the epithelium).

Results
Week 52 outcomes were comparable among patients with mild-moderate UC compared to those with histologically active disease and MES of 1. At week 52, a similar proportion of patients achieved HEMI [19/79 (24.1%) vs. 28/113 (24.8%), p=0.908], ER [23/79 (29.1%) vs. 35/113 (31.0%), p=0.782], histologic improvement [23/79 (29.1%) vs. 36/113 (31.9%), p=0.685] and CR [38/79 (48.1%) vs. 66/113 (58.4%), p=0.158].

Conclusions
Disease outcomes in patients with MES 1 and a Geboes score &gt; 3.2 were comparable to those with conventional mild-to-moderate UC. These results highlight the need for clinical trialists to revisit and expand the current definition of mild-to-moderate UC. Further validation of these findings in other patient cohorts is recommended.

Funding Agencies
None
A219 SHORT-TERM OUTCOMES OF UPADACITINIB IN PEDIATRIC IBD: A RETROSPECTIVE REVIEW
Authors: Alharbi A , Rozka L , Lawrence S , Jacobson K 
Published: February 2025

Abstract

Background
Pediatric inflammatory bowel disease (IBD) requires innovative treatments to improve symptoms and reduce steroid use. Upadacitinib, a selective JAK-1 inhibitor, has shown efficacy in adults but pediatric data remain limited

Aims
To assess clinical remission at 8 weeks in pediatric IBD patients treated with upadacitinib. Secondary aims include evaluating clinical response, steroid reduction, symptom improvement, biomarker changes, and adverse events

Methods
This retrospective review included pediatric UC and CD patients treated with upadacitinib (45 mg daily for 8-12 weeks). Clinical remission was defined as wPCDAI/PUCAI ≤10 at 8 weeks. Secondary outcomes included clinical response (wPCDAI decrease &gt;17.5 for CD, PUCAI ≥20 for UC), steroid reduction, symptom scores (abdominal pain, urgency, rectal bleeding, stool frequency), biomarkers (CRP, calprotectin), and adverse events. The Naranjo scale assessed adverse event probability

Results
Seven patients (5 CD, 2 UC) with complete 8-week data were analyzed. Median age was 16 years (IQR: 14-17), with a 3:4 male-to-female ratio

Clinical remission
At baseline, 4 patients were on both upadacitinib and steroids, and 3 on upadacitinib alone
At 8 weeks, 3/4 on steroids achieved remission, with 1 fully weaned
All 3 patients on upadacitinib alone achieved steroid-free remission
85.7% (6/7) achieved remission at 8 weeks, p = 0.01
33.3% (2/6) of remissions remained on steroids, and 66.7% (4/6) were steroid-free
Secondary outcomes:

Clinical response
85.7% (6/7) achieved response, with wPCDAI/PUCAI scores improving from 40 (IQR: 30-52.5) to 5 (IQR: 0-15) CD scores improved from 52.5 (IQR: 40-60) to 7.5 (IQR: 0-25), and PUCAI from 32.5 (IQR: 25-40) to 0 (IQR: 0-0), p = 0.01

Steroid reduction
4 patients were on steroids at baseline, with 1/4 fully weaned by 8 weeks
Baseline prednisone: 40 mg (IQR: 30-50) vs. 25 mg (IQR: 10-30) at 8 weeks, p = 0.02

Symptom scores
Abdominal pain: 2 (IQR: 1-3) to 0 (IQR: 0-0), p = 0.03
Urgency NRS: 5 (IQR: 3-6) to 0 (IQR: 0-2), p = 0.01
Rectal bleeding: 2 (IQR: 0-3) to 0 (IQR: 0-0), p = 0.04
Stool frequency: 2 (IQR: 1-3) to 0 (IQR: 0-1), p = 0.02

Biomarker response
CRP: 25 mg/L (IQR: 3.1-39) to 10 mg/L (IQR: 2-18), p = 0.03
Calprotectin: 2000 µg/g (IQR: 580-5449) to 800 µg/g (IQR: 74-1378), p = 0.04

Adverse events
71.4% (5/7) experienced acne, 28.6% (2/7) headaches, and 28.6% (2/7) nausea
No serious adverse events were reported. Median Naranjo score: 2

Conclusions
Upadacitinib improved symptoms and reduced steroid use in pediatric IBD, with 85.7% (6/7) achieving remission at 8 weeks. Of these, 66.7% (4/6) achieved steroid-free remission. Clinical response was achieved in 85.7% (6/7), with significant improvements in both UC and CD. Mild adverse events were reported, supporting further exploration of upadacitinib in pediatric IBD. Additional patients will be recruited in the coming months to expand this dataset

Funding Agencies
None
A220 LONG-TERM EFFECTIVENESS AND SAFETY OF USTEKINUMAB DOSE ESCALATION IN PATIENTS WITH REFRACTORY ULCERATIVE COLITIS: A MULTICENTER RETROSPECTIVE COHORT STUDY
Authors: Albino L , van Lierop L , Rosentreter R , Thomas P , Lu C , Siffledeen J , Kroeker K , Ma C , Peerani F , Halloran B , Baumgart D C , Dieleman L , Du L , Hoentjen F , Wong K 
Published: February 2025

Abstract

Background
Ustekinumab dose escalation (DE) may be an effective strategy to recapture clinical response in patients with ulcerative colitis (UC).

Aims
The aim of this study was to assess the real-world long-term effectiveness and safety of ustekinumab DE in patients with refractory UC.

Methods
This multicenter retrospective cohort study included patients with refractory UC who received at least one IV induction ustekinumab dose between January 2016 and November 2021. We compared ustekinumab DE to no DE, examining clinical, biochemical, and endoscopic disease outcomes. The primary endpoint was corticosteroid-free clinical remission (partial Mayo score ≤ 2 without systemic corticosteroids) at the end of follow-up. Cox-proportional hazards regression analysis was performed for factors associated with time to DE and a Kaplan-Meier plot was created for visualizing drug persistence probabilities.

Results
We enrolled 121 patients. Eighty-one patients (67%) underwent DE during a median follow-up of 141 weeks. Corticosteroid-free clinical remission at the end of follow-up was achieved for 53.2% (DE group) and 59.0% (non-DE group). In the DE group, 53% discontinued ustekinumab, mainly due to a lack of effectiveness. At the end of follow-up, 47% of DE patients remained on ustekinumab, compared to 55% in the non-DE group. Ustekinumab persistence probability after 2 years was 40% (DE group) versus 79% (non-DE group). Only 2 patients discontinued ustekinumab for adverse events.

Conclusions
Our results indicate that DE is a common method for optimizing ustekinumab treatment in refractory UC. While DE appears safe, effectiveness and drug persistence of DE beyond 2 years are limited.
Table 1

Proportion of participants in corticosteroid-free clinical, biochemical, combined clinical/biochemical, endoscopic, and combined clinical/biochemical/endoscopic remission at year 1, year 2, and end of follow up for the DE group vs non-DE group. *In the DE group, 8 discontinued ustekinumab before 1 year and an additional 14 before 2 years. **In the non-DE group, 12 discontinued ustekinumab before 1 year and an additional 4 before 2 years. ***Additional patients missing from the denominators had missing values at the presented timepoints.

Kaplan-Meier plot for probabilities of continued ustekinumab usage over the duration of follow-up in years. The green (upper) line represents the non-DE group, the red (middle) line represents the entire cohort, and the blue (bottom) line represents the DE group.

Funding Agencies
None
A227 VEDOLIZUMAB EXPOSURE ASSOCIATED WITH THE RESOLUTION OF OROFACIAL CROHN’S DISEASE: A CASE REPORT
Authors: Alseiari K , Darling M , Mora M , Wilson A 
Published: February 2025

Abstract

Background
Orofacial Crohn’s disease (CD) is a rare and often debilitating manifestation of Crohn’s disease, characterized by deep ulcerations, cobblestone lesions of the buccal mucosa, and hallmark granulomas(1,6). Orofacial Crohn’s disease remains a challenging condition to manage, with limited available data on the use of advanced non-TNF-α therapies (3). Vedolizumab, a gut-selective integrin antagonist, has been shown to be effective for inflammatory bowel disease, but its role in treating orofacial CD has not been fully explored(2,3,5).

Aims
The aim of this case report is to explore the potential efficacy of vedolizumab in treating orofacial Crohn’s disease, a rare and challenging manifestation of Crohn’s disease, by presenting a clinical case where vedolizumab led to significant resolution of both orofacial and gastrointestinal symptoms. This report aims to contribute to the limited data available on the use of non-TNF-α therapies, such as vedolizumab, in managing orofacial Crohn’s disease and to encourage further studies on its therapeutic role in this context.

Methods
This is a case report of a 68-year-old female with a 33-year history of ileo-colonic Crohn’s disease developed severe orofacial CD after infliximab discontinuation due to peri-prosthetic infection. She presented with severe vomiting, oral ulcerations, and diarrhea, along with ileal inflammation and gastric outlet obstruction. Physical examination revealed angular stomatitis and cobblestone ulcers in the buccal mucosa and palate. Histopathology confirmed CD with granulomatous inflammation. Initial treatment with dexamethasone mouthwash and budesonide showed minimal improvement. The patient was transitioned to vedolizumab, receiving three induction doses followed by monthly maintenance.

Results
Within two months of starting vedolizumab, the patient showed significant clinical and endoscopic improvement. By the fourth month, complete healing of the oral ulcerations was achieved, alongside resolution of her gastrointestinal symptoms, including gastric outlet obstruction. Vedolizumab was well-tolerated with no significant adverse effects reported.

Conclusions
This case demonstrates the potential efficacy of vedolizumab in treating orofacial Crohn’s disease, a rare and challenging presentation of Crohn’s disease. Nonetheless, vedolizumab binds to the α4β7 integrin, blocking its interaction with MAdCAM-1 on the surface of gastrointestinal endothelial cells (5). Since MAdCAM-1 is also expressed in the oral mucosa (4), we believe that vedolizumab may offer a promising alternative for patients with orofacial Crohn’s disease who do not respond to traditional therapies. Further studies are needed to establish its role in managing this condition

Funding Agencies
None
A229 THE ASSOCIATION OF MENTAL HEALTH DISORDERS WITH FATIGUE AND PHYSICAL ACTIVITY IN PERSONS WITH IBD
Authors: Dolovich C L , Chochinov S , Ly G , Oketola A , Narvey S , Larance S , Raman M , Webber S , Bernstein C N 
Published: February 2025

Abstract

Background
Fatigue is one of the most common symptoms among persons with inflammatory bowel disease (IBD) that impairs their quality of life. Fatigue acts as one of the greatest barriers of physical activity (PA) participation in adults with chronic disease, while PA is a strong contributor to improving fatigue symptoms.

Aims
The aim of this study was to assess the relationship between fatigue and PA in patients with IBD. A secondary aim was to assess the impact of mental health and disease activity on both PA and fatigue outcomes.

Methods
Participants from the University of Manitoba IBD Research Registry (n=2740) were invited to complete a cross-sectional survey to understand how persons with IBD experience PA and exercise. The international Physical Activity questionnaire (IPAQ) was used to define low vs. moderate/high levels of PA. The Modified Fatigue Impact Scale (MFIS) was used to define participants as Fatigued (MFIS ≥38) vs. non-fatigued (MFIS&lt;38). Mental health and disease activity were defined based on Generalized Anxiety Disorders-7 (GAD), Patient Health Questionnaire (PHQ-9) and Inflammatory Bowel Disease Symptom Inventory (IBDSI). Descriptive statistics, bivariate and logistic regression analysis were used to assess the relationships defined in the aims.

Results
Among 1257 (46%) who completed the survey, there was 1075 (86%) and 1119 (89%) completed data for fatigue and PA, respectively. 93/706 (13%) of persons participated in low PA and were fatigued. Older patients were both less fatigued & less active than younger patients (median IQR: 62 (53-70) vs 60 (50-68), p=0.045). Nonactive to low physically active and high fatigued patients were more likely to have an education of high school degree or less (39% vs 25%, p&lt;0.01), an income less than $50,000 (32% vs 14%, p&lt;0.0001), not in a relationship (27% vs 17%, p&lt;0.01), have an ostomy bag (14% vs 7%, p=0.02), and ever smoked (19% vs 6%, p&lt;0.0001) compared to moderate/high physically active non-fatigued patients. The odds of low PA and high fatigue were greater for persons with anxiety [aOR 95%CI; 3.0 (1.2-7.2)], depression [23.5 (10.8-53.6)], and active disease [3.97 (1.9-8.3)].

Conclusions
Patients with IBD are more likely to be participating in low levels of PA & be fatigued when they have a lower education & income, not in a relationship, have an ostomy bag and are a current or previous smoker. The odds of low PA and fatigue are up to 23 times greater for persons with a mental health disorder. New insights on PA and fatigue provide an impetus for PA intervention as it may help alleviate fatigue symptoms and enhance quality of life among persons with IBD.

Funding Agencies
CAGn/a
A230 DEATH, MITOCHONDRIA, AND INFLAMMATION IN E. COLI-LF82 INFECTION
Authors: Mohan A , Wang A , McKay D , Shutt T E 
Published: February 2025

Abstract

Background
The Crohn’s disease-associated adherent invasive E. coli (AIEC) (strain LF82) decreases mitochondrial membrane potential and fragments the epithelial mitochondrial network. Other groups have also reported activation of NF-κB-mediated inflammation and generation of reactive oxygen species in AIEC-LF82 infected epithelia. It remains unclear how these findings integrate over the course of AIEC-LF82 infection and how they influence each other over the course of infection.

Aims
To characterize the sequence of events following AIEC-LF82 infection in a non-cancer derived epithelial cell model focusing on mitochondrial disruption, cell death, mtDNA release, and inflammatory gene expression.

Methods
The fetal derived human colon epithelial cell line (FHC) were infected with E. coli-LF82 or the commensal E. coli-HB101 at multiplicity of infection (MOI) of 100 or uninfected over the course of various experiments. FHCs were stained with SYTOX green and imaged on a CellCyte X system for 24h to measure cell death or stained with MitoTracker Deep Red and imaged on a spinning disc-confocal microscope for 16h to assess mitochondrial morphology. Also, in fixed-cell preparations mitochondrial networks were imaged by staining with anti-TOMM20 antibodies. Imaging of cytosolic DNA was performed via immunofluorescent staining of mtDNA and the mitochondrial network. As markers of inflammation, CXCL10 and IL-6 mRNA were assessed via qRT-PCR.

Results
Epithelia infected with E. coli-LF82 but not E. coli-HB101 displayed dramatic fragmentation of their mitochondrial network at 6h (p &lt; 0.0001) (n=6), while SYTOX green imaging revealed significant cell death beginning at 9h (p &lt; 0.001) (n=3). Furthermore, our preliminary data indicates that transcription of inflammatory cytokines including CXCL10, and IL-6 occurs at 8h while cytosolic escape of mtDNA occurs at 6h, after mitochondrial network disruption, but prior to cell death.

Conclusions
The data begins to unravel the sequence of events in a non-cancer derived epithelium after infection with E. coli-LF82, integrating mitochondrial function, inflammatory gene expression, and cell viability and providing a more fulsome understanding of the course of E. coli-LF82 infection. Together, these data advance understanding of relationship between mitochondrial fragmentation and cell death in the context of a Crohn’s disease-relevant pathobiont, AIEC-LF82.

Funding Agencies
TRIANGLE
A231 SINGLE GUIDEWIRE MAIN PANCREATIC DUCT CANNULATION AS A RISK FACTOR FOR POST-ERCP PANCREATITIS: FINDINGS FROM A MULTI-CENTER PROSPECTIVE ENDOSCOPY REGISTRY
Authors: Gupta M , Chau M , Howarth M , Cartwright S , Ficaccio S , Elmunzer B J , Forbes N 
Published: February 2025

Abstract

Background
Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) remains a relatively common adverse event. Though multiple cannulations of the main pancreatic duct (PD) are a known risk factor for PEP, the impact of a single cannulation of the main PD remains controversial.

Aims
Given the importance of identifying those at risk for PEP, especially in light of the growing evidence for preventative interventions such as PD stenting, we aimed to identify if single PD cannulation is a risk factor for PEP.

Methods
We analyzed data from a multi-center, prospective registry collected from 2018-2024 with associated protocolized 30-day follow-up for patients undergoing ERCP for any biliary indication. PEP was defined as recurrent admission or prolongation of existing admission due to the development of characteristic abdominal pain occurring after ERCP with pancreatic enzyme elevation &gt;3 times the upper limit of normal at least 1-day post ERCP and/or imaging findings characteristic of pancreatitis. The association of single PD cannulation and PEP was evaluated with multivariable logistic regression utilizing known risk factors and preventive interventions as covariates. Results were reported as odds ratios (OR) with associated 95% confidence intervals.

Results
PEP complicated 287 (3.8%) of the 7,479 ERCPs studied. Single main PD cannulation (OR 2.14, 1.45-3.12), and multiple main PD cannulation (OR 2.58,1.76-3.76), were independent risk factors for PEP in all comers. This trend was also maintained in those with native papilla for single PD (OR 2.20, 1.43-3.24) and multiple PD (OR 2.50, 1.65-3.77) cannulations. Single main PD cannulation to both the pancreatic head (OR 1.89, 1.02-3.30) and the pancreatic body (OR 2.61, 1.44-4.57) were associated with PEP compared to no main PD cannulation. Further, a trend towards increased risk with any number of side PD cannulations (OR 1.15, 0.63-2.00) was seen, though these analyses were likely underpowered.

Conclusions
Single main PD duct canulation, to the pancreatic head or body, represents an independent risk factor for PEP in this analysis. Additionally, there appears to be additive risk associated with multiple main PD cannulations and deeper main PD cannulations. These results highlight the risk of any degree of PD cannulation, supporting the potential utility of routine preventative interventions, such as PD stenting in these cases.

Funding Agencies
None
A236 BOTH METABOLIC UNHEALTHINESS AND OBESITY ARE REQUIRED TO INCREASE GALLSTONE DISEASE RISK: A LARGE-SCALE CROSS-SECTIONAL STUDY
Authors: Baeg M , Ko S 
Published: February 2025

Abstract

Background
Obesity and metabolic unhealthiness are well-known risk factors of gallstones. However, as obesity and metabolic health are closely related, it is difficult to differentiate its effects.

Aims
The aim of our study was to investigate the relationship between metabolic health status, obesity, and gallstone disease.

Methods
We performed a retrospective cross-sectional study of subjects undergoing health screening at a university hospital. Subjects with abdominal ultrasonography and fasting insulin results were included. Subjects were classified into 4 groups based on metabolic and obesity criteria: metabolically healthy nonobese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy nonobese (MUNO), and metabolically unhealthy obese (MUO). Gallstone disease was defined as those with gallstones on ultrasonography or a history of cholecystectomy. Multivariable analysis was used to identify gallstone disease risk factors with MHNO subjects as reference.

Results
We included 12,052 subjects (6,014 MHNO, 1,662 MHO, 2,211 MUNO, 2,165 MUO). There were 568 subjects with gallstones and 241 with prior cholecystectomy history. The prevalence of gallstone disease was 5.5% in MHNO, 7.1% in MHO, 7.2% in MUNO, and 9.2% in MUO. Gallstone disease risk was significantly increased in the MUO group (OR 1.449, 95% CI 1.198-1.752, P&lt;0.001). but showed only a tendency in the MHO group (OR, 1.219, 95% CI, 0.976–1.522, P=0.080) and was insignificant in the MUNO group (OR, 0.989, 95% CI, 0.808–1.211, P=0.917). Older age significantly increased gallstone disease risk, but alcohol consumption was protective. When metabolic unhealthiness and obesity were analyzed separately, obesity significantly increased gallstone disease risk while metabolic unhealthiness did not.

Conclusions
We demonstrated that gallstone disease risk was significantly increased only in those with both metabolic unhealthiness and obesity.

Funding Agencies
None
A239 PERFORMANCE OF CLINICAL RISK PREDICTION MODELS FOR POST-ERCP PANCREATITIS: A SYSTEMATIC REVIEW
Authors: Sabrie N , Minahs G , Vaska M , Meng Z W , Brenner D , Forbes N 
Published: February 2025

Abstract

Background
Pancreatitis is common following endoscopic retrograde cholangiopancreatography (ERCP). Despite increased vigilance of post-ERCP pancreatitis (PEP), both its incidence and associated mortality are rising. Risk prediction models may provide more accurate stratification of patient risk and proactive mitigation of PEP incidence and/or severe associated outcomes.

Aims
We aimed to systematically review and summarize the available literature on PEP risk prediction models and their respective peformance.

Methods
We conducted an electronic search of MEDLINE, PubMEd, Cochrane, and CINAHL from inception through April 9, 2024 for studies evaluating the details and performances of available PEP prediction models. Studies were eligible if they used statistical measures to quantify their model’s predictive ability. Risk of bias was determined using the PROBAST tool.

Results
Nineteen studies met eligibility criteria and were included. Logistic regression models were used in 15 studies, with machine learning models representing the second most commonly employed approach. Ten studies reported the performance of their risk prediction models using derivation data, with areas under the receiver operating curve (AUC) ranging from 0.68 to 0.86. Fifteen studies reported the performance of their risk prediction models on internally validated data, with AUCs ranging from 0.66 to 0.97. Eight studies reported on the performance of their risk prediction models on external validation data, with AUCs ranging from 0.67 to 0.98.

Conclusions
Numerous PEP clinical prediction models exist with variable performances. The use of PEP prediction tools can support the management of patients following ERCP. Implementation studies assessing the optimal usability of these tools, followed by prospective evaluations, are needed to evaluate their potential impacts on reducing PEP in real-world practice.
Table 2. Summary of methods used to inform post-ERCP pancreatitis prediction models.

Funding Agencies
None