bluuebunny/crossref_metadata_2025_split huggingface dataset:
A154 TEMPORAL TRENDS OF DEPRESSION HOSPITALIZATION AND SUICIDE DEATH IN THOSE WITH INFLAMMATORY BOWEL DISEASE
Authors: Markovinovic A , Coward S , Ma C , Shaheen A , Kaplan G G 
Published: February 2025

Abstract

Background
Individuals with inflammatory bowel disease (IBD) are known to be more susceptible to mental health disorders such as depression. However, literature examining severe outcomes of depression in IBD, including hospitalizations due to depression and death by suicide, is limited.

Aims
To describe trends in depression hospitalizations and suicide deaths in individuals with IBD living in Alberta compared to matched controls.

Methods
This population-based study used a validated algorithm in administrative data to identify the prevalent IBD population and 10 to 1 age- and sex-matched controls in Alberta from fiscal year 2002/03 to 2021/22. The primary outcomes were hospitalization for depression and suicide death. Annual prevalence rates of depression hospitalization were calculated per 1,000 persons. Average annual percent change (AAPC) with 95% confidence intervals (CI) were calculated from Poisson or negative binomial models. Rates and AAPCs for depression hospitalization in IBD cases were stratified by age (&lt;18, 18–40, 41–64, and ≥65), sex (male or female), and IBD type (Crohn’s disease or ulcerative colitis and inflammatory bowel disease unclassified [IBD-U]). Suicide deaths were reported as a proportion of the prevalent IBD population and as an AAPC (95% CI) calculated from a log-binomial model.

Results
Table 1 describes depression hospitalizations in the prevalent IBD population (n=42,903). Hospitalization rates for depression in those with IBD decreased with an AAPC of −4.25% (95% CI: −5.51, −2.96) from 4.42 per 1,000 in 2002/23 to 2.08 per 1,000 in 2021/22, while hospitalization rates for depression in controls decreased with an APPC of −2.37% (95% CI: −2.90, −1.94) (Table 1, Figure 1). Hospitalization rates for depression in those with IBD decreased for all stratifications except pediatric cases (AAPC: 2.03%; 95% CI: −5.99, 10.72) (Table 1). Suicide deaths occured in 0.23% (n=99) of the prevalent IBD population and remained stable over time (AAPC: −0.09%; 95% CI: −3.82, 3.79).

Conclusions
Despite the decreasing hospitalization rates for depression in individuals with IBD, suicide deaths have remained stable at 0.23%.
AAPCs and rates of depression hospitalization in those with IBD, stratified by age, sex, and IBD type

*denotes statistical significance

Temporal trends in depression hospitalization in IBD cases and matched controls

Funding Agencies
CIHR
A162 INTERLEUKIN-4 SIGNALING IS NOT A PREREQUISITE FOR HELMINTH-THERAPY PROTECTION AGAINST COLITIS
Authors: Kraemer L , McKay D , Wang A 
Published: February 2025

Abstract

Background
Infection with helminth parasites drives Th2 immunity, characterized by the cytokines IL-4, -5, -13, and IL-10, and expansion of regulatory cells. These orchestrated immune responses promote an immunomodulatory/immunosuppressive environment, which can protect the host from concomitant inflammation. Mice infected with the tapeworm Hymenolepis diminuta display a strong Th2 immune response and they are protected from DNBS-induced colitis. Surprisingly, preliminary data indicated that il-4ra-/- mice (where the worm establishes) were protected from DNBS-induced colitis. Here we sought to confirm or refute the findings in il-4ra-/- and, if positive, investigate the role of IL-10 and macrophages in the anti-colitic effect.

Aims
To determine if IL-10 and macrophages play key roles in the protection against colitis in il-4ra-/- mice infected with H. diminuta.

Methods
BALB/c (WT) and il-4ra-/- mice (IL-4ra-/-) (n=4-15/group) were orally infected with 5 cysticercoids of H. diminuta and 8 days post-infection (dpi) were treated with 2.5 mg of dinitrobenzene sulfonic acid (DNBS) to induce colitis. In some experiments, mice were treated 3 times i.p. with neutralizing anti-IL10 antibody (100 mg/mouse) or clodronate-liposomes (100 ml/mouse) to deplete macrophages (5 days and 24h before and after DNBS). Mice were necropsied 72h post-DNBS and disease was assessed through macroscopic disease activity score (DAS), colon length, weight loss, colonic MPO activity, blood leucocyte profile and histopathological score. Cytokine production by antigen-specific (H.d. antigen 200mg/mL; 48h) stimulated splenocytes was measured by ELISA.

Results
DNBS treatment induced colitis in WT and IL-4ra-/- and prior infection with H. diminuta was anti-colitic in both groups as shown by reduced DAS, weight loss, MPO activity, and histopathology. Compared to WT, il-4ra-/- mice had less blood eosinophilia, and il-5 and il-10 production by worm-antigen stimulated splenocytes, although il-10 production was increased compared to splenocytes from uninfected control mice. Immunoneutralization of il-10 and macrophage depletion abolished the protective effects of infection with H. diminuta, with the clondronate-treated mice displaying severe disease.

Conclusions
Despite harbouring a patient infection with H. diminuta, il-4ra-/- mice are protected from DNBS-induced colitis that is, at least in part dependent on IL-10 and likely a phenotype of regulatory macrophage. The data suggest redundancy in the anti-colitic effects of H. diminuta infection, such that absence of il-4ra is compensated for via other, yet to be determined, mechanisms.

Funding Agencies
CAG, CIHRTRIANGLE
A168 DIFFERENTIAL ASSOCIATION OF DIETARY FIBER INTAKE WITH METABOLOMIC AND PROTEOMIC SIGNATURES LINKED TO THE RISK OF CD
Authors: Kim J , McShane C , Xue M , Lee S , Leibovitzh H , Shao J , Khorasaniha R , Griffiths A , Armstrong H , Moayyedi P , Croitoru K , Turpin W 
Published: February 2025

Abstract

Background
Epidemiologic studies have shown that increased dietary fiber intake may be associated with a reduced risk of developing Crohn’s disease (CD). Our previous research identified specific patterns of serum proteomics and metabolomics associated with CD onset.

Aims
We aimed to understand how specific dietary fibers might be associated with risk biomarkers of CD in a high-risk population.

Methods
In the CCC-GEM Project, a nested case-control cohort was established involving healthy first-degree relatives (FDRs) of individuals with CD. This cohort was matched in a 1:4 ratio, comparing those who developed CD with those who remained healthy. The intake of five energy-adjusted dietary fibers, including inulin, fructooligosaccharides (FOS), β-glucan, pectin, and arabinoxylan, was assessed using a food frequency questionnaire completed at recruitment. Of the serum markers measured at recruitment, 63 metabolites (Metabolon®) and 25 proteins (Olink®), and C-reactive protein (Prometheus®) were associated with future CD risk; 34 metabolites and 15 proteins were associated with increased CD risk, while 29 metabolites and 10 proteins were protective against CD risk. To evaluate the association between dietary fibers and these serum markers, we used generalized estimating equations, considering a false discovery rate-adjusted p &lt; 0.05 as significant.

Results
Among 215 healthy FDRs, 41 developed CD during a median follow-up of 9.4 years, while 173 remained healthy. We found that 14 metabolites and eight proteins previously associated with an increased risk of developing CD in future were negatively associated with the intake of at least one dietary fiber, whereas six metabolites and five proteins linked to a decreased risk of CD development were positively associated with dietary fibers. In particular, the intake of inulin, FOS, and β-glucan was negatively associated with the CD-associated markers TREM1, MMP9, HGF, and sphingomyelin species (p &lt; 0.001), and positively associated with isocitrate (p &lt; 0.001), previously linked to a reduced CD risk. Furthermore, the consumption of inulin, FOS, β-glucan, anarabinoxylan were negatively associated with C-reactive protein levels (p &lt; 0.05).

Conclusions
Our findings suggest that select fermentable dietary fiber intake may be protective against the development of CD by influencing the abundance of specific proteins and metabolites associated with CD risk. Further research is needed to directly explore the mechanisms of specific fermentable dietary fibers on CD development.
Submitted on behalf of the Crohn’s and Colitis Canada GEM Project Research Consortium, list available at www.gemproject.ca.

Funding Agencies
CCC, CIHRHelmsley Charitable Trust
A171 IL-23 RECEPTOR VARIANT PREDICTS ANTI-TNFα INDUCED PARADOXICAL PSORIASIS IN INFLAMMATORY BOWEL DISEASE
Authors: Natt N , Gindi M , Wilson A 
Published: February 2025

Abstract

Background
Anti-tumor necrosis factor (TNF)-α therapy is frequently used to treat inflammatory bowel disease (IBD). Paradoxical psoriasis (PP) is a known adverse effect of this drug class resulting in disfiguring skin lesions that impact quality of life and lead to treatment discontinuation. To date, there are no tools to identify individuals who are susceptible to developing PP. Variation in the IL-23 receptor (IL23R) gene has been linked to psoriasis onset and may be implicated in PP.

Aims
To study the incidence and outcomes of PP in anti-TNFα treated IBD patients at an academic centre in London, Ontario and examine risk factors associated with PP including the IL23R variant (IL23R1142G&gt;A).

Methods
We performed a retrospective study of adult IBD patients treated with anti-TNFα therapies at London Health Sciences Centre between 2012 and 2024. Patient charts were reviewed for clinical variables and disease outcomes from the time of anti-TNFα exposure to treatment discontinuation or last follow-up. Patients’ serum was retrospectively genotyped for the IL23R1142G&gt;A variant.

Results
We identified 496 IBD patients with 570 unique anti-TNFα exposures between 2012 and 2024. 26 patients developed 29 cases of PP while the remaining 473 patients did not develop PP after exposure to 542 anti-TNFα therapies. There was an increased proportion of patients with PP who had a positive family and personal history of psoriasis, though the latter was not significant (Table 1). The IL23R variant was more common in patients who developed PP compared to those who did not (46.2% vs. 5.1%, OR 16.04, 95% CI 6.69-38.41, Figure 1). The average time to develop PP was 9.5 months, with 55% of patients receiving high-dose anti-TNFα drugs. Majority of patients had moderate-to-severe disease (72.4%) and required treatment cessation (69.0%). All participants had complete resolution of PP following interruption of anti-TNFα therapy.

Conclusions
IL-23R mutations may identify those at risk for anti-TNFα induced PP. Personal and family history of psoriasis may also predict those at higher risk and should be elicited on assessment.
Table 1 - Baseline Characteristics

Funding Agencies
None
A179 A CANADA-WIDE STUDY OF TRENDS IN HOSPITALIZATION RATES FOR INFLAMMATORY BOWEL DISEASE
Authors: Coward S , Benchimol E , Bernstein C N , Avina-Zubieta A , Bitton A , Hoentjen F , Kuenzig E , Lu N , Leal J , Ma C , Murthy S , Novak K , Nugent Z , Otley A , Panaccione R , Peña-Sánchez J , Singh H , Targownik L , Kaplan G G 
Published: February 2025

Abstract

Background
Hospitalizations among individuals with inflammatory bowel disease (IBD) place a strain on healthcare resources. The decline in hospitalization rates during the era of anti-TNF therapies remains debated in the literature.

Aims
To examine temporal trends in hospitalization rates among individuals with in IBD across Canada.

Methods
We used population-based administrative healthcare data (2002–2014) from seven Canadian provinces (AB, BC, MB, NS, QC, ON, SK) to identify hospitalizations in prevalent IBD cases. Hospitalizations were categorized as: 1. all-cause, any hospitalization of an IBD patient; 2. IBD-related, admission for IBD or symptoms/comorbidities associated with IBD (eg. venous thromboembolism). We calculated hospitalization rates per 100 IBD persons with 95% confidence intervals (CIs) using IBD prevalence data. Hospitalization rates were forecast from 2015–2025, with 95% prediction intervals (PIs), using auto regressive integrated moving average models on log transformed data. We calculated average annual percentage change (AAPC) using Poisson models with quadratic equations applied for non-linear trends. We stratified by IBD subtype (CD, UC), age (&lt;18, 18–64, 65+), and sex (female, male). We calculated AAPCs for counts to assess the actual number of hospitalizations.

Results
From 2002–2014, hospitalizations rates decreased for both all-cause and IBD-related admissions for IBD patients, and across age, sex, and IBD type (Table 1). In 2025, we forecast hospitalization rates to be 15.82 (95%CI:14.17,17.66) per 100 for all-cause and 7.87 (95%CI:6.16,9.90) per 100 for IBD-related. Hospitalization rates are falling, but AAPCs for hospitalization counts significantly increased for all-cause (2.65%; 95%CI: 2.42,2.89) and IBD-related (1.52%; 95%CI: 1.29,1.76). The disparity between decreasing rates and increasing counts is due to the faster rise in the AAPC of IBD prevalence (denominator) compared to hospital counts (numerator).

Conclusions
During the anti-TNF era (2002–2014), hospitalization rates for IBD steadily declined across Canada and are projected to continue decreasing through 2025. Despite this decline, the actual number of hospitalizations is increasing, likely driven by the rising prevalence of IBD.

¥ Includes IBD-Unclassified *Non-linear

Funding Agencies
CIHR
A182 THE IMPACT OF DISEASE STATUS AFTER BIOLOGIC INDUCTION THERAPY ON LONG-TERM OUTCOMES IN PERSONS WITH CROHN’S DISEASE
Authors: Brar G S , Tandon P , Haque M , Butt N , Sanon M , Naessens D , Pone E , Targownik L 
Published: February 2025

Abstract
NOT PUBLISHED AT AUTHOR’S REQUEST
Please acknowledge all funding agencies listed below
Funding Agencies: Study Supported by funding from Janssen
A185 ERYTHEMA NODOSUM AS A MARKER FOR OBJECTIVE DISEASE ACTIVITY IN INFLAMMATORY BOWEL DISEASE: A SINGLE CENTER RETROSPECTIVE STUDY
Authors: Sasson S , Kalisky I , Rosenfeld G , Bressler B 
Published: February 2025

Abstract

Background
Erythema Nodosum (EN) is an inflammatory condition characterized by tender, erythematous nodules, typically found on the extensor surfaces of the extremities. EN is linked to both immune-mediated conditions, such as inflammatory bowel disease (IBD), Behçet’s syndrome, and sarcoidosis, as well as non-immune-mediated conditions. In patients with IBD, EN affects 3–10% of those with ulcerative colitis (UC) and 4–15% with Crohn’s disease (CD), particularly in patients with colonic involvement. While EN has been thought to be associated with disease activity, this conclusion has been primarily based on symptom assessment, and a definitive association with objective measures, such as inflammatory markers or endoscopic activity, has not yet been established.

Aims
To investigate the association of EN to objective inflammatory assessments among IBD patients.

Methods
Using the IBD Center of British Columbia database, patients with active EN were assessed. For each patient, disease activity based on symptoms was evaluated. Objective assessments, such as colonoscopy and imaging modalities such as CT, MR, or video capsule enterography, were included if they were performed within a three-month window of the EN presentation. Fecal calprotectin and C-reactive protein (CRP) were collected if obtained within four weeks of the EN presentation, using thresholds of 250 µg/g and 5 mg/L respectively.
Standard descriptive analyses were conducted to evaluate any association between both objective and subjective measures of disease activity and the presence of EN.

Results
The initial search identified 165 patients with a documented presentation of EN. The mean age at presentation of EN was 40 years. The majority of EN patients had Crohn’s disease (89, 76%), and were predominantly female (86, 74%). Among those, 116 patients had at least one objective assessment within the prespecified time with 71 patients (61%) having a colonoscopy as a sole method to identify disease activity, while CRP, imaging, and fecal calprotectin were used in 28 (24%), 10 (9%), and 7 (6%) of the cases, respectively.
In regards to disease activity, 68 (58%) patients had gastrointestinal symptoms at the time of EN presentation. However, out of 116 cases, a total of 93 (80%) had objective evidence of active disease.

Conclusions
In this analysis of IBD patients with active EN, objective evidence of intestinal disease activity was found in a significant majority (80%) of cases, despite only 58% of patients reporting gastrointestinal symptoms at the time of EN presentation. These findings suggest that EN may be closely associated with underlying intestinal inflammation even in the absence of overt clinical symptoms. This highlights the potential importance of pursuing objective assessments in patients who present with EN, even with no overt clinical symptoms.

Funding Agencies
None
A187 VANCOMYCIN CAN INDUCE AND MAINTAIN REMISSION OF REFRACTORY INFLAMMATORY BOWEL DISEASE IN PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS – A CASE SERIES
Authors: Cintosun A , Narula N 
Published: February 2025

Abstract

Background
The microbiome is suspected to play a role in the pathogenesis of inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC). Meta-analyses have shown a positive response for antimicrobials in IBD, although the results are difficult to apply clinically given the wide variability in antimicrobial modality and treatment regimen as well as perceived reduced effectiveness compared to advanced therapies. Fewer antimicrobial studies have been performed in the PSC population. There is some evidence that vancomycin may represent a treatment option with concurrent IBD and PSC.

Aims
To determine the clinical and endoscopic effect of vancomycin for patients with refractory PSC-IBD.

Methods
Retrospective chart review.

Results
We identified 6 patients (4 male) with IBD and PSC who were started on vancomycin (Figure 1). Four had ulcerative colitis (UC) and 2 had Crohn’s disease. Three had pre-existing cirrhosis; 1 of these patients had undergone liver transplantation for PSC. All had failed multiple therapies for IBD with up to 4 advanced therapies failed. One patient had previously required surgery for UC.
Patients were started on induction vancomycin at 125 mg 4 times daily or BID (twice daily) for 8 weeks followed by maintenance therapy at 125 mg BID or daily.
The initial response to vancomycin therapy was demonstrated for all 6 patients at early follow-up ranging from 1 to 3 months. All had improvement of clinical symptoms with reduction in stool frequency and improvement in consistency. Some had bloody stools, nocturnal symptoms, and abdominal pain, which also improved.
One patient is awaiting post-vancomycin endoscopy. The remaining 5 started with moderate-to-severe inflammation and improved to mild or no inflammation on follow-up endoscopy 2 months to 2 years after starting vancomycin. Two patients had documented repeat endoscopy at a longer period of follow-up (4 and 6 years) and maintained remission.
The follow-up duration ranged from 2 months to 6 years. No adverse effects to vancomycin were reported. None of the 6 patients required steroids, addition of alternative therapy, admission, or surgery.
All patients were on concurrent therapy (vedolizumab, ustekinumab, or 5-ASA) either started prior to or at the same time as vancomycin. Three of these patients discontinued their ustekinumab at 6, 8, and 14 months respectively given treatment effectiveness and maintained remission on vancomycin alone.

Conclusions
In a subset of patients with PSC-IBD, vancomycin can induce clinical and mucosal remission for refractory IBD. We present two dosing regimens which produced rapid clinical improvement and those with longer follow-up sustained durable results. Prospective studies with larger sample sizes are needed.

Funding Agencies
None
A188 NATURAL HISTORY OF PERIANAL FISTULAS IN PATIENTS WITH ILEAL POUCH ANAL ANASTOMOSIS
Authors: Fujiyoshi M , McCurdy J 
Published: February 2025

Abstract

Background
The natural history of perianal fistulas (PAF) in patients with ileal pouch-anal anastomosis (IPAA) remains poorly understood. Perianal fistulas can significantly impact the quality of life and clinical outcomes in patients who have undergone IPAA. To date, there is limited data available on the long-term progression, treatment responses, and overall outcomes of PAF in this unique patient population.

Aims
The primary aim of this study is to report the clinical outcomes of PAF in patients with IPAA.

Methods
We performed a retrospective, observation cohort study between 2000 and 2024. We included adults (&gt;17 years) with an IPAA who developed a perianal fistula and a minimum of 1 year follow-up after PAF diagnosis. PAF disease activity was categorized on an annual basis according to the following disease activity patterns: remission, minimally active, relapsing-remitting, and chronic persistent. We also determined medication utilization, medication effectiveness and major adverse fistula outcomes (MAFO): a composite of hospitalization, surgical drainage of PAF and fecal diversion.

Results
A total of 29 patients with an IPAA and PAF were identified: mean (SD) age 49.3 (13.2); 19 (65.5%) female, and 17 (63.0%) with complex fistulas radiologically at the time of diagnosis. After a mean (SD) follow-up of 9.7 years (7.4), 7 (25.0%) patients required fecal diversion, and 2 (7.1%) patients underwent pouch excision. Annual PAF disease patterns are reported in Figure 1. At the last date of follow-up, 26 (92.9%) patients achieved fistula remission. A total of 16 (55.2%) patients underwent treatment with an advanced therapy: 14 (87.5%) anti-TNF and 2 (12.5%) Risankizumab. After initiating a first advanced therapy, 10 (62.5%) patients achieved fistula remission at 12 months. Furthermore, 3 (18.8%) patients developed a MAFO after initiating their first advanced therapy: 3 (18.8%) underwent surgical drainage, 1 (6.3%) was hospitalized, and 1 (6.3%) underwent fecal diversion for PAF.

Conclusions
This study demonstrated that the majority of patients with PAF in the setting of IPAA achieved fistula remission clinically, particularly after treatment with advanced therapies. Despite the high remission rates, a substantial subset of patients still required fecal diversion and pouch excision.

Annual perianal fistula disease patterns

Funding Agencies
None