bluuebunny/crossref_metadata_2025_split huggingface dataset:
A245 CROHN’S DISEASE-ASSOCIATED BACTERIAL PATHOBIONT EVOKED EPITHELIAL MITOCHONDRIAL DAMAGE DRIVES TYPE I INTERFERON EXPRESSION
Authors: Mohan A , Wang A , McKay D , Shutt T 
Published: February 2024

Abstract

Background
The Crohn’s disease-associated adherent invasive E. coli (AIEC) (strain LF82) decreases mitochondrial membrane potential and fragments the epithelial mitochondrial network. Due to the evolutionary history of mitochondria as former bacteria, they present a variety of molecular patterns known to trigger innate immune responses. Specifically, mitochondrial DNA (mtDNA) released following mitochondrial damage causes upregulation of type I interferons, priming inflammatory signalling. Thus, we hypothesized that AIEC-induced mitochondrial dysfunction results in mtDNA release to activate innate immune signalling that could contribute to disease pathogenesis in the gut.

Aims
We aimed determine if an inflammatory response occurs downstream of mitochondrial damage evoked by E. coli-LF82 infection.

Methods
Control T84 epithelial cells, T84s infected E. coli-LF82 (108 cfu, MOI=100, 4h) and T84s infected with the commensal E. coli-HB101 (108 cfu for an MOI=100, 4h) were collected for protein and RNA extraction. RNA was used to measure IFNα and IFNβ expression following infection, while protein was used to measure upstream mediators including phosphorylation of TANK Binding Kinase-1 (TBK1) via Western blot.

Results
Epithelia infected with E. coli-LF82 but not E. coli-HB101 displayed dramatic fragmentation of their mitochondria network and increased levels of phosphorylated-TBK1 compared to control T84 cells (pampersand:003C0.01). Assessment of IFNα and IFNβ mRNA revealed significant up-regulation E. coli-LF82 infected T84 cells and human colon organoids.

Conclusions
Our findings identify a novel role for E. coli-LF82 in activating type I interferon response and for the first time show AIEC-induced activation of TBK1 and type I interferons, which may occur through mitochondrial damage, rather than through response to bacterial molecular patterns. As a result, our findings suggest that the AIEC colonization seen in Crohn’s disease may dysregulate inflammatory signalling through mitochondrial damage. Ultimately, we believe this dysregulation of inflammatory signalling may sensitize the host to further inflammatory signalling, contributing to the pathogenesis of inflammatory bowel disease.

Funding Agencies
CIHR
A255 COMMUNICATING NEEDS AND FEATURES OF IBD EXPERIENCES (CONFIDE) SURVEY: PATIENT PERSPECTIVES ON EXPERIENCE OF ULCERATIVE COLITIS SYMPTOMS IN CANADA
Authors: Glass J , Panaccione R , Bessissow t , Hunter Gibble T , Atkinson C , Braun M , Ellis H , Dewar T , Jairath V 
Published: February 2024

Abstract

Background
Moderate-to-severe ulcerative colitis (UC) can be associated with impairment in quality of life (Kawalec, 2016).

Aims
The Communicating Needs and Features of IBD Experiences (CONFIDE) study aims to increase understanding of patients’ experiences and the impact of IBD on their lives in the United States, Europe, Japan, and Canada. These data focus on Canadian patients.

Methods
An online, quantitative, cross-sectional survey was conducted (panel recruitment) between February and March 2023 in patients diagnosed with active moderate-to-severe UC in Canada. Moderate-to-severe UC was defined using criteria based on previous treatment, steroid use, and/or hospitalization. Data collected included patient perspectives on their experiences with UC, including symptom burden. Results were summarised descriptively.

Results
The survey was completed by 82 (of 373 contacted – 22% response) patients (65% male, mean age 43.5 years (SD 12.6), mean time since diagnosis 6.3 years (SD 7.6, range 1-33 years)). The top 3 patient-reported symptoms experienced in the past month were diarrhea (39%, n=32), bowel urgency (BU, 31%, n=25), and fatigue/tiredness (29%, n=24). Overall 73% (n=60/82) were receiving advanced therapies (biologic or novel oral therapy), and BU was currently experienced by 28% (n=17) of these patients. Over half of patients had ever experienced BU (56%, n=46); of these, 48% (n=22) reported doing so at least once a week in the past 3 months. Due to fear/anticipation of bowel urgency related accidents, 68% (n=56) of patients with UC reported wearing diaper/pad/protection at least once in the past 3 months. Of those who had worn diaper/pad/protection, 32% (n=18) reported that they suffered from BU in the past month. Due to fear of BU-related accidents, 31% (n=25) of patients declined participating in work/school, 34% (n=28) declined participating in social events, and 26% (n=21) declined participating in sports/physical exercise in the last 3 months.

Conclusions
Out of the top 3 symptoms reported by patients, BU was the second-most common in patients with moderate-to-severe UC in this study of Canadian patients. A substantial proportion of patients with moderate-to-severe UC continue to report BU, despite receiving advanced therapies; with two-thirds requiring to wear diapers or pads. Further work is needed to understand the pathophysiology of urgency and the efficacy of medical therapies to improve urgency using validated outcome measures.
References
Kawalec P. Indirect costs of inflammatory bowel diseases: Crohn's disease and ulcerative colitis. A systematic review. Arch Med Sci. 2016 Apr 1;12(2):295-302

Funding Agencies
Eli Lilly and Company
A256 NAVIGATING IBD CARE : HEALTHCARE PROVIDERS’ INSIGHTS ON IMPLEMENTATION OF NURSE NAVIGATOR-LED IBD FLARE PATHWAY
Authors: Reuangrith J , Jones J , Rohatinsky N , Nguyen G 
Published: February 2024

Abstract

Background
Disparities in access to healthcare for persons living with inflammatory bowel disease (IBD) persist. An IBD nurse navigational role promises to improve access to evidence-based specialist care by minimizing inequities in access to care. Little is known about how to implement a provincial nurse navigational role in the Canadian health system.

Aims
This study aims to explore healthcare providers' perceptions of barriers and facilitators to the implementation of an evidence-based IBD flare pathway through a provincial nurse navigational role.

Methods
This was a national qualitative study performed in collaboration with the CCC PACE Program, in which two virtual semi-structured group interviews were conducted in 2022. One group interview was with six IBD nurses from three provinces, and the second was with five gastroenterologists from five provinces. Participants were purposefully recruited. The Consolidated Framework for Implementation Research (CFIR) and the Capability, Opportunity, Motivation, and Behaviour (COM-B) frameworks informed the interview script development. Data were transcribed verbatim and subjected to content analysis, with major themes categorized into the COM-B domains. The results of preliminary data analysis are presented.

Results
While IBD nurses emphasized the critical role of effective communication tools, standardized referral systems, strong administrative support and patient education and engagement as facilitators, they also highlighted challenges like patient resistance, variability of training and the necessity for tailored patient care. Other barriers identified were the medical complexity of managing overlapping conditions, remote vs in-person considerations and the perception and definition of a flare. On the other hand, IBD-focused gastroenterologists emphasized the potential of integrating pathways into electronic medical records and the value of empowering nurse navigators. However, they pointed out concerns regarding the inherent variability in disease presentation, entrenched medical beliefs, comfort levels with nurse-led pathways and the inherent diversity in medical practices. Both groups identified resource constraints as a barrier and an effective triage process as a facilitator.

Conclusions
This study sheds light on the multifaceted perceptions of healthcare providers concerning the implementation of an evidence-based IBD flare pathway through a provincial nurse navigational role. These insights underline the complexity of implementing a nurse navigational role and the need for targeted interventions and resources to address the identified barriers while leveraging the facilitators.

Funding Agencies
CCC
A258 ULTRASOUND ASSESSMENT OF CROHN’S DISEASE PATIENTS FOLLOWING RISANKIZUMAB INITIATION; BASELINE, 3 AND 6 MONTH FOLLOW UP
Authors: Rosentreter R E , Ingram R , Ma C , Chan M , Shukla T , Devlin S , Kaplan G G , Seow C , Panaccione R , Novak K , Lu C 
Published: February 2024

Abstract

Background
Risankizumab (RIS), an interleukin-23 inhibitor specific to the p19 subunit, was approved for the treatment of moderate to severe Crohn’s Disease (CD) in December 2022. Intestinal ultrasound (IUS) is an accurate and well-tolerated modality for evaluating response to therapy.

Aims
We aim to assess IUS response at 3 and 6 months following RIS therapy.

Methods
Consecutive patients initiating RIS for CD were recruited to be evaluated by IUS at baseline (within 14 days of initiation), 3 months, and 6 months. Baseline demographics, medication exposure, surgical history, and inflammatory biomarkers were obtained. IUS response (decrease in bowel wall thickness (BWT) ≥ 25%)) and transmural remission (TR) (normalization of BWT normalization, color doppler signal (CDS, modified Limberg (ML) score 0), wall stratification, inflammatory fat) for each segment were evaluated. Paired t-tests compared values at baseline, 3 and 6 months.

Results
Thirty-three (20, 60.6% female) patients were recruited; 30 completed baseline and 3 month IUS, while 18 patients have 6 month IUS. Median age was 55 years (IQR 39-63), with a 12 year median CD duration (IQR 5-28). Five had inflammatory, 19 stricturing, and 6 fistulizing behaviour. CD distribution was 18 ileal, 1 colonic, and 11 ileocolonic. 20% (6/30) were bio-naïve, while 30% (9/30) had failed ≥ 3 biologics. Baseline mean CRP (4.1 ± 4.9 mg/L) did not significantly differ at 3 months (5.0 ± 6.8 mg/L, p=0.16), nor at 6 months for patients with values available (6.2mg/L ± 8.3, p = 0.38). Of patients with FC concentrations, 3 month mean FC (129.4 ±70 mcg/g) (9 patients) had significantly decreased from baseline (427.6 ± 271 mcg/g) (p=0.008), and similarly at 6 months (9 patients; baseline 396 ± 299 vs. 129 ± 75, p = 0.02). 80.0% (4/5) patients with colonic BWT ampersand:003E 3mm had IUS response (baseline mean BWT 5.6 ±1.4mm vs 3.5 ± 0.8mm at 3 months (p=0.011). IUS response was not achieved in those with ileal CD at 3 months (BWT 6.3 ± 2.1mm vs 3 month 6.0 ± 2.5mm (p=0.31). However, 21.4% (3/14) of ileal CD patients had an IUS response at 6 months. There is a non-significant ileal BWT reduction (5.4 ± 1.6mm) from baseline (6.0 ± 1.7mm) at 6 months. Of the 9 with moderate to severe CDS, 55% (5/9) had reduction to mild CDS by 3 months. TR was achieved by one patient with ileal CD at 6 months.

Conclusions
IUS response was achieved in 80.0% of CD patients with colonic disease at 3 months follow RIS initiation. IUS response was not detected for ileal CD at 3 months, but detected in 21.4% at 6 months A significant FC reduction by 3 and 6 months was attained. Further prospective patient recruitment and IUS at 6 and 12 months to assess preliminary results and longer-term response is needed.

Funding Agencies
None
A263 IRONING OUT THE DETAILS: CROHN’S DISEASE PATIENT DERIVED MACROPHAGES ARE MORE SUSCEPTIBLE TO FERROPTOSIS
Authors: Sousa J A , Callejas Pina B E , Munazza Y , Wang A , Raman M , McKay D 
Published: February 2024

Abstract

Background
Death of intestinal epithelial cells is ubiquitous in Crohn’s disease (CD) but the death of immune cells such as macrophages is less explored. We have found that monocyte derived macrophages from patients with active CD are more susceptible to H2O2-induced cytotoxicity but the form of regulated cell death these cells undergo remains to be elucidated. Selenium (Se)—a common micronutrient deficiency in patients with CD—is used in the synthesis of selenoproteins that have antioxidant properties (e.g., glutathione peroxidases (GPx)) and are highly expressed in macrophages. Whether Se deficiency plays a role in the increased cytotoxicity also remains to be elucidated.

Aims
To determine the form of cell death of macrophages in response to H2O2-induced cytotoxicity and whether selenium deficiency plays a role in the increased susceptibility to H2O2-induced cytotoxicity.

Methods
Blood collected from healthy volunteers and patients with active CD was analyzed for serum GPx activity. Monocytes isolated by plastic adherence were treated with M-CSF (10ng/ml, 7d) to derive macrophages. Macrophages were treated with H2O2 (500μm, 2h) and lactate dehydrogenase release was measured. GPX1, SLC7A11 and PTGS2 mRNA expression were determined by qPCR. The presence of cleaved caspase 3 was determined by immunoblotting and IL-1β by ELISA. Lipid peroxidation a marker of ferroptosis was assessed by staining macrophages with Bodipy C-11 (± liproxstatin-1, an inhibitor of ferroptosis).

Results
CD macrophages were two times more susceptible to H2O2-evoked cell death. In response to H2O2 macrophages did not express cleaved caspase 3 or IL-1β, but there was an induction of ferroptosis markers (SLC7A11 and PTGS2). Moreover, lipid peroxidation was induced and could be blocked with liproxstatin-1. Dietary Se intake did not differ between groups but serum GPx activity was greater in patients with CD compared to control. In contrast, GPX1 mRNA expression and GPx1 protein expression were decreased in CD macrophages compared to healthy controls.

Conclusions
Macrophages derived from patients with CD are inherently more sensitive to ferroptosis potentially through reduced GPx1 expression. Future studies warrant testing if GPx1 prevents ferroptotic macrophage cell death and if it holds therapeutic relevance in CD pathophysiology.

Funding Agencies
Helmsley Charitable Trust, Crohn's and Colitis Foundation of America
A266 TISSUE-SPECIFIC FUNCTION OF THE CIRCADIAN GENE, BMAL1, DURING COLITIS RECOVERY
Authors: Taleb Z , Carmona-ALcocer V , Wan R , Karpowicz P 
Published: February 2024

Abstract

Background
The circadian clock is a self-sustained molecular oscillator which drives 24-hour physiological rhythms in nearly every cell of the body. It consists of the genes Bmal1 and Clock that positively regulate Cry and Per, their negative regulators, resulting in a 24-hour transcription/translation feedback cycle. Shift work, which causes disruptions to 24-hour physiological rhythms, has been linked with an increased incidence of inflammatory bowel disease (IBD).

Aims
We have previously established that mice lacking the non-redundant circadian regulator, Bmal1, exhibit more severe colitis compared to controls. The loss of Bmal1 also negatively impacts post-colitis regeneration and recovery. However, the role of Bmal1 in specific cell types remains unknown in regard to regenerative capacity following colitis. The intestinal stem cell niche includes stromal cells that provide signaling factors to regulate the proliferation of epithelial cells in the colonic crypt.

Methods
To test the role of the circadian clock in these cell types, we conditionally disrupted Bmal1 in intestinal epithelial versus stromal cells using VilCre/+;Bmal1flox/flox and PdgfraCre/+;Bmal1flox/flox mice, respectively. Dextran Sulfate Sodium (DSS) was applied to induce acute colitis, disease progression was evaluated, and regeneration at different stages of recovery was analyzed. We hypothesize that the cell-specific disruption of Bmal1 in both intestinal epithelial and stromal cells negatively impacts the regenerative capacity following colitis, leading to delayed recovery and increased inflammation.

Results
No differences in survival and colitis disease activity were observed between Vil+/+;Bmal1flox/flox control and VilCre/+;Bmal1flox/flox but increases in lesion number, inflammation, and disrupted recovery are evident in VilCre/+;Bmal1flox/flox colons histologically. Whereas control animals are able to recover two weeks following DSS treatment, regenerative proliferation is still present in conditional knockouts. Thus, Bmal1 is required in intestinal epithelial cells for efficient repair. Preliminary results in the PdgfraCre/+;Bmal1flox/flox conditional stromal mutanats do not show differences in survival or disease severity, and we are currently evaluating effects on regeneration.

Conclusions
Our results support a critical role for Bmal1 in intestinal epithelial cells during post-colitis regeneration and recovery.

Funding Agencies
CCC, CIHR
A267 RECENT IMMIGRANTS WITH INFLAMMATORY BOWEL DISEASE HAVE SIGNIFICANT HEALTH-CARE UTILIZATION FROM PRECONCEPTION TO POSTPARTUM: A POPULATION-BASED COHORT STUDY
Authors: Tandon P , Huang V , Feig D , Saskin R , Maxwell C , Fell D , Seow C , Snelgrove J , Nguyen G 
Published: February 2024

Abstract

Background
Previous studies have demonstrated an increase in health-care utilization, such as hospitalizations and emergency department (ED) visits, in immigrant people with IBD compared to non-immigrants. This may be even higher from preconception to postpartum due to heightened provider and patient concerns, though this remains to be confirmed.

Aims
To characterize differences in health-care utilization from preconception to postpartum amongst immigrant and non-immigrant women with IBD.

Methods
We accessed administrative databases to identify women (age 18-55) with IBD with a singleton pregnancy between 2003-2018. Immigration status was defined as recent (ampersand:003C 5 years of date of conception), remote (ampersand:003E5 years since date of conception), and none. Differences in ambulatory, ED, hospitalization and endoscopic visits during 12-months preconception, pregnancy and 12-months postpartum were characterized. World region of immigration origin was also ascertained. Adequate prenatal care was defined by using the validated R-GINDEX which assesses the date of first prenatal visit and total number of prenatal visits. Multivariable negative binomial regression was used to report adjusted incidence rate ratios (aIRR) and modified Poisson regression with quasi-likelihood models and robust error variance procedures were used to report adjusted relative risks (aRR) with 95% confidence intervals (95% CI).

Results
8880 pregnancies were included, 8304 in non-immigrants, 96 in recent immigrants, 480 in remote immigrants. Compared to non-immigrants, recent immigrants had the highest rates of IBD-specific ambulatory visits during preconception (aIRR 3.06, 95% CI, 1.93-4.85), pregnancy (aIRR 2.15, 95% CI, 1.35-3.42), and postpartum (aIRR 2.21, 1.37-3.57) and the greatest rates of endoscopy visits during preconception (aIRR 2.69, 95% CI, 1.64-4.41) and postpartum (aIRR 2.01, 95% CI, 1.09-3.70). There were no differences in ED and hospitalization visits between groups. Compared to non-immigrants, immigrant women were much less likely to have a first trimester prenatal visit (remote: aRR 0.78, 95% CI, 0.65-0.93; recent: aRR 0.61, 95% CI, 0.42-0.88) or receive adequate prenatal care (remote: aRR 0.67, 95% CI, 0.46-0.98; recent: aRR 0.46, 95% CI, 0.22-0.96). Those immigrating from the Americas, Africa, or the Middle East were the most likely to be hospitalized during pregnancy, have a postpartum endoscopy visit, and receive inadequate prenatal care.

Conclusions
There remain significant disparities in health-care utilization amongst immigrant women with IBD from preconception to postpartum. Health policy endeavors are required to provide standardized and equitable care to all women with IBD during these otherwise high risk periods.

Funding Agencies
CCC, CIHR
A274 COVID-19 INFECTION RISK BETWEEN VACCINATED PATIENTS WITH ULCERATIVE COLITIS AND CROHN’S DISEASE : A RETROSPECTIVE COHORT STUDY IN TAIWAN
Authors: WU Y , Chou J 
Published: February 2024

Abstract

Background
The effectiveness of coronavirus disease 2019 (COVID-19) vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with inflammatory bowel disease (IBD) is well established, but it is not clear whether patients with ulcerative colitis (UC) and Crohn’s disease (CD) have different risks of COVID-19 infection after vaccination.

Aims
The aim of this study was to compare the risk of COVID-19 infection after vaccination in patients with UC and CD. Moreover, we also investigated risk factors related to COVID-19 infection and collected data on any adverse events and disease symptoms.

Methods
We conducted a retrospective cohort study in adult IBD patients who had received at least two doses of COVID-19 vaccination and compared the prevalence of infection between UC patients and CD patients using the medical records of China Medical University Hospital between 1 January 2020 and 31 March 2023. All data management and odds ratios calculations were performed using version 9.4 of SAS software (SAS Institute, Cary, NC, USA).

Results
Total 169 IBD patients (96 with UC, 73 with CD) were included in this study. UC patients were older than CD patients (44.92±13.72 vs. 37.27±15.27 years, p=0.0008)(Table 1). A high proportion were male (IBD 70.41%; UC 65.63%, and CD 76.71%). Most (57.4%) received three doses of COVID-19 vaccines. Azathioprine, steroid, and mesalazine medication histories were different between the groups (pampersand:003C0.05). COVID-19 infection prevalence was 49.11% (UC 56.25%, CD 39.73%; p=0.0333) (Figure 1). Logistic regression analysis suggested UC patients had an odds ratio of 1.95 (95% CI=1.05-3.62) and adjusted odds ratio of 2.78 (95% CI=1.20-6.44) for COVID-19 infection compared to CD patients, indicating a 1.95-fold to 2.78-fold higher risk (Figure 2). There was a trend towards a decreasing risk of COVID-19 infection with increasing number of vaccine doses. Medication was not identified as a risk factor. (Figure 3)

Conclusions
Our study identified a greater risk of COVID-19 infection in vaccinated patients with UC than those with CD. However, most patients who became infected with COVID-19 did not have severe symptoms and only one case was hospitalized. The mortality rate of COVID-19 in IBD patients is not specifically higher than the general population. Supporting the view that SARS-CoV-2 vaccination is effective in patients with IBD.
Odds ratios (95% confidence interval) for logistic regression model predicting COVID-19 infection among vaccinated IBD patients

Figure 1. The medications used before COVID-19 infection between vaccinated patients with ulcerative colitis (UC) and Crohn’s disease (CD).
Figure2. The prevalence of COVID-19 infection between vaccinated patients with ulcerative colitis (UC) and Crohn's disease (CD).
Figure 3. The symptoms after COVID-19 infection between vaccinated patients with ulcerative colitis (UC) and Crohn's disease (CD).

Funding Agencies
None