bluuebunny/crossref_metadata_2025_split huggingface dataset:
A164 PATTERNS IN MEDICAL THERAPY AND CLINICAL OUTCOMES IN PATIENTS WITH CONCOMITANT INFLAMMATORY BOWEL DISEASE AND PRIMARY SCLEROSING CHOLANGITIS: A SINGLE CENTRE RETROSPECTIVE ANALYSIS
Authors: Donaldson K , Mitchell R A , Enns R A , Bressler B , Rosenfeld G , Leung Y , Ramji A , Ko H 
Published: March 2021

Abstract

Background
Inflammatory bowel disease (IBD) in patients with primary sclerosing cholangitis (PSC) is characterized by pancolitis with rectal sparing and is associated with an increased risk of colorectal and biliary malignancies. Currently, pharmacologic management of IBD in the setting of PSC is the same as in IBD alone.

Aims
To assess patterns in medical therapy, and incidence of adverse outcomes in patients with concomitant IBD and PSC.

Methods
A retrospective review was conducted on all PSC-IBD patients followed between January 2010 and June 2018. The Endoscopic Mayo Score was used to grade IBD severity in PSC-ulcerative colitis (UC).

Results
69 patients were identified, 44 (63.8%) were male. The mean ages of IBD and PSC diagnosis were 28.6 (SD 14.9) and 37.0 (SD 18.9) years, respectively. The median length of follow up was 12 (range 2–49) years. 52 (75.4%) patients had UC, and 17 (24.6%) had Crohn’s disease (CD). 28 (87.5%) PSC-UC patients had pancolitis, and 4 (12.5 %) had proctitis. Among those with pancolitis, 8 (28.6%) had relative rectal sparing. 4 (14.3%) patients had more severe inflammation proximally, whereas only 1 (3.6%) had more severe distal inflammation. 23 (82.1%) patients had the same degree of inflammation throughout. 14 (93.3%) PSC-CD patients had colitis/ileocolitis and 1 (6.7%) had ileitis. Among those with PSC-UC, 16 (50.0%), 12 (37.5%), and 4 (12.5%) patients had grade 1, 2, and 3 disease, respectively. 62 (89.9%) PSC-IBD patients were treated with aminosalicylates, and 26 (37.7%) with biologics at some point in their IBD course. 26 (37.7%) were treated with aminosalicylates alone. 4 (5.8%) did not require any IBD therapy. Cholangiocarcinoma, colorectal cancer, and gallbladder cancer developed in 8 (11.6%), 1 (1.4%), and 1 (1.4%) PSC-IBD patients, respectively. 16 (23.2%) patients required partial or total colectomy. Indication for surgery was inflammation or stenosis, dysplasia, and neoplasia in 13 (81.3%), 2 (12.5%), and 1 (6.3%) patients, respectively.

Conclusions
The majority of this cohort had UC with mild disease activity. Pancolitis was common, with frequent rectal sparing and more severe right-sided inflammation. Despite the predominance of low-grade colitis, a large portion of patients required treatment with biologics. The incidence of adverse outcomes underscores the need for strict adherence to recommended surveillance practices. Low grade endoscopic activity, typical of the quiescent IBD course in PSC-IBD, may mask low grade histologic inflammation, which in turn may contribute to the increased risk of colonic neoplasia. Further studies are needed to determine the best management strategy for IBD in patients with PSC.

Funding Agencies
None
A171 FACTORS OF SOCIAL PARTICIPATION IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE
Authors: Su S , Marrie R , Bernstein C N 
Published: March 2021

Abstract

Background
Inflammatory bowel disease (IBD) including Crohn’s disease (CD) and ulcerative colitis (UC) imposes a significant burden on health-related quality of life, particularly in social domains. We sought to investigate the factors that limit social participation in patients with IBD.

Aims
Our first aim was to identify if active IBD symptoms had an effect on an objective measure of social participation. Our secondary aim was to determine if psychiatric comorbidity and/or active psychiatric symptoms in IBD patients had an influence on social participation.

Methods
We assessed a cohort of 239 Manitobans with IBD. We collected sociodemographic information, medical comorbidities, disease phenotype, symptom activity and psychiatric comorbidity (using the Structured Clinical Interview for DSM-IV). Participants completed the 8-item Ability to Participate in Social Roles and Activities questionnaire, which assesses participation restriction, including problems experienced in social interaction, employment, transportation, community, social, and civic life.

Results
Poorer social participation score were associated with earning less than average income (p&lt;0.001), being unemployed (p&lt;0.001), actively smoking (p=0.006), higher symptom scores, and having an increasing number of chronic medical conditions (R= -0.296). History of depression (p&lt;0.001) and anxiety (p=0.001) and having active depression (p&lt;0.001) and anxiety (p=0.001) all predicted poor social participation scores. Patient’s with UC on 5-ASA (PO/PR) seem to have higher social participation than other therapies. Phenotype was not predictive. Based on multivariate linear regression analysis, 38.8% of variability in social participation was explained by medical comorbidity, psychiatric comorbidity, psychiatric symptoms, and IBD related symptoms.

Conclusions
The factors that predict social participation by IBD patients include income, employment, smoking, medical comorbidities, IBD symptom burden, and psychiatric comorbidities. Multivariate linear regression suggests that the most relevant factors are medical comorbidity, psychiatric comorbidity, psychiatric symptoms, and IBD symptoms.

Funding Agencies
CIHRCrohn’s and Colitis Canada
A187 ASSOCIATION OF IL-17 INHIBITOR TREATMENT WITH NEW OR WORSENING INFLAMMATORY BOWEL DISEASE: A CASE SERIES
Authors: Liu J , Aruljothy A , Narula N , Marshall J 
Published: March 2021

Abstract

Background
Interleukin 17 (IL-17) inhibitors, monoclonal antibodies that target IL-17A (secukinumab, ixekizumab) or the IL-17 receptor (brodalumab), are effective treatments for patients with psoriasis (PsO), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). IL-17A inhibitors are rarely associated with new or worsening inflammatory bowel disease (IBD), with an estimated incidence rate of 1.1/1000 patient-exposure years in Crohn’s disease (CD) and 1.0/1000 patient-exposure years in ulcerative colitis.

Aims
Describe 3 patients treated with IL-17 inhibitors who developed IBD.

Methods
Case series.

Results
Case 1: 50 year-old male with PsO developed bloody diarrhea after 2 months of ixekizumab therapy. Colonoscopy showed proctitis with a cobblestone appearance and anal ulceration. He failed topical 5-ASA and repeat colonoscopy 1 month later showed chronic inflammatory changes in the transverse colon and rectum. Patient was hospitalized for a right colonic perforation requiring hemicolectomy and loop ileostomy. Pathology showed mucosal ulcerations with acute transmural inflammation of the cecum, ascending colon, and ileum, with crypt architectural distortion and no granulomas. Colonoscopy 6 months later showed chronic mild patchy active colitis with granulomas. Infliximab and methotrexate were started with clinical remission of his CD and partial response of his PsO.
Case 2: 39 year-old male with AS who failed golimumab and etanercept started on secukinumab, and reported acute worsening of diarrhea and abdominal pain. Colonoscopy after a year of persistent symptoms showed ulceration of the ileum and ileocecal valve. Biopsies showed mild active chronic ileitis, and architectural distortion with reactive lymphoid follicles in the right colon. He was treated with adalimumab with partial clinical response of his CD and AS.
Case 3: 63 year-old female with PsA reported a 3 week history of diarrhea, abdominal pain, and fever. She was maintained on ixekizumab for 4 months and previously failed adalimumab, secukinumab, and etanercept. CT showed diffuse circumferential pancolonic wall thickening and terminal ileal involvement. Stool cultures and C. difficile were negative. CRP was 154.9 mg/L and fecal calprotectin was 1710 mcg/g. Colonoscopy showed patchy erythema and aphthous ulcers in the colon. Terminal ileal biopsies showed crypt architectural distortion and patchy acute inflammation. She started on infliximab therapy. Her diarrhea resolved prior to treatment, with no clinical improvement of her arthritis.

Conclusions
IL-17 inhibitors are effective in the treatment of PsO, PsA, and AS, however, in all cases described, it is unclear whether IL-17 inhibition led to new-onset IBD, or an exacerbation of previously asymptomatic IBD. Patients being considered for IL-17 inhibition with baseline gastrointestinal symptoms should be investigated for IBD.

Funding Agencies
None
A190 ATP-INDUCED INFLAMMASOME ACTIVATION GENERATES MITOCHONDRIAL ROS PRODUCTION IN MACROPHAGES
Authors: Bording-Jorgensen M , Armstrong H , Wine E 
Published: March 2021

Abstract

Background
The etiology of Inflammatory Bowel Diseases is unknown; however, a dysfunctional immune response has been well characterized. The role of the NLRP3 inflammasome in IBD is controversial with both beneficial and detrimental results. This pathway is required for the secretion of the proinflammatory cytokine IL-1β. Extracellular ATP is a well characterized inflammasome activator, which we have previously shown can increase the ability of J774A.1 macrophages to clear the mouse pathogen Citrobacter rodentium in an in vitro environment through the generation of reactive oxygen species (ROS).

Aims
Our objectives were to determine: 1) if extracellular ATP was inducing mitochondrial stress, causing the production of ROS, leading to microbial death; and 2) what effects these activated macropahges have on naïve macrophages.

Methods
Murine macrophage J774A.1 cells were infected with C. rodentium; extracellular ATP was added as an inflammasome activator and YVAD as an inhibitor. Lysotracker red and MitoSOX were used to determine cellular location of bacteria and quantify mitochondrial ROS, respectively. Secreted cytokines were measured using ELISA and a proteome profiler, ROS was measured using DCFDA, Gasdermin D and Caspase 11 activities were determined by Western Blot. Supernatants taken from infected macrophages were filtered and then added to naïve macrophages during infection with C. rodentium.

Results
Activation of mitochondrial ROS by ATP was found to be independent of infection. Secreted cytokines sICAM-1, MIP-1α, and MCP-2 were all increased by ATP but not inhibited by YVAD. Cleavage of Gasdermin D was increased with the addition of ATP but not inhibited by YVAD whereas Caspase 11 was unchanged between treatments. Supernatants from ATP-induced macrophages were able to induce IL-1β secretion in naïve macrophages and increase bacterial killing.

Conclusions
Mitochondrial ROS production in response to extracellular ATP may be involved in the decrease of bacterial survival. ATP induces the secretion of cytokines, chemokines, and other factors that affect newly infected macrophages. Gasdermin D cleavage, independent of caspase 11, suggests that a noncannonical pathway is activated; this may explain the lack of pyroptotic cells in our study. In addition, we have shown that these macrophages are able to illicit the same behavior in naive macrophages, suggesting that a corrected dysfunctional pathway in macrophages can have beneficial effects downstream. Understanding how the NLRP3 inflammasome is activated and what the downstream pathways are may lead to potential therapies for inflammatory conditions, including IBD.

Funding Agencies
CCC, CIHR
A191 TEN YEARS FOLLOW UP OF EARLY ONSET INFLAMMATORY BOWEL DISEASE PATIENTS- A SINGLE CENTER RETROSPECTIVE COHORT STUDY
Authors: Eindor A , Meleady L , Alam L , Gena K , Hamilton Z , Lawrence S , Jacobson K 
Published: March 2021

Abstract

Background
Early onset inflammatory bowel disease (EOIBD) and Very early onset inflammatory bowel disease (VEOIBD) prevalence has been increasing over the last decades. These young patients have been known to have special disease characteristics and disease location. Although it is known that only a low percentage of these patients require biologic treatment after diagnosis, there is only scarce evidence about their long- term outcome and biologic requirements.

Aims
To assess the ten year outcome of early onset and very early onset IBD patients.

Methods
We retrospectively reviewed IBD patients diagnosed under 10 years of age, between January 2005 and December 2009, from the British Columbia (BC) Pediatric IBD database. Disease characteristics and symptoms at diagnosis were documented. The disease location and severity at diagnosis were documented according to the Paris classification. Data collected retrospectively included a ten year treatment follow up period, number of hospitalizations, corticosteroid courses and surgeries. These parameters were documented at three time points: after the first year, after five years and ten years.

Results
68 patients under the age of 10 were diagnosed with IBD during the study period. 2 patients failed to meet inclusion criteria and were excluded. Median age at diagnosis was 6.06 (IQR 4.5–8.6). 47.7% of patients had Crohn’s disease and 71.2% were males. 63 patients completed the 5 year follow up, and 52 the 10-year period due to lack of follow up or transfer to adult care. After the first year of follow up 0% patients in the VEOIBD group and 5% patients in the EOIBD group were treated with biologic treatment, whereas after the 10-year period 42.3% and 29.6% of patients were treated with biologic therapy respectively (p=0.282). Overall, 4 patients underwent colectomy and 2 a small bowel resection.

Conclusions
Although the percentage of VEIBD and EOIBD patients receiving biologic treatment after ten years is higher than after the first year, it is still lower than what is reported in the literature in older pediatric IBD patients and adults.

Funding Agencies
None
A193 DGAT1 DEFICIENCY WITHOUT DIARRHEA
Authors: Desai L , Friesen M , Stoffman S , Galante G 
Published: March 2021

Abstract

Background
Acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) catalyzes the final step in triglyceride (TG) synthesis and is highly expressed in enterocytes (EC). DGAT1 deficiency (DGAT1D) is a rare autosomal recessive protein losing enteropathy (PLE) classified as a congenital diarrheal disorder (CDD). Presumably, fat ingestion causes accumulation of DGAT1 substrates within the EC causing lipotoxicity-induced EC dysfunction and death.

Aims
Report a presentation of DGAT1D atypical for a CDD.

Methods
We present an infant with DGAT1D with protracted emesis and failure to thrive (FTT) in the absence of diarrhea despite enteral nutrition with varied fat containing formulas (FCF).

Results
A male infant presented with emesis and FTT requiring multiple admissions. He was initially diagnosed with cow’s milk protein allergy due to concurrent bloody stools, which resolved with hypoallergenic formula. Reportedly watery stools when exclusively breastfed became formed following switch to formula at 2 weeks of age. Interestingly, he subsequently required intermittent suppositories. However, emesis and malnutrition progressed, refractory to omeprazole, baclofen, and varied hypo- and non-allergenic FCF (all containing &gt;0.02g/ml fat, mixtures of medium and long chain FA). He had persistently low serum albumin, ceruloplasmin, and IgG, but SA1AT was normal. TGs were normal, although not measured on FCF. Low fecal elastase (FE) normalized after nutritional support but sweat chloride was intermediate. CFTR sequencing revealed CFTR mutations S466X and R1070 in cis. TPN was started for severe malnutrition at 2 months. Emesis resolved while fasted or receiving enteral electrolyte solution.
Endoscopic biopsies on FCF showed increased lamina propria cellularity, no villous abnormalities in the duodenum, chronic inflammation in the gastric body, and normal colonic mucosa. Whole exome sequencing at 2 months showed homozygous c.838C&gt;T (p.Arg280Ter) mutations in DGAT1, explaining his clinical presentation and biochemical features of PLE. After diagnosis, he was started on Tolerex® formula (fat = 0.017g/ml), which was tolerated.

Conclusions
DGAT1D is classified as a CDD, with vomiting often reported. This case describes a unique presentation of this rare condition, with emesis the predominant symptom, and notable constipation, demonstrating the variable phenotype of this condition. Fat malabsorption may contribute to constipation by altering viscosity of luminal contents or activating the ileal brake. Thus, DGAT1D should be considered on the differential for congenital PLE, even without diarrhea.
This case also demonstrates the limitations of stool testing in DGAT1D as random SA1AT concentrations may not reflect A1AT clearance in the diagnosis of PLE. Low FE has been detected in children with malnutrition or dietary restriction and has been reported in DGAT1D, where it likely represents a physiologic consequence of FTT.

Funding Agencies
None
A194 A POSSIBLE ASSOCIATION BETWEEN SECUKINUMAB AND NEW-ONSET INFLAMMATORY BOWEL DISEASE: A CASE SERIES
Authors: Sarker A , Shukla T , Rostom A , Sim J , McCurdy J D 
Published: March 2021

Abstract

Background
Secukinumab is a monoclonal antibody targeting interleukin-17A and is commonly used for managing autoimmune diseases such as, psoriasis, psoriatic arthritis, and ankylosing spondylitis. Prior studies have suggested that anti-IL17 therapy may worsen symptoms in patients with pre-existing inflammatory bowel disease (IBD). However, it remains unclear if secukinumab is associated with new-onset IBD or in provoking a flare of previously quiescent IBD.

Aims
We evaluated patients referred to our IBD clinic who developed intestinal inflammation after starting secukinumab for the management of autoimmune diseases.

Methods
We performed a retrospective, observational study at a single tertiary care center between 2017 and 2020. Patients referred to our IBD clinic who developed intestinal inflammation after starting secukinumab were included. We excluded patients with an established pre-existing diagnosis of IBD and patients who had positive stool testing for infectious organisms. Patient demographics, disease characteristics, distribution of intestinal inflammation and clinical outcomes were assessed. The pathology slides were reinterpreted by a single pathologist with a specialty in gastroenterology to determine the histologic characteristics of the inflammation.

Results
A total of 8 patients developed gastrointestinal symptoms after starting secukinumab: 4 (50%) males with a median age of 42.5 (IQR: 35–50 years old). Secukinumab was initiated for psoriasis in 3 (37.5%) patients, psoriatic arthritis in 2 (25%) patients, ankylosing spondylitis in 2 (25%) patients and juvenile idiopathic arthritis in 1 (12.5%) patient. The median time of onset for gastrointestinal symptoms after starting secukinumab was 7 months (IQR: 4–15 months). Of the patients who underwent testing for inflammatory biomarkers, the median CRP was 25.5 (IQR 25.4–34.2). Endoscopic disease distribution involved the colon in 5 (62.5%) patients and the ileum and colon in 3 (37.5%) patients. In this series of patients, the histologic characteristics demonstrated three patterns of colitis: IBD-like (ulcerative colitis or Crohn’s disease) in 6 (75%) patients based on mucosal granulomas and/or chronic inflammatory changes, MMF-like histology in 1 (12.5%) patient, characterized by an abundance of intraepithelial eosinophils in the lamina propria and numerous crypt apoptotic bodies, and finally active colitis in 1 (12.5%) patient characterized by an absence of chronic mucosal injury or granulomas. The treatment for these patients was cessation of secukinumab and initiating alternative therapies with close clinical monitoring.

Conclusions
In this small case series, Secukinumab was temporally associated with the development of gastrointestinal inflammation. Further larger studies are required to confirm this association and to determine if IL-17 contributes to the pathogenesis of IBD.

Funding Agencies
None
A199 SEVERE COLITIS FOLLOWING PELVIC RADIOTHERAPY: CASE REPORT AND REVIEW OF THE LITERATURE
Authors: Gozdzik M , Murthy S 
Published: March 2021

Abstract

Background
Mild-to-moderate proctocolitis is a well-known complication of pelvic radiation therapy, occurring in 43% and 6% of patients following external beam radiotherapy (EBRT) and brachytherapy (BT), respectively. This typically presents as recurrent painless rectal bleeding, diarrhea, urgency, and/or iron-deficiency anemia. Severe ulcerating proctocolitis is a less common complication of pelvic radiotherapy and is rare following BT. We report two cases of severe ulcerating proctocolitis mimicking inflammatory bowel disease (IBD) following pelvic radiotherapy in patients without known IBD, including an elderly male undergoing EBRT, and an elderly female undergoing vaginal vault BT.

Aims
To describe two cases of severe ulcerating proctocolitis, mimicking IBD, following pelvic radiotherapy.

Methods
Case descriptions and literature review.

Results
A 71-year-old male without antecedent gastrointestinal disease developed bloody diarrhea 3 months following EBRT for treatment of prostate cancer. Infectious work-up was negative. Blood work showed anemia and an elevated CRP. CT scan showed distal large bowel inflammation concerning for proctocolitis. Flexible sigmoidoscopy revealed severe proctosigmoiditis with circumferential thickening and nodularity of the mucosa and multiple ulcers. Biopsies showed ulcer tissue with fibrinopurulent exudate. He was treated with systemic corticosteroids and symptoms gradually resolved. Repeat colonoscopy 8 months later showed healed inflammation with scarring and residual radiation proctosigmoiditis.
A 74-year-old female without antecedent gastrointestinal disease developed watery diarrhea 2 weeks after initiating low dose vaginal vault BT for treatment of endometrial cancer. Infectious work-up was negative. Blood work showed an elevated CRP and CT scan revealed proctocolitis extending to the descending colon. Flexible sigmoidoscopy revealed severe ulcerating proctosigmoiditis with tram tracks of denuded mucosa. Biopsies showed moderate diffuse chronic active colitis with crypt abscesses and apoptotic bodies. She was treated with systemic corticosteroids followed by infliximab and methotrexate, with mild symptomatic improvement. However, repeat endoscopy revealed persistent severe ulceration. Unfortunately, she developed a sigmoid perforation with pelvic abscess, leading to bacteremia and fungemia, and subsequently passed.

Conclusions
While rare, severe ulcerating proctocolitis mimicking IBD can occur following pelvic radiotherapy, including BT. The decision to manage these patients as IBD using immunosuppressive therapy should be weighed against the risks of these therapies, considering a patient’s age and underlying health, and in collaboration with a patient’s health care team. Careful assessment for risk factors and pathological findings from biopsy specimens may help in predicting the likelihood of IBD in such patients.

Funding Agencies
None