bluuebunny/crossref_metadata_2025 huggingface dataset:
A91 ECONOMIC EVALUATION OF A FECAL MICROBIOTA TRANSPLANTATION PROGRAM FOR RECURRENT CLOSTRIDIOIDES DIFFICILE INFECTION IN ALBERTA
Authors: Yang D Y , Mullie T , Sun H , Russell L , Roach B , Wong K , Zhang W , Kao D H
Published: March 2021

Background

Fecal microbiota transplantation (FMT) is the most effective therapy for recurrent C. difficile infection. Although studies using statistical modeling have shown FMT to be cost-effective, real-world data is lacking.

Aims

To assess the impact of FMT program on the healthcare cost of recurrent C. difficile infections using real-world data from Alberta’s public healthcare system.

Methods

C. difficile infection patients were identified through provincial laboratory database with positive C. difficile results in Edmonton, Alberta between 2009–16. If an initial positive test was followed by ≧2 positive tests within 183 days, an individual was categorized as recurrent C. difficile infection (RCDI). Otherwise, non-recurrent C. difficile infection (non-RCDI) was assigned. Since the Edmonton FMT program was established in 2013, patients were further divided into pre-FMT (2009–12) and post-FMT (2013–16) eras. This divided patients into four study groups as outlined in Table 1. Administrative data, including inpatient stays, ambulatory or emergency room visits, outpatient prescriptions, and physician billings, were extracted. A cost of $389 was assigned to each FMT procedure to account for cost of donor screening and sample preparation. A difference in differences (DID) approach, a tool which estimates the effect of a treatment by comparing outcome difference between treatment group and control group over time, was used to analyze the impact of FMT program on the cost of RCDI. Non-RCDI patients were used as control group to account for changes in treatment costs over time. Ordinary least squares regression, with log-transformed healthcare cost as the dependent variable, was used for the analysis.

Results

4717 non-RCDI and 548 RCDI patients were identified and divided into the 4 groups (Table 1). RCDI patients were significantly older than non-RCDI patients (71.13 vs 62.49; P < 0.001). After adjusting for differences in age, sex, and baseline healthcare utilization, cost for RCDI patients were significantly lower relative to costs for non-RCDI patients in the post-FMT era. Cost of non-RCDI increased by $5,300.08 between the pre- and post-FMT eras, while the cost of RCDI decreased by $7,654.92 in the same time frame (Table 2). FMT program was estimated to have saved $12,954 annually for RCDI patients at mean age, sex, and baseline cost of our overall sample.

Conclusions

Our data suggest that the healthcare cost of RCDI has decreased with the introduction of an FMT program.

Funding Agencies

Alberta Health Services, University of Alberta Hospital Foundation
A128 ACUTE GASTRIC VOLVULUS DISGUISED AS ACUTE CORONARY SYNDROME.
Authors: Lee J G , Nap-Hill E , Bressler B
Published: March 2021

Background

Acute gastric volvulus is a rare but potentially life-threatening condition that warrants emergent assessment. Its clinical presentation may encompass the Borchardt’s triad of vomiting, epigastric pain, and inability to insert a nasogastric tube. However, it can also present as chest pain and is often not cited within the typical differential diagnosis of non-cardiac causes of chest pain. We report the first known case of mesenterico-axial gastric volvulus presenting as acute coronary syndrome with a normal electrocardiogram, complete with radiographic and endoscopic images.

Aims

To present a case of acute gastric volvulus disguised as an acute coronary syndrome and describe its management.

Methods

Case report and review of literature.

Results

A 68 year-old female with history of recent coronary artery bypass graft surgery presented to hospital with sudden onset chest pain radiating to her left shoulder and jaw while having dinner. Initial high sensitivity troponin (normal <9ng/L) was 15ng/L, which increased to a modest peak at 115ng/L. ECG at presentation and through admission consistently showed normal sinus rhythm x 5. She was assessed by Cardiology and given her rising troponin and chest pain, she was treated as a non-ST elevation myocardial infarction with dual antiplatelet therapy. She underwent cardiac catheterization showing distal graft anastomotic site stenosis and was stented x2. Post procedure, her severe retrosternal chest pain recurred. GI was consulted for dysphagia and odynophagia, which was then noted to be present concurrent with her initial chest pain presentation.

An urgent CT scan of the abdomen and pelvis revealed acute mesenterico-axial gastric volvulus (Figure 1A), a rarer form of gastric volvulus in the adult population compared to its organo-axial counterpart. After a failed nasogastric decompression, an emergent upper endoscopy was attempted and demonstrated mucosal necrosis (Figure 1B) but was unsuccessful in relieving the volvulus. The patient then underwent overnight surgery, which showed gastric volvulus with contained perforation and 50% necrosis of the stomach with sparing of the cardia and antrum. This resulted in a subtotal gastrectomy, hiatus hernia repair, pyloromyotomy, jejunostomy, and bilateral chest tube insertion. She then recovered in ICU before being successfully discharged home from hospital.

Conclusions

Acute gastric volvulus can present while disguised as more common causes of chest pain, such as acute coronary syndrome. Those who present with chest pain who also have a history of a large hiatal hernia, or an intrathoracic stomach should be evaluated with gastric volvulus in the differential diagnosis as its prompt management is critical to reduce morbidity and mortality.

Funding Agencies

None
A129 VIDEOCAPSULE ENDOSCOPY RETENTION: WHAT ARE THE RISK FACTORS?
Authors: Li Fraine S , Langevin C , Mahdi N , Bouin M
Published: March 2021

Background

The most feared complication of videocapsule endoscopy (VCE) is retention in the intestine. It is estimated to occur in 1.4% of cases but the risk factors are not well known.

Aims

To determine the prevalence of VCE retention at a tertiary care centre as well the associated risk factors.

Methods

Retrospective study between 2016 and 2019. All patients at a tertiary care centre undergoing VCE were recruited. The patients with an incomplete endoscopy report or who were unable to complete VCE were excluded. Clinical and endoscopic information was compiled from patients’ medical charts as well as the indications and results of the endoscopic procedure. VCE retention, evaluated by radiography or CT scan, was defined as persistence of the videocapsule in the gastrointestinal tract for ≥14 days or the need for an intervention for removal.

Results

In total, 126 patients underwent VCE (average age: 66±16, 52% female). There was 6% of patients with Crohn’s disease, and 40% of patients had a previous abdominal surgery. The indications for endoscopy were: iron deficient anemia (48%), gastrointestinal bleeding (32%), suspicion/follow up of IBD (10%), and other (11%). The VCE findings (n=146) were: angiodysplasia (30%), inflammation (30%), normal (20%), polyp (5%), and other (15%). 77% of results were not previously found by conventional endoscopy or imaging. The prevalence of VCE retention was 1.6%. The patient risk factors for retention were Crohn’s disease (OR 19.67; 95CI 1.09–354.11; p<0.05) and corticosteroid use in the previous 2 weeks (OR 19.67; 95CI 1.09–354.11; p<0.05). There was no risk of retention associated with ulcerative colitis, sex, abdominal surgery, or opioid use. The finding of stenosis on VCE was associated with an increased risk of retention (OR 123; 95% CI 4.11-3683.43; p<0.01).

Conclusions

VCE retention remains a rare complication. There is increased risk of retention in patients with known Crohn’s disease or recent use of corticosteroids.

Funding Agencies

None
A138 ENDOSCOPIC SUBMUCOSAL DISSECTION FOR BARRETT’S NEOPLASIA IN A NORTH AMERICAN ACADEMIC CENTRE
Authors: Motomura D , Bechara R
Published: March 2021

Background

Endoscopic submucosal dissection (ESD) is carving out an increasing role in the treatment of Barrett’s associated neoplastic lesions. Though endoscopic therapy is classically performed with endoscopic mucosal resection (EMR) and radiofrequency ablation (RFA), ESD provides the advantage of en-bloc resections, and greater R0 resection rates, which are defined as negative deep and lateral margins on histology.

Aims

Our aim is to present procedural outcomes and subgroup analysis from one of the largest single centre cohorts of esophageal ESD in North America, and the first from Canada.

Methods

All patients undergoing esophageal ESD for Barrett’s neoplasia between Oct 2016 and June 2020 at a single tertiary care centre in Canada were included in the cohort. Demographic, procedural data and lesion characteristics are presented. Subgroup analysis was performed on patients who underwent extensive resection (≥75% of esophageal circumference) and patients who developed strictures. Statistical analysis included chi square testing on categorical variables and unpaired t-test for continuous variables. Binomial univariable logistic regression was performed to investigate factors associated with stricture formation.

Results

Thirty-four patients underwent esophageal ESD for Barrett’s associated neoplasia during the study period. The median lesion diameter was 5.7 cm (IQR 4.2 -7.5) and median procedure time 129 min (IQR 66–200). The en-bloc resection rate was 97%, and the R0 resection rate was 91%. Curative resection was achieved in 82% of patients. Upstaging from the pre-resection biopsy to post-ESD histology occurred in 59% of cases. Two adverse events occurred (1 delayed bleed, 1 aspiration event). There were no perforations. Procedural outcomes were similar between patients with extensive resections, but patients with ≥75% circumferential resection developed more strictures (65% vs 13%, p=0.001). Stricture formation was associated with extensive resection (OR 15.4, 95%CI[2.50 - 95.01]) and longer lesion diameter (OR 1.73, 95%CI [1.11 - 2.70]).

Conclusions

Our experience with ESD for Barrett’s related neoplasia shows excellent en-bloc and R0 resection rate, and provides more accurate histological specimens. Curative resection is possible in the vast majority of cases, including those with extensive resections. Further investigation into stricture prophylaxis will be useful as larger resections are attempted.

Funding Agencies

None
A153 RECURRENT HENOCH-SCHONLEIN PURPURA FOLLOWING TREATMENT WITH ADALIMUMAB
Authors: Stallard L , Church P
Published: March 2021

Background

Anti Tumour Necrosis Factor-α agents have revolutionised the management of inflammatory bowel disease. Cutaneous adverse events complicate therapy in up to 20% of cases. Most reactions are mild and do not warrant a change of therapy. Henoch–Schönlein purpura (HSP) has rarely been associated with anti-TNFα therapy. It is an acute vasculitis of small vessels that presents with cutaneous purpura of the lower limb, arthritis, nephritis and gastrointestinal involvement.

Aims

To describe the clinical course of a 16-year-old male presenting with recurrent HSP secondary to adalimumab for treatment of inflammatory bowel disease

Methods

A retrospective chart review of the patient’s electronic medical record.

A literature review of the relevant medical literature.

Results

History

16 year old boy with Crohn’s disease, initial induction with exclusive enteral nutrition and maintained on adalimumab monotherapy since May 2017. Adalimumab initially 40 mg every 2 weeks, increased to every 10 days in September 2019 due to loose stool and mild inflammation throughout the colon on reassessment colonoscopy.

Four separate incidences of purpuric rashes occurring 2–3 days after receiving adalimumab between November 2019 and July 2020. Purpura and petechiae of the lower limb with associated swelling of the feet and heel pain consistent with HSP. Purpura resolved within 1 to 3 weeks, treated with oral steroids on 1 occasion. First episode occurred following increase in dose frequency to every 10 days. Adalimumab frequency was further increased to every 7 days in March 2020. Following this he had 3 further HSP episodes.

There was no history of preceding illness or other clear inciting event for HSP.

Physical Exam

Scattered petechiae on the lower limb bilaterally with large palpable purpura to his feet. Mild swelling to the right foot with tenderness to heel on palpation. Nil other joint swelling. No petechiae elsewhere.

Investigations

Urinalysis showed trace blood, no proteinuria. Mildly elevated CRP and ESR. Fecal calprotectin elevated >1800.

Clinical Progress

Rheumatology and Dermatology were consulted. Due to recurrent HSP and active luminal Crohn’s disease on repeat colonoscopy, adalimumab was discontinued and he started Ustekinumab September 2020. There has been no recurrence of relapsing rash and joint pains.

Conclusions

Four previous cases of HSP associated with Adalimumab have been described, three with Crohn’s disease and 1 with Ulcerative Colitis. Cutaneous manifestations occurred within 18 months of treatment in all previously reported cases. Our patient was treated with Adalimumab for 30 months prior to his first episode of HSP. This association with HSP is not unique to adalimumab, extending to other members of the anti TNFα class including infliximab and etanercept. Hypothesized mechanisms include antibody production, eosinophil activation, shifts in T cell responses and direct drug toxicity to vessel walls.

Funding Agencies

None
A157 REAL-WORLD TIGHT OBJECTIVE MONITORING WITH ADALIMUMAB LEADS TO EARLIER DOSE OPTIMIZATION AND HIGHER CLINICAL REMISSION RATES AT 12 MONTHS.
Authors: Xiao Y , Al Khoury A , Golovics P , Kohen R , Afif W , Wild G , Friedman G , Galiatsatos P , Hilzenrat N , Szilagyi A , Wyse J , Cohen A , Bitton A , Bessissow T , Lakatos P L
Published: March 2021

Background

Data suggests that tight objective monitoring of inflammatory bowel diseases (IBD) may improve one-year clinical outcomes.

Aims

The goal of this study is to assess the adherence to serial tight objective monitoring, via clinical symptoms and biomarkers, and the effect of such tight monitoring on one year outcome in IBD patients at an academic and an university-affiliated center.

Methods

We retrospectively reviewed the chart of 428 consecutive IBD patients who started adalimumaby at the McGill University Health Center and Jewish General Hospital (Montreal, Canada) between January 1, 2015 and January 1, 2019 [338 Crohn’s disease(CD), 90 ulcerative colitis(UC)]. Clinical symptoms (assessed by Harvey-Bradshaw-Index and partial Mayo), C-Reactive Protein(CRP), and fecal calprotectin(FCAL) were captured at treatment initiation and at 3, 6, 9, and 12 months. Combined adherence was defined as the evaluation of ≥2 of 3 parameters(clinical, CRP, FCAL). Dose optimization and drug sustainability curves were plotted by Kaplan-Meier method.

Results

Clinical symptoms were assessed in nearly all patients at 3 (CD-UC:95-94%), 6 (90-83%), 9 (86-85%) and 12 (96-89%) months. CRP was also available for most patients but the frequency of assessment decreased in CD patients over the study period. In comparison, compliance to serial FCAL testing was low throughout the follow-up period. Clinical remission at one-year was significantly higher in patients who were adherent to early assessment visit at 3 months (p=0.001 both for CD and UC). Adherence to early follow-up also resulted in earlier dose optimisation in both CD and UC patients(pLogrank=0.026 for UC and p=0.09 for CD). However, the overall drug sustainability did not differ.

Conclusions

Clinical assessment and CRP, but not FCAL, were frequently assessed in patients starting adalimumab. Adherence to early objective combined follow-up visits resulted in earlier dose optimization and improved one-year clinical outcomes but did not change drug sustainability rates.

Funding Agencies

None
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

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

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<0.001), being unemployed (p<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<0.001) and anxiety (p=0.001) and having active depression (p<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

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

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

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

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 >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>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

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

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
A205 PEMBROLIZUMAB ASSOCIATED SCLEROSING CHOLANGITIS RESPONDS TO COMBINATION OF STEROIDS AND MYCOPHENOLIC ACID: A CASE REPORT
Authors: Zhao X , Huang R , Chen Y , Deschênes M
Published: March 2021

Background

Pembrolizumab is a check point inhibitor that targets programmed cell death receptor ligand 1 (PD-L1). However, check-point inhibitors are associated with its characteristic adverse event know as immune related adverse events that can affect a myriad of organ systems. In the hepatobiliary system, the most commonly described iRAE is hepatitis/hepatotoxicity and latest oncology guidelines offer recommendations on treatment and followup of immunotherapy related hepatitis (1). However, a more rare presentation of iRAE, that have only been described as case reports or case series, is secondary cholangitis. We report one of such a case.

Aims

Case report

Methods

Case report

Results

The patient is a 55 year-old Caucasian female know for lung adenocarcinoma presented to the emergency room on May 5th, 2020, having received her 8th cycle of pembrolizumab. Her blood works mildly elevated transaminitis; ALT 78 U/L, AST 11 U/L, alkaline phosphate of 130 U/L, and total bilirubin of 3.5 umol/L.

MRI of the abdomen showed a normal appearing liver without focal parenchymal lesion, no biliary stones or obstructing masses, dilated common bile duct at 11 mm with small pericholecystic free fluid, and normal gall badder thickness of 2 mm. There was also notion of minimally prominent intrahepatic biliary radicles seen within the CBD.

Etiology workup of cholestatic transaminitis was negative. A diagnosis of immunotherapy related sclerosing cholangitis was posed and the patient was treated with MMF and prednisone with good response.

Conclusions

Discussion

This patient seems to have developed immunotherapy mediated cholangitis. Liver biopsy when performed in liver injury tend to show lobular hepatitis, with liver parenchyma infiltrated with lymphocytes and focal necrosis with acidophilic bodies. However, there seems to be another, less frequent pattern of injury described with pembrolizumab and associated with cholangiopathy, resembling primary biliary cholangitis. It is characterized with portal tracts enlarged with fibrosis and inflammatory cells infiltration; infiltrating cells are lymphocytes (2). Biliary epithelium with fibrosis with CD8+ T cells infiltration seem to be recurrently reported in case reports. (3, 4).

Other cases have been describe in the literature. In many cases, steroid therapy was attempted, but response rates seem to be inconsistent. Nivolumab related cholangitis have been also been described and characterized by extra hepatic bile duct dilatation along with negative immunological markers such as ANA and IgG4 in patients with non-small cell lung cancer, and seems to respond only moderately to steroid therapy (6). Retrospective data of nivolumab related cholangiopathy seems to suggest that there is favourable response to the combination of MMF and steroid therapy (7).

Funding Agencies

None
A233 AGING AND ESOPHAGEAL MOTILITY: A HIGH-RESOLUTION MANOMETRY STUDY
Authors: Djinbachian R , Marchand E , Yan W , Bouin M
Published: March 2021

Background

Studies have found possible physiologic changes to esophageal motility with aging that are not currently taken into account in routine high-definition esophageal manometry (HDEM) interpretation.

Aims

We aimed to quantify the relationship between these physiologic changes and aging to improve HDEM interpretation.

Methods

We conducted a retrospective analysis of medical records for all patients who underwent HDEM at a tertiary hospital center between January 2015 and December 2019. Inclusion criteria were patients ≥18 years with normal HDEM. Exclusion criteria were abnormal HDEM; abnormal upper digestive endoscopy or imagery. Outcomes were median integrated relaxation pressure (IRP); mean lower esophageal sphincter (LES) pressure; mean distal contractal integral (DCI); mean distal latency (DL); mean peristaltic break (PB) according to the v3.0 Chicago classification criteria. Data was extracted from electronic patient medical records into a database for analysis. Effect of age on outcomes was examined through univariate and multivariate linear regression analysis.

Results

We identified 1917 patients with HDEM and included 790 patients with normal exams [mean age 55.8 yrs (IQR 46 – 66), 64% female]. Indications for HDEM included dysphagia (41.3%); gastroesophageal reflux disease (29.2%); chest pain (11.0%); other (13.3%). There was a statistically significant relationship between age and IRP [Coef=0.08 (95%CI 0.05 – 0.1), p<0.001, R^2=0.04] as well as DCI [Coef=10.9 (95%CI 4.1 – 17.8), p=0.002, R^2=0.01] and DL [Coef=-0.01 (95%CI -0.02 – -0.002), p=0.01, R^2=0.008]. No statistically significant relationship was found between age and LES pressure [Coef=0.03 (95%CI -0.01 – 0.08), p=0.16] or PB [Coef=0.007 (95%CI -0.002 – 0.016), p=0.14]. Multivariate analysis showed statistically significant relationships between IRP and age (p<0.001), BMI (p=0.001), NSAID use (p=0.034), and female sex (p=0.048).

Conclusions

We found that IRP, DCI, and DL are significantly correlated with the normal aging process. Modifications could therefore be considered for normal diagnostic cutoffs for both age extremes to prevent over or under-diagnosis of motility disorders.

Funding Agencies

None
A240 HOME PARENTERAL NUTRITION IN OLDER VERSUS YOUNGER PATIENTS: CLINICAL CHARACTERISTICS AND OUTCOMES
Authors: Daoud D , Cartagena E M S , Somlaw N , Schwenger K , Gramlich L , Armstrong D , Raman M , Duerksen D , Whittaker S , Jurewitsch B , Marliss E , Allard J
Published: March 2021

Background

There is a demographic shift toward older patients receiving home parenteral nutrition (HPN) but there is little data on their clinical characteristics and outcomes versus younger HPN patients.

Aims

The objective of this study was to determine if there are any differences between older (> 60 years) and younger (18–59 years) HPN patients in regard to HPN indications, prescriptions and outcomes over the first 2 years receiving HPN.

Methods

This was a retrospective analysis of prospectively collected data from HPN adult patients entered in the password protected web-based Canadian HPN Registry. New HPN patients enrolled between 2003 and 2017 and receiving HPN for 2 years were selected from 8 participating programs across Canada. Data included demographics, anthropometrics, PN prescriptions, line sepsis events, survival and quality of life based on the Karnofsky Performance Status (KPS).

Results

402 patients met the inclusion criteria: 184 patients were 60 years old or above (older group) and 219 patients were between 18 and 59 years old (younger group). Around 64% of both groups were female. There were no significant differences in the main indications for HPN, body mass index (BMI), and PN prescriptions at baseline. At 2-years, younger patients received more calories from PN than older patients (27.88 vs 19.56 Kcal/kg respectively, p <0.001) but BMI remained comparable between groups. There were less line sepsis in the older group versus the younger group (20% vs 36%, p=0.0023) but 78% of younger patients remained alive versus 69 % in the older group (p=0.0401). In those alive, the proportion of patients remaining on HPN was comparable (older group: 77%; younger; group 81%, p=0.4709) and the proportion of patients with a reasonable quality of life (KPS > 60) was similar (older group: 58%; younger group: 63%, p=0.2156).

Conclusions

Older HPN patients have similar clinical characteristics as younger patients but with reduced line sepsis events and higher 2-year mortality.

Funding Agencies

Ontario Medical Supply, Takeda, Fresenius Kabi and Baxter Inc