bluuebunny/crossref_metadata_2025 huggingface dataset:
A143 ACUTE ESOPHAGEAL NECROSIS: A COMPLICATION OF DIABETIC KETOACIDOSIS
Authors: Mahmood T , Moss K , Spaziani R
Published: March 2021

Background

Acute esophageal necrosis (AEN) is a rare entity associated with diabetic ketoacidosis (DKA). The pathogenesis is thought to be linked to low volume state, microvascular disease, impaired gastric and esophageal motility increasing acid reflex, all rendering the esophagus prone to injury.

Aims

We report a case of AEN as a complication of DKA in a patient without any overt gastrointestinal bleeding (GIB), along with a literature review.

Methods

Keywords “esophageal necrosis” and “diabetic ketoacidosis” were used in MEDLINE and BASE to retrieve English articles reporting cases of AEN in DKA.

Results

A 63 year old male with history of hypertension, dyslipidemia and non-insulin dependent diabetes mellitus presented to Emergency with 5 day history of severe epigastric pain, dysphagia to solids and liquids, nausea and vomiting (without any overt GIB). Most recent HbA1c was 8.4%. His diabetes was managed with metformin and semaglutide. Bloodwork revealed a hemoglobin of 165g/L and leukocytes of 17.9x109/L. Chemistries showed an anion gap of 25 with bicarbonate of 5mmol/L. Venous blood gas showed acidemia (pH=7.02). B-hydroxybutyrate level was 10.2mmol/L. Urinalysis was negative for leukocytes or nitrites. An abdominal CT ruled out bowel obstruction or intra-abdominal infection/abscess as the source of his discomfort but demonstrated circumferential wall thickening of the distal esophagus. No other triggers were found for this patient’s DKA except perhaps a recently started ketogenic diet. After resolution of DKA, he continued to experience severe epigastric pain, reflux symptoms, and dysphagia. An esophagogastroduodenoscopy (EGD) was performed, which showed AEN with circumferential black, necrotic inflammatory changes in the mid to distal esophagus. Erosions were seen in the body and antrum of the stomach, and multiple clean based ulcers were seen in the duodenum. Patient was started on an insulin regimen prior to discharge. Review of literature shows a total of 13 cases of AEN in DKA, with only one case where the patient did not present with any clinical bleeding. Risk factors for AEN include, hypertension, diabetes mellitus, malignancy, male gender, older age, chronic kidney disease, alcohol abuse and cardiovascular disease. While no medications have been linked to AEN, our patient was recently started on semiglutide, which has been implicated in impaired gastric emptying and increased GERD symptoms. This may further explain why the patient developed AEN.

Conclusions

AEN is a rare entity, especially in the context of DKA. Usually patients present with overt GIB; however, on occasion dysphagia, nausea, and vomiting can be the predominant symptoms. Hence, the threshold to perform EGD in patients with DKA should be low, given their low volume state and potentially impaired gastrointestinal motility due to microvascular disease or medications, putting them at higher risk for AEN.

Funding Agencies

None
A144 ISOLATED UPPER ESOPHAGEAL VARICES DUE TO SUPERIOR VENA CAVA SYNDROME: A CASE OF UPPER GI BLEEDING
Authors: Squirell E , Ropeleski M , Fardy J
Published: March 2021

Background

Esophageal varices represent a cause of upper gastrointestinal bleeding (UGI) with significant associated morbidity and mortality. The majority of variceal bleeds are due to portal hypertension and cirrhosis. In some very rare cases isolated upper esophageal varices may occur. These present management challenges, as typical management options for varices in cirrhosis are not applicable due to differences in pathophysiology. Infusions to decrease portal pressure and TIPS procedures may be used in cirrhosis, but are not effective in patients with SVC syndrome.

Aims

We present a literature review on isolated upper esophageal varices due to SVC syndrome, and present a case that provides further confirmation that surgical vascular reconstruction is a viable option in these cases.

Methods

The case of a 49 year old female with variceal hemorrhage secondary to SVC syndrome was reviewed. A search of the literature was undertaken using the terms “varices + superior vena cava syndrome” and “upper esophageal varices + management.”

Results

Overall, the majority of cases of isolated upper esophageal varices are secondary to SVC syndrome. They typically occur in cases of benign, rather than malignant SVC syndrome. Only one previous case was reported to be managed with surgical vascular reconstruction. We present the case of a 49-year old woman with SVC syndrome secondary to a thrombosed dialysis line who went on to develop isolated upper esophageal varices and large volume UGI bleeding. The pathophysiology of these “downhill” varices differs enough from portal hypertension that typical variceal management options may not be appropriate. Given a previous history of unsuccessful balloon angiography and the risk associated with variceal bleeding, she was taken back to the operating room for surgical vascular reconstruction. A surgical bypass was performed. She did well post-surgery and was discharged. She had no recurrence of bleeding and had a resolution of her edema at 6 month follow up.

Conclusions

Isolated upper esophageal varices are a potentially serious complication of SVC syndrome, and should be considered in cases of upper GI bleeding in patients with dialysis lines as they can have limited management options. This case was successfully managed by surgical vascular reconstruction, which represents an important treatment option in these difficult cases.

Funding Agencies

None
A158 THE EFFECTIVENESS AND SAFETY OF HYPERBARIC OXYGEN THERAPY IN INFLAMMATORY BOWEL DISEASE AND ITS ASSOCIATED CONDITIONS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Chin Koon Siw K , Kandel R , Rosenfeld G , Boet S , Larrigan S , McCurdy J D
Published: March 2021

Background

Hyperbaric oxygen therapy (HBOT) corrects tissue hypoxia, mobilizes stem cells and has immunomodulatory effects, all of which are key mechanisms for healing wounds. A number of studies have suggested that HBOT may be effective for healing inflammatory bowel disease (IBD).

Aims

Our systematic review aimed to quantify the effectiveness and safety of HBOT in IBD and its associated conditions.

Methods

We performed a proportional meta-analysis. MEDLINE, EMBASE, Web of Knowledge and The Cochrane Central Register of Controlled Trials were systematically searched from inception through November 2020 with no language restriction. We included randomized controlled studies, cohort studies and case series that contained a minimum of three patients and reported effectiveness and/or safety outcomes for HBOT in patients with IBD. Studies were stratified by IBD phenotype and weighted summary estimates with 95% confidence intervals (CI) were calculated for clinical response and remission using random-effects models. Study quality was assessed using the Cochrane risk-of-bias tool for randomized trials and a modified version of the National Institutes of Health (NIH) checklist for observational studies.

Results

Nineteen studies met our study criteria: 3 randomized controlled trials and 16 case series. The studies reported outcomes for luminal ulcerative colitis (UC) (n=373), luminal Crohn’s disease (CD) (n=250), enterocutaneous fistulae (ECF) (n=21), perianal CD (n=115), pouch disorders (n=60), pyoderma gangrenosum (PG) (n=5) and perianal sinus/metastatic CD (n=7). Rates of clinical response were 86% (95% CI, 66–95%) for luminal UC, 86% (95% CI, 81–90%) for luminal CD, 85% (95% CI, 61–95%) for ECF, 80% (95% CI, 70–87%) for perianal CD, 65% (95% CI, 52–76%) for pouch disorders, 92% (95% CI, 38–99%) for PG and 79% (95% CI, 36–96%) for perianal sinus/metastatic CD. Rates of clinical remission were 87% (95% CI, 10–100%) for luminal UC, 88% for luminal CD (95% CI, 46–98%), 50% for ECF (95% CI, 12–88%), 64% (95% CI, 52–75%) for perianal CD, 31% (95% CI, 16–50%) for pouch disorders, 92% (95% CI, 38–100%) for PG and 65% (95% CI, 10–97%) for perianal sinus/metastatic CD. Of the ten studies that reported on safety of HBOT, 19 patients (10.5%) had minor adverse events and no major event was reported. Study quality was low in the majority of studies due to an absence of comparator arms, inadequate description of interventions, and poorly defined outcomes.

Conclusions

Limited high-quality evidence suggest that HBOT is safe and associated with high rates of clinical response and remission for luminal IBD, perianal CD and pouch disorders. A well-designed large multicenter randomized controlled trial is warranted to confirm the benefit of HBOT in IBD.

doi:10.17605/osf.io/gpz6d

Funding Agencies

None
A166 INCIDENCE OF INFLAMMATORY BOWEL DISEASE IN SOUTH ASIAN AND CHINESE PEOPLE: A POPULATION-BASED COHORT STUDY FROM ONTARIO, CANADA
Authors: Dhaliwal J , Tuna M , Murthy S , Shah B , Griffiths A , Benchimol E I
Published: March 2021

Background

Studies using population-based data from Ontario previously found South Asian (SA) and East Asian immigrants develop IBD at lower rates than non-immigrants. However, incidence among the Canadian-born children of SA immigrants was comparable to those of non-immigrants, and younger age at arrival to Canada was associated with an increased risk.

Aims

The primary aim of the study was to determine the incidence of IBD in South Asian and Chinese people compared with the general Ontario population.

Methods

All incident cases of IBD in children (1994–2015) and adults (1999–2015) were identified from population-based health administrative data in Ontario, Canada using validated algorithms. Ethnicity was assigned by linkage of a validated surname-based database to health administrative data, immigration records, and hospital birth data. We determined standardized incidence of IBD and the adjusted incidence rate ratio (aIRR) in SAs and Chinese comparable to the general population. Based on existing evidence, we adjusted for confounders selected a priori: immigration status, sex, income and rurality.

Results

Amongst 14,483,769 people in the general population, standardised incidence of IBD per 100,000 person-years (PY) was 24.7 (95%CI 24.4–25.0), compared with 14.6 (95%CI 13.7–15.5) in 982,472 SAs and with 5.4 (95%CI 4.8–5.9) in 764,397 Chinese. The risk of IBD in SAs was lower to the general population prior to adjusting for immigration, IRR 0.82 (95%CI 0.78–0.86), but comparable after adjusting for confounders (aIRR 1.10, 95%CI 1.05–1.16). Only SA adults (18-64y) had a higher risk of IBD (aRR 1.10, 95% CI 1.02–1.18), not children or seniors. Compared to the general population, SAs had a lower risk of Crohn disease (CD), irrespective of age (aIRR 0.66, 95%CI 0.60–0.77), but a higher risk of ulcerative colitis (UC) (aIRR 1.47 (95% CI 1.34–1.61).). SAs were more likely to develop UC than CD (aIRR 1.51, 95%CI 1.38–1.66). The risk of IBD was much lower in Chinese people, irrespective of age (aIRR 0.24, 95%CI 0.20–0.28). This lower risk was similar in CD (aIRR 0.21, 95%CI 0.17–0.26) and UC (aIRR 0.28, 95%CI 0.23–0.25). The SA population had a considerably higher risk of developing IBD compared to the Chinese population (aIRR 4.29, 95%CI 3.62–5.08), and were more likely to develop UC (aIRR 1.36, 95% CI 1.08–1.73).

Conclusions

Canadian SAs had a similarly high risk of developing IBD compared with the general population after adjusting for immigration status, a finding distinct from the Chinese population. There was an age-response relationship in SAs only. Furthermore, SAs were more likely to develop UC than people of Chinese origin, potentially owing to differences in genetic susceptibility and/or environmental factors.

Funding Agencies

None
A167 UNDERSTANDING THE IMPACT OF DOWNSTREAM OF KINASE 4 (DOK4) DAMAGING GENETIC VARIANTS IN THE PATHOGENESIS OF PEDIATRIC INFLAMMATORY BOWEL DISEASE (IBD).
Authors: Batura V , Ricciuto A , Warner N , Guo C , Kotlarz D , Klein C , Muise A
Published: March 2021

Background

IBD is a chronic inflammatory disorder of the gastrointestinal (GI) tract whose precise pathological mechanisms remain elusive. It is thought that in pediatric IBD, pathogenic exposure does not appear sufficient to cause disease, thus genetic variations are critical to disease pathogenesis. The Muise Lab uses genetic sequencing of patients with IBD from all over the world to identify crucial genetic variations that are critical to IBD development.

We report two patients with IBD from unrelated families with mutations in DOK4. Both patients had profound extra-intestinal disease complicating their IBD.

Downstream of kinase (DOK) proteins are a family of adaptor molecules that are important in regulating cell signaling, especially in immune cells. They are known to suppress MAPK and PI3K/AKT pathways, whose dysregulation result in cancer. DOK4 has not been extensively studied, but research suggests that this gene produces two isoforms. It is known to have negative regulatory effects on immune cell activation but is also expressed across various other tissues, where its function is yet to be determined.

Aims

We hypothesize that these variations in DOK4 lead to immune cell dysregulation, which manifests in both gastrointestinal and systemic chronic inflammatory disease. Through this study, we aim to elucidate the mechanism of novel genetic defects in DOK4.

Methods

It will be critical to understand how variants within both patients are contributing to the onset of IBD through in vitro studies. Therefore, we will characterize and quantify how changes in expression of DOK4 alters essential cell signaling pathways. We have established immortalized cell lines from patients bearing these mutations to specifically characterize potential immune defects. We will also be using knock out cell models to understand the effect of loss of function of DOK4 in different cell types.

Results

Preliminary data shows variation in expression of the protein within patient peripheral blood mononuclear cells (PBMCs) compared to a healthy donor. Overexpression in HEK293T cells shows changes in MAPK and NFkB signaling.

Conclusions

With this study, we hope to identify new therapeutic targets for patients with DOK4 mutations.

Funding Agencies

CIHRThe Leona M. and Harry B. Helmsley Charitable Trust
A172 THE ASSOCIATION OF EFFICACY, OPTIMISM, UNCERTAINTY AND HEALTH ANXIETY IN INFLAMMATORY BOWEL DISEASE ACTIVITY OVER TIME
Authors: Stone J , Shafer L , Graff L A , Witges K , Lix L , Haviva C , Targownik L E , Bernstein C N
Published: March 2021

Aims

We aimed to assess if the presence of positive or negative psychological attributes are associated with disease activity in a prospective inflammatory bowel disease (IBD) cohort using validated psychological assessment tools and various measures of disease activity.

Methods

The study included 146 adults with confirmed and recently active IBD enrolled in a prospective longitudinal cohort study. Demographics, disease information, validated measures of psychological functioning related to self-efficacy, optimism, health anxiety and intolerance of uncertainty were collected at baseline, week 26 and week 52. Disease activity indicators included fecal calprotection (FCAL), the Inflammatory Bowel Disease Symptom Inventory (IBDSI), and self-reported flares and were collected at study baseline, week 26 and week 52. Logistic regression was used to identify the relationship between psychological functioning and disease activity.

Results

Participants’ mean age was 42.9 years (SD 12.6; range 18–70), with 70.5% women. Almost two thirds (65.1%) had a diagnosis of Crohn’s disease (CD), 34.2% had ulcerative colitis (UC), and 0.7% (n=1) was IBD unclassified. 22% had income <$50,000 and 63% were in a current relationship. Patient-reported active disease (i.e., IBDSI; flare self-report) was significantly less likely with higher self-efficacy [OR= 0.87, 95% CI 0.82–0.93 (IBDSI); OR= 0.86, 95% CI 0.81–0.91 (self-report)] and significantly more likely with higher health anxiety (OR=1.09, 95% CI 1.04–1.15) with the association remaining for self-reported flares after adjusting for demographic variables. The psychological attributes were not associated with active disease based on FCAL levels.

Conclusions

Higher health anxiety increases the likelihood of experiencing an IBD flare, while higher general self-efficacy may be protective of a disease flare.

Funding Agencies

None
A176 THE IMPACT OF COVID-19 ON ANXIETY, DEPRESSION, AND STRESS IN WOMEN WITH INFLAMMATORY BOWEL DISEASE: A CROSS-SECTIONAL SURVEY
Authors: Tandon P , O’Connor K , Maxwell C , Nguyen G C , Huang V W
Published: March 2021

Background

Women with inflammatory bowel disease (IBD) are at an increased risk of mental-health illness and reduced fertility.

Aims

To determine the impact of the coronavirus disease 2019 (COVID-19) pandemic on the mental-health and pregnancy plans of women with IBD.

Methods

Women with IBD (age 18–45) were asked to anonymously complete surveys on baseline demographics, IBD characteristics, and mental health comorbidities. They were also asked to comment on prior symptoms consistent with COVID-19 and whether they were tested for the virus. Finally, patients were asked to complete three mental health surveys to reflect on anxiety (Generalized Anxiety Disorder-7 (GAD7)), depression (Patient Health Questionnaire-9 (PHQ9)), and stress (Perceived Stress Scale (PSS)) symptoms prior to and during the pandemic. Total scores were reported as continuous variables and means with standard deviations (SD) were compared using paired T-tests.

Results

Twenty-nine patients (12 UC, 17 CD) were included. 14 patients were preconception, 12 were pregnant, and 3 were post-partum. The mean age was 31.4 (SD 3.7). Fifteen of 29 (51.7%) of patients were on anti-tumor necrosis factor therapy. Twelve (41.4%) and 6 (20.7%) patients had pre-morbid anxiety and depression prior to the pandemic. COVID-19 symptoms were reported in 8 patients (27.5%). Six patients had undergone COVID-19 testing, all of whom had a negative test. Four patients indicated that COVID-19 had negatively affected their plans for pregnancy, with reasons reported including fear of the hospital (n=1), fear of COVID-19 impact on the fetus (n=2), and uncertainty on the duration of COVID-19 (n=1). During the pandemic, fourteen of 28 (50%) patients experienced symptoms of anxiety (GAD score > 5), with a majority (70%) experiencing mild symptoms (score 5–9). During the pandemic, 60.7% (17/28) and 71.4% (20/28) reported symptoms of depression (PHQ9 > 4) and at least moderate stress (PSS > 14) respectively. Furthermore, compared to pre-pandemic, 57.1% (16/28) and 67.9% (19/28) had an increase in depression and stress symptoms during the pandemic respectively. This appeared to only apply to those with CD, but not UC (Table 1). Compared to pre-pandemic, those with stricturing CD appeared to have higher stress scores whereas those with fistulizing and perianal disease appeared to have higher depression scores during the COVID-19 pandemic (Table 1). A lower house-hold income and a reduction in exercise during the COVID-19 pandemic appeared to increase the risk of stress, depression, and anxiety symptoms.

Conclusions

Over half of women with IBD indicate worsening of anxiety, depression, and stress symptoms during the COVID-19 pandemic. It remains critical that health-care professionals address these mental health concerns during these otherwise difficult times.

Funding Agencies

None
A181 CAUSES FOR C-SECTION IN IBD PATIENTS: A RETROSPECTIVE REVIEW
Authors: Govardhanam V , Tandon P , huang V
Published: March 2021

Background

Inflammatory bowel disease (IBD) is a group of chronic inflammatory conditions including ulcerative colitis (UC), Crohn’s disease (CD) or IBD-unclassified. Current expert guidelines recommend only two IBD-related reasons to consider C-section: perianal CD and ileal pouch-anal anastomosis (IPAA) history. However, the incidence of C section among IBD patients is higher than the non-IBD patients. There is a sparsity of literature on what other factors influence the decision to perform caesarean delivery among IBD patients.

Aims

To investigate IBD-related and non-IBD related reasons leading to C-section in IBD patients.

Methods

A retrospective chart review was performed on women with IBD, >18 years of age and/or older, who delivered at Mount Sinai Hospital, Toronto 2016–2019. OB records and OR records were reviewed to obtain information specific to C-section.

Results

A total of 119 deliveries were reviewed. 47 out of the 119 had C-section delivery. 42.9% (N=21) of C-section was in UC patients and 57.1% (N=28) was in CD patients. Maternal request comprised 2.1% (N=1) and arrest of cervical dilation 6.4% (N=3). 20.4% (N=10) patients failed vaginal delivery. Only 8.7% of C-section deliveries were Primiparous. 42.9% (N=12) of patients from the CD category that underwent C-section had fistulizing CD. 46.4% (N=13) of patients with CD had stricturing CD and underwent C-Section. 63.8% (N=30) of the patients that had C-section had planned C-Section. 26.6% (N=8) of the planned C-section was due to a history of the perianal disease and only 13.3% (N=4) had an active perianal disease. Other causes for planned C-section included J-pouch (10%, N=3) and active UC (2.1%, N=1). As per expert recommendation, we would anticipate 14% of patients to have C-section due to IBD related reasons however we found that 30% of the patients had C-section due to IBD related reasons.

Conclusions

Based on the preliminary data from our retrospective study we find that 30% of the C-sections were due to IBD related reasons and 70% C-sections were from non-IBD related reasons.

Funding Agencies

None
A186 OLDER AGE IS ASSOCIATED WITH INCREASED EXTRAINTESTINAL MANIFESTATIONS IN INFLAMMATORY BOWEL DISEASE
Authors: Chattha Z , Chattha R , Reza S , Moradshahi M , Fadida M , Naddaf Dezfooli N , Piracha Y , Mann R , Singh G , Samji K , Narula N
Published: March 2021

Background

The relationship between older age and extraintestinal manifestations (EIMs) in patients with inflammatory bowel disease (IBD) remains unknown.

Aims

This study aims to determine whether older age is associated with increased risk of EIMs in IBD patients.

Methods

This was a retrospective study of IBD patients seen at the McMaster University Medical Centre, in Hamilton, ON, Canada from 2012–2020. Patients were identified to have the primary outcome of interest if their gastroenterologist documented the presence of any EIM either during the baseline assessment or during the period of follow up. The independent variable, age at start of follow-up, was dichotomized into two categories age >=40 vs. <40.Prior knowledge in combination with forward selection was used to develop a logistic regression model. The variables utilized for the forward selection model included gender, disease duration, and current biologic use.

Results

A total of 995 IBD patients (625 with CD) were considered for the regression analysis, all for whom the EIM status was recorded. Out of the 995 patients, 270 patients reported at least one EIM – 99 with arthritis/arthralgia, 79 with dermatologic manifestations, 16 with ophthalmic manifestations, 30 with liver manifestations, and 116 with other EIMs. A univariate regression analysis foundincreased odds of EIMs in older patientsas compared to younger patients (odds ratio (OR) 1.41 (95% CI, 1.05 – 1.89)). In the multivariate regression analysis, current biologic use was found to have a significant relationship with odds of having EIMs (OR 1.49; 95% CI, 1.06 – 2.09). After adjustment for biologic use, patients aged 40 or over had 1.46 times higher odds of having EIMs (95% CI 1.03 – 2.05). A sub-analysis of individual EIM categoriesdid not show a significant association with older age.

Conclusions

Older age is associated with increased risk of EIMs in IBD patients. Patients with EIMs were also more likely to be treated with biological therapies. Clinicians should inquire about the presence of EIMs in older IBD patients.

Funding Agencies

None
A188 TARGETING RIPK2 TO TREAT INTESTINAL INFLAMMATION CAUSED BY SHIP DEFICIENCY
Authors: Pang Y , Menzies S , Baksh S , Sly L M
Published: March 2021

Background

Crohn’s disease (CD) is a form of inflammatory bowel disease characterized by chronic inflammation along the gastrointestinal tract. We have described the SHIP-/- mouse model of CD-like intestinal inflammation. SHIP-/- mice develop spontaneous ileal inflammation that is characterized by villus hyperplasia and disorganization, edema, immune cell infiltration, ulceration, loss of goblet cells, and muscle wall thickening. SHIP deficiency in people with CD has been associated with a more severe and treatment-refractory disease. Interestingly, NOD2 gene variants, which are the most profound genetic associations for CD, are also associated with a more severe CD phenotype. Muramyl dipeptide (MDP) is a molecular associated microbial pattern, which activates the NOD2 signalling pathway. Recently, SHIP has been reported to play a role in the NOD2 pathway by disrupting the downstream interaction between RIPK2 and XIAP required for NOD2-mediated NFκB activation and pro-inflammatory cytokine production.

Aims

Based on this, we hypothesized that SHIP deficiency contributes to inflammation in CD by increasing NOD2-mediated pro-inflammatory cytokine production. Moreover, RIPK2 inhibitors will block intestinal inflammation caused by SHIP deficiency by blocking RIPK2-XIAP interactions required for NOD2 signalling and resultant pro-inflammatory cytokine production. To test this hypothesis, my aim was to determine the effect of RIPK2 inhibitors on the development of spontaneous intestinal inflammation in SHIP-/- mice.

Methods

6 week-old SHIP-/- mice (and SHIP+/+ mice controls) were treated with RIPK2 inhibitors, FCG806791773 or Z1210264067, by intra-pertioneal injections every other day for 2 weeks and compared to SHIP-/- mice treated with 2% DMSO in PBS, as a vehicle control. On Day 14, distal ilea were harvested and gross pathology was assessed. Cross-sections of the ilea were H&E stained to evaluate histological damage based on villi architecture, edema, immune cell infiltration, ulceration, goblet cell loss, and muscle wall thickening.

Results

As expected, SHIP+/+ mice did not have gut pathology and their healthy gut phenotype was not affected by RIPK2 inhibitors. SHIP-/- mice had ileal inflammation that was evident in gross pathology and in H&E-stained tissue sections. Importantly, SHIP-/- mice treated with RIPK2 inhibitors, FCG806791773 or Z1210264067, had reduced gross pathology compared to vehicle control-treated mice. Z1210264067 treated SHIP-/- mice also had significantly lower histological damage compared to vehicle control-treated SHIP-/- mice.

Conclusions

RIPK2 inhibitors reduced gross and histopathology in SHIP-/- mice suggesting that RIPK2 inhibitors may be an effective treatment for people with CD, and may be particularly effective in people with CD, who harbor NOD2 risk variants and/or have low SHIP activity.

Funding Agencies

CCC, CIHR
A192 A MEDICAL SUMMARY TEMPLATE FOR THE TRANSFER OF PATIENTS WITH INFLAMMATORY BOWEL DISEASE TRANSITIONING FROM PEDIATRIC TO ADULT CARE
Authors: Benchimol E I , Afif W , Plamondon S , Newhook D , Nicholls S G , Lévesque D
Published: March 2021

Background

The transfer of information in a medical summary letter is a key aspect of the transition of adolescent patients with IBD from pediatric to adult care. The existing template from the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) is nearly 20 years old, and the many intervening changes to the care of children with IBD necessitate a new template to reflect modern care.

Aims

We developed a standardized medical summary template based on the feedback of adult and pediatric IBD health care providers.

Methods

We purposively sampled gastroenterologists (GIs) or nurse practitioners (NPs) caring for patients with IBD in Montreal, Ottawa, Toronto or Vancouver and invited them to take part in focus group discussions. Gastroenterologists caring for <50 IBD patients in the past 2 years were excluded. We invited 30 local academic or community-based physicians and nurse-practitioners, of whom 17 (56.7%) agreed to participate. Four focus groups were conducted, consisting of: 1) adult GIs practicing in Ottawa; 2) adult GIs practicing in Montreal and Sherbrooke; 3) paediatric GIs and NPs practicing in Ottawa, Montreal, Toronto or Vancouver; 4) a mixed group consisting of most participants from the preceding three groups. Focus groups employed a semi-structured approach and were recorded with consent. Informed by conventional content analysis, we inductively coded the focus group transcripts to identify all areas of priority for inclusion in the template. The final mixed focus group finalized the template content based information from the preceding groups.

Results

Content areas of importance (see Table) were: patient/disease characteristics, therapeutics history, clinical history and current status, noteworthy investigations, history of complications, family history, immunization history, and psychosocial history. In addition, the template addressed health system process factors (i.e., urgency of transfer, mode of delivery, confidentiality) to ensure a seamless transfer to adult care.

Conclusions

The standardized medical summary template should be used by pediatric providers to ensure that essential information is sent to the receiving adult provider.

Funding Agencies

Transition des patients avec Crohn et colite (TRACC) program
A200 VEDOLIZUMAB IS AN EFFECTIVE TREATMENT OPTION FOR NON INFLAMMATORY BOWEL DISEASE RELATED ENTEROPATHY
Authors: Akhtar H , Nguyen T , Jairath V
Published: March 2021

Background

Vedolizumab is an α4β7 integrin antagonist which inhibits intestinal T-cell translocation by blocking integrin interactions with mucosal vascular addressin cell adhesion molecule 1, reducing lymphocyte mediated inflammation. Its gut selective mode of action and safety profile have lead to reports of off-label use of vedolizumab for non-IBD related inflammatory intestinal disorders.

Aims

We conducted a literature review to assess clinical, endoscopic and histologic improvement in patients treated with Vedolizumab for non-IBD enteropathies refractory to conventional therapy.

Methods

EMBASE, Medline, Clinicaltrials.gov and Cochrane CENTRAL were searched on September 12, 2019 for case studies, case series and cohort studies without language restriction yielding 356 studies with 164 duplicates, 74 non-applicable studies, leaving 118 studies. After full text review, 98 studies were excluded, leaving 20 included studies.

Results

65% of patients (51/79) achieved clinical response. 40.5% (15/37) of patients experienced endoscopic improvement and 33% (17/51) of patients experienced histologic improvement. The duration of treatment varied from patients receiving only induction doses to up to 70 months for maintenance therapy. There were four reported cases of withdrawal due to adverse events from Vedolizumab.

Conclusions

In a treatment refractory population, over 60% of patients reported to have a clinical response and one-third endoscopic/histologic response, indicating that Vedolizumab is a viable option for patients with refractory non-IBD enteropathy.

Funding Agencies

None
A208 PREDICTORS OF OUTCOMES IN PSC: RETROSPECTIVE ANALYSIS OF TWO TERTIARY CARE CENTERS IN BC
Authors: Chahal D , Bedi H K , Marquez V , Yoshida E M , Ko H , Salh B
Published: March 2021

Background

Primary sclerosing cholangitis (PSC) is a chronic inflammatory disorder of the bile ducts. PSC can rapidly progress to cholangiocarcinoma and death. Many clinical features of PSC, as well as its relationship with diseases such as IBD, remain ill-defined. These features are important for disease modeling and clinical trial design.

Aims

To identify features of PSC that may aid in disease modeling and outcomes prediction.

Methods

Patients with a diagnosis of PSC with visits between 2012 and 2018 were identified and data were extracted. Survival analysis was performed, with time defined as time of PSC diagnosis to time at clinical endpoint. The clinical endpoint for survival analysis was defined as development of cholangiocarcinoma, liver transplantation or death. Univariate and multivariate Cox-regression was then performed.

Results

169 patients (99 male, 70 female) were identified. Of these, 102 (60.4%) had a diagnosis of IBD (84 UC). 138 were Caucasian, 9 East Asian, 9 South Asian and 13 Middle East. Mean age at PSC diagnosis was 39.3, IBD diagnosis 29.3 years. Mean time to next diagnosis in those with PSC-IBD was 7.7 years. Of those with PSC-IBD, IBD preceded the diagnosis of PSC in 69 (67.6%) patients. 22 (13.0%) had concurrent liver disease, including 14 AIH and 1 PBC overlap. In those with UC, disease was most often pancolitis (57.8%), with noticeable rate of backwash ileitis (23.3%). There were 26 patients with current or prior use of Infliximab, 14 with Humira, and 6 with Vedolizumab. 28 (16.6%) patients had a partial or total colectomy. 35 (20.7%) patients had diagnoses of cancer, including 16 cholangiocarcinoma, 2 gall bladder carcinoma, and 4 colorectal. 33 (19.5%) patients received liver transplant, and 31 (18.3%) died. Most frequent cause of death was cholangiocarcinoma (12, 38.7%). Univariate analysis identified increased age at PSC diagnosis, presence of IBD, increased age at IBD diagnosis, diagnosis of IBD prior to PSC, increased time from diagnosis of IBD to PSC, diagnosis of UC as opposed to Crohn’s, and lack of Infliximab use as significant predictors of our clinical endpoints (p<0.05). Multivariate analysis only identified increased age at PSC diagnosis, presence of IBD, and diagnosis of IBD prior to PSC as predictors.

Conclusions

PSC affects persons of various ethnic backgrounds. Diagnosis of IBD appears to precede PSC in most PSC-IBD cases, and the temporal relationship may impact outcomes, possibly due to delayed diagnosis of PSC. UC has a worse disease course than Crohn’s. Cholangiocarcinoma still accounts for a large burden of overall death in PSC, and strategies for early diagnosis should be explored. More studies are required to delineate the relationship between biologic use and PSC outcomes. The major limitation of our study is the smaller sample size that may have limited statistical power.

Funding Agencies

NoneNone
A209 NON-INVASIVE ASSESSMENT OF LIVER FIBROSIS USING APRI, FIB-4, AND TRANSIENT ELASTOGRAPHY IN CHRONIC HEPATITIS B PATIENTS
Authors: Little D H , Fischer S , Fung S K
Published: March 2021

Background

Accurate assessment of liver fibrosis is important to identify patients with chronic hepatitis B (CHB) who require antiviral therapy. As liver biopsy is invasive and costly, non-invasive tests of liver fibrosis are increasingly being used.

Aims

We aimed to evaluate the performance of the aspartate aminotransferase-to-platelet ratio index (APRI), Fibrosis 4 index (FIB-4), and transient elastography (TE) in predicting fibrosis in patients with CHB.

Methods

We retrospectively analyzed a prospectively enrolled cohort of consecutive adults with CHB who underwent liver biopsy for routine clinical indications (ALT > ULN and HBV DNA > 2,000 IU/ml) from January 2018 to December 2019. Demographic information, routine biochemistry, HBV serology including HBV DNA, abdominal ultrasound, fibrosis stage by liver biopsy and TE data were collected. Positive predictive values (PPV) and negative predictive values (NPV) were calculated using published cut-off values with liver biopsy as the reference standard.

Results

Fifty-five patients of Asian ethnicity (mean age 46 years, 65% male) were included. Most patients were HBeAg-negative (67%) and treatment-naïve (80%). Eleven (20%) patients had advanced fibrosis (F3-F4 METAVIR) and 4 (7%) patients had cirrhosis (F4). APRI <0.50 had a NPV of 73% for significant fibrosis (F2-F4) and APRI >1.50 had a PPV of 33% for significant. All 4 patients with cirrhosis were misclassified as having no cirrhosis with an APRI <1. FIB-4 <1.45 had a NPV of 90% for advanced fibrosis (F3-F4). No patient, including 11 patients with advanced fibrosis, had a FIB-4 above the cut-off value to detect advanced fibrosis (>3.25). TE data was available for 38 patients. TE <7.25 kPa had a NPV of 78% for significant fibrosis and TE >12.4 kPa had a PPV of 50% for cirrhosis.

Conclusions

In Asian patients with CHB and a low prevalence of advanced fibrosis or cirrhosis, APRI, FIB-4, and TE performed well in excluding those with advanced fibrosis but were unable to accurately identify those with significant/advanced fibrosis and cirrhosis. Further studies with larger numbers of CHB patients are needed to confirm our results.

Funding Agencies

None
A212 INCIDENCE OF HEPATITIS C VIRUS INFECTIONS AMONG USERS OF HUMAN IMMUNODEFICIENCY VIRUS PRE-EXPOSURE PROPHYLAXIS
Authors: Tabatabavakili S , Aleyadeh W , Cerrocchi O , Janssen H L , Hansen B E , Bogoch I , Feld J
Published: March 2021

Background

Sexual transmission of hepatitis C virus (HCV) is well-documented among HIV-uninfected individuals. The use of HIV pre-exposure prophylaxis (PrEP) may lead to increased engagement in activities that facilitate the transmission of sexually transmitted infections (STI) and possibly HCV among PrEP users.

Aims

To assess the incidence of Hepatitis C Virus Infections among HIV negative pre-exposure prophylaxis (PrEP) users

Methods

Between 2012 and 2019, the incidence of HCV and bacterial STIs were calculated among HIV-negative patients receiving PrEP at the University Health Network HIV Prevention Clinic. Mucosal, anal and blood samples were taken to test for HIV, syphilis, and anti-HCV antibodies.

Results

Among 344 HIV-uninfected patients receiving PrEP, 86% were men having sex with men (MSM). Five individuals were HCV-antibody positive at the time of PrEP initiation. Serological and virological follow-up was available for 109 HCV-negative individuals over 282 patient-years (PY). Two new infections were recorded, yielding an incidence of primary HCV infection of 0.7/100 PY. In contrast with HCV, the incidence rates of chlamydia, gonorrhea, and syphilis were 49.2/100 PY, 36.3/100 PY, and 5.2/100 PY, respectively. Both individuals with new HCV diagnoses reported being MSM with a history of unprotected intercourse and one also reported recreational drug use. Both individuals were asymptomatic at the time of diagnosis and were detected by routine laboratory monitoring.

Conclusions

The low incidence of HCV infections despite significantly higher rates of other STIs suggests that sexual transmission of HCV is uncommon in HIV-negative MSM PrEP users. Performing routine risk-based HCV surveillance among PrEP users should be evaluated. The high incidence of STIs in this population indicates a vital role for periodic STI monitoring in those receiving PrEP.

Funding Agencies

vircan
A219 EARLY PREDICTORS OF UNFAVORABLE OUTCOME IN NORTH AMERICAN INDIAN CHILDHOOD CIRRHOSIS
Authors: Khendek L , Alvarez F , Beaunoyer M , Drouin E , Lallier M , Paganelli M
Published: March 2021

Background

North American Indian Childhood Cirrhosis (NAIC) has only been described in the Cree-Ojibway First Nations of Northern Quebec. NAIC presents with transient neonatal jaundice and progresses to biliary cirrhosis often requiring liver transplantation (LT) in childhood. Only 30 patients have been described to date and risk factors associated with an earlier progression to LT have not yet been identified. Moreover, NAIC patients seem to experience more fractures than other cholestatic patients, but this has not been confirmed.

Aims

With this study, we aimed to identify predictors at 6 months from presentation that might suggest progression to end-stage liver disease as well as evaluate bone health in affected patients.

Methods

The records of all NAIC patients diagnosed between 2000–2020 were reviewed. Subjects were split into 2 groups based on whether they had undergone LT or not (No_LT) before age 18. Recorded complications included: hepatic encephalopathy (HE), variceal bleeding (VB), ascites, spontaneous bacterial peritonitis (SBP), bacteremia, and pulmonary shunts. Laboratory data (alanine aminotransferase, ALT; total bilirubin, TB) were collected at presentation and follow-up. Bone mineral density (BMD) of the lumbar spine (Z-scores) and number of fractures were compared between groups. NAIC patients were then compared to cohorts with other chronic cholestatic diseases such as biliary atresia (BA, n=24) and Alagille syndrome (AS, n=11).

Results

A total of 14 patients (M=9, F=5) were diagnosed with NAIC. Average age at presentation was 2.1 months (IQR 1–16.9 months), with 3 patients older than 18 months. Overall, 6 patients were transplanted (avg 8.6±1.7 years), one was listed for LT but died waiting, and 7 remained in a state of compensated cirrhosis. All complications were only observed in the LT group except for VB which also occurred in 2 patients of the No_LT group. Between presentation and 6 months, ALT and TB levels increased more in the LT vs No_LT group (p=ns). There was a greater variation of ALT/TB levels in the LT group (p=0.0047) even once the 3 patients with late referral were excluded (p=0.0381). No patient in the No_LT group had fractures, while 3 did in the LT group. BMD was lower in the LT group vs No_LT group (-2.2±1.2 vs. -1.1±1.3, p=ns). NAIC patients had lower BMD (-1.7±1.3) than those with AS (0.7±0.9, p=0.003) or BA (-0.9±1.4, p=ns) and had a higher prevalence of fractures (21.4% vs. 12.5% for BA and 18.2% for AS patients).

Conclusions

In patients with NAIC, variation of ALT/TB levels at 6 months from presentation may be used as an early predictor of unfavorable outcome and progression towards end-stage liver disease. Patients who evolved to LT had more complications, higher prevalence of fractures and lower BMD values. Compared to children with BA or AS, NAIC patients had poorer bone health.

Funding Agencies

None
A220 AN UNEXPECTED CAUSE OF ACUTE JAUNDICE IN A POST-TRANSPLANT PATIENT
Authors: Wong K W , Silverman J
Published: March 2021

Background

Complications post liver transplantation are common. These may include thromboses, primary graft nonfunction, biliary complications, chylothorax, infection, and rejection. Hepaticojejunostomy with Roux-en-Y limb is a common technique for pediatric liver transplantation. Complications of hepaticojejunostomy include small bowel obstruction due to incarceration of the Roux-en-Y limb within an internal hernia. Acquired diaphragmatic hernia has previously been reported in liver transplant patients. Here we present a unique case of acute biliary obstruction secondary to incarceration of a Roux limb within an acquired diaphragmatic hernia.

Aims

To describe a unique case of incarcerated Roux-en-Y limb in a diaphragmatic hernia leading to acute jaundice in a pediatric liver transplant patient.

Methods

Retrospective chart review and case review with the surgical and medical teams.

Results

A 14 month old girl with unresectable hepatoblastoma received a living donor, left lateral segment liver transplant using standard venous reconstruction, microvascular plastics arterial reconstruction, and the recipient common hepatic duct was anastomosed to the donor left hepatic duct. Serial ultrasounds showed persistent intrahepatic duct dilatation with cholestasis. Given the concern of biliary obstruction, 10 days post-transplant, she underwent repeat laparotomy and was found to have a dilated common bile duct with a proximal obstruction. A Roux-en-Y hepaticojejunostomy was performed to establish adequate biliary drainage.

Three months post-transplant she developed lung metastases that required wedge resection and chemotherapy. 7 months post-transplant, while admitted for routine chemotherapy she acutely developed jaundice, pruritus, and transaminitis. Liver ultrasound showed an apparent fluid collection at the cut surface of the liver and biliary dilatation. Extrinsic compression of the biliary tree was suspected, and so a percutaneous biliary drain was placed to drain the collection and decompress the biliary system.

Despite improvement in the transaminitis and cholestasis, several days later, she developed severe abdominal pain and associated grunting respirations. An MRI with MRCP to reassess the previous findings and rule out a new intraabdominal cause for her symptoms was completed and unexpectedly showed herniation of her Roux-en-Y limb into a diaphragmatic hernia. She had urgent diaphragmatic hernia repair with reduction of the incarcerated bowel loop, with resolution of her pain and jaundice.

Conclusions

Post liver transplant Roux-en-Y herniation is uncommon, but can occur with internal hernias and in diaphragmatic hernias. This uncommon complication should be considered for the post liver transplant patient with hepaticojejunostomy in the setting of acute jaundice, particularly if accompanied by acute onset abdominal pain and/or increased work of breathing.

Funding Agencies

None
A231 THE MICROBIOTA-NOCICEPTORS-MICROGLIA AXIS CONTROLS THE DEVELOPMENT AND MAINTENANCE OF CHRONIC VISCERAL HYPERSENSITIVITY
Authors: Abdullah N , Altier C
Published: March 2021

Background

Pain is the most common cause of disability in inflammatory bowel disease (IBD). Current medical interventions control the debilitating clinical symptoms by reducing gastrointestinal (GI) inflammation. Despite successful treatment of active disease, abdominal pain persists during remission, suggesting a high level of plasticity in pain-sensing circuits (hyperalgesic priming) caused by inflammation. What drives this remodelling has remained elusive. We have identified microglia as active players of hyperalgesic priming in IBD. Furthermore, it was recently shown that commensal bacteria control the maturation of microglia in the CNS, suggesting that dysbiosis could influence visceral sensitivity through regulating colonic nociceptors-microglia interaction. Here we test the hypothesis that microbiome-nociceptors-microglia interactions control visceral sensitivity and pain in IBD.

Aims

We investigated the role of the microbiota in the developmental regulation of colonic nociceptors that express the pain receptor TRPV1. We will identify the microbial factors that control neuron-microglia interactions during bacterial colonization and post-inflammatory dysbiosis.

Methods

We have developed a germ-free TRPV1-GFP reporter mouse to be used for a combination of behavioural tests and phenotypic characterization of TRPV1+ nociceptors. RNA-sequencing of FACS isolated TRPV1+ neurons of germ-free mice will be used to identify genes that are under the control of the microbiota. We will restore discrepancies observed in germ-free mice by recolonization to assess the impact of the microbiota. Furthermore, we will investigate the regulation of Ahr in TRPV1+ neurons by the microbiota and the effect of its ligands on microglial activation and post-inflammatory visceral pain.

Results

Measuring somatic pain sensation in naive germ-free and SPF mice, we showed a 15% reduction in thermal pain threshold, as measured by the Hargreaves test, and a 50% reduction in mechanical pain threshold, as measured by the Von Frey test, in germ-free mice. When looking at the dorsal root ganglia of germ-free and SPF mice, we saw a 15% increase in the percentage of neurons that were TRPV1-GFP positive in germ-free mice.

Conclusions

Our results thus far highlight the importance of the microbiota in regulating the lineage of nociceptive neurons and the threshold of mechanical and thermal pain responses. These findings suggest a major contribution of the microbiota in shaping the neuro-immune axis, with major implications for visceral sensitization in the context of dysbiosis. My project will be looking further into the phenotype of nociceptors in germ-free mice and the effect of microbial-derived Ahr agonists on the maturation and function of colonic TRPV1+ nociceptors. My work will advance our understanding of mechanisms by which commensal bacteria regulate GI pain.

Funding Agencies

CIHR