bluuebunny/crossref_metadata_2025 huggingface dataset:
A155 ASEPTIC ABSCESS SYNDROME IN INFLAMMATORY BOWEL DISEASE: A CASE REPORT
Authors: Tam L , Akhtar D , Salh B
Published: February 2022

Background

Aseptic abscess syndrome (AAS) is a rare extraintestinal manifestation of inflammatory bowel disease (IBD) and it is characterized by the formation of sterile collections of neutrophils in various organs. Misdiagnosis frequently leads to unnecessary surgical procedures and prolonged courses of antibiotics. There are only 61 reportable cases of AAS in the international literature and 2 cases in Canada. This case and the associated literature review highlight the diagnostic considerations, treatment options and disease course of this rare disease.

Aims

To describe a case of AAS in IBD.

Methods

Case report and review of the literature.

Results

A 24-year-old male with a history of ulcerative pancolitis (UC) initially presented with a 3-week history of malaise, abdominal pain, and fevers with a computed tomography (CT) scan showing multiple splenic abscesses. Over the next year, he had multiple readmissions for recurrent sepsis from culture negative multi-focal abscesses. Serial CT scans revealed new abscesses in the liver, scrotum, and lungs with interval progression in size. Unsuccessful attempts to isolate a culprit organism which included serological markers and cultures from blood, bronchial washings, aspirate from abscesses, and surgical tissue. All samples demonstrated frank pus with suppurative granulomatous inflammation. The patient was trialed on various courses of antibiotics without improvement. Therefore, a decision was made to treat for AAS given his IBD history. Antibiotics were discontinued and prednisone was initiated with rapid improvement in symptoms and biochemistry. In the three years following, he was transitioned to a combination of infliximab and azathioprine. He had rapid resolution of his abscesses on serial CT scans following steroid and anti-TNF therapy. Currently, he is no longer on steroids and his CRP has normalized with no recurrence of his symptoms.

Conclusions

AAS has often been associated with IBD, particularly Crohn’s disease and more rarely in UC. Case series have shown that AAS is not strongly associated with IBD activity as only 55% of cases have concomitant IBD flare and abscess formation. The syndrome continues to pose a diagnostic conundrum among specialists as there is no established diagnostic criteria and thus AAS remains a diagnosis of exclusion. This has led many patients to suffer from AAS for prolonged periods and receive unnecessary investigations and treatments. Steroids remain the gold standard for initial induction of remission. However, the ideal regimen for maintenance therapy is still evolving and case reports have described the effects of immunotherapy and biologics on AAS. AAS has a substantial impact on quality of life and is very responsive to therapy; this case report reminds the clinician that AAS should be considered in patients with IBD presenting with multifocal abscesses unresponsive to antimicrobials.

Serial CT scan (coronal view) of abdomen demonstrating multiple hepatic abscesses (blue arrows)

Funding Agencies

None
A157 DEFINITIONS OF MEDITERRANEAN DIET INCONSISTENTLY ASSOCIATE WITH MARKERS OF GUT BARRIER FUNCTION OR SUBCLINICAL INFLAMMATION IN A POPULATION-BASED COHORT
Authors: Neustaeter A , Timpano J , Lee S , Xue M , Leibovitzh H , Madsen K , Meddings J , Espin-Garcia O , Goethel A , Griffiths A , Moayyedi P , Steinhart H , Panaccione R , Huynh H Q , Jacobson K , Aumais G , Mack D R , Bernstein C N , Marshall J , Xu W , Turpin W , Croitoru K
Published: February 2022

Background

The Mediterranean Diet (MD) is proposed to reduce the risk of Crohn’s disease (CD) onset in cohort studies, with inconsistent results. This inconsistency may be due to heterogeneity in defining MD scores. Additionally, relationships between MD compliance and intestinal permeability or sub-clinical inflammation are not defined.

Aims

We examined correlations between different MD scores, and determined associations between MD compliance and intestinal permeability or subclinical inflammation in a cohort of first degree relatives of CD patients.

Methods

We used food frequency questionnaire data from 2,112 subjects of the Crohn’s Colitis Canada- Genes, Environment, Microbial (CCC-GEM) project. We obtained 12 MD definitions from the literature and calculated daily percent compliance, we further compared MD scores via pairwise correlations (Kendall’s Tau). We measured intestinal permeability via urinary fractional excretion ratio of lactulose to mannitol (LMR) (LMR≥0.03 defined abnormal), and subclinical inflammation via fecal calprotectin (FCP) measured with BÜHLMANN fCAL® ELISA (FCP≥250 defined abnormal). We fit multivariable regression models between MD compliance and abnormal LMR and FCP, respectively. Two-sided p<0.05 defined significance.

Results

There was large variation in cross-correlations among MD scores, from nil (t=0.0, p=0.54) to highly significant (t=0.97, p<2.2e-16). Associations of MD compliance and abnormal LMR or FCP were in both directions of effect, largely non-significant. Of the 12 MD scores, none associated with abnormal LMR, while 4 associated with abnormal FCP-Odds Ratios =1.22, 1.23, 1.24, and 1.30; p=0.02, 0.02, 0.01, and 0.009, and 95% Confidence Intervals = [1.03,1.45], [1.04,1.45], [1.05,1.47], and [1.07,1.59] respectively. No diet remained significant after correcting for multiple testing.

Conclusions

Currently MD definitions vary widely. Despite discrepancies, we expected consistent directions of effect for MD compliance on LMR or FCP. The largely non-significant associations between MDs suggest limitations in definition, interpretation, and relation to biological outcomes.

Submitted on behalf of the CCC-GEM consortium.

Funding Agencies

CIHRCrohn’s and Colitis Canada Genetics Environment Microbial (CCC-GEM) III;The Leona M. and Harry B. Helmsley Charitable Trust; Justine Timpano is a recipient of a fellowship award from Mount Sinai Hospital; Kenneth Croitoru is the recipient of the Canada Research Chair in Inflammatory Bowel Diseases
A158 COMPARING CORTIMENT® AND PREDNISONE IN ULCERTATIVE COLITIS: A POPULATION-BASED STUDY OF OUTCOMES
Authors: Coward S , Martins K , Klarenbach S , Kroeker K , Ma C , Panaccione R , Richer L , Seow C , Targownik L E , Kaplan G G
Published: February 2022

Background

In August 2016 Cortiment® was approved for use in ulcerative colitis (UC) patients in Canada, but not approved for reimbursement; the Canadian Agency for Drugs and Technology in Health cited no comparable benefit for its use over other approved UC medications. Real-world data comparing Cortiment® to other UC medications is limited, especially during the COVID-19 pandemic where the use of steroids is counter-indicated for COVID-19-related outcomes.

Aims

To examine the comparative risk of hospitalization, surgery, and infection after initiation of Cortiment® or oral corticosteroids among UC patients using real-world data

Methods

Using population-based data from Alberta Canada, two cohorts were compared: 1. Patients dispensed Cortiment® and an ICD diagnostic code for UC [9: 556.X; 10: K51.X] (August 1, 2016 to October 31, 2019); and, 2. Validated (algorithm) UC patients dispensed a >30 day supply or >500mg in 24 hours of prednisone/prednisolone (April 1, 2016 to October 31, 2019). All hospitalizations, IBD-surgery, or infections (i.e., pneumonia, c.diff, sepsis, tuberculosis) that occurred 6 or 12 months from initial medication dispensing were identified. Cox-proportional hazard models, with Hazard Ratios (HR), assessed comparative outcomes. Kaplan-Meier survival curves were created, and Poisson regression (or negative binomial) used to assess the Average Monthly Percentage Change (AMPC) with associated 95% confidence intervals (CI).

Results

We identified 917 Cortiment® and 2,404 Prednisone patients. Over the study period, prednisone dispensing significantly decreased (AMPC:-2.53% [CI:-2.85,-2.21]) while Cortiment® remained stable. Dispensing of Cortiment® significantly decreased the hazard of hospitalization (all types, except surgery) at 12 months as compared to prednisone, and significantly decreased the hazard of an infection at both 6 and 12 months (Table 1, Fig 1).

Conclusions

The use of Cortiment® in a real-world setting is associated with fewer deleterious outcomes, and its use during a pandemic should be preferred, especially when it’s counterpart can exacerbate negative COVID-19-related outcomes.

Table 1

Kaplan-Meier Survival Curves of 1-year Outcomes: A) All Hospitalizations; B) IBD-Related Hospitalizations; C) IBD-Specific Hospitalizations; and, D) Any Infection.

Dashed Line

Cortiment Cohort

Solid Line

Prednisone/Prednisolone Cohort

Funding Agencies

Ferring Pharmaceuticals
A163 EVALUATING THE ASSOCIATION BETWEEN PERIPHERAL BLOOD EOSINOPHILS AND DRUG RESPONSE IN CROHN’S DISEASE: A PRELIMINARY REPORT
Authors: Cai B , Wilson A
Published: February 2022

Background

Th1, Th2, and Th17 immune pathways are variably activated in inflammatory bowel disease (IBD). The degree to which pathway having a more dominant role in propagating Crohn’s disease (CD) is not considered when selecting a treatment strategy. Th2 cytokines, IL-5 and IL-13 enhance eosinophil survival, recruitment and degranulation, facilitating inflammation. Mucosal eosinophilia has been documented in CD and its presence is a surrogate marker of Th2 pathway activation. Peripheral eosinophilia has an established role in asthma to help prognosticate treatment response to Th2-cytokine-specific therapies. We hypothesize the pattern of peripheral blood eosinophils (PBE) at CD diagnosis will identify distinct subsets within a larger CD population and correlate with response to treatments such as prednisone or anti-TNFs.

Aims

We aim to evaluate the pattern of PBE of CD patients at time of diagnosis (prior to drug exposure) and with each subsequent treatment; and if baseline PBE or any changes seen with drug exposures are predictive of treatment response.

Methods

A retrospective cohort study is ongoing with CD patients exposed to glucocorticoids and an anti-TNF seen at one of 3 hospitals affiliated with University of Western Ontario. Patients were identified using administrative databases and reviewed for biochemical data (complete blood count) and disease activity (Harvey Bradshaw Index) at baseline as well as before and after each drug exposure. Participants were classified as having high PBE (eosinophils >200 cells/μl) versus low PBE (eosinophils <200 cells/μl).

Results

To date,10 of 200 CD patients are included in the preliminary analyses with a mean age of 47. 8 had PBE >200 cells/μL at baseline, while 2 did not. The median number therapies used was 4 (IQR=0.75). All received glucocorticoids followed by an anti-TNF. There was no difference in the occurrence of hospitalization or surgery between the two cohorts. Overall 75% (n=6/8) participants with high PBE had clinical response to glucocorticoid exposure, seen as a 3-point decrease in HBI compared to 0% (n=0/2, p=0.5) in the low PBE cohort. With subsequent anti-TNF exposure, PBE rebounded in 6 participants. More patients in the high PBE group required anti-TNF dose escalation versus the low PBE group (63%, n=5/8 versus 50%, n=1/2, p=0.99). The proportion of patients with anti-TNF discontinuation was similar in both groups (high PBE, 50%, n=4/8 versus low PBE, 50%, n=1/2, p=1.00).

Conclusions

Peripheral eosinophilia is seen in varying degrees in CD patients. Participants with high PBE appear to be more steroid-responsive which is typical for Th2-mediated pathways. They were less responsive to Th1-targeting anti-TNF therapies, requiring more dose-escalation and discontinued anti-TNF treatment. Completion of this study will help clarify the association between PBE in CD and treatment response.

Funding Agencies

None
A164 RISKS OF SKIN CANCERS PRE- AND POST-INFLAMMATORY BOWEL DISEASE DIAGNOSIS
Authors: Narous M , Nugent Z , Singh H , Bernstein C N
Published: February 2022

Background

Inflammatory bowel disease (IBD) has been shown to be associated with an increased risk of non-melanoma skin cancers (NMSC), specifically squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), with the use of immunosuppressants such as thiopurines and tumor necrosis factor inhibitors (anti-TNFa). However, there is no literature exploring risk of skin cancers prior to formal Crohn’s disease (CD) or ulcerative colitis (UC) diagnoses. An increased risk pre IBD diagnosis could potentially suggest varied immunological impairments in patients with IBD.

Aims

To compare risks of NMSC and melanoma preceding and following a diagnosis of IBD and to evaluate the effect of thiopurines and anti-TNFa on risk of skin cancers in IBD.

Methods

This is a retrospective, historical cohort study using population-based data sources including the University of Manitoba IBD Epidemiology Database and the Manitoba Cancer Registry. Individuals with IBD diagnosed between 1987 and 2018 (N = 9344 / 636 NMSC) were identified and matched with randomly selected controls (N = 88916 / 3839 NMSC) based on age, sex, and postal area of residence on the date of IBD diagnosis (index date). Logistic and Cox regression analyses were performed to calculate adjusted risks skin cancers prior to and after IBD diagnosis.

Results

Subjects with IBD were more likely to have BCC pre-dating their IBD diagnosis (OR 1.50, 95% CI 1.24–1.81). Risks of SCC, other non-melanoma skin cancers, or melanoma prior to IBD diagnosis were not significantly increased. Post-IBD diagnosis, risk of BCC and SCC were significantly increased across all IBD groups (HR 1.60, 95% CI 1.45–1.76 and HR 1.65, 95% CI 1.37–1.99), except for SCC in UC. There was no significant association between melanoma and IBD post-IBD diagnosis. Thiopurines are associated with higher risks of BCC, SCC, and melanoma in IBD. Anti-TNFa use also raised risks of BCC and melanoma, but anti-TNFa alone did not increase risk of SCC in IBD. Nested case-control analysis confirmed a higher baseline risk of BCC in patient with IBD with censoring of both thiopurines and anti-TNFa. Similarly, censoring of both medications produced no effect on risk of SCC in IBD corroborating the absence of a baseline SCC risk in IBD.

Conclusions

The risk of BCC preceding a formal diagnosis of IBD is higher than in non-IBD controls, compared to a generally increased risk of NMSC post-IBD diagnosis. IBD is not associated with a significant risk of melanoma, although risk for melanoma is increased with thiopurine or anti-TNFa exposure. Our study suggests a possible inherent immune impairment in patients with IBD that leads to BCC. Thiopurine and anti-TNF therapy increase the risks for skin cancers evident in persons with IBD after their diagnoses.

Funding Agencies

None
A172 PSYCHOSOCIAL VARIABLES RELATED TO J-POUCH SURGERY FOR INFLAMMATORY BOWEL DISEASE: A SCOPING REVIEW
Authors: Hanna Q , Tripp D A , Beyak M J , Moayyedi P
Published: February 2022

Background

Ulcerative Colitis (UC) and Crohn’s Disease (CD) are subtypes of Inflammatory Bowel Disease (IBD) which is a condition with an unclear etiology causing inflammation of the small and large intestine (Public Health Agency of Canada, 2021). IBD is treated by diet, medications, and/or surgeries, with the most common surgery recommended to UC patients being j-pouch surgery (Crohn’s and Colitis Canada, n.d.). J-pouch surgery is often accompanied by numerous side effects (e.g., leakage, pouchitis), but it has been shown to help manage symptoms and restore function (Crohn’s and Colitis Canada, n.d.). While noteworthy research has examined the functional and biological outcomes of j-pouch surgery (e.g., Kayal et al., 2020), far less has considered the perioperative psychosocial implications.

Aims

The aim of this scoping review is to assess the current literature concerning psychosocial factors related to j-pouch surgery for patients with IBD.

Methods

We used the PRISMA-ScR (Tricco et al., 2018) and JBI recommendations (Peters et al., 2020) as methodological guidelines for conducting this review. We conducted our search during the summer and fall of 2021 and searched the following sources: Medline, PsychInfo, CINAHL, EBM Reviews, ProQuest Dissertations and Theses Global, ResearchGate, Prospero, and PrePubMed. We included articles from 1980-September 13, 2021.

Results

Our initial search produced 718 articles. Of those that met our inclusion criteria, the majority discussed quality of life as their sole psychosocial variable. Among these studies, however, many used quality of life measures (e.g., IBDQ, SF-36) that prioritize health-related factors, with only a subset of questions directly addressing quality of life. The second most investigated psychosocial variables were those related to sexual health and functioning. When considering the levels of evidence, very few of our results were randomized control trials (RCT), while many were reviews (but not exclusively of RCT) and non-randomized controlled studies.

Conclusions

We have identified a substantial need for studies examining psychosocial implications of and for j-pouch surgery among patients with IBD. In our discussion, we identify common variables and outline the strongest articles in the current literature, investigate the disadvantages of currently used measures, and propose specific directions for future research.

Funding Agencies

None
A182 THE LACK OF CHROMOGRANIN A IMPACTS COLONIC EPITHELIAL CELLS MARKERS IN AN EXPERIMENTAL MODEL OF ULCERATIVE COLITIS
Authors: Tshikudi D M , Eissa N , Diarra A , Ghia J
Published: February 2022

Background

Ulcerative colitis (UC) is a chronic and acute inflammatory disorder of the colon linked to dysregulated gut mucosal immune response and compromised colonic epithelial barrier function and integrity. Chromogranin-A (CHGA), a pro-peptide secreted by enteroendocrine cells, is highly expressed in colonic tissues of patients with UC. Elevated CHGA has been shown to correlate with UC disease activity and severity. Moreover, complete deletion of CHGA was shown to result in a diminution of pro-inflammatory markers known to disrupt the colonic epithelial barrier function and gut mucosal healing process. However, little is known about the effect of the absence of CHGA on colonic epithelial barrier function and gut mucosal integrity.

Aims

Here, we characterized the impact of the lack of CHGA on the colonic mucosa and epithelial barrier structure and function using CHGA knockout (CHGA-/-) mice treated with dextran sulfate sodium (DSS) to induce colitis.

Methods

13–17 weeks old male C57BL/6 wild-type (CHGA+/+) and C57BL/6 CHGA-/- mice were treated for 5 days with 5% DSS to induced acute colitis, control mice received regular water. CHGA mRNA expression, disease activity index (DAI), and macroscopic score (MS) were analyzed. Distal colonic tissues were isolated, and mRNA expression of markers associated with regenerative stem cells (fast-cycling stem cells [Lgr5+] and reserve stem cells [HOPX+] and [LY6a+], Goblet cells functions mucus barrier mucin 2 [MUC2], resistin-like molecule β [RELMβ], WAP 4-disulphide core domain 2 [WFDC2]) and trefoil factor 3 (TFF3) was evaluated by qRT-PCR.

Results

We validated a beneficial effect of the Lack of CHGA on colitis severity, associated with significantly lower DAI and MS. In colitic CHGA+/+ and CHGA-/- mice, Lgr5+ and HOPX+ were both highly down-regulated, although, compared to CHGA+/+, CHGA-/- mice presented a 10.5fold higher expression of HOPX+. Compared to non-colitic states, Ly6a+ expression was significantly elevated in both colitic CHGA+/+ and CHGA-/- mice, however, no differences in Lgr5+ and Ly6a+ expression were noted between CHGA+/+ and CHGA-/- mice in all conditions. In CHGA+/+ mice, inflammatory conditions led to higher MUC2 and RELMB expression, although, compared to CHGA+/+, these markers were significantly lower in CHGA-/- mice. In colitic conditions, compared to CHGA+/+, CHGA-/- had a significant increase of WFDC2. In non-colitic conditions, mRNA expressions of all markers evaluated between CHGA+/+ and CHGA-/- in this study were unaltered. Finally, no differences were observed in TFF3 gene expression.

Conclusions

These results indicate in the absence of CHGA, the colonic epithelial barrier integrity and function are maintained through the modulation of goblet cells functions and elevated gut mucosa regenerative potential, thus enhancing the mucosal protection to colitis damage.

Funding Agencies

CIHR
A186 CHANGES IN THE CLINICAL PHENOTYPE AND BEHAVIOR OF PEDIATRIC LUMINAL CROHN’S DISEASE AT DIAGNOSIS IN THE LAST DECADE
Authors: Sassine S , Savoie-Robichaud M , Lin Y , Djani L , Cambron-Asselin C , Qaddouri M , Fadela Zekhnine S , Grzywacz K , Groleau V , Dirks M , Drouin É , Halac U , Marchand V , Girard C , Courbette O , Patey N , Dal Soglio D , Deslandres C , Jantchou P
Published: February 2022

Background

Crohn’s disease (CD) triggers are incompletely understood and the incidence of the disease has been increasing.

Aims

The aims of this study were to describe the trends in the clinical, endoscopic, histological, and laboratory characteristics of pediatric CD during the last decade and to describe the seasonal variation of disease presentation at diagnosis.

Methods

Patients under 18 years old and diagnosed between 2009 and 2019 were included. Patients clinical, endoscopic, histological, and laboratory data were collected from the medical records. Data were analyzed for the cohort as a whole and according to diagnostic periods (2009–2014 and 2015–2019) and seasons.

Results

654 patients were included in the study. The total number of incident CD cases significantly increased yearly. Patients diagnosed between 2015 and 2019 were younger at diagnosis (OR: 2.30, p<0.0001), had more perianal diseases (OR= 2.30, p<0.001) and more intestinal biopsy granulomas (OR= 1.61, p=0.003) as compared to the 2009–2014 cohort. Also, there was a strong association between intestinal biopsy granulomas, young age at diagnosis and perianal fistulas or abscesses; the presence of granulomas was associated with greater perianal involvements (OR= 2.25, p<0.001) and younger age at diagnosis (OR = 0.90, p=0.0002). PCDAI and SES-CD scores at diagnosis, disease location and behavior and laboratory markers did not change over time.

There were fewer CD diagnosis during winter. The highest vitamin D levels in patients occurred in summer and fall, but the majority of patients had, regardless of the season of diagnosis, severe vitamin D deficiency (the median vitamin D level was 60.0 nmol/L in summer and fall compared to 47.0 nmol/L in winter-spring, p=0.003). Vitamin D levels at diagnosis are inversely correlated with PCDAI (Pearson correlation coefficient = -0.19, p=0.03) and SES-CD (-0.20, p=0.04). Patients diagnosed in fall had lower PCDAI and SES-CD scores, less failure to thrive, less digestive symptoms and less extensive digestive involvement. Colonic disease was significantly more frequent during summer and fall (27.3% of patients diagnosed in summer and fall versus 18.2% of cases in winter and spring, p=0.01).

Conclusions

The disease phenotype has changed over the years and there are important seasonal trends in the frequency and severety of the disease suggesting possible disease triggers. Our findings provide interesting avenues for future research, such as identifying the clinical significance of granulomas, vitamin D deficiency and microbiota on pediatric CD activity.

PCDAI at diagnosis according to the season.

Funding Agencies

NoneFonds Recherche Santé Québec / Fondation du CHU Sainte-Justine
A207 COMMON BILE DUCT OBSTRUCTION FROM RADIOGRAPHICALLY OCCULT LITHIASIS: A CASE REPORT AND CAUTIONARY TALE
Authors: Wang D , Jalali S , Tsoi K
Published: February 2022

Background

Biliary obstruction from choledocholithiasis (CDL) can lead to many serious complications, such as cholangitis and pancreatitis. Among noninvasive diagnostic tests for CDL, MRCP is superior to US and CT with a sensitivity of 89–95%. Despite this, MRCP may not always identify the cause of obstruction, leading to diagnostic dilemmas.

Aims

We aim to review the various ways that CDL can hide on imaging, specifically MRCP.

Methods

A 22-year-old male with pyruvate kinase deficiency was admitted to General Surgery for acute cholecystitis, for which he had a laparoscopic cholecystectomy. Preoperative MRCP showed a 3 mm common bile duct (CBD) with no stones; however, gross inspection of the gallbladder showed multiple green stones. Around one month later, he was readmitted to General Surgery for symptomatic biliary obstruction, with total bilirubin 923, ALP 457 and ALT 559. He was not febrile and did not require antibiotics. An MRCP showed a CBD of 10 mm with intra- and extrahepatic biliary dilation, but no obstructing focus was seen. Gastroenterology was consulted for undifferentiated hyperbilirubinemia. After further discussion, an ERCP with sphincterotomy was done the next day which also did not show obstruction. An abdominal US done the day after ERCP showed improvement in biliary dilation. After ERCP, the patient’s symptoms improved. Total bilirubin, ALP, and ALT one month later decreased to 121, 134, and 139 respectively. The hypothesis was that he had an obstructing gallstone that camouflaged within bile on imaging.

Consent was obtained from the patient to present this case report.

Results

Although MRCP is one of the best noninvasive diagnostic tests for CDL, some stones may not appear on imaging. On MRCP, stones usually appear as hypointense spots surrounded by hyperintense bile on T2-weighted imaging. However, sludge can be isointense compared to bile. Additionally, stones impacted at the ampulla of Vater typically are not surrounded by bile and thus may evade detection on MRCP. Small stones <4 mm can be missed as well. CBD dilation greater than 10 mm is also associated with reduced sensitivity of MRCP for CDL. Even with ERCP, small stones may be missed unless seen on direct optical visualization after a blind balloon sweep.

Even if no obstructing lesion is seen on imaging, other clinical features can still suggest CDL requiring ERCP. The ASGE 2019 Guidelines on CDL recommend prompt ERCP for patients with total bilirubin >68.4 µmol/L and CBD dilation on imaging. Other radiographic signs suggesting CDL include CBD dilation, papillitis, and pericholecystic fat infiltration on CT, and MRCP findings of CDL-associated inflammation such as biliary wall thickening and periductal edema.

Conclusions

Even if MRCP does not show obvious obstruction, ERCP should still be considered if the likelihood of CDL remains high.

Funding Agencies

None
A214 SIMPLIFICATION OF CARE FOR HCV IS EFFECTIVE DURING THE COVID PANDEMIC: A RETROSPECTIVE STUDY OF HCV TREATMENT UTILIZING THE BRITISH COLUMBIA HEPATITIS C NETWORK
Authors: Jiang S X , Feizi Farivar J , MacIsaac J , Tam E , Choi M , Luyun P , Ko H , Ramji A
Published: February 2022

Background

The COVID-19 pandemic has impacted healthcare access, including to curative treatment for hepatitis C (HCV) infection in the form of direct-acting antivirals (DAAs). A 49% decrease in DAA dispensations in Canada during the pandemic has been reported, but little is known about these treated populations.

Aims

To explore the patient characteristics and treatment patterns in those who were treated for HCV during the COVID pandemic.

Methods

A retrospective chart review was conducted at one site of utilizing the British Columbia Hepatitis C Network. Only patients included into the database were analyzed. Patients started on treatment between 03/17/2020-03/16/2021 were included as the “pandemic group” and patients from the 03/17/2019-03/16/2020 were included as a comparison “pre-pandemic group”. Data were extracted for clinicodemographic variables, laboratory investigations, treatment start date, regimen, and sustained virologic response at 12 weeks (SVR12).

Results

97 patients were treated during the pandemic compared to 143 patients the year prior, representing a 32% decline. Patients treated during the pandemic were predominantly new referrals (n=70, 72% vs n=64, 45% pre-pandemic, p<0.01) and had fewer total appointments (median 2 per patient vs 4 per patient pre-pandemic, p<0.01). There was a median of 1 in-person visit and 1 telehealth appointment per patient during the pandemic (vs median 2 per patient of each type pre-pandemic).

Pandemic patients were younger (mean age 56.0 years vs 59.6 pre-pandemic, p=0.04), and a greater proportion were on opioid agonist therapy (28% vs 13% pre-pandemic, p<0.01). Less transient elastography (TE) was performed during the pandemic (69% vs 89% pre-pandemic). Amongst those with TE scores, a lower proportion of those treated during the pandemic were cirrhotic (13% vs 21% pre-pandemic).

During the pandemic, treatment patterns shifted towards more prescriptions for glecaprevir/pibrentasvir (56% of all prescriptions vs 44% pre-pandemic) and sofosbuvir/velpatasvir (37% vs 29% pre-pandemic). There was slightly less use of sofosbuvir/velpatasvir/voxilaprevir at (2% vs 4% pre-pandemic).

The proportion of patients who completed lab work for SVR was similar during the pandemic (n=83/97, 85.6%) compared to pre-pandemic (n=120/143, 83.9%). Similarly, SVR12 remained high during the pandemic at 98.7% (vs 99.3% pre-pandemic). Of all 97 patients prescribed DAAs during the pandemic, 92 (94.8%) completed treatment.

Conclusions

Less persons were treated during the COVID pandemic, which may deter progress towards HCV elimination targets. Very high SVR12 and treatment completion rates during the pandemic suggest that patients can be effectively treated with less pre-treatment investigations and fewer appointments.

Funding Agencies

None
A217 TREATMENT ADHERENCE OF CHRONIC HEPATITIS B PATIENTS WITH HEPATOCELLULAR CARCINOMA FROM THE CANHEPB NETWORK
Authors: Rahman S H , Scharr Y , Jeyaparan J , Manko A , Coffin C S , Congly S E , Ramji A , Fung S , Cooper C , Ma M , Bailey R , Minuk G , Wong A , Doucette K , Elkhashab M , Wong P , Brahmania M
Published: February 2022

Background

Chronic hepatitis B (CHB) is the most common cause of hepatocellular carcinoma (HCC) worldwide.

Aims

The primary aim of this study is to explore the degree of treatment adherence to the American Association For The Study of Liver Disease (AASLD) HCC treatment guidelines for patients with CHB-HCC.

Methods

This is a retrospective, cross-sectional study of available data (2005–2020) in patients mono-infected with CHB collected from the Canadian HBV Network; a national consortium across 8 Canadian provinces. We analyzed data using descriptive statistics along with parametric and nonparametric statistical methods with a significance level of p < 0.05.

Results

Of the 6500 patients, 132 (2.0%) patients met inclusion criteria. The median age was 64 (IQR: 53.5- 71.5) with 101 (76%) being male. The median ALT was 40 (IQR: 26–59.5) and the median tumor number was 1(IQR: 1- 2) with a median tumor size of 2.6 cm (IQR: 1.9- 4.5). 98 (74.5%) patients were HBeAg negative with a median viral load of 3.8 logs (IQR 1.9 – 5.8). 58 (43%) patients had cirrhosis at diagnosis. 36% of patients were diagnosed with HCC on their first screening imaging whereas 39% were found to have HCC on repeated surveillance imaging. 116 (87.9%) were on treatment at the time of diagnosis or after (70 (60.3%) NA and 46 (39%) Combination therapy with double NA or NA plus interferon). Out of the 132 patients, BCLC stage 0, A, B, and C represented 30 (23%), 42 (32%), 17 (13%), and 5 (4%) patients, respectively, with 38 (28%) patients with unknown BCLC stage. The overall adherence to AASLD guidelines was 61%. The HCC treatment adherence rate for patients with BCLC stage 0, A, B were 63%, 97.5%, and 23.5%, respectively. BCLC stages C and D did not have a sufficient sample size for analysis. The adherence rate ranged from 53% (Eastern Canada) to 71% (Western Canada) across Canada.

Conclusions

In this retrospective nationwide cohort study of patients with CHB-related HCC, the overall treatment adherence rate to AASLD guidelines was low with notable regional differences. Further analysis will determine the cause of regional differences.

Funding Agencies

None
A223 THE CHAIR STAND TEST IS A RELIABLE FRAILTY METRIC FOR PREDICTING WAITLIST MORBIDITY AND MORTALITY IN PATIENTS WITH CIRRHOSIS
Authors: Nguyen V V , Wang S , Whitlock R , Xu C , Taneja S , Singh S , Abraldes J , Burak K , Bailey R , Lai J , Tandon P
Published: February 2022

Background

Frailty is defined as a clinical state of increased vulnerability to health and age associated stressors. The liver frailty index (LFI), composed of grip strength, chair stand and balance testing, is an accepted predictor of morbidity and mortality in cirrhosis. With the need for COVID-19 related social distancing, many appointments are being carried out virtually. The chair stand subcomponent of the LFI has the potential to be evaluated virtually, with a high reliability as compared to in-person testing noted in other disease populations.

Aims

To determine if the chair stand test is an independent predictor of morbidity and mortality in patients with cirrhosis.

Methods

822 adult patients with cirrhosis were prospectively enrolled from five centers (3 in Canada, 1 in the United States, and 1 in India). Inclusion criteria included adult patients with cirrhosis. 787 of these patients completed a chair stand test at baseline, measured as the time (seconds) a patient takes to rise from sitting with their arms folded across their chest five times (measured in-person). The times were divided into 3 categories: >15 seconds, between 10 and 15 seconds, and <10 seconds. Patients who could not complete 5 chair stands were classified in the >15 seconds category. Primary outcome was all-cause mortality. Secondary outcome was unplanned all-cause hospital admission. Fine-Gray proportional hazard regression models were used to evaluate the association between the chair stand time and the outcomes. We adjusted for baseline age, sex, and MELD score and accounted for liver transplantation as a competing risk. Cumulative incidence functions were used to create a graphical representation of the survival analysis.

Results

Patients were divided into three groups: group 1, <10 seconds (n = 276); group 2, 10–15 seconds (n = 290); and group 3, >15 seconds (n = 221). Mortality was increased in group 3 in comparison to group 1 (HR 3.21, 95% CI: 2.16–4.78, p<0.001). Similarly, the hazard of non-elective hospitalizations was higher in group 3 in comparison to group 1 (HR 2.24, 95% CI: 1.73–2.91, p<0.001). Overall, patients with chair stand times greater than 15 seconds had increased all-cause mortality (HR 2.78, 95% CI 2.01–3.83, p<0.001) and non-elective hospitalizations (HR 1.84, 95% CI 1.48–2.29, p<0.001) when compared to patients with times less than 15 seconds.

Conclusions

A time to complete 5 chair stands of >15 seconds predicts morbidity and mortality in patients with cirrhosis. This test shows promise as a frailty measure that could be evaluated over a virtual platform.

Funding Agencies

None
A226 SEX-BASED DISPARITY COMPLICATIONS FOLLOWING LIVER TRANSPLANTATION
Authors: Singh N , Chow J , Ebadi M , Ma M , Montano-Loza A J , Bhanji R
Published: February 2022

Background

Sex-based disparity exists in liver transplantation (LT) with women being disadvantaged at every stage of the process starting from assessment to post transplantation (Bryce et al., 2009). The reasons for this are multifactorial and include biological disparities, psychosocial, and allocation inequalities (Burra et al., 2013).

Aims

The purpose of this study was to identify differences in immediate or long-term complications post-LT by sex.

Methods

We analyzed 702 patients who underwent LT at the University of Alberta from 2002 to 2015. Patients aged < 18 years or requiring a repeat or multivisceral transplant were excluded. Renal dysfunction was defined according to the KDIGO criteria. Cardiovascular disease (CVD) was defined as hospitalization for or death from coronary artery disease, cardiac arrest or cerebrovascular disease.

Results

Male patients comprised 69% of the population. Time on the waitlist was similar for men (9.3 ± 11.7 months) and women (9.9 ± 12.3 months; p=0.57). Both sexes were comparable in age (males: 53 ± 10 years; females: 52 ± 11 years; p=0.19), MELD (males: 18 ± 9; females: 19 ± 10; p=0.16) and BMI (males: 27.7 ± 5.7 kg/m2; females: 27.3 ± 6.6 kg/m2; p=0.58). Women had lower creatinine pre-LT (males: 1.1 ± 0.60 mg/dL; females 0.96 ± 0.51 mg/dL; p<0.01). There were no differences in donor age, sex or BMI. Women had significantly longer hospital length of stay (males: 18 days [IQR: 11, 32]; females: 25 days [IQR: 14, 43]; p <0.001). There was no difference in risk of acute kidney injury (OR 1.4 [95% CI: 0.98, 2.1]; p=0.06), infection (OR 1.1 [95% CI: 0.8, 1.5]; p=0.52) or rejection episodes (OR 1.1 [95% CI: 0.8, 1.5]; p=0.74) following LT. Women had a higher risk of CKD post-LT (OR 2.3 [95% CI: 1.6, 3.2]; p<0.0001). There was no difference in de-novo diabetes (males: 22%; females: 16%; p=0.10), hypertension (males: 45%; females: 48%; p=0.41), dyslipidemia (males: 37%; females: 39%; p=0.67) and CVD (males: 20%; females: 19%; p=0.84) post-LT. Graft (males: 11.4 ± 0.4 years; females: 11.8 ± 0.5 years; p=0.32) and patient survival (males: 11.8 ± 0.4 years; females: 12.4 ± 0.5 years; p=0.18) were similar over a median follow up of 6.3 years [IQR: 3.5, 9.9].

Conclusions

Women spend a longer time in hospital and are at an increased risk of CKD following LT. Despite these differences, overall graft and patient survival are comparable. Our data suggest the disparity between sexes likely exists pre-LT and females that undergo LT have similar outcomes to their male counterparts.

Funding Agencies

None
A230 THE ROLE OF THE MICROBIOTA IN NOCICEPTOR DEVELOPMENT AND PAIN SENSITIVITY
Authors: Abdullah N , Defaye M , Hassan A , Cumenal M , Iftinca M , Young D , Ohland C L , Dufour A , McCoy K , Altier C
Published: February 2022

Background

Pain is the most common cause of disability in IBD. What causes inter-individual variability in chronic pain after successful treatment of inflammation remains elusive. We have shown that activation of TRPV1+ colonic nociceptors is essential for the establishment of persistent pain in DSS colitis. Nociceptor development coincides with microbial colonization, while early life dysbiosis can lead to visceral hypersensitivity in adulthood. Whether the microbiota dictates nociceptor development and pain susceptibility remains unknown. Here we test the hypothesis that the microbiota programs nociceptor specification during early development, rendering them more susceptible to sensitization later in life. We have identified the aryl hydrocarbon receptor (AHR) that senses bacterial-derived metabolites as a candidate target that orchestrates transcriptional regulation in nociceptors.

Aims

We investigated the developmental regulation of nociceptors by the microbiome and how it influences pain sensitivity. We will determine the effects of AHR activation on nociceptor lineage and function as well as the long term impact of AHR signaling on pain sensitivity.

Methods

We have developed a germ-free (GF) TRPV1-GFP reporter mouse that was used to phenotype and visualise TRPV1+ nociceptors in the absence of a microbiota. We will isolate TRPV1+ neurons by FACS to identify genes that are under the control of the microbiota and to characterise the phosphoproteome of TRPV1+ nociceptors in GF conditions. Finally, we will investigate the role of AHR signaling in nociceptors both acutely and during development.

Results

We showed a reduction in thermal pain threshold and a reduction in capsaicin test responses in GF mice. The number and size of DRG neurons was unchanged in GF mice. Examination of molecular markers for peptidergic (CGRP) and non-peptidergic (IB4) neurons did not show a difference. Finally, there was no difference in the expression of TRPV1, suggesting post-translational modification of the channel. In cultured DRG neurons, we found a decrease in capsaicin induced action potentials and a decrease in the amplitude of the capsaicin response in GF mice. Using RNAscope, we showed that TRPV1+ neurons express AHR.

Conclusions

Our results highlight the importance of bacterial composition in regulating the development of nociceptors and pain sensitivity in adulthood. Furthermore, we are the first to demonstrate the expression of AHR in sensory neurons. These findings point to a role of the microbiota in programming nociceptors during development. My work will advance our understanding of the role of commensal bacteria in regulating pain and could lead to recommendations for the treatment of neonates in early life to reduce their risk of developing chronic pain later in life.

Funding Agencies

CAG, CIHR
A249 RETROSPECTIVE CHART REVIEW OF PATIENTS WITH MALNUTRITION REQUIRING ADVANCED NUTRITIONAL SUPPORT POST BARIATRIC SURGERY
Authors: Tsang L , Fredriksen M , Jin J , Gramlich L
Published: February 2022

Background

Obesity is a global pandemic with a steady increase in global BMI since 1975. Bariatric surgery is an effective treatment for patients with severe obesity in order to sustain long-term weight loss and reduce comorbidity burden and mortality associated with obesity. However, post-bariatric surgery patients face nutritional complications ranging from micronutrient deficiencies to intestinal failure requiring total parenteral nutrition (TPN). From our institution of home TPN patients, 6.4% of patients had bariatric surgery. Intestinal failure is a burdensome diagnosis for patients, and there is a paucity of literature characterizing patients post-bariatric surgery who develop intestinal failure.

Aims

We aim to identify the patient characteristics, surgical details, and nutritional traits that predisposed patients to developing intestinal failure requiring advanced nutritional support.

Methods

This is a retrospective chart review of 48 patient admitted to the Royal Alexandra Hospital post-bariatric surgery for nutritional support and followed by the TPN program dieticians and nurses.

Results

Our results show the mean BMI was 49.94 kg/m2 pre-bariatric surgery. Interestingly, the mean BMI at time of hospitalization for bariatric-surgery related complications was 33.210 kg/m2 which is classified as overweight but most of patients were severely malnourished with SGA C (43.8%), SGA B (29.17%), and 8.3% were SGA A. Patients requiring parenteral nutrition post-bariatric surgery are mostly female, developed barriers to oral intake, 15% engaged in medical tourism, 58.3% had an underlying mental health diagnosis, and only 18.8% were on a multivitamin even though it is standard of post-bariatric surgery care. The time between initial bariatric surgery to hospital admission was 11.2 years, and most required ≥1 revisional surgery. The mean age at bariatric surgery was 33.2-years old and the average age at initial hospitalization was 48.9-years old. Patients requiring ≥2 admissions had vertical band gastroplasty or sleeve gastrectomy (both 36.8%) while 21.1% had Roux-en-Y gastric bypass. Of these patients, 39.6% of patients required ≥2 hospital admissions and the mean total days spent in hospital was 57.15 days. While these complications are uncommon, these patients result in multiple prolonged hospitalizations and can be difficult to manage.

Conclusions

Overall, the results of our study will allow the multidisciplinary teams that care for post-bariatric surgery patients to identify patients at risk of intestinal failure and potentially intervene with early enrollment into home nutrition program. With increasing awareness, patients at higher risk can be closely monitored in order to prevent micronutrient deficiencies before they progress to intestinal failure and require lifetime parenteral nutrition.

Funding Agencies

None
Rapid Evolution of Seed Dormancy During Sunflower De-Domestication
Authors: Hernández Fernando , Vercellino Roman B , Pandolfo Claudio , Mandel Jennifer R , Presotto Alejandro
Published: February 2022

Hybridization between crops and their wild relatives may promote the evolution of de-domesticated (feral) weeds. Wild sunflower (Helianthus annuus L.) is typically found in ruderal environments, but crop–wild hybridization may facilitate the evolution of weedy populations. Using 1 crop-specific mitochondrial marker (CMS-PET1) and 14 nuclear SSR markers, we studied the origin and genetic diversity of a recently discovered weedy population of sunflower (named BRW). Then, using a resurrection approach, we tested for rapid evolution of weedy traits (seed dormancy, herbicide resistance, and competitive ability) by sampling weedy and wild populations 10 years apart (2007 and 2017). All the weedy plants present the CMS-PET1 cytotype, confirming their feral origin. At the nuclear markers, BRW showed higher genetic diversity than the cultivated lines and low differentiation with one wild population, suggesting that wild hybridization increased their genetic diversity. We found support for rapid evolution towards higher seed dormancy, but not for higher competitive ability or herbicide resistance. Our results highlight the importance of seed dormancy during the earliest stages of adaptation and show that crop–wild hybrids can evolve quickly in agricultural environments.
Open the Doors: Towards Complete Freedom of Movement for Human Rights Defenders in Exile in Uganda
Authors: White Nastassja , Agostini Nicolas , Bandera Memory , Bikanda Joseph , Grandolfo Francesca , Hakizimana Janvier , Kabachwezi Estella , Netuwa Tabitha , Nsiku Leon , Shire Hassan
Published: February 2022

Uganda attracts the highest number of migrants, refugees, and asylum-seekers in the East and Horn of Africa sub-region. Factors including an ‘open door’ policy, relative political stability, and a central geographical location have contributed to Uganda becoming an attractive hub for human rights defenders. The right to freedom of movement is enshrined in all significant human rights treaties and many regional and sub-regional economic treaties, including the one establishing the East African Community. However, in practice many exiled human rights defenders and refugees face various obstacles to move freely.

This article explores the scope and meaning of freedom of movement into, within, and out of Uganda. Uganda remains one of, if not the most open country in the region for asylum-seekers, where everyone, including refugees and exiled human rights defenders, may move and settle wherever they choose. However, the majority of human rights defenders struggle to leave Uganda as they usually do not possess a national passport. While Convention Travel Documents, or refugee passports, are provided for under Ugandan and international refugee law, they are elusive in the refugee community and the majority of those interviewed face overwhelming challenges in obtaining one. This leaves many feeling hopeless and not in control of their own future or opportunities, as they are unable to travel within the East African Community, or beyond, for any reason. In particular, women human rights defenders and those who identified as, or advocated for the LGBTIQ (lesbian, gay, bisexual, transgender, intersex and queer) community, face compounded difficulties when moving within and out of Uganda, including arbitrary restrictions by authorities, violations by private actors, and protection concerns when moving.