bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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 &gt;30 day supply or &gt;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

Abstract

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 &gt;200 cells/μl) versus low PBE (eosinophils &lt;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 &gt;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

Abstract

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

Abstract

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

Abstract

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

Abstract

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&lt;0.0001), had more perianal diseases (OR= 2.30, p&lt;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&lt;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

Abstract

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 &lt;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 &gt;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

Abstract

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&lt;0.01) and had fewer total appointments (median 2 per patient vs 4 per patient pre-pandemic, p&lt;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&lt;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