bluuebunny/crossref_metadata_2025 huggingface dataset:
A139 CANADIAN GASTROENTEROLOGY CAREER PATHWAY EXPERIENCES: A GENDER DIVIDE UNDER EXAMINATION
Authors: Jawaid N , Boctor M , Lomonaco J , Bollegala N
Published: February 2020

Background

The number of Canadian gastroenterologists has been on the rise in the last 20 years but female representation has stayed disproportionately low (30%). Gastroenterology has remained a male dominated subspecialty despite research showing as early as 1990’s that systemic gender-based barriers exist.

Aims

To determine whether GI career profiles differ between male and female gastroenterologists and understand barriers to career advancement related to gender in order to help shape future interventions to counteract these issues.

Methods

A 51-question survey was disseminated to gastroenterologists practicing in Canada. Using provincial College of Physicians and Surgeons websites, an electronic survey was sent to GIs with email addresses and a paper copy to those with fax numbers. The Canadian Association of Gastroenterology sent our survey link in their September 2019 membership email. The survey included questions pertaining to personal, professional, financial and practice characteristics of participants. Data was analyzed using SAS statistical program, and descriptive analysis with 95% confidence intervals was used to compare proportions of men and women. Nonparametric tests were used for continuous data. Qualitative thematic analysis was applied for short answer responses.

Results

Total 98 responses received (14.7% response rate) with 35% female respondents. Majority had adult, urban practices (86%) but males reported significantly more endoscopy time (42% v. 30%) vs. females who spent more time on research (23% v. 10%). Men were more likely to be married and have children than females. Women were more likely to not only have to choose between their marriage and their career, but more chose marriage compared to men specifically taking time off for maternity or childcare needs. Men were more likely to leave childcare predominantly to their spouse whereas women were more likely to share responsibility of childcare with spouse and hired help. Even after adjusting for age, males earned a significantly higher income than females (>$100,000 difference). 40% of men reported a salary over $600,000, compared to only 4% of women. Several gender-based biases were cited by females during their staff GI career: receiving less recognition for their work, challenging relationships with senior colleagues and support staff, inferior promotion opportunity, more difficulty publishing research and having their competency challenged by peers.

Conclusions

This survey shows that there are still many differences in the Canadian GI career pathway experience based on gender. Female GIs are disproportionately negatively affected in their clinical and academic practices, renumeration and work-life balance. Understanding these disparities is the first step towards remedying gender inequality in GI workplace culture.

Funding Agencies

None
A141 ENDOSCOPIST PROCEDURAL VOLUME AND COLONOSCOPY OUTCOMES: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Forbes N , Boyne D , Brenner D R , Mazurek M S , Hilsden R J , Ruan Y , Sutherland R L , Pader J , Shaheen A M , Lamidi M , Heitman S
Published: February 2020

Background

In addition to monitoring adverse events (AEs) and post-colonoscopy colorectal cancers (PCCRC), several indicators are used to assess the overall quality of colonoscopy performance, including adenoma detection rate (ADR) and cecal intubation rate (CIR). It is unclear whether there is an association between an endoscopist’s annual colonoscopy volumes and ADR, CIR, AEs or PCCRC.

Aims

We performed a systematic review and meta-analysis to determine whether there is an association between annual colonoscopy volume and colonoscopy quality indicators, or between annual volume and colonoscopy outcomes.

Methods

A comprehensive electronic search was performed through March of 2019 for any studies assessing the potential association between annual colonoscopy volume and outcomes, or quality indicators, including ADR, CIR, AEs or PCCRC. Pooled odds ratios (OR) were calculated using DerSimonian and Laird random effects models. Subgroup and sensitivity analyses were also performed to assess for any potential methodological or clinical factors associated with outcomes. These included dividing procedural volume into total procedures or screening procedures performed.

Results

Out of an initial 9,235 studies, 27 were included in our systematic review, representing 11,276,244 colonoscopies performed by over 530 endoscopists. There was no association between procedural volume and ADR (OR 1.00, 95% confidence intervals, CI, 0.98 to 1.02 per additional 100 annual total colonoscopy procedures performed by an endoscopist). CIR was improved with each additional 100 annual colonoscopy procedures (OR 1.17, 95% CI 1.08 to 1.28). There was a trend toward decreased overall adverse events per additional 100 annual procedures that did not meet significance (OR 0.95, 95% CI 0.90 to 1.00), although there was a decreased incidence of colonic perforations with increasing colonoscopy volume. Figure 1 - Forest plots demonstrating the odds of A) detecting an adenoma, B) intubating the cecum, and C) incurring an overall or specific adverse event, per additional 100 annual procedures, for total and screening procedures.

Conclusions

In this meta-analysis, higher annual colonoscopy volumes correlated with higher CIR, but not with ADR or PCCRC. Trends toward lower AE rates were also demonstrated with higher volumes. All studies included in this review examined endoscopists performing above respective recommended minimum volume thresholds for their health region. Thus, data are lacking on endoscopists performing very low numbers or very high numbers of colonoscopies annually. Future studies should focus on measuring colonoscopy quality metrics and outcomes among these extreme performers to more clearly determine associations between annual volume and colonoscopy outcomes.

Funding Agencies

Alberta Health Services Digestive Health Strategic Care Network
A144 A MULTIDISCIPLINARY TEAM APPROACH REDUCES PEG SITE COMPLICATIONS
Authors: Truax A M , Reardon J , Naranian T , Liu L W
Published: February 2020

Background

Education provided to patients and their family on how to care for the percutaneous enteroscopic gastrotomy (PEG) tube is limited and varies widely. This can result in site and tube complications, patient discomfort and increased health care utilization. In addition, a lack of practitioner expertise and variability in practice can affect timely treatment of PEG site complications. Continuous Levodopa/Carbidopa Intestinal Gel (LCIG) has become a standard of treatment option for patients with advanced Parkinson Disease. This medication is delivered by a jejunal tube through a PEG tube (PEG-J). Previous studies in this population reported up to 40% of adverse events related to the PEG site. At Toronto Western Hospital, we developed a multidisciplinary team (MDT), involving a gastroenterologist, a clinical nurse specialist (CNS) with expertise in wound and stoma care and the movement disorder clinical nurse to care for the PEG-J in this patient population.

Aims

To evaluate the effectiveness of our MDT in reducing PEG site complications and health care utilization.

Methods

Consecutive PEG-J patients (n=33) assessed by the MDT between October 2018 and September 2019 were provided standard education on the routine care and maintenance of PEG site complications. The CNS uses a systematic approach to prevent, assess and treat PEG site complications. Before and after the MDT approach, patients were seen the day after the PEG insertion (POD 1), 2 weeks after (titration) and then ad hoc determined by incidence of mild, moderate and severe complications. Post implementation of a MDT approach, patients are seen POD 1, at titration and every 3–6 months during routine visits to the Movement Disorder Clinic. Table 1 outlines classification and suggested treatment based on severity for mild, moderate and severe PEG site complications.

Results

The systematic MDT approach completely eliminated all unscheduled, urgent contact to the health care providers by patients who have been assessed and provided education by the MDT (n=33), including new PEG-J (n=7) and previously inserted PEG-J (n=26). 28.5% of new PEG-J patients had moderate or severe site complication rate, 71.5% had mild or no complications. In the group of patients with previously inserted PEG-J tubes, 58% had moderate or severe site complications, 42% had mild or no complications.

Conclusions

An interprofessional MDT systematic approach drastically reduces PEG site complications and urgent health care utilization. Patients who receive standardized education pre- and post-insertion have a lower incidence of moderate or severe classification of PEG site complications and unscheduled clinic visits.

Funding Agencies

None
A194 PRESENCE OF CELIAC DISEASE IN PATIENTS WITH BARRETT’S ESOPHAGUS IS ASSOCIATED WITH FASTER DEVELOPMENT OF DYSPLASIA AND HIGHER RATES OF ESOPHAGEAL ADENOCARCINOMA
Authors: Rueda G H , Wolfe M , Nardelli A , Chauhan U , Moayyedi P , Armstrong D , Verdu E , Pinto-Sanchez M I , Bercik P
Published: February 2020

Background

Celiac disease (CD) has an estimated prevalence of 1% worldwide, including North America. Barrett’s esophagus (BE) is a complication of chronic gastroesophageal reflux disease (GERD), which predisposes to development of dysplasia, which can transition to esophageal adenocarcinoma (EAC). GERD is commonly found in patients with CD and there is evidence that reflux symptoms improve after starting the gluten-free diet. However, the prevalence of CD in patients with BE, and its impact on progression to EAC have not been studied.

Aims

To assess the prevalence of CD in patients with BE and its impact on development of dysplasia and EAC.

Methods

We performed a retrospective review of medical records of patients attending the Digestive Diseases Clinic and the specialized Barrett’s Clinic at McMaster University Medical Centre. We collected information related to demographics, esophageal and duodenal biopsies, as well as CD serological markers. CD diagnosis was based on the presence of Marsh III lesions in duodenal biopsies and/or positive tissue transglutaminase IgA antibodies (TTG). Categorical data was presented as n/N and %, continuous data as mean ±SD. Logistic regression was performed to estimate the association between BE and CD. For dysplasia development, Kaplan Meyer Breslow survival curve was used.

Results

CD was found in 1.8% of patients attending the Digestive Diseases Clinic (n=4800). Two hundred and sixteen patients with BE from the Digestive Diseases Clinic and the Barret’s Clinic (age 63 ±11.2, 70.3% males; follow-up period 7.0 ±5.5 years) were included in the analysis. Patients with or without CD were similar in demographic factors, concomitant diseases or previous surgeries, use of PPI, presence of symptoms and duration of treatment. The prevalence of CD was increased 5-fold in patients with BE (OR=6.0; 95% CI 2.1–17.4; p=0.006). BE patients with CD developed dysplasia earlier than those without CD (Long Rank 0.004; mean 6.0; 95% CI 3.0–4.97[PB1]). The risk of EAC was higher in BE patients with CD compared to those without CD (2/11 vs 2/205; OR=22.5; 95% CI 2.8–178.8; p= 0.003). The mean time for development of EAC from the time of BE diagnosis [PB2] was 1.5 years in patients with CD and 6.5 years in patients without CD.

Conclusions

The prevalence of CD is higher in patients with BE compared with the population attending a tertiary gastroenterology clinic, and with the general population. Patients with BE and concomitant CD are at increased risk of accelerated development of dysplasia and EAC, suggesting that both conditions may have a synergic detrimental effect.

Funding Agencies

CIHR
A199 BLACK ESOPHAGUS: AN UNDER-RECOGNIZED CAUSE OF UPPER GASTROINTESTINAL BLEEEDING
Authors: Arora A , Tsoi K
Published: February 2020

Background

“Black esophagus” is a term that refers to the endoscopic manifestation of acute esophageal necrosis (AEN), a rare but potentially under-recognized cause of upper gastrointestinal bleeding, characterized by the presence of strikingly black necrotic esophagus on upper endoscopy. The etiology is unclear although ischemic insults and caustic injury from gastric acid exposure are thought to play prominent roles. This condition is often seen in patients who are systemically unwell and have underlying comorbidities such as diabetes mellitus and vascular diseases.

Aims

We present a case of an elderly woman with diabetes and poor glycemic control who developed coffee ground emesis with her upper endoscopy revealing evidence of acute esophageal necrosis. AEN is an important diagnosis to consider in diabetic patients, as it generally carries a poor prognosis with mortality rates as high as 32% reported in the literature.

Methods

Case report and review of the literature

Results

A 61-year-old woman with medical history significant for poorly controlled insulin dependent diabetes (hemoglobin A1c, 11%) developed coffee ground emesis (confirmed via insertion of nasogastric tube) three days after initial admission to hospital for left tibial plateau fracture. Her bloodwork did not reveal any underlying diabetic ketoacidosis or hyperosomlar hyperglycemic state. Her esophagogastroduodenoscopy (EGD) showed black, necrotic-appearing discoloration of the esophageal mucosa circumferentially within the mid to distal part of the esophagus with a sharp transition point towards normal appearing mucosa at the gastroesophageal junction. Biopsies were deferred due to high risk of bleeding and perforation, and the previously placed nasogastric tube was not removed.

After endoscopy, conservative management was advised with restricted oral intake, intravenous proton pump inhibitor (PPI) inhibitor therapy for 72 hours and aggressive treatment of ongoing hyperglycemia. There were no signs or symptoms of esophageal rupture. The patient gradually recovered and in fact had her orthopedic surgery within a week of EGD. Furthermore, three days into the post operative period she developed venous thromboembolism and was placed on full dose oral anticoagulation and tolerated this without any further gastrointestinal bleeding.

Conclusions

AEN is an important diagnostic consideration in elderly diabetic patients presenting with acute upper gastrointestinal bleeding, particularly as timely recognition and management can significantly lower the unfavorable mortality associated with this condition.

Funding Agencies

None
A202 DYSREGULATED ENDOPLASMIC RETICULUM STRESS PATHWAYS IN COLON-DERIVED ENTEROIDS FROM INFLAMMATORY BOWEL DISEASE PATIENTS DRIVE DC MATURATION LEADING TO A PRO-INFLAMMATORY PHENOTYPE
Authors: Rees W D , Stahl M , Jacobson K , Bressler B , Sly L M , Vallance B , Steiner T
Published: February 2020

Background

Intestinal epithelial cells (IECs) rely on danger signals such as adenosine triphosphate (ATP) and endoplasmic reticulum (ER) stress to form an appropriate, coordinated immune response. Moreover, ER stress in IECs contributes to the pathogenesis of inflammatory bowel disease (IBD), and an increase in extracellular ATP concentrations is a risk factor for Crohn’s disease (CD).

Aims

We hypothesized that cells exposed to ER stress or ATP modulate innate immune responses, creating a pro-inflammatory environment that drives dendritic cell (DC) maturation.

Methods

Caco-2 cells and human colon-derived enteroid monolayers were exposed to ATP or the ER stress inducer thapsigargin, stimulated with E. coli FliC flagellin, and ER stress markers CHOP, GRP78, and XBP1 s/u were measured via qPCR and western blot, and cytokine release was measured by ELISA. Next, monocyte-derived dendritic cells (moDCs) were cultured in Caco-2 or enteroid conditioned supernatants and their activation status measured via flow cytometry, and cytokine analysis was performed using Luminex platform. We also assessed ER stress markers, TLR5 expression, and cytokine expression differences between IBD and healthy controls (HC).

Results

We found that ER stress amplified FliC-induced IL-8 and decreased CCL20 in Caco-2 cells. Moreover, in IBD subjects, we found an increase FliC-induced IL-8 response, and decreased TNFa and CCL20. moDCs cultured with conditioned media from Caco-2 or enteroid monolayers showed a proinflammatroy phenotype, with an increase in CD80, CD86, MHCII, and a decrease in CD103. Moreover, moDCs cultured in stressed Caco-2 supernatants increased release of IL-6, TNFa, and IL-12p70, and decreased IL-10, suggesting potential to induce inflammatory Th1 and/or Th17 cells.. DC activation correlated with the amount of FliC-induced IL-8. Interestingly, there were distinct differences in cytokine expression and basal ER stress between IBD and HC enteroid monolayers, suggesting a dysregulated ER stress pathway in IBD-derived enteroids.

Conclusions

ER stress in Caco-2 cells and colon-derived enteroid monolayers enhances FliC-induced TLR5 responses, leading to a pro-inflammatory environment that drives DC maturation, which may link epithelial ER stress and immune cell activation in IBD. Furthermore, the cytokine and ER stress pathway differences between IBD and HC-derived enteroids suggests that prolonged periods of stress in IBD patients may rewire the IEC stem cell compartment, further perpetuating inflammation and disease.

Funding Agencies

CCC, CIHR
A208
HLA-DQA1*05 GENOTYPE PREDICTS ANTI-DRUG ANTIBODY FORMATION AND LOSS OF RESPONSE DURING INFLIXIMAB THERAPY FOR INFLAMMATORY BOWEL DISEASE
Authors: Peel C , Wang Q , Pananos A , Kim R , Wilson A
Published: February 2020

Background

The underlying mechanism for immunogenicity in anti-TNFa-exposed patients with inflammatory bowel disease is poorly understood. Anti-drug antibodies are a leading contributor to infliximab loss of response and adverse drug events. Currently, it is not feasible to identify patients at risk of antibody formation prior to initiating infliximab. The genetic variation HLADQA1*05(rs2097432) has been linked to infliximab antibody formation in a cohort of patients with Crohn’s disease.

Aims

Due to the wide variation in the frequency of HLADQA1* 05 across ethnic groups, we aim to independently evaluate the association between HLADQA1*05and infliximab antibody formation, infliximab loss of response, treatment discontinuation and adverse drug events, in a Canadian inflammatory bowel disease cohort.

Methods

In a retrospective cohort study, infliximab-exposed patients with inflammatory bowel disease (n=262) were screened for the genetic variation, HLADQA1*05A>G(rs2097432). The risk of infliximab anti-drug antibody formation, infliximab loss of response, adverse events, and discontinuation were assessed in wild type (GG) and variant-carrying (AG or AA) individuals.

Results

Forty percent of all participants were HLADQA1*05A>Gvariant carriers, with 79% of participants with infliximab antibodies carrying at least one variant allele. The risk of infliximab antibody formation was higher in HLADQA1*05A>Gvariant carriers in an IBD population (adjusted HR=7.29, 95%CI=2.97–17.191, p=1.46x10-5) independent of age, sex, weight, dose and co-immunosuppression with an immunomodulator. Variant carrier status was associated with an increased risk of infliximab loss of response (adjusted HR=2.34, 95%CI=1.41–3.88, p=0.001) and discontinuation (adjusted HR=2.27, 95%CI=1.46–3.43, p=2.53x10-4) though not with infliximab-associated adverse drug events.

Conclusions

HLADQA1*05 is independently associated with a high risk of infliximab antibody formation in addition to infliximab loss of response and treatment discontinuation. As a result, we propose that pre-emptive genetic screening for the HLADQA1* 05A>Gvariant would be useful in order to predict individuals at risk of developing immunogenicity. There may be a role for genotype-guided application of combination therapy in inflammatory bowel disease.

Funding Agencies

NoneWolfe Medical Research Chair in Pharmacogenomics (MOP-89753 to RBK), the Academic Medical Organization of Southwestern Ontario (INN18-005 to RBK and AW; S17-004 to AW), and Lawson Health Research Institute (IRF-05-19 to AW)
A215 PATIENTS WITH INFLAMMATORY BOWEL DISEASE ARE FREQUENTLY PRESCRIBED OPIOID ANALGESICS WHEN DISCHARGED FROM THE EMERGENCY DEPARTMENT
Authors: Chhibba T , Panaccione R , Seow C , Lu C , Novak K L , Kaplan G G , Ma C
Published: February 2020

Background

Patients with inflammatory bowel disease (IBD) suffer a substantial burden of morbidity related to chronic abdominal pain and are susceptible to opioid dependence and abuse that is associated with increased rates of depression, hospitalization, and mortality. While opioid prescription and renewal by a single provider minimizes the long-term risk of misuse, many patients with IBD will seek out care in the emergency department (ED) where short-term, ‘to-go’ use of narcotic analgesia is associated with potential treatment-related complications.

Aims

To assess rates of opioid prescription in IBD patients presenting to the ED and to assess factors associated with opioid use.

Methods

This is a retrospective analysis of cross-sectional data collected in the United States National Hospital Ambulatory Medical Care Survey (NHAMCS) from 2006–2015. We compared a study population of adult IBD patients (International Classification of Diseases ICD-9 555.X, 556.X) ≥18 years discharged from the ED to a control group of patients presenting with non-specific abdominal pain (ICD-9 789.0, 564.1, 536.8). The proportion of patients given opioids in ED and at ED discharge were calculated with relative standard error (RSE), and national level estimates were produced using survey weights. Univariable and multivariable logistic regression was used to evaluate predictors of opioid prescription at discharge, expressed as odds ratios (OR) with 95% confidence intervals (CI).

Results

A total of 767,577 IBD patients were compared to 71,359,257 patients with non-specific abdominal pain. A total of 37.3% (RSE 4.7%) of IBD patients compared to 24.7% (RSE 0.8%) of controls (p<0.01) received an opioid prescription on ED discharge. 49.1% (RSE 5.6%) of IBD patients compared to 37.2% (RSE 0.8%) of patients with non-specific abdominal pain (p=0.02) received an opioid while in ED. Significant predictors of narcotic prescription at discharge in multivariable analysis included: age <50 (OR 6.83 [95% CI: 1.21, 38.48], p=0.03), non-white race (OR 4.73 [95% CI: 1.46, 15.39], p=0.01), and narcotic use in the ED (OR 5.27 [95% CI: 1.96, 14.21], p<0.01).

Conclusions

Nearly 40% of IBD patients were prescribed an opioid at discharge from the ED. This rate is significantly higher than for patients who present with non-specific abdominal pain and younger, non-white IBD patients were disproportionately more likely to receive an opioid prescription. Given the risks associated with on-demand narcotic use in IBD patients, our data highlight a potential gap in care for accessing comprehensive pain management solutions.

Funding Agencies

None
A228 EVOLUTION OF MRE FINDINGS IN PAEDIATRIC PATIENTS WITH SMALL BOWEL CROHN’S DISEASE ON MAINTENANCE METHOTREXATE
Authors: Kellar A , Carmen N , Greer M , Walters T , Griffiths A , Church P
Published: February 2020

Background

Observational data in children and RCT data in adults indicate that methotrexate (MTX) is associated with induction and maintenance of clinical remission in luminal Crohn’s disease, but efficacy in achieving intestinal healing has not been examined.

Aims

To examine the evolution of MRE signs of inflammation in children treated with MTX.

Methods

In this retrospective cohort study, we reviewed paediatric CD patients on maintenance MTX monotherapy for >4 months who underwent serial MREs between July 2010 and October 2015. MREs were reviewed by a radiologist blind to clinical data. Overall inflammatory activity on each MRE was scored as minimal, mild, moderate or severe, informed by the presence of bowel wall thickness, wall enhancement, T2 hyperintensity, comb sign, mesenteric edema, penetrating disease, stricturing, diffusion restriction and motility. The radiologist’s global assessment of change from MRE 1 to MRE 2 was scored as improved, unchanged or worsened. Clinical findings, disease activity (assessed by weighted paediatric CD activity index [wPCDAI]) and surgical history were also extracted from medical records by a clinician blind to MRE results.

Results

Thirty-five patients were included (median age at diagnosis 12 [IQR 11–14] years; 77% male; 60% inflammatory (B1), 17% stricturing (B2), 23% penetrating (B3) disease). Between baseline and follow-up MRE, wPCDAI (median 15 [IQR 7–43] decreased to 8 [IQR 0–18]; p=0.006) and CRP (median 9 [IQR 2–36] decreased to 5 [IQR 5–9]; p=0.013) and 74% (N=26) were in clinical remission (wPCDAI < 12.5) at MRE 2. MRE features that significantly improved from MRE 1 to 2 were comb sign from 63% (N=37) to 38% (N=14) (p=0.02) and penetrating disease from 14% (N=8) to 0 (p=0.03). After a median of 17 months (IQR 13–23), 51% (N=18) of patients improved, 29% (N=10) worsened and 20% (N=7) had no change based on the radiologist’s global assessment. Of the 21 patients with moderate/severe disease at MRE 1, 33% (N=7) had minimal/mild disease by MRE 2. 66% (N=14/21) continued to have moderate/severe disease at MRE 2. Additionally, a further 14% (N=2/14) of those with minimal/mild disease at baseline MRE progressed to moderate/severe disease at MRE 2. Complete details of change between MRE 1 and MRE 2 are displayed in Figure 1.

Conclusions

Despite signs of clinical improvement, many paediatric CD patients on maintenance MTX therapy for >4 months have unchanged or worsened MRE findings. This underscores the need for follow-up imaging in these cases.

Funding Agencies

None
A229 USTEKINUMAB FOR THE TREATMENT OF REFRACTORY PEDIATRIC CROHN’S DISEASE: A SINGLE CENTRE EXPERIENCE
Authors: Cohen A , Sant’Anna A , Ahmed N
Published: February 2020

Background

Despite the well-established efficacy of Tumor Necrosis Factor (TNF) antagonists as treatment options for Crohn’s Disease, many pediatric patients need a change in therapy due to adverse events, as well as primary and secondary loss of response, highlighting the necessity for medications with a different mechanism of action. Ustekinumab, a monoclonal antibody targeting IL-12 and IL-23, has been approved to treat psoriatic arthritis, plaque psoriasis, and adults with Crohn’s disease. While utekinumab has been shown to be effective in inducing clinical remission in adults with Crohn’s disease refractory to anti-TNF agents, minimal data exists in the pediatric population.

Aims

We retrospectively describe 11 pediatric patients who received ustekinumab at the Montreal Children’s Hospital with the goal of assessing its efficacy in inducing clinical, biochemical, and endoscopic remission.

Methods

We abstracted baseline data, prior treatment and response, indications for starting ustekinumab, clinical response, endoscopic data, and laboratory parameters pre- and post- therapy. Clinical response was defined as decrease in abbrPCDAI (Pediatric Crohn’s Disease Activity Index) score.

Results

Patients ranged in age from 12–17 years old upon initiation of treatment with ustekinumab and had all previously failed either one (N=8) or both (N=3) anti-TNF therapies. Follow-up ranged from 6 to 22 months. We examined three indices of response to ustekinumab: symptomatic improvement, biomarker normalization, and endoscopic changes. Five of eleven patients demonstrated a clinical response – two maintained clinical remission across available follow-up data, while the remaining three experienced a secondary loss of response. The other six patients studied were primary non-responders. Two of these patients had normal abbrPCDAI scores upon initiation of ustekinumab and terminated therapy due to persistent stricturing disease. The other four non-responders either remained unwell or demonstrated clinical worsening, as measured by the abbrPCDAI. Of the clinical responders, 3/5 had elevated CRP values prior to initiating ustekinumab therapy, all of which normalized within one month of clinical improvement. Endoscopic data both pre- and post- ustekinumab was available in two responders and two non-responders, with endoscopic improvement seen in both of the responders and in one of the two non-responders.

Conclusions

These results demonstrate that ustekinumab has the potential ability to induce not only clinical and biochemical remission, but also endoscopic improvement, in the pediatric population. An area of concern is the fact that only one patient maintained remission for longer than one year. Future research should focus on maximizing and lengthening the effect of ustekinumab, as well as determining factors that influence response to therapy.

Funding Agencies

None
A232 EFFICACY OF TOFACITINIB FOR THE TREATMENT OF MODERATE-TO-SEVERE ULCERATIVE COLITIS: REAL-WORLD DATA
Authors: Xiao Y , Lakatos P L , Bourdages R , Bitton A , Afif W , Kohen R , Berberi M , Bessissow T
Published: February 2020

Background

A significant proportion of patients with moderate to severe ulcerative colitis (UC) do not respond to therapy, which includes thiopurines, glucocorticoids, and antagonists to tumour necrosis factor-α and integrin. Tofacitinib, a Janus Kinase inhibitor, has emerged as an efficacious and safe treatment for moderate to severe ulcerative colitis. However, it is not known if this efficacy translates into real-life effectiveness in a regular clinical practice.

Aims

We aimed to assess the rate of clinical response and clinical remission at 3 and 6 months after tofacitinib initiation. Secondary endpoints included rate of biomarker normalization, corticosteroids-free clinical remission and severe infections.

Methods

We conducted a multi-center retrospective observational study of adult patients with active UC started on tofacitinib from January 1, 2015 to October 1, 2019 at the McGill University Health Center and Hotel-Dieu de Lévis. A positive clinical response was defined as a decrease of ≥3 in the partial Mayo score. Clinical remission was defined as partial Mayo score of ≤2. Biomarker normalization was defined as fecal calprotectin ≤250ug/g. Severe infection was defined as an infection requiring hospitalization.

Results

During the study period, 40 patients with UC were started on tofacitinib. Amongst the patients, 85% (n=34) had failed ≥1 biologic and 50% (n=20) had failed ≥3 biologics. At the time of this preliminary analysis, 38 patients had undergone 3 months of treatment and 30 patients had undergone 6 months of treatment. At 3 months, a clinical response was seen in 89.5% of patients (n=34) and clinical remission occurred in 63.2% (n=24). At 6 months, clinical response occurred in 73.3% of patients (n=22) and clinical remission was sustained in 53.33% (n=16). Biochemical normalization occurred in 29.0% (n=11) and 30.0% (n=9) at 3 and 6 months, respectively. Additionally, 63.2% (n=24) and 43.3% of patients (n=13) achieved steroid-free clinical remission at 3 and 6 months, respectively. In the interim, one patient developed a serious infection requiring discontinuation of drug.

Conclusions

Our preliminary analysis demonstrates that in a real-life setting, tofacitinib is an effective treatment for inducing clinical remission in refractory UC patients. Further data will be complied to better assess the efficacy over a longer follow up.

Funding Agencies

None
A240 ASSESSING THE IMPACT OF AGE AT DIAGNOSIS ON TRANSITION PROCESS IN PATIENTS WITH INFLAMMATORY BOWEL DISEASES FROM PEDIATRIC TO ADULT CARE
Authors: Yang X , Tchogna S A , Deslandres C , Jantchou P
Published: February 2020

Background

Twenty-five percent of pediatric patients with inflammatory bowel disease (IBD) are diagnosed between the age of 16 and 18 years. They represent a unique challenge associated with the short follow-up time between diagnosis and transition to adult care.

Aims

The primary aim was to compare the current practices related to the transitional process in adolescents diagnosed before 16 years (early-adolescence (EA)) or after 16 years (late-adolescence (LA)). The secondary aim was to investigate clinical factors associated with age at transfer.

Methods

Patients diagnosed between 2013 and 2015, at the IBD clinic of CHU Sainte-Justine were included in the study. The date of transfer to adult care was defined as the date of the last visit in the pediatric unit. The factors associated with transition process and transfer included: disease type, disease severity at diagnosis and last pediatric visit, age at diagnosis, treatment group, disease burden (hospitalizations/relapses) and disease education.

Results

We included 144 patients (77 males; median (interquartile range (IQR) age at diagnosis 15.2(14.3–16.2) years; Crohn’s disease (N=98), ulcerative colitis (N=31) and IBD-unclassified (N=15). The median (IQR) duration of pediatric follow-up was 3.6 (2.7–4.1) years in the EA group as compared to 1.4 (1.0–1.8) yrs in the LA group; P< 0.01. While most of the patients completed the transition at a median (IQR) age of 18.0 (17.9–18.3) years, 15 % of patients were transferred at an older age (18.5 to 20 years). Overall, 75.7% were in remission, 13.9% with mild disease activity and 10.4% with moderate activity at the last pediatric visit. Patients with moderate activity at last pediatric visit tend to be transferred at an older age as compared to patients in remission or mild activity. The median (IQR) age were respectively 18.4 (18.2–19.1), 18.0 (17.9–18.1), 18.0 (17.9–18.3) years; P=0.024. There was a modest correlation between age at diagnosis and age at transfer (R = 0.22; P = 0.0068). Patients were transferred to adult gastroenterologists in academic hospitals (50.8%) or non-academic hospitals (43.1%). However, the disease activity at transfer was not associated with the adult care setting (academic vs non-academic). The number of relapses and hospitalizations during pediatric care were associated with older age at transfer: (> 18.5 yrs vs < 18.5 years): median(IQR) of 0.8(0.4–1.4) vs 0.3 (0.-0.6) for relapses; P=0.009 and 0.4 (0.0–1.1) vs 0.3 (0.0–0.7) for hospitalizations; P=0.009.

Conclusions

Pediatric IBD diagnosed at late adolescence tend to have more active disease and older age at transfer. Therefore, efforts to design a structured transitional care program are needed in order to improve transition outcomes for IBD patients with a special focus for subjects diagnosed in late adolescence.

Funding Agencies

CAG
A241 PRICE: PREVENTING READMISSIONS IN IBD CENTRES OF EXCELLENCE
Authors: Dang F , Habashi P , Gallinger Z , Nguyen G C
Published: February 2020

Background

Hospital readmission rates are high in the IBD population, with 20% of patients readmitted within the same calendar year. Hospital discharge processes are not routinely standardized and deficiencies in the transition of care after discharge puts patients at increased risk of illness, hospital utilization and healthcare cost. In addition to increased healthcare expenditure, hospitalizations for IBD patients are associated with nosocomial complications such as venous thromboembolism and infection.

Aims

We hypothesize that implementing standardized follow-up by an IBD practice nurse and electronic health outcome monitoring through NoviSurvey can reduce the risk of hospital readmission compared to current approaches of hospital discharge alone.

Methods

This parallel randomized control trial is powered for N=400 and will include patients admitted for an IBD flare without requiring surgical intervention from the gastroenterology service or consulted from general internal medicine. Patients randomized to the control arm are discharged with usual standard of care. Patients in the intervention group will be eligible for usual post-discharge care in addition to organized telephone follow-up by an IBD practice nurse at 1, 7 and 30 days post-discharge. In addition, these patients will receive bi-weekly correspondence from NoviSurvey to complete a short questionnaire on clinical disease severity and medication adherence. Based on telephone interaction and survey scores, the IBD nurse may arrange readmission or expedited ambulatory visit for high-risk patients.

Results

15 patients are currently enrolled into our study, with 7 randomized to the intervention and 8 to the control group. In the control group, 25% of patients were readmitted to hospital within 30 days of discharge and 13% failed to follow their steroid taper. There were no patients in the intervention group who were readmitted to hospital within 30 days and none who failed their steroid taper. In both the control or intervention group, there were no occurrences of deep vein thrombosis within 30 days post-discharge.

Conclusions

The preliminary findings in our small sample study indicate that a nurse led post-discharge intervention may translate to benefits including decreased readmission rates to hospital, better patient satisfaction and better medication adherence.

Funding Agencies

CCC
A253 ADMINISTRATIVE DATA CAN ACCURATELY IDENTIFY PATIENTS WITH PERIANAL CROHN’S DISEASE
Authors: Fairclough J , Tang T , Fung M , Golden S , Kukaswadia A , Powers S , Ward R , McCurdy J
Published: February 2020

Background

Perianal fistulas (PAF) are a frequent complication of Crohn’s disease (CD) associated with substantial morbidity. Population-based studies with CD are lacking, in part due to the difficulty in identifying these patients from health administrative databases.

Aims

To determine if administrative claims and diagnostic codes can reliably identify patients with perianal fistulas in a cohort of patients with CD.

Methods

A retrospective cohort study was performed using data from The Ottawa Hospital (TOH), which was linked to The Institute for Clinical Evaluative Sciences (ICES) Ontario Crohn’s and Colitis Cohort (OCCC) data using Ontario Health Insurance Plan (OHIP) numbers. Patients admitted with CD from 1 Jan 2009 to 31 Dec 2016 were identified from TOH data warehouse using the ICD-10 code K50.x. Confirmation of CD diagnosis and determination of the presence or absence of PAF was achieved by a longitudinal, manual chart review. Patients with and without PAF were abstracted in a 1:2 ratio to serve as a reference gold standard for PAF status. ICES captures all publicly reimbursed diagnostic tests, interventional procedures and physician billing codes, including MRI pelvis utilization and surgical procedures associated with perianal fistulas in Ontario. Sixteen case definitions for PAF in ICES were specified a priori. Two by two contingency tables were constructed to assess the sensitivity, specificity, positive predictive value (PPV) and negative predicative value (NPV) of each case definition against the gold standard PAF status as determined by TOH data. Youden’s index and Kappa were used to select a case definition that best identified TOH PAF patients.

Results:

A total of 136 patients with active PAF and 351 without PAF were included in the linked analysis. There were a similar proportion of male patients with and without PAF (49% vs. 43%). Patients with PAF were slightly younger; 69% were aged 18–44 compared to 58% of patients without PAF. Sensitivity of the case definitions ranged from 0.44 to 0.98, and specificity from 0.45 to 1.00. A case definition that combined at least two of fistula diagnosis code, perianal surgical procedures associated with fistulas, and radiologic imaging codes of the pelvis, all within 2 years, had the best performance using Youden’s index and Kappa. It discriminated between patients with or without PAF with sensitivity of 0.80 and specificity of 0.92.

Conclusions

Using a cohort of CD patients from a single tertiary care center we derived a case definition that could accurately distinguish CD patients with and without PAF in a provincial health administrative database. Once validated this will allow for future population-based studies to assess trends in PAF.

Funding Agencies

Takeda Pharmaceuticals
A257 NEW ONSET ULCERATIVE COLITIS IN A PATIENT WITH KNOWN AUTOIMMUNE HEPATITIS TYPE 1
Authors: Hasan M , Gallinger Z
Published: February 2020

Background

Elevated transaminases can occur in up to 17 per cent of cases of Inflammatory Bowel Disease (IBD)1, with many cases related to concurrent autoimmune conditions of the liver. Primary Sclerosing Cholangitis (PSC) is the most common autoimmune disease of the liver that is associated with IBD. Other causes of liver inflammation in patients with IBD can include Autoimmune Hepatitis (AIH).

Aims

We aim to report a case of new onset ulcerative colitis in a patient with autoimmune hepatitis type 1 in the absence of concomitant PSC.

Methods

Case report and review of literature.

Results

A 25-year-old male with painless jaundice and was found to have Autoimmune hepatitis type 1 with typical morphological changes, positive Antinuclear antibodies and elevated IgG levels. Histopathological exam of the liver did not show any direct changes to the bile ducts to suggest PSC. The patient was started on steroids and Mycophenolate Mofetil (MMF) and developed new onset diarrhea. Colonoscopy was performed and both endoscopic and pathological findings were suggestive of likely inflammatory bowel disease, although drug induced colitis (MMF) could not be excluded.

Conclusions

We conclude that there is a link between autoimmune hepatitis with IBD, in absence of concomitant PSC.

Funding Agencies

None
A277 DISCREPANCIES IN EUS-FNA CYTOPATHOLOGY AND SURGICAL SPECIMEN PATHOLOGY FOR HIGH RISK PANCREATIC MUCINOUS CYSTIC LESIONS: A CASE SERIES
Authors: Li S , Monachese M , James P
Published: February 2020

Background

Endoscopic ultrasound guided fine needle aspiration (EUS-FNA) is the primary method of sampling pancreatic cystic lesions with reported specificity near 100% for diagnosing malignancy. Discrepant positive malignant cytopathology with final surgical pathology of pancreatic cystic lesions has not previously been described.

Aims

To present a case series and review the literature regarding the implications of positive malignant cytology with discrepant surgical pathology for high risk pancreatic mucinous cystic lesions.

Methods

Patient demographics, clinical history, procedure details, pathology evaluations and follow-up were collected. A thorough literature review was performed.

Results

Three patients with high-risk pancreatic cystic lesions on cross-sectional imaging underwent EUS-FNA evaluation. None of these patients had a history of pancreatitis. Cytology was reported as positive for adenocarcinoma in all patients by separate gastrointestinal cytopathologists. All patients underwent surgical resection. The pathology for all resected specimens were reported as intraductal papillary mucinous neoplasm. The resected cysts for two patients demonstrated foci of high-grade dysplasia and the third noted low grade dysplasia. All surgical pathology underwent consensus review by three separate gastrointestinal pathologists. None of the patients were treated with adjuvant chemotherapy. All patients have been followed post-operatively with surveillance magnetic resonance imaging with no evidence of recurrence to date (median follow-up time 239 days, range 133 – 447 days).

Conclusions

This phenomenon sheds light on the potential for variable interpretations of EUS-FNA cytopathology and surgical resection pathology for high risk pancreatic cystic neoplasms. EUS-FNA may identify foci of adenocarcinoma that is not seen on surgical pathology specimens. Further research is required to examine the long-term outcomes of these patients.

Funding Agencies

None
A279 EUS-GUIDED BILIARY DRAINAGE IN MALIGNANT DISTAL BILIARY OBSTRUCTION: AN INTERNATIONAL SURVEY TO IDENTIFY BARRIERS OF TECHNOLOGY IMPLEMENTATION
Authors: Palmieri V , Ramana-Kumar A , Martel M , Forbes N , Mohamed R , Chatterjee A , Kenshil S , Desilets E , Donnellan F , Gan I , Lam E , Telford J J , Sandha G S , Teshima C W , May G , Mosko J , Paquin S , Sahai A , Barkun A N , Chen Y
Published: February 2020

Background

Endoscopic ultrasound-guided biliary drainage (EUS-BD) is a promising alternative to endoscopic retrograde cholangiopancreatography (ERCP) in malignant distal biliary obstruction (MDBO). Recent small randomized controlled trials comparing EUS-BD with ERCP suggest that EUS-BD achieves a similar technical success rate and safety profile while potentially being associated with lower rates of stent dysfunction However, its application in clinical practice has been impeded by various undefined barriers.

Aims

To evaluate the current practice of EUS-BD and the determinants for its clinical implementation in MDBO.

Methods

An online survey was generated using Google Forms. Five endoscopy societies have distributed the survey as of October 10th, 2019. Survey questions measured participant characteristics, EUS-BD in different clinical scenarios, and potential barriers to implementation. Descriptive statistics were calculated using frequencies, chi-square statistics were used for inferential analysis, and a standard step-wise multivariable analysis was performed to identify independent variables for and against the use of EUS-BD.

Results

To date, 102 physicians have participated in the survey (response rate 7.97%). The majority of participants are from North America (39.2%), Asia (31.4%), and Europe (19.6%). Most participants are gastroenterologists with formal therapeutic endoscopy training (66.7%), though only 28.4% have received EUS-BD training. In unresectable cancer, 85.1% of respondents favoured EUS-BD over percutaneous biliary drainage following ERCP failure (p<0.0001), while in borderline resectable disease, 72.3% preferred EUS-BD. On multivariable analysis, male gender, formal training in EUS-BD, and unresectable cancer were independent variables for the use of EUS-BD. Conversely, independent discouraging factors for EUS-BD included fear of adverse events, limited high-quality data, lack of local expertise, and inadequate access to EUS technology.

Conclusions

In this international survey, it appears that EUS-BD is gaining traction, especially in the setting of unresectable disease following ERCP failure. However, barriers to implementation include the lack of high-quality data, fear for adverse events, limited experts in the field, and inadequate access to EUS technology. This suggest the need for high-quality clinical trials, increased endoscopist training in this field, and further technology development in EUS-BD in order to increase its uptake in clinical practice.

Funding Agencies

None
Dispatches from Cairo to India: Editors, Publishing Houses, and a Republic of Letters
Authors: Khan Ahmad
Published: February 2020

This article documents the existence of a vibrant republic of letters stretching from Cairo to Karachi in the middle of the twentieth century. On the basis of private letters, memoirs, and modern editions of classical texts, this article recreates the scholarly and personal commitments of a new class of professional editors (muḥaqqiqūn). These editors were responsible for the emergence of some of the most influential publishing houses in the Islamic world, and their contribution to the production and circulation of pre-modern texts has had a profound impact on the intellectual development of Islam in the twentieth and twenty-first centuries. They believed that cultivating a republic of letters was necessary because it served the world of learning and scholarship. In this way was fashioned a virtual community, separated by national and political borders, but united by visions of history and a shared sense of moral and intellectual duty.