bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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&gt;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&gt;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&gt;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&gt;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

Abstract

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&lt;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 &lt;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&lt;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

Abstract

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 &gt;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 &lt; 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 &gt;4 months have unchanged or worsened MRE findings. This underscores the need for follow-up imaging in these cases.

Funding Agencies
None