bluuebunny/crossref_metadata_2025_split huggingface dataset:
A156 SERUM TUMOUR NECROSIS FACTOR-α ANTAGONIST DRUG CONCENTRATIONS IN PATIENTS WITH PYODERMA GANGRENOSUM ASSOSCIATED WITH INFLAMMATORY BOWEL DISEASE
Authors: Mikail M , Wilson A 
Published: March 2021

Abstract

Background
The utility of therapeutic drug monitoring for guiding the dosing of tumor necrosis factor-α antagonists (TNFAs) in luminal inflammatory bowel disease (IBD) is well-established and well-accepted. TNFAs, specifically infliximab and adalimumab, have become integral to the management of the rare, neutrophilic dermatosis, pyoderma gangrenosum (PG) in IBD. Little is known regarding the target serum TNFA concentrations to guide dosing to achieve resolution of PG in IBD.

Aims
To describe the serum TNFA concentrations (infliximab or adalimumab) associated with the resolution of PG lesions in patients with IBD.

Methods
Patients with IBD and associated PG treated with one of infliximab or adalimumab (collectively known as TNFAs) seen at two academic hospitals affiliated with Western University were identified. Serum TNFA concentrations were assessed at the time of PG treatment.

Results
Nine patients were identified. All patients had IBD-associated PG. Seven patients were treated with infliximab and 2 patients were treated with adalimumab. All patients received standard dosing. Eight patients had complete resolution of their PG, while one had near complete resolution at the time of last follow-up. A median serum infliximab concentration of 3.00 (IQR, 3.52) µg/ml at week 14 and a median serum adalimumab concentration of 2.02 (IQR, 0.98) µg/ml at week 12 were seen at the time of PG treatment.

Conclusions
Herein, we report low serum TNFA concentrations despite PG healing in a cohort of IBD patients. This is lower than what is in patients for successful TNFA treatment in luminal and fistulising IBD.

Funding Agencies
NoneNone.
A173 INNOVATIVE CARE FOR INFLAMMATORY BOWEL DISEASE PATIENTS DURING THE COVID-19 PANDEMIC: USE OF BEDSIDE INTESTINAL ULTRASOUND TO OPTIMIZE MANAGEMENT
Authors: Novak K L , Ma C , Kheirkhahrahimabadi H , heatherington j , Ingram R , Martin M , Panaccione R , Kaplan G G , Devlin S , Seow C , Chan M , Lu C 
Published: March 2021

Abstract

Background
The COVID-19 pandemic has led to significant alterations in the ability to deliver outpatient care to patients with inflammatory bowel disease (IBD) including endoscopic evaluation. This has highlighted the need for alternative, accurate, non-invasive strategies to safely assess disease activity.

Aims
The aim of this study is to describe the impact of point of care intestinal ultrasound (IUS) in a university-based tertiary care IBD urgent access clinic.

Methods
We prospectively evaluated a comprehensive care pathway which incorporated outpatient sigmoidoscopy and intestinal ultrasound with the purpose of directing further ambulatory clinical care and avoiding hospitalization or hospital-based investigations including endoscopy during the COVID pandemic for patients with established IBD with symptoms suggestive of a disease flare, or those at high risk of a new diagnosis of IBD. Non-invasive markers C Reactive Protein (CRP) and fecal calprotectin (fCal) were collected where available. Patients were pre-screened for influenza-like illness, as COVID-19 testing was not available for this population during the study period. Substantial management changes were defined as addition of any medications, biologic switch/ optimization, and or referral for surgical consultation.

Results
Between March 15th and June 30th 2020, a total of 72 patients were seen in the urgent access clinic. All patients were seen within 7 days of referral. The majority were female 57% (41/72) and/ or had Crohn’s disease 65.5% (47/72) (Table 1). Of these, 84.7% (61/72) underwent a substantial management change based on features of active inflammation detected by either IUS alone (53% 38/72) sigmoidoscopy alone (12.5% 9/72) or combination IUS with in-clinic sigmoidoscopy (32% 23/72) in addition to CRP and fCal. Three new diagnoses of IBD were made: one colonic Crohn’s and 2 with ulcerative colitis. One pregnant patient avoided all acute care utilization. Five patients were referred to colorectal surgery for urgent resection including two patients admitted directly for emergent operations. No patients required visits to the emergency department. Furthermore, there have been no unscheduled hospitalizations occurred in this cohort since inception March 23, 2020 til November 15th 2020.

Conclusions
The implementation of IUS in a centralized, urgent access clinic pathway resulted in efficient and meaningful changes in IBD management while sparing the need for acute care services including ER visits, need for in-hospital endoscopy, and hospitalization. The pandemic highlights the utility of this patient-center tool and supports expansion of wider IUS adoption.

Funding Agencies
None
A184 INCIDENCE OF VENOUS THROMBOTIC EVENTS AND RISK FACTORS IN CHILDREN HOSPITALIZED WITH INFLAMMATORY BOWEL DISEASE: A RETROSPECTIVE, CASE-CONTROL STUDY
Authors: Ding Z , Sherlock M , Zachos M 
Published: March 2021

Abstract

Background
Limited research has been published to describe the incidence of venous thromboembolism (VTE) and relevant risk factors in Canadian children with inflammatory bowel disease (IBD).

Aims
The present study aimed to investigate the incidence of VTE amongst hospitalized pediatric IBD patients over a 10-year period and identify risk factors for the development of VTE.

Methods
A retrospective, matched case-control study was performed at McMaster Children’s Hospital. Hospitalized pediatric patients with IBD (&lt;18 years old) from September 2009 to August 2020 were selected. Inpatient data was extracted from the medical record database, including baseline demographic data, thromboembolic events and potential risk factors for VTE.

Results
There were 890 hospitalizations of IBD patients during the study period. 15 (1.69%) were diagnosed with a VTE, including 4 males and 11 females (mean age 13.4±2.9 years old). 12 ulcerative colitis (UC) (80%) and 3 Crohn’s disease (CD) (20%) hospitalizations were comprised in the VTE group. There was a significant difference in VTE rate between females (2.7%) and males (0.8%) (P = 0.03). The VTE rate in the UC group (4.2%) was significantly higher than in the CD group (0.6%) (P = 0.001). The incidence of VTE amongst hospitalized IBD patients did not vary over the 10-year period (P = 0.496). Length of stay in hospital, albumin level and central venous catheter were shown to be significantly different, although they were not identified as independent risk factors (P &gt;0 .05). Of the 15 hospitalizations with VTE, 6/15 (40%) were superficial VTEs in the extremities and 9/15 (60%) had a deep vein thrombosis (DVT) including 6 in the extremities and 3 in the abdomen. VTEs were associated with a peripheral line in 7 patients and with a PICC line in 4 hospitalizations. 2 of 9 (22%) with extremity DVT developed symptomatic pulmonary embolism. An inherited thrombotic condition was identified in 2 of 15 with VTEs. 12/15 (80%) with VTEs were symptomatic and all VTE related symptoms happened in patients with extremity thrombosis and pulmonary embolism. 7 of 15 (47%) VTEs were treated with anticoagulation therapy for 1–6 months. VTE related symptoms and repeat imaging tests significantly improved, and no patient developed a bleeding complication as a result of treatment.

Conclusions
The VTE rate in pediatric IBD patients was relatively low at McMaster Children’s hospital. Children with VTE were disproportionately females with ulcerative colitis compared with children with no VTE. Central venous line insertion may be correlated with the risk for VTE in children with IBD. Most VTEs and related symptoms happened in patients with extremity thrombosis and secondary pulmonary embolus. Anticoagulation therapy in children with IBD with active disease appears to be safe.

Funding Agencies
Kids Dig Health Funding from McMaster Children’s Hospital, McMaster University
A185 THE IMPACT OF PRIOR SURGERY ON ADVERSE PREGNANCY OUTCOMES IN PREGNANT PATIENTS WITH INFLAMMATORY BOWEL DISEASE
Authors: Chis R , Tandon P , Huang V W 
Published: March 2021

Abstract

Background
During the course of inflammatory bowel disease (IBD), approximately 20% of patients with ulcerative colitis (UC) and 80% of Crohn’s disease (CD) patients will require surgery. The most common operation is total proctocolectomy and ileoanal pouch anastomosis (IPAA) for UC patients and ileocecal (IC) resection for CD. In pregnant IBD patients, guidelines name the presence of IPAA as a relative indication for Cesarean section (C-section). The effect of prior IBD-related surgery on mode of delivery and pregnancy-related outcomes remains unknown.

Aims
To describe pregnancy-related outcomes in pregnant women with IBD who have undergone prior IBD-related surgery.

Methods
We performed a retrospective cohort study of pregnant women with IBD including those with prior IBD-related surgeries including IPAA, IC resection, total or partial colectomy and ileostomy formation who delivered an infant at our medical center from 2016 to 2020. We assessed the mode of delivery, delivery characteristics (emergency vs. planned C-section) and maternal and neonatal outcomes

Results
Fifty-six UC patients and 64 CD patients were included in the analysis, of which 10 and 24 had undergone prior IBD-related surgery, respectively. The mean age at conception was 34.10 years in the surgical UC group and 30.30 years in the surgical CD group.
Mode of delivery: C-section rates were higher in post-surgical compared to non-surgical UC patients (70% vs. 30.4%, p = 0.02). Similar numbers of C-sections were performed emergently in the surgical compared to non-surgical UC group (10% vs. 18%, p = 0.53). Comparatively, there was no significant difference in C-section rates in post -surgical compared to non-surgical CD mothers (50% vs. 40%, p = 0.44), with 13% performed emergently in both groups.
Maternal outcomes: Gestational diabetes developed in 10% of surgical UC and 4.5% of surgical CD patients. Premature rupture of membranes developed in 10% of surgical UC and 9.1% of surgical CD patients. There was no difference in pre-eclampsia rates in the surgical and non-surgical CD groups (9.1% vs 13.2%, p = 0.64).
Neonatal outcomes: There was no significant difference in pre-term birth rates in post-surgical compared to non-surgical UC mothers (10% vs. 15.2%, p = 0.67) or in surgical compared to non-surgical CD mothers (13.6% vs. 5.1%, p = 0.29). Neonatal Intensive Care Unit (NICU) requirements were higher in infants born to post-surgical CD compared to non-surgical CD mothers (18.2% vs. 2.7%, p = 0.04). More low birth weight (LBW) infants were born to post-surgical CD vs non-surgical CD mothers (13.6% vs. 0%, p = 0.02).

Conclusions
Women with IBD who have had prior IBD-related surgery may be at increased risk of developing adverse gestational and neonatal outcomes. Women with surgical UC have an increased incidence of Cesarean delivery.

Funding Agencies
None
A195 A RARE CAUSE OF SEVERE REFRACTORY DIARRHEA IN A PATIENT WITH COMMON VARIABLE IMMUNE DEFICIENCY ASSOCIATED INTESTINAL ENTEROPATHY
Authors: Markandey B , Beyak M J , Perez S , Manley P , Ropeleski M 
Published: March 2021

Abstract

Background
CVID is the most common type of severe antibody deficiency. Gastrointestinal manifestations affect approximately 20–50% of patients. Boland et al. described in a case series that 2/3 CVID patients were able to achieve clinical and endoscopic remission with Vedolizumab. This α4β7 integrin antagonist inhibits intestinal T cell translocation by blocking integrin interactions with mucosal vascular addressin cell adhesion molecule 1, reducing lymphocyte mediated inflammation. However, despite its novel use for this indication, limited data is available on the consequences of this therapy in patients with CVID.

Aims
To report on a case assessing the efficacy and outcomes of Vedolizumab for the treatment of CVID associated autoimmune enteropathy.

Methods
We present the case of a 50-year-old male presenting with severe refractory diarrhea and malnutrition. A colonoscopy demonstrated patchy ulceration and biopsies revealed ulcerated active colitis, negative for CMV. He was treated with Vedolizumab and Total Parental Nutrition (TPN). His diarrhea resolved, he gained 20 kg and he was weaned off TPN. In 2019, he re-presented with severe diarrhea. Subsequently endoscopic evaluation revealed patchy edematous colonic mucosa and biopsies demonstrated minimally active colitis, negative for CMV. He again responded to Vedolizumab re-induction, however shortly after, his diarrhea returned aggressively. CT enterography demonstrated active jejunal inflammation. Subsequently, an EGD revealed multiple duodenal ulcers and luminal narrowing. Biopsies of the small bowel were sent to histopathology.

Results
CMV superinfection was diagnosed on pathology (image 1). This patient’s diarrhea completely resolved with IV Gancyclovir and he was discharged on maintenance treatment with oral Valganciclovir.

Conclusions
This represents the first reported case of CMV enteritis secondary to Vedolizumab for the treatment of CVID associated autoimmune enteropathy. In this case, clinical and endoscopic remission was observed with Vedolizumab, however subsequently hampered by CMV reactivation. Hommel et al., published a positive correlation in a single centre retrospective cohort study of CMV reactivation in patients with ulcerative colitis treated with Vedolizumab. A large retrospective review of data from a multicenter consortium database of over 1000 Vedolizumab treated IBD patients reported CMV colitis in only 4 patients. CMV reactivation appears to be an exceptionally rare but important event in patients treated with Vedolizumab. Based on this report, patients with CVID associated enteropathy and refractory diarrhea should be carefully screened for CMV when treated with Vedolizumab. Further prospective data assessing the incidence of CMV reactivation in patients with Vedolizumab therapy is required to further define these findings.

Funding Agencies
None
A196 MORE MICROSCOPIC THAN WAS THOUGHT: A RARE CASE OF ISOLATED LYMPHOCYTIC ILEITIS WITHOUT MICROSCOPIC COLITIS
Authors: Singh K S , Yanofsky R , Haegert D , Gao Z , Bessissow T 
Published: March 2021

Abstract

Background
Microscopic colitis (MC) is a chronic inflammatory disease of the colon characterized by lymphocytic infiltration with (collagenous colitis) or without (lymphocytic colitis) the expansion of collagen fibres, and the normal macroscopic appearance of the mucosa on ileocolonoscopy. Recent studies have shown that the ileum may be involved in MC, occurring concurrently with colonic disease, however there is sparse literature on isolated lymphocytic ileitis without colitis.

Aims
We describe the case of isolated small bowel lymphocytosis without evidence of lymphocytic colitis to highlight the utility of random biopsies of the terminal ileum in cases where microscopic colitis is a diagnostic consideration.

Methods
A 70-year-old female known for cutaneous mastocytosis presented with six weeks of abdominal pain, non-bloody diarrhea, intolerance to oral intake and significant weight loss. Computed-tomography showed evidence of possible mesenteric panniculitis. Colonoscopy revealed a normal colon and normal-appearing mucosa of the terminal ileum. Random mucosal biopsies were taken to assess for microscopic colitis, with terminal ileal biopsies revealing significant lymphocytic infiltration consistent with lymphocytic ileitis. Biopsies throughout the colon revealed normal colonic mucosa without evidence of concurrent microscopic colitis. Gastroscopy was macroscopically unremarkable and random biopsies in the stomach and duodenum were negative for Helicobacter pylori and lymphocytosis. Immunostaining of the gastric, duodenal, terminal ileal and colonic biopsy specimens were negative for CD25, CD117 and tryptase, indicating the absence of gastrointestinal mastocytosis.

Results
The patient was diagnosed with lymphocytic ileitis and given the known response of MC to budesonide, she was treated with eight weeks of budesonide with clinical improvement leading to remission of her symptoms.

Conclusions
This case illustrates a rare incidence of isolated ileal microscopic ileitis without colitis that responded well to standard MC treatment, thereby underscoring the utility of random biopsies in the terminal ileum and throughout the colon when microscopic colitis is on the differential diagnosis.

Funding Agencies
None
A201 UNDERSTANDING THE INFECTION DYNAMICS OF MYCOBACTERIUM PARATUBERCULOSIS (MAP)
Authors: Baruta G M , Zhang H , Alston L , Hirota S A 
Published: March 2021

Abstract

Background
Mycobacterium avium subspecies paratuberculosis (MAP) is the causative agent of Johne’s disease (JD) in ruminants. Following infection, JD may present as enteritis, leading to wasting, often causing premature culling of livestock. Beyond veterinary medicine, several mycobacterium species, including MAP, have been implicated in human gastrointestinal disease. While MAP has been incriminated in causing Crohn’s disease (a claim that has yet to be substantiated), there are confirmed cases of MAP infection in immunocompromised individuals, causing profuse diarrhea, fever, and drastic weight loss. Given the economic burden associated with MAP infection, considerable efforts have sought to understand its dynamics. However, these processes have not been completely characterized, hindering our ability to generate novel anti-infective agents. While the current paradigm suggests that MAP travels to the small intestine, gaining entry through the epithelium, the exact cellular tropism and the mechanism(s) of entry are not well defined. Therefore, we have developed an ex vivo enteroid-based system to visualize invasion of MAP in distinct cells of the intestinal epithelium using a GFP-expressing MAP strain. With this, we sought to test the hypothesis that MAP invasion occurs via M cells through receptor-mediated transcytosis.

Aims
1) Characterize experimental system and visualize MAP invasion 2) Determine cellular tropism 3) Uncover mechanisms underlying MAP invasion

Methods
Enteroids (2D and 3D) were generated and M cell differentiation induced via addition of RANKL. Confluent ileal monolayers were exposed to GFP-expressing MAP strain (K10 pWES4). Confocal microscopy was performed, and barrier function was measured via transepithelial electrical resistance (TEER).

Results
We generated 3D enteroids and confluent enteroid-derived monolayers with functional M cells capable of transcytosis. MAP was detected mainly within M cells. We further confirmed this finding using a human in vitro M cell model, the Caco-2/Raji-B co-culture system. Furthermore, alterations in TEER following MAP exposure in monolayers cultured with RANKL, triggering M cell differentiation, suggest the existence of a novel mechanism by which MAP disrupts the barrier to invade the mucosa.

Conclusions
Our results suggest that MAP translocates across the epithelium predominantly via M cells, as shown both in a human and murine model. This newly optimized approach provides an experimental system that will enable us to better characterize M cell-MAP interactions, with the hopes of identifying new therapeutic targets to prevent the spread of MAP and reduce economic impact of JD. Beyond MAP infection, this novel ex vivo system has potential to elucidate other host-pathogen interactions.

Funding Agencies
Natural Sciences and Engineering Research Council of Canada (NSERC)
A211 SPONTANEOUS HBV REMISSION AFTER HBV REACTIVATION FOLLOWING TREATMENT WITH SOFOSBUVIR AND VELPATASVIR IN A PATIENT WITH HCV AND HBV CO-INFECTION: CASE REPORT
Authors: Chiang A , Tsoi K 
Published: March 2021

Abstract

Background
In co-infected patients with hepatitis B (HBV) and hepatitis C (HCV), the treatment of HCV with direct-acting antiviral agents (DAA) can cause HBV reactivation. However, there are no clear guidelines on the timing of treatment initiation, especially in the absence of clinical signs of flare.

Aims
Here we discuss the case of a 34-year-old female with HBV and HCV genotype 3 who had HBV reactivation following HCV treatment, but did not require nucleos(t)ide therapy.

Methods
She initially presented with chronic inactive hepatitis B and chronic hepatitis C with HBV DNA level of 67.5 IU/mL and HCV RNA level of 3.33 x 106 IU/mL. She completed a 12 week course of sofosbuvir and velpatasvir for HCV and achieved sustained virologic remission, but subsequently developed reactivation of her HBV with HBV DNA peaking at 3.41 x 104 IU/mL twelve weeks post-treatment. She did not develop any signs of hepatitis and a decision was made to monitor her clinically.

Results
Two years later, she spontaneously went into remission with her HBV DNA levels being &lt;10 IU/mL.

Conclusions
The significance of this case is to illustrate HBV reactivation following treatment of HCV with DAAs may not necessitate immediate treatment, especially if there are no signs of flare. There have been similar reported cases, but larger prospective studies are required to determine the appropriate clinical context where monitoring may be acceptable instead of immediate treatment.

Funding Agencies
None