bluuebunny/crossref_metadata_2025_split huggingface dataset:
A17 EFFICACY AND SAFETY OF FILGOTINIB AS MAINTENANCE THERAPY FOR PATIENTS WITH MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS: RESULTS FROM THE PHASE 2B/3 SELECTION STUDY
Authors: Peyrin-Biroulet L , Loftus E V , Danese S , Vermeire S , Sandborn W J , Fogel R , Nijhawan S , Kempinski R , Filip R , Hospodarskyy I , McNally J , Yun C , Zhao S , Liu X , Tasset C , Besuyen R , Watanabe M , Schreiber S , Rogler G , Hibi T , Feagan B G 
Published: March 2021

Abstract

Aims
SELECTION (NCT02914522) Maintenance evaluated filgotinib (FIL), a preferential JAK1 inhibitor, as maintenance therapy for patients (pts) with moderately to severely active ulcerative colitis (UC) who achieved clinical remission or Mayo Clinic Score (MCS) response after 10 weeks of FIL 200mg QD, FIL 100mg QD or placebo (PBO) induction.

Methods
Pts randomized to FIL induction were rerandomized 2:1 to their induction FIL dose or PBO; pts randomized to PBO induction continued PBO maintenance. Steroid tapering was mandatory. The primary endpoint was clinical remission at Week 58. Key secondary endpoints and exploratory endpoints were assessed at Week 58.

Results
664 pts were treated in the Maintenance Study (n=93, 270, and 301 from induction with PBO, FIL 100mg and FIL 200mg); efficacy analyses included only FIL induction pts. Baseline demographics and disease characteristics were generally balanced across treatment arms; 40% were biologic experienced. Significantly higher proportion of pts on FIL 200mg or FIL 100mg were in clinical remission vs PBO. Significantly higher proportions of pts achieved key secondary endpoints with FIL 200mg vs PBO. More pts on FIL 200 mg or FIL 100mg achieved an MCS response and endoscopic improvement vs PBO.
Incidences of adverse events (AEs), serious AEs and discontinuations due to AEs were similar across arms. Serious infection (&lt;2%) and herpes zoster (&lt;1%) were infrequent among FIL-treated patients. There were no venous thromboses, including pulmonary embolism, among FIL-treated pts. Two pts on FIL 200mg died, both AEs leading to death were considered unrelated to FIL.

Conclusions
FIL 200mg and FIL 100mg were effective as maintenance treatment for pts with moderately to severely active UC who had achieved clinical response to FIL induction treatment. FIL 200 mg met all key secondary endpoints including endoscopic, histologic and 6-month corticosteroid-free remission. FIL was well tolerated in pts with moderate to severely active UC.

Funding Agencies
None
A24 FCGBP MAINTAINS MUC2 MUCUS STRUCTURAL INTEGRITY BY STABILIZING THE MUCUS LAYER IN RESPONSE TO THE COLONIC PATHOGEN, ENTAMOEBA HISTOLYTICA
Authors: Gorman H , Moreau F , Kim A , Chadee K 
Published: March 2021

Abstract

Background
MUC2 mucin is the major component of the colonic mucus bilayer that serves as the first line of innate host defense against pathogens while supporting a healthy microbiota and regulating epithelial barrier function. Proteomic studies of colonic mucus have identified various mucus-associated proteins. One of the most abundant is FCGBP, similar to MUC2 mucin, but its interaction with MUC2 or function is not known. Here, we elucidated FCGBP functional role in stabilizing MUC2 mucus and in innate host defence against Entamoeba histolytica (Eh).

Aims
Hypothesis: MUC2 mucin and FCGBP are coordinately produced and play an important role in innate host defense. The specific aims are:
1. To determine if FCGBP alters the structural integrity of the mucus layer
2. To determine the role of FCGBP in Eh infection

Methods
FCGBP mRNA and protein expression induced by Eh, in WT and FCGBP CRISPR/Cas9 LS174T goblet cells were analysed by RT-PCR and Western blotting. To compare integrity of the mucus layer, fluorescent Eh and 1μM fluorescent beads were inoculated on WT and KO monolayers and adherent Eh and bead penetrability analyzed. To quantify MUC2 and FCGBP degradation by Eh, purified MUC2 and recombinant FCGBP were incubated with Eh proteases (SPs) and Western blotted using highly specific antibodies against various regions of the proteins.

Results
In response to live Eh, FCGBP and MUC2 mRNA and protein expressions were significantly increased in a time-dependent manner. Surprisingly, FCGBP KO cells elicited robust expression of pro-inflammatory cytokine mRNA and protein as compared to WT cells. More fluorescent Eh were attached to the mucus layer of FCGBP KO cells as compared to WT or MUC2 KO cells. Fluorescent beads penetrated further towards the epithelial cell surface in KO as compared to WT cells. Interestingly, while both MUC2 and FCGBP from purified polymeric mucins were degraded by Eh SPs, FCGBP cleavage occurred at a faster rate than MUC2. Degradation of FCGBP and MUC2 was mediated by EhCP-A5 cysteine proteinase using purified MUC2 and recombinant FCGBP.

Conclusions
In WT goblet cells, FCGBP and MUC2 were upregulated temporally in response to Eh. The increase in pro-inflammatory cytokine expression in FCGBP KO cells in response to Eh suggests that Eh directly interacted with the cell surface suggesting an impaired protective mucus layer. In support of this, fluorescent beads penetrated the mucus layer close to the cell surface and more Eh were attached to FCGBP KO mucus demonstrating that FCGBP was critical in providing structural integrity of the mucus layer. In response to Eh, FCGBP degradation was a prerequisite for MUC2 cleavage, providing direct evidence that FCGBP and MUC2 interactions conferred biophysical properties of the protective functions of the mucus gel.

Funding Agencies
CIHR
A43 LONG-TERM EFFICACY AND SAFETY OF OBETICHOCLIC ACID IN PRIMARY BILIARY CHOLANGITIS: RESPONDER ANALYSIS OF OVER 5 YEARS OF TREATMENT IN THE POISE TRIAL
Authors: Hirschfield G , Jones D , Carbone M , Bowlus C L , Nevens F , Kremer A E , Liberman A , MacConell L , Hansen B E 
Published: March 2021

Abstract

Background
Obeticholic acid (OCA), a potent farnesoid X receptor agonist, is approved as second-line treatment for primary biliary cholangitis (PBC) in patients with an incomplete response or intolerance to ursodeoxycholic acid.

Aims
We evaluated the effect of OCA in PBC patients enrolled in the POISE trial, comparing those who did or did not achieve the POISE response criteria.

Methods
The phase 3, randomized, double-blind, 1-year POISE trial evaluated the efficacy and safety of OCA 5 and 10 mg vs placebo in patients with PBC; a 5-year open-label extension followed in which all patients received OCA. This analysis evaluated longer-term efficacy and safety in patients who achieved the POISE primary endpoint of alkaline phosphatase (ALP) &lt;1.67 × upper limit of normal (ULN), total bilirubin &lt;ULN, and ALP decrease &gt;15% from baseline after 1 year of OCA and in patients who were incomplete responders.

Results
The analysis included 86 patients who achieved the POISE primary endpoint at year 1 of OCA treatment and 107 incomplete responders (mean baseline ALP, 268 vs 356 U/L, respectively; P&lt;0.0001). Mean change from baseline in ALP at year 5 was –101 U/L for responders and –121 U/L for incomplete responders (P&lt;0.0001; Figure). Median (Q1, Q3) baseline GLOBE 10-year risk of event scores were 16 (11, 23) for responders and 25 (15, 43) for incomplete responders. Change from baseline in median (Q1, Q3) GLOBE 10-year risk of event at year 1, which includes age and thus increases with time, was –2 (–4, 2) for responders and –2 (–6, 4) for incomplete responders; at year 5, these changes were 2 (–2, 7) and 4 (–4, 11), respectively. Median (Q1, Q3) baseline UK-PBC 10-year risk of event scores were 5 (3, 8) for responders and 8 (4, 16) for incomplete responders. Change from baseline in median (Q1, Q3) UK-PBC 10-year risk of event at year 1 was –1 (–3, 0.2) for responders and –1 (–3, 1) for incomplete responders; at year 5, these changes were –0.8 (–2, 0.2) and –0.05 (–2, 2), respectively. The most frequently reported AEs among responders and incomplete responders were pruritus (67%, 86%) and fatigue (35%, 31%).

Conclusions
OCA treatment improved key biochemical markers of PBC, regardless of achieving the POISE primary endpoint after 1 year of OCA treatment. Changes in biochemical parameters over time were often similar between groups.

Funding Agencies
Intercept Pharmaceuticals
A48 USE OF ENDOSCOPIC ULTRASOUND FINE NEEDLE ASPIRATE AND ENDOSCOPIC ULTRASOUND FINE NEEDLE BIOPSY FOR DETECTION OF GATA6 EXPRESSON IN PANCREATIC DUCTAL ADENOCARINCOMA
Authors: Law C , Fischer S , Knox J , Gallinger S , Ramotar S , Anna D , May G , James P D 
Published: March 2021

Abstract

Background
GATA6 is a transcription factor that can be used to distinguish between the basal-like and classical subtypes of pancreatic ductal adenocarcinoma (PDAC). The basal-like subtype has been demonstrated to be less responsive to modified FOLFIRINOX chemotherapy and thus can be used to predict response to specific chemotherapies. To date, GATA6 expression has only been evaluated in surgically resected PDAC specimens. Less than 15% of patients with PDAC are eligible for surgery. Endoscopic ultrasound guided fine-needle aspirate (EUS-FNA) and biopsy (EUS-FNB) can potentially help assess GATA6 expression in PDAC and in turn, help guide personalized treatment selection in all cases of PDAC.

Aims
The primary objective of this study was to explore the yield of EUS-FNA and EUS-FNB for the detection of GATA6 among patients with PDAC. The study also aimed to explore the impact of lesion location on sample adequacy and type of fixative on validity of GATA6 staining.

Methods
This study was conducted from November 2017 to October 2019. Consecutive patients with a diagnosis of PDAC confirmed by biopsy were included. Patients underwent either EUS-FNB or EUS-FNA to obtain tissues samples. Samples were fixed in either neutral buffered formalin (NBF) or a methanol based buffered solution (Cytolyt) and evaluated by a specialized cytopathology team. Fisher’s exact test was used and a p-value ≤0.05 was considered to indicate statistical significance.

Results
Forty-four patients were included in the study. Twenty-three (52%) patients were male and the median age of patients was 67.5 years. Twenty-five lesions were located in the head and neck of the pancreas, 14 were located in the body, and 4 were located in the tail. One patient was found to have a local recurrence of PDAC at the surgical bed of a previous Whipple procedure.
Eighteen lesions were sampled by EUS-FNA and 26 were sampled using EUS-FNB. Thirty-eight (86%) samples were adequate for assessment of GATA6. Sampling technique (p=0.68) and fixative type (p=1.00) did not appear to affect sample adequacy. Compared to pancreatic body or tail specimens, samples obtained from the head or neck of the pancreas were more likely to be inadequate for analysis (p=0.03).

Conclusions
EUS-FNA and EUS-FNB samples are efficacious methods of assessing GATA6 expression in PDAC. This is the first predictor of treatment response that has been demonstrated to be obtained without surgical resection. Neither EUS needle type or alcohol fixation before cell block preparation appear to impact GATA6 detection. Lesions in the pancreatic head or neck appear to be associated with higher rates of sample inadequacy. Larger, prospective studies are required to confirm our findings.

Funding Agencies
None
A61 USE OF ADJUNCTIVE REMOVAL TECHNIQUES FOR ENDOSCOPIC MUCOSAL RESECTION OF LARGE NON-PEDUNCULATED COLONIC POLYPS IS PREDICTIVE OF POLYP RECURRENCE
Authors: Li S , Mosko J , May G , Kandel G , Kortan P , Marcon N , Teshima C 
Published: March 2021

Abstract

Background
Endoscopic mucosal resection (EMR) allows for safe and effective removal of large non-pedunculated colon polyps. However, prior studies have shown significant recurrence rates between 10–30% after EMR, which have led to recommendations for close endoscopic follow-up and the use of techniques such as snare tip soft coagulation (STSC) to EMR margins to prevent recurrence. Models such as the Size/Morphology/Site/Access score (SMSA) have been developed to aid in identifying polyp complexity and patients at high risk of recurrence. Numerous individual risk factors for recurrence have previously been reported, however the significance of these factors have varied between studies, with limited data from Canadian centres.

Aims
To evaluate predictors of recurrence for large non-pedunculated polyps following EMR.

Methods
Consecutive patients between April 1, 2017 to March 1, 2019 who underwent EMR were retrospectively identified from endoscopy unit administrative records. Patients with non-pedunculated colorectal polyps ≥ 2 cm that were removed by EMR were included if follow-up endoscopy data were available. Polyps found to contain invasive adenocarcinoma on histology and/or were referred for surgical resection were excluded. Patient demographic, pre-procedural, intra-procedural, and post-procedural data to time of first follow-up colonoscopy were extracted. Recurrence was defined as a positive pathology specimen from the EMR scar at follow-up. Adjunctive techniques were defined as the use of any non-snare resection or ablation technique for removal of visible adenoma at the time of the EMR. Chi-square and multivariate regression analyses were conducted for variables of interest.

Results
517 patients underwent large polyp EMR during the study time period with 265 patients satisfying inclusion criteria. Median age of patients was 67 years (IQR 14); 48% were female. STSC was performed to EMR margins in 94% of cases. 30.9% and 69.1% of polyps were SMSA grade 3 and grade 4 respectively. Adjunctive removal techniques were utilized in 31% of patients, 95% of which was hot avulsion. 15% of patients had recurrence on follow-up endoscopy. Higher SMSA grade was associated with the use of adjunctive techniques (20% vs. 37%, p=0.006). The use of adjunctive removal techniques (OR 2.92, p=0.007) and male gender (OR 3.45, p=0.002) were the only factors found to be significantly predictive of recurrence on multivariate analysis.

Conclusions
Male gender and the use of adjunctive removal techniques, particularly hot avulsion, are independently predictive of recurrence after EMR of large complex colorectal polyps. Male patients and those who require hot avulsion may be considered high risk for recurrence and warrant closer follow-up.

Funding Agencies
None
A62 THE UTILITY OF FECAL IMMUNOCHEMICAL TEST IN HOSPITALIZED PATIENTS: A RETROSPECTIVE CHART REVIEW
Authors: Vantomme E , Chetty K , Ho K , O’Byrne M 
Published: March 2021

Abstract

Background
Fecal immunochemical test (FIT) is a colorectal cancer (CRC) screening tool that uses antibodies to detect the globin moiety of human hemoglobin. On average, one test costs approximately $35 CAD. It has been widely validated as an effective screening tool that is both more sensitive than fecal occult blood testing, and less likely to react to non-human sources of blood, such as from dietary sources. Despite an absence of evidence for use in hospitalized patients, it is commonly ordered in this setting.

Aims
To assess the value and appropriateness of FIT in hospitalized patients in an urban health authority.

Methods
All FITs ordered for hospitalized patients between August 1, 2017 and June 1, 2018 in one academic hospital in Regina, Saskatchewan were examined. Of the 626 cases that were identified, information regarding demographics, clinical presentation, consultations, laboratory values, and endoscopy results were recorded.

Results
Of all 626 FITs ordered, 204 were positive and 422 were negative. Hospitalist physicians ordered 41% of these FITs. Of the 197 patients with negative FITs whose clinical data were available, 39% proceeded to gastroscopy and 23% proceeded to colonoscopy/flexible sigmoidoscopy during admission. Of the 201with positive FITs whose clinical data were available, 58% proceeded to gastroscopy and 40% proceeded to colonoscopy/flexible sigmoidoscopy during admission. FIT had a sensitivity of 100% (95% CI: 94–100%) and specificity of 3% (95% CI: 0–15%) to detect abnormal colonoscopy/flexible sigmoidoscopy results while having a sensitivity of 67% (95% CI: 57–78%) and specificity of 45% (95% CI:36–55%) to detect abnormal gastroscopy. Using a composite of uninvestigated iron deficiency, age &gt;75 or &lt;50 years, clinically overt bleeding, endoscopy despite negative FIT, and up-to-date CRC screening as a definition for inappropriate use of FIT, we found that 7% of negative FITsand 4% of positive FITs were appropriately ordered.

Conclusions
FIT tests had excellent sensitivity for lower gastrointestinal bleeding but had a high false positive rate in this population. FIT tests performed poorly in upper gastrointestinal bleeding. Using FIT for its validated purpose of CRC screening was done in a minority of cases. Importantly, 60% of patients with negative FIT tests proceeded to endoscopy, which may suggest that FITs in hospitalized patients does not significantly alter clinical decision making in a majority of cases.

Funding Agencies
None
A66 GASTRIC HETEROTOPIA OF THE COLON IN A PATIENT WITH A POSITIVE FECAL IMMUNOCHEMICAL TEST
Authors: Nassiri S , Emery J S , Lee L H 
Published: March 2021

Abstract

Background
Gastric heterotopia (GH), indicates the presence of ectopic gastric tissue and is a rare entity outside of the small intestine. Abdominal pain and bleeding are described but most colonic GH is found incidentally.

Aims
We report a case of colonic GH found on routine screening colonoscopy.

Methods
Case report and review of the literature.

Results
Case Report: A 60-year-old woman with a history of alcohol use disorder, chronic Hepatitis C, and gastroesophageal reflux disease was referred for colonoscopy after a positive fecal immunochemical test. Remote colonoscopy was notable for a large tubular adenoma with low-grade dysplasia. The patient denied constitutional symptoms, change in bowel habits, or evidence of gastrointestinal (GI) bleeding. No family history of colorectal cancer was reported. Complete blood count, renal function, electrolytes, and carcinoembryonic antigen were normal.
At colonoscopy, a 2 cm sessile polyp (0-Is Paris classification) was identified with a normal vascular pattern, but unclassifiable pit pattern. Submucosal injection was suboptimal suggesting tethering. However, given the history of previous polypectomy and favorable endoscopic appearance, piecemeal resection was attempted and achieved fair results. Histology showed abundant pyloric-type glands with overlying foveolar epithelium (Figure 1). Endoscopic follow-up at 8 months confirmed complete resection.

Literature Review
GH is observed throughout the GI tract but is predominantly seen in the esophagus and duodenum. Colonic involvement is uncommon with only 12 cases reported. Despite the lack of epidemiological studies, there is a male predominance across all age groups. Pathogenesis is thought to be either congenital, with deposition as the stomach descends during embryogenesis, or acquired secondary to metaplasia following injury to normal intestinal mucosa.
Presenting complaints may include altered bowel habits or haematochezia, but most lesions are detected incidentally on surveillance colonoscopy. Endoscopic descriptions are diverse with variations in size (1-60mm), Paris classification (sessile or pedunculated), and appearance (erythematous patch, ulcer, or diverticulum). Endoscopic resection is recommended given association with bleeding but may be technically difficult due to submucosal involvement which may theoretically increase risk of complications such as perforation. Definitive diagnosis rests on histological examination. The risk of malignant transformation of GH in the colon is unknown with only two such cases reported. However, some propose the incidence of malignant change is underestimated as the growing tumor may eliminate the focus of heterotopic gastric mucosa.

Conclusions
GH in the colon is a rare entity with diverse endoscopic appearances and poorly understood natural history. Careful endoscopic resection is feasible in the absence of other high-risk endoscopic features.

Funding Agencies
None
A67 DELAYED PRESENTATION AND SURGICAL MANAGEMENT OF PRIMARY PNEUMOCOCCAL PERITONITIS
Authors: Klemm N K , Trasolini R , Chatur N 
Published: March 2021

Abstract

Background
S. pneumoniae intraabdominal infections are rare in healthy individuals, but the literature reveals a female dominance for primary peritonitis in the early post-partum period. Limited studies exist evaluating the timing of surgical management.

Aims
We present a case of primary pneumococcal peritonitis in which the presentation and surgical intervention was delayed.

Methods
A case chart review and literature review was conducted.

Results
A 41-year-old female with a spontaneous vaginal delivery 4 months prior presented with progressive abdominal pain, distention, and emesis over 10 days. She was septic with a firm, distended abdomen and rebound tenderness. A CT revealed significant panenteritis and ascites. She received intravenous fluids and was empirically started on ceftriaxone, vancomycin and metronidazole. The gastrointestinal virus panel, stool cultures and C. difficile toxin were negative. However, her blood cultures revealed Strep. pneumoniae and the purulent peritoneal fluid contained gram-positive cocci. Despite sensitivity to ceftriaxone, and several paracenteses, her ascites, pain and new fever continued. Twenty-eight days after admission, she underwent a laparoscopic abdominal lysis of adhesions and drainage of three intraabdominal abscess collections. Cultures of the purulent peritoneal fluid were negative. She was stepped down to amoxicillin-clavulanate and discharged six weeks after symptom onset.
Despite the development of pneumococcal vaccines, worldwide S. pneumoniae is a common pathogen with high morbidity and mortality. It is a rare cause of intraabdominal infections; however, primary peritonitis has been widely recognized in children. Prior to antibiotics, the mortality of pneumococcal peritonitis was 31.5–100%. Secondary pneumococcal peritonitis is established in adult patients with cirrhosis, nephrotic syndrome and immunocompromised conditions. In healthy individuals, pneumococcal peritonitis often mimics appendicitis and is diagnosed with positive blood cultures. The majority of primary pneumococcal peritonitis cases occur in females, are associated with the early post-partum period (less than two months), IUD placement, and pelvic inflammatory disease. Theories of pathogenesis include direct hematogenous spread or translocation. Transient colonization of the genital tract after IUD placement or during the post-partum period may allow for ascension from the fallopian tubes into the peritoneum. The majority of cases undergo surgery within one week of symptom onset. While it has not been studied in randomized trials, early surgical intervention for source control may decrease morbidity and hospital stay.

Conclusions
Primary pneumococcal peritonitis has a female predominance and can occur later in the post-partum period than previously reported. Surgery should be considered early to achieve source control and improve patient outcomes.

Funding Agencies
None