bluuebunny/crossref_metadata_2025_split huggingface dataset:
A63 THE COLONIC PATHOGEN, ENTAMOEBA HISTOLYTICA ACTIVATES CASPASE-4 IN HUMAN MACROPHAGES THAT CLEAVES GASDERMIN D TO FACILITATE IL-1β SECRETION IN THE ABSENCE OF CELL DEATH
Authors: Wang S , Moreau F , Chadee K 
Published: February 2022

Abstract

Background
A hallmark of Entamoeba histolytica ( Eh) invasion in the gut is acute intestinal inflammation dominated by the secretion of pro-inflammatory cytokines. Live Eh in contact with macrophages activates caspase-1 by the recruitment of the NLRP3 inflammasome in a Gal-lectin and Eh cysteine proteases 5 ( EhCP-A5)-dependent manner, resulting in the maturation and secretion of IL-1β. Eh in contact with macrophages also activates caspase-4 by outside-in signaling but it is unclear how Eh-induced caspase-1/4 regulates gasdermin D (GSDMD) cleavage to drive both pore formation and IL-1β secretion without causing cell death. In this study, we interrogated the requirements and mechanism of Eh-induced caspase-4 activation in cleaving GSDMD to mediate bioactive IL-1β release.

Aims
Hypothesis: Eh-induced activation of caspase-4 regulates GSDMD mediated pro-inflammatory responses.
Specific aim: To quantify caspase-1/4 cleavage of GSDMD in Eh-induced pro-inflammatory responses.

Methods
Human PMA-differentiated THP-1 macrophages were used for Eh-macrophage studies. Caspase-1/4 activation and GSDMD cleavage were detected by immunoblot analysis. Bioactive IL-1β secretion was quantified by HEK-BlueTM IL-1β reporter cells via the measurement of secreted embryonic alkaline phosphatase (SEAP) and cell pyroptosis (inflammatory cell death) was determined by LDH assay. Immunoprecipitation was performed in HEK 293T cells transfected with human GSDMD plasmid followed by in vitro caspase cleavage assay.

Results
Unlike caspase-1, Eh-induced caspase-4 activation and IL-1β secretion was independent of the NLRP3 inflammasome as revealed with the use of CRISPR-Cas9 gene edited caspase-1, 4, ASC and NLRP3 macrophages. In the absence of caspase-1, caspase-4 activation was significantly upregulated that promoted the cleavage of GSDMD to induce robust IL-1β secretion. Eh-induced caspase-4 played a major role in triggering IL-1β release and GSDMD pore formation as quantified by SEAP assay and immunoprecipitation of overexpressed GSDMD in HEK 293T cells followed by in vitro caspase cleavage assay. Pharmacological inhibition of GSDMD pore formation and in CRISPR-Cas9 gene edited GSDMD macrophages, Eh-induced IL-1β secretion was highly dependent on GSDMD pore formation and independent of pyroptosis. This was in marked contrast to the positive control, LPS + Nigericin that induced high expression of caspase-1 but not caspase-4 that enhanced GSDMD cleavage and IL-1β secretion and induced massive pyroptosis.

Conclusions
These results suggest that Eh induced a state of “hyperactivated macrophages” that led to caspase-4 dependent GSDMD cleavage and IL-1β secretion in the absence of pyroptosis important in disease pathogenesis.

Funding Agencies
NSERC
A87 CHANGES IN CLINICIAN KNOWLEDGE, COMFORT, PREPAREDNESS, AND ATTITUDES ABOUT ALCOHOL USE DISORDER AND CIRRHOSIS AFTER A BRIEF EDUCATIONAL INTERVENTION
Authors: Johnson E , Ghosh S M , Daniels V J , Tandon P 
Published: February 2022

Abstract

Background
Alcohol use disorder (AUD) is increasing in prevalence and has a substantial impact on morbidity and mortality in people with cirrhosis. The use of screening, brief intervention and referral to treatment (SBIRT) and relapse prevention medications (e.g. acamprosate) are recommended by recent guidelines. Unfortunately, many clinicians report insufficient training to feel confident using these interventions

Aims
We aimed to compare the effect of a brief educational intervention on AUD knowledge, comfort, attitudes, and preparedness in clinicians who provide care to patients with cirrhosis.

Methods
Clinicians were invited to participate in a 1.5-hour educational session conducted by a hepatologist and addiction medicine specialist. The session included information about SBIRT and pharmacotherapy. Pre-training knowledge, comfort, and practice behaviors were assessed using previously published questions. Baseline attitudes were measured using the Short Alcohol and Alcohol Problems Perception Questionnaire. Participants were invited to repeat the questionnaires immediately post-training and statistical analysis conducted.

Results
Eighty-two clinicians attended the session. Among the 38 attendees who completed both the pre- and post-questionnaires, 34% were GIs/internists, 45% were family medicine physicians, and the remainder (21%) did not specify or were not prescribers. Scores for self-reported intention and preparedness to treat AUD, comfort, and knowledge improved significantly from the pre-training phase. Attitudes also improved from the pre-training phase, with significant improvements in the SAAPPQ subscales of role adequacy (p=0.03) and motivation (p=0.04).

Conclusions
Recognizing the small sample size, a brief educational session demonstrated promising results in the promotion of knowledge, attitudes, preparedness, and comfort for clinicians managing AUD in patients with cirrhosis. Feedback from these sessions will be used to design an accredited educational series for roll-out in 2022.

Funding Agencies
Alberta Innovates Health Solutions
A97 DEVELOPMENT OF PREDICTION MODELS FOR THE TRIAGING OF REFERRALS OF INDIVIDUALS WITH SUSPECTED INFLAMMATORY BOWEL DISEASE TO IMPROVE PROMPT ACCESS TO CARE
Authors: St-Pierre J , Frolkis A , Seow C , Oshiomogho J , Bindra G , Heatherington J , Kaplan G G , Panaccione R , Novak K L , Nasser Y , Jijon H 
Published: February 2022

Abstract

Background
The negative impact of a delayed inflammatory bowel disease (IBD) diagnosis has been well established. We created a clinical pathway referred to as the “High-Risk IBD clinic” within a centralized referral program in a tertiary referral centre, in order to improve access to subspecialist care for individuals suspected but not yet diagnosed with IBD. Despite the creation of this specialized clinic, wait times continue to be above the recommended benchmarks established by the Canadian Association of Gastroenterology (CAG).

Aims
The purpose of our study was to create predictive models to identify factors associated with an IBD diagnosis in order to improve triage of referrals of individuals with features highly suggestive of IBD. We hypothesized that features suggestive of IBD could be used to create discriminating prediction models between IBD and IBS.

Methods
We conducted a retrospective cohort study of referrals to the High-Risk IBD clinic from February 2014 to December 2018. Referral information, investigations, endoscopic findings and final diagnosis were obtained from 316 consented individuals. Information required included symptoms (e.g. diarrhea, abdominal pain, rectal bleeding), risk factors (e.g. family history, rheumatological disease) and investigations (e.g. hemoglobin, CRP, abdominal imaging). Univariate logistic regression was performed to explore the association between factors included in the referral form, and a diagnosis of Crohn’s disease (CD) and ulcerative colitis (UC). For creation of predictive models, any variable with a p-value of &lt;0.1 in univariate logistic regression was selected for entry into the multivariate model for CD and UC.

Results
For UC, the predictive model included weight loss, the presence of rectal bleeding and abdominal pain. Using these criteria, the sensitivity and specificity of the model were 62.5% and 74.1%, respectively. The negative predictive value (NPV) was high at 94.2%. For CD, the predictive model included male gender, elevated CRP, presence of anemia and presence of weight loss. The sensitivity and specificity of this model were 61.7% and 71.2%, respectively. As for UC, the NPV was also high (89.2%). For IBS, the most common diagnosis encountered in patients referred to the HR-IBD clinic, the model included absence of weight loss, presence of abdominal pain and female gender. The sensitivity and specificity were 71.6% and 64.0%, respectively. The positive predictive value was 60.6% and NPV was 74.5%.

Conclusions
We established predictive tools associated with a final diagnosis of IBD and IBS as a means to expedite the care of individuals with undiagnosed IBD.

Funding Agencies
CCC
A110 FEASIBILITY OF EUS-GUIDED PORTAL PRESSURE GRADIENT MEASUREMENT WITHOUT DEEP SEDATION: A PATH TO ACCURATE PORTAL PRESSURE DETERMINATION
Authors: Zhao X , Chen Y , Deschenes M , Wong P , Sebastiani G , Chen T , Benmassaoud A 
Published: February 2022

Abstract

Aims
Hepatic venous pressure gradient (HVPG) is the gold standard for the diagnosis and staging of portal hypertension. Previous studies have shown that it underestimates pre-sinusoidal portal hypertension. Endoscopic ultrasound-guided portal pressure gradient (EUS-PPG) can safely measure direct portal vein pressure (PVP) and bridge this diagnostic gap. However, EUS-PPG has so far been performed with patients under deep sedation which can alter HVPG measurement and lead to misclassification of portal hypertension. Ketamine, a conscious sedation agent, has minimal effect on portal hemodynamics. We present our center’s experience with EUS-PPG under ketamine and low dose midazolam.

Methods
We retrospectively reviewed consecutive patients undergoing EUS-PPG with conscious sedation using ketamine and low-dose midazolam (&lt;0.02 mg/kg) at the McGill University Health Centre from February to May 2021. Patients were placed in the left lateral position. Hepatic vein and portal vein were located through EUS via a trans-gastric/hepatic approach. A through the scope 25-gauge needle attached to a manometer was advanced through the liver to measure hepatic vein pressure (HVP) and portal vein pressure (PVP). Three measurements were sampled per vessel and mean pressure differences calculated to obtain PPG. PPG was considered reliable if the differences between the values was no more than 1mmHg.

Results
Three patients underwent EUS-PPG for evaluation of pre-sinusoidal portal hypertension. Cirrhosis was excluded in all patients based on recent liver biopsy or transient elastography. The first patient is a 69-year-old man with splenomegaly and recanalization of the paraumbilical vein on imaging. He received 80 mg of ketamine and no midazolam. HVPG measured was 1 mmHg. EUS-PPG was successful with PPG of 6 mmHg (HVP= 7 mmHg, and PVP= 13 mmHg). The second patient is a 42-year-old woman with previous sleeve gastrectomy and known with portal cavernoma. She received 120 mg of ketamine and 1 mg of midazolam. EUS-PPG was technically difficult due to respiratory movements. The measurement was not considered reliable as differences in PPG were as high as 2mmHg. In this case, PPG was 0mmHg (HVP= 15mmHg, and PVP= 15mmHg). The third patient, a 74-year-old man with hepatic steatosis and splenomegaly received 70 mg of ketamine and 1 mg of midazolam. EUS-PPG was successful (HVP= 3mmHg, PVP= 3mmHg) yielding a PPG 0mmHg. All patients tolerated the procedure well with no procedural or sedation-related complications

Conclusions
Our early experience suggests that EUS-PPG can be successfully and safely performed in patients under conscious sedation with ketamine and low-dose midazolam. This combination may avoid deep sedation with high dose midazolam or propofol which are known to alter accuracy of HVPG.

Measurement of HVP (left) and PVP (right)

Funding Agencies
None
A112 VIDEO CAPSULE ENDOSCOPY REGISTRY OF ONTARIO (VCERO) - RETROSPECTIVE PHASE (NORTHERN ONTARIO REGION)
Authors: Lavalle C , Yaghoobi M , Armstrong D , Tilbe K 
Published: February 2022

Abstract

Aims
The primary aim of this project is to determine the feasibility of establishing and maintaining a registry of all video capsule endoscopy procedures performed at a large regional center. Secondary aims include the determination of indications for capsule endoscopy, quality measures, and procedural outcomes at a large regional center and the comparison of these metrics to other locations globally.

Methods
A retrospective collection and analysis of all video capsule endoscopies performed at Health Sciences North in Sudbury Ontario between 2016 and 2020 has been performed. Information was collected with the aid of a standardized data collection tool and stored under anonymized patient profiles. Once this pilot registry was created, data was pooled for further analysis. Data regarding indications for capsule endoscopy, patient factors, previous investigations, anticoagulant usage, procedure interpretation, need for subsequent interventions, and need for blood transfusion among others was then established for this group. Findings were then compared to previously published regional and global norms where available.

Results
In total 98 video capsule endoscopies encompassing 94 individual patients have been catalogued at the end of the study period. With available information through individual patient records, complete information for all fields of the standardized collection tool was obtained for 91 individual patients. The most common indications for VCE include gastro-intestinal bleeding (38%), anemia (38%), Crohn’s disease (13%) and abdominal pain (3%). In total, 45% of all procedures noted an acute finding in the report. Of VCE performed for gastro-intestinal bleeding, 50% reported on an acute finding while in those performed for anemia, 47% reported on an acute finding. Mortality during the study period was 12% while there was 1 documented incident of capsule retention. The rate of acute findings is greater than previously published international studies.

Conclusions
This project has established the feasibility of the creation of a regional capsule endoscopy registry. Further work to expand the patient pool as well as move to a prospective collection model are reasonable next steps to expand this project. We have also demonstrated significant differences regarding indications for VCE as well as the rate of significant findings of VCE of a our northern cohort compared to previously reported international sites. In particular the high rate of significant findings in anemia warrants further investigations.

Funding Agencies
None
A114 QUALITY AND EFFICACY OF PERCUTANEOUS ENDOSCOPIC GASTROSTOMY: A RETROSPECTIVE CHART REVIEW STUDY
Authors: Aljabri R S , Kwan P 
Published: February 2022

Abstract

Background
Passage of food along the digestive tract can be compromised by a number of conditions. Nasogastric tube (NGT) feeding is used in these cases but prolonged use can lead to various complications. Percutaneous endoscopy gastrostomy (PEG) has been reported as an effective and safe alternative to NGT. Clinical efficacy and adverse events related to PEG insertion are largely dependent on post-procedure care.

Aims
To assess the clinical significance of PEG tube insertion procedure and impact of post-procedure care and diet protocol on associated adverse events and success rate at two Canadian tertiary care units.

Methods
The retrospective electronic chart review was conducted on all patients who underwent endoscopic PEG fixation or replacement procedure at University of British Columbia Gastroenterology clinic and Vancouver General hospital Endoscopy Unit from 1st April 2020 to 31st March 2021. Data related to patient demographics, indications for insertion, insertion technique, quality of PEG insertion protocol, antibiotic prophylaxis, success rate, and rate of PEG-related complications were collected and analysed. An evaluation protocol was devised to evaluate the impact of indication-based diet protocols on frequency of adverse events and success rate. Results are suggested to be analysed using SPSS v 2021 with significance threshold of P-value &lt; 0.05.

Results
43 PEG insertion procedures were performed, of which 3 failed due to structural reasonsincluding post gastric sleeve surgery, small stomach and difficulty in finding transillumination point. 25 cases underwent PEG insertion endoscopically for the first time, and 14 required exchanges, of which 2 underwent non-endoscopic exchange. Of 37 patients who underwent endoscopic PEG insertion 18(48.64%) were males and 19(51.36%) were females. Acute infection was reported in 6(14%) and chronic infection in 4 patients (9.3%). Tube dislodgment was reported in 10(23%), peristomal leak in 4(9.3%), miinor bleeding in 3(6.9%), and post-operative granulation in 4(9%) procedures. The evaluation protocol divides patients into two groups: Group a included d subjects who would receive low-volume (≤150 mL/d) and Group b who would receive a high-volume (≥300 mL/d) of feeding formula.

Conclusions
PEG tube insertion is a very successful procedure with high clinical significance and low complications rate at VGH and UBC. A follow-up plan is therefore being initiated to evaluate impact of feeding volumes on rate of success and adverse events. Combined, the previous studies, suggest that the high-feeding volumes can be safely administered to rapidly attain calorie targets to increase the procedure efficacy. .

Funding Agencies
CAG
A119 ACUTE DIVERTICULITIS & CONCURRENT DIVERTICULAR BLEED: A RARE CLINICAL ENTITY
Authors: Hasan S , Ilnyckyj A 
Published: February 2022

Abstract

Aims
Colonic diverticula are mostly asymptomatic incidental findings on cross sectional imaging or colonoscopy. In the setting of known diverticulosis, complications like diverticulitis and diverticular bleeding occur in only 4% and 1% of patients respectively. It is unusual to see both complications expressed in the same patient and moreover, rare to see them expressed concurrently. We report a case of concurrent diverticulitis with diverticular bleed and expand on the clinical course.

Methods
Case report

Results
A 73-year old was diagnosed with sigmoid diverticulitis based on her clinical presentation and an abdominal CT scan. She was discharged home on oral antibiotics but presented a week later with painless rectal bleeding. In view of the ongoing diverticulitis, a colonoscopy was not pursued although it is the typical procedure of choice to manage active gastrointestinal bleeding. A CT scan was recommended as the alternate initial investigation, which revealed active colonic bleeding in the region of the hepatic flexure immediately adjacent to a diverticulum. A subsequent CT angiogram identified the middle colic artery to be the responsible blood supply to the region and embolization coils were deployed within this vessel in an attempt to achieve hemostasis.
Despite vascular intervention the patient continued to bleed and resuscitation with blood products was insufficient. A repeat CT scan ruled out any areas of colonic ischemia as well as any further active areas of extravasation. A decision was made to proceed with a total colectomy to provide definitive treatment of the diverticular disease and manage the bleeding. An urgent intraoperative colonoscopy was attempted but quickly abandoned due to suboptimal preparation and ongoing bleeding obscuring the view. The patient underwent a total colectomy with ileorectal anastomosis. On pathology there was extensive diverticulosis of the ascending and the sigmoid colon with diverticulitis and diverticular abscess cavities within the sigmoid colon.

Conclusions
Diverticulitis and diverticular bleed are thought to be unrelated complications of diverticulosis involving distinct physiologic pathways (Figure 1). Although diverticular bleed may occur in patients with a history of prior diverticulitis, concurrent presentation of these two entities is extremely rare. In addition, diverticular bleed is mostly self-limiting. While endoscopic and vascular embolization are established treatment options, colectomy is rare for the management of diverticular bleeding.
We report a rare case of concurrent diverticulitis and lower GI bleeding. The presence of the sigmoid diverticulitis made interventional radiology a relatively safer option over endoscopy, which is the typical first line diagnostic and interventional procedure. Ongoing bleeding led to total colectomy and provided the patient with a definitive cure for her diverticular disease.

Funding Agencies
None
A123 MINIMALLY INVASIVE ENDOSCOPIC RESECTION TECHNIQUE PERFORMANCE FOR PERI-APPENDICEAL COLORECTAL NEOPLASIA: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Arif A A , Donaldson K , Qian H , Lam E , Shahidi N C 
Published: February 2022

Abstract

Background
Minimally invasive endoscopic resection techniques, including endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD) and endoscopic full-thickness resection (EFTR) have revolutionized the management of peri-appendiceal colorectal neoplasia. However, questions remain about their comparative performance.

Aims
We sought to evaluate the performance of EMR, ESD and EFTR for peri-appendiceal colorectal neoplasia.

Methods
Two authors independently searched MEDLINE, EMBASE and Cochrane Libraries (Jan 2000 – Aug 2021) for citations evaluating the performance of endoscopic resection techniques (EMR, ESD, EFTR) for peri-appendiceal colorectal neoplasia (defined as those involving or in close proximity to the appendiceal orifice). The incidence rates and 95% confidence intervals (95% CI) of technical success (complete removal of all neoplastic tissue at index procedure), clinically significant post-endoscopic resection bleeding (CSPEB), delayed perforation, recurrence and referral to surgery were assessed using random-effects modelling.

Results
12 studies were included in the analysis (479 patients: 185 EMR, 171 ESD, 123 EFTR). Technical success was achieved in 93.5% (95% CI 90.9%-95.4%, EMR 93.5%, ESD 94.1%, EFTR 92.7%). Clinically significant post-endoscopic resection bleeding occurred in 1.3% (95% CI 0.4%-4.3%, EMR 3.8%, ESD 1.2%, EFTR 0%). Delayed perforation occurred in 1.9% (95% CI 0.9%-3.9%, EMR 0%, ESD 2.4%, EFTR 2.4%). Recurrence occurred in 5.7% (95% CI 2.3%-13.8%, EMR 14.3%, ESD 0.2%, EFTR 12.2–14.3%). Referral to surgery occurred in 9.0% (95% CI 6.7%-12.0%, EMR 8.1%, ESD 9.5%, EFTR 9.8%).

Conclusions
Minimally invasive endoscopic resection techniques including EMR, ESD and EFTR demonstrate high frequencies of technical success with comparable adverse event profiles. They should now be viewed as first-line therapeutic modalities for the management of peri-appendiceal colorectal neoplasia.

Funding Agencies
None