bluuebunny/crossref_metadata_2025 huggingface dataset:
A144 ZENKER’S PERORAL ENDOSCOPIC MYOTOMY (Z-POEM) OUTCOMES IN TREATMENT OF ZENKER’S DIVERTICULUM: A RETROSPECTIVE CASE SERIES
Authors: Youssef M , Ching Hui Yee C , Bechara R
Published: February 2024

Background

Zenker’s diverticulum (ZD) is an outpouching of tissue in an area of the posterior hypopharynx called the Killian triangle. ZD is associated with dysphagia, regurgitation, cough and recurrent aspirations. Open surgical repair has been the traditional treatment approach but has high morbidity (0-40%) and mortality (0-9.5%). Endoscopic intervention with septotomy is a less invasive approach with lower complications and shorter recovery times. However, technical success rates range between 56.4-100%, and recurrences occur in 0-32% of patients. Recent studies have shown promising results for peroral endoscopic myotomy treatment of ZD (Z-POEM), although data is limited.

Aims

In this first Canadian case series, we assess the safety and efficacy of Z-POEM, a novel approach for managing ZD.

Methods

This is a retrospective case series of all patients who underwent Z-POEM for ZD at Kingston Health Sciences center between July 2021-2023. Data collected included patient demographics, symptoms [Kothari Haber Score (KHS)] pre and post Z-POEM, ZD size and prior treatments. Technical outcomes were also analyzed including the procedure time and the Z-POEM Difficulty Score (ZPDS), which ranges from 0-3 based on maneuverability, fibrosis, and oozing. Clinical success was defined as complete or near-complete resolution of symptoms (i.e. KHS ampersand:003C2), and recurrence was defined as KHS of 3 or more. Lastly, we recorded adverse events and hospital length of stay.

Results

This case series included 9 patients (6 males and 3 females). The mean age ± standard deviation (SD) was 66.1 ± 10.64 years. One patient had two separate Z-POEM procedures and those were analyzed separately (total sample size = 10). The mean duration of symptoms before the procedure was 31.2 ± 10.12 months and the mean size of ZD was 2.25 ± 1.10 cm. Two patients had prior treatments before their Z-POEM procedure. The median preprocedural KHS was 6 (range 3-10) with dysphagia being the most commonly reported symptom in 80% of patients. In terms of technical outcomes, the mean procedural time was 32.3 ± 13.21 mins, and the median ZPDS score was 2. Most patients required 4-6 clips, with one patient requiring 11 clips for closure. No adverse events or periprocedural complications were reported. 9/10 patients (90%) were discharged one day after the procedure, and one patient required a longer stay (4 days) for observation. Clinical success was achieved in 8/10 patients (80%) of patients with a KHS score of 0 at mean 12 months follow-up. The remaining two patients (20%) had a KHS score of 3 at follow-up suggesting some persistent symptoms.

Conclusions

Z-POEM is safe and effective in management of ZD with high technical and clinical success rates in the short-term. Larger-scale studies are required to determine the long-term clinical efficacy of Z-POEM in treatment of ZD.

Funding Agencies

None
A145 UNDERWATER EMR FOR LARGE FLAT DYSPLASTIC COLORECTAL LESIONS IN PATIENTS WITH CHRONIC ULCERATIVE COLITIS
Authors: Yu R , Barclay R
Published: February 2024

Background

Patients with chronic ulcerative colitis are at increased risk of colorectal cancer, in part due to increased prevalence of dysplastic lesions. To reduce CRC risk, endoscopic resection is preferable to surgery if feasible. However, large flat lesions can be challenging to remove endoscopically. We report our experience with underwater EMR for large, flat ulcerative colitis-associated dysplastic lesions.

Aims

To evaluate the safety and efficacy of UEMR for treatment of flat/sessile colorectal lesions with dysplasia, without overt signs of invasive cancer. To analyze rates of complications and outcomes for patients undergoing UEMR and compare to alternative methods of treatment for similar lesions.

Methods

We reviewed our IBD patient database from 2021 to 2023 for ulcerative colitis patients referred for large (≥ 20 mm diameter) flat/sessile colorectal lesions without overt signs of invasive cancer, who subsequently underwent underwater EMR. The procedure was performed by an endoscopist with extensive experience in UEMR for large colorectal lesions.

Results

Eleven de novo lesions in 8 patients (4 female; age 58 ± 14) were successfully treated with single-session UEMR. Mean lesion size was 42 ± 22 mm (range 20 to 80 mm); all morphologically flat (Paris IIa or IIb). Three cases were resected en bloc; the remainder piecemeal. Pathology showed tubulovillous adenoma, N=4 (36%); tubular adenoma, N=5 (45%); traditional serrated adenoma, N=1 (9%); sessile serrated lesion, N=1, (9%); high-grade dysplasia, N=1 (9%). There were no cases of invasive cancer. Endoscopic follow-up available for 5 patients over 10.4 ± 2 months showed benign diminutive recurrent/residual lesions in 2 cases, both amenable to UEMR. There were no procedural complications.

Conclusions

In this series of large, flat dysplastic CUC-associated lesions, UEMR was safe and effective, obviating surgery and endoscopic submucosal dissection.

Funding Agencies

None
A148 OSTEOSARCOMA GASTROINTESTINAL METASTASIS: A RARE ENTITY IN ADULTS
Authors: Alabdulkarim B , Habal F
Published: February 2024

Background

Osteosarcoma is highly aggressive and is the most common primary bone malignancy for both children and adults with a bimodal age distribution. The first peak coincides with pubertal growth spurt and the second is in the seventh and eighth decade of life. They frequently metastasize to the lungs. Metastasis to the gastrointestinal tract is extremely rare and to our knowledge, there have only been 15 cases reported in the literature since 1987, of those only three in the second peak.

Aims

Describe a case of 61-year-old female with periampullary metastatic osteosarcoma. Describe the demographics of osteosarcoma patients who develop gastrointestinal metastasis.

Methods

Search Pubmed using the terms: ("Osteosarcoma"[MeSH Terms] OR "Osteosarcoma"[Title/Abstract]) AND ("Gastrointestinal Tract"[MeSH Terms] OR "Gastrointestinal Tract"[Title/Abstract] AND "Case Reports"[Publication Type]. 113 articles were identified and screened by title. 15 articles were further screened by abstract or full text. 7 articles were identified. the remainder 7 articles were located by screening the references of the previously identified articles.

Results

A 61-year-old woman with a medical history significant for metastatic Osteosarcoma was referred to Gastroenterology clinic July 2023 for anemia investigation. Her Osteosarcoma was first diagnosed in the left femur in 2009. She was known for extensive bilateral lung metastasis, subcutaneous metastatic deposits, and distant bone metastasis. She had undergone over 37 surgeries and multiple sessions of radiotherapy. Aside from neoadjuvant and adjuvant chemotherapy for the primary tumor and the first occurrence of lung metastasis, she refused to undergo further cycles of chemotherapy. She had a 60 mg/dl hemoglobin drop from a previous one in December 2023 and intermittent melena. On gastroscopy, she was found to have a 2 cm bleeding mass in the periampullary area. The pathology report of the biopsies was consistent with metastatic osteosarcoma. It showed fragments of ampullary mucosa incorporating a malignant spindle cell neoplasm with a fascicular growth pattern, including scattered osteoclast-like giant cells, morphologically consistent with the known history of metastatic osteosarcoma.

Of the 15 cases published, 9 were in patients 27 years old and younger, 3 were in patients 50 and older, and 3 were only available as titles. 50% of cases presented with intussusception while the rest had anemia or melena. The site of metastasis was the jejunum in the majority of patients (58%). Other sites included the ileum, stomach, colon, and esophagus. Only one other patient had periampullary metastasis. All patients had lung metastasis.

Conclusions

Gastrointestinal metastasis of osteosarcoma remains a rare occurrence. Our case report describes the second case reported in the literature of periampullary metastasis and the first case reported in older patients

Funding Agencies

None
A152 THE RISK OF UNFAVORABLE HISTOLOGIC FEATURES, LYMPH NODE METASTASIS AND METACHRONOUS ADVANCED NEOPLASIA IN PATIENTS WITH COLORECTAL INTRAMUCOSAL CARCINOMA
Authors: Medawar E , Popescu Crainic I , Djinbachian R , Zarandi-Nowroozi M , Taghiakbari M , Marques P , Kaufman D , von Renteln D
Published: February 2024

Background

Very few studies have described the risk of unfavorable histologic features (UHFs), lymph node involvement (LNI), distant metastasis (DM) and metachronous advanced neoplasia (MAN) after the detection of colorectal intramucosal carcinoma (IMC).

Aims

This study aimed to determine the risk of UHFs, LNI, DM and MAN in patients with IMC, compared to high-grade dysplasia (HGD) or T1 colorectal cancer (CRC).

Methods

A retrospective cohort study was conducted. Through a pathology database search, we identified all consecutive patients with HGD (epithelial) (n=908) or either IMC (lamina propria or muscularis mucosa) or T1 CRC (submucosa) (n=496) diagnosed between 2010 and 2019 at the University of Montreal Hospital Center. We excluded patients with age ampersand:003C40 or ampersand:003E90, IBD, hereditary CRC or post-neoadjuvant therapy. Primary outcome was the risk of UHF, LNI and DM in IMC vs T1. Secondary outcome was the risk of MAN (metachronous advanced adenoma or advanced serrated lesion or CRC) in the IMC group, compared to HGD and T1. Files were reviewed for demographics and index and follow-up findings. The metachronous analysis excluded follow-ups ampersand:003C6 months, no follow-up or previous CRC. Follow-up continued until MAN or last colonoscopy within 10 y. Variables were compared between groups using ANOVA, chi-squared tests or Kruskal-Wallis tests, followed by post-hoc tests. We performed multivariate Cox regressions, adjusting for age, sex, family history of CRC, main lesion location, villous histology, adenomas ≥10 mm, and number of adenomas.

Results

The primary cohort included 90 patients with IMC (mean age 69.4 y., 44.4% female) and 207 with T1 CRC (mean age 69.8 y., 43.5% female), as well as 797 with HGD. The rates of lymphatic invasion, vascular invasion, intermediate differentiation/grade and mucinous histology were 2/90, 1/90, 7/90 and 4/90 in the IMC group compared to respectively 30/207 (2.2% vs 14.5%, pampersand:003C0.01), 15/207 (1.1% vs 7.2%, p=0.06), 68/207 (7.7% vs 32.9%, pampersand:003C0.01) and 15/207 in the T1 group (4.4% vs 7.2%, p=0.52). No other UHFs were present. No patients with IMC had LNI or DM.

In the metachronous outcomes analysis, 464 patients were eligible (mean age 67.1 y., 42.2% female, median follow-up 3.0 y.): 274 with HGD, 58 with IMC and 132 with T1 CRC. Compared to HGD, patients with IMC had a lower likelihood of MAN (HR 0.46, 0.22-0.96), and T1 CRC had a similar likelihood of MAN (HR 0.65, 0.41-1.02). Compared to IMC, T1 CRC had a similar likelihood of MAN (HR 1.39, 0.63-3.09).

Conclusions

Patients with colorectal IMC have a small risk of UHFs, but LNI and DM were not identified in this cohort study and have not been reported. Patients with IMC and T1 CRC do not have an increased risk of MAN compared to patients with HGD.

Funding Agencies

None
A157 ASSOCIATION OF SUBMUCOSAL INVASION WITH THE PARIS CLASSIFICATION OF POLYPS IN THE LOWER GASTROINTESTINAL TRACT
Authors: Scaffidi M , Bechara R
Published: February 2024

Background

Endoscopic evaluation of the colorectum allows for diagnosis of colorectal cancer (CRC) and advanced polyps. In particular, polyps can be described in terms of gross morphology using the Paris classification. Previous work has demonstrated that submucosally invasive (SMI) cancer may correlate with the Paris classification subtypes.

Aims

To determine whether the Paris classification is associated with SMI in a Canadian setting.

Methods

We conducted a retrospective single-centre study using data from 2016 to 2023 of patients with colorectal lesions that were referred for endoscopic submucosal dissection (ESD). Using the Paris classification, we classified polyps as either protruding type (0-I) or flat type (0-IIa, 0-IIb, 0-IIc, 0-III) lesions. Protruding type lesions were further classified as sessile (0-Is), pedunculated (0-Ip) and pseudo-pedunculated (0-Isp) subtypes. Mixed lesions, with two concomitant subtypes, were categorized using the higher classification subtype. We categorized polyps as: protruded lesions, including any mixed lesions with a flat lesion; isolated flat elevated lesions; and flat lesions, both mixed and isolated lesions. We also recorded polyp location, prior endoscopic mucosal resection (EMR), previous biopsy, and polyp diameter (in cm), age, sex, and American Society of Anesthesiology (ASA) class. The primary outcome was SMI as identifed on histopathology. We used logistic regression with backward stepwise entry, Fisher exact test with relative risk (RR) and 95% confidence interval (95% CI), and independent samples t-test. Statistical tests were two-tailed and significant at Pampersand:003C0.05.

Results

In our sample of 130 patients, the mean age was 69.2 years (standard deviation [SD] 10.4), most were male (n=78, 60%), and typically had an ASA score of 3 (n=77, 59.2%). Most polyps occured in the rectum (n=65, 50%) with a mean length was 4.5 cm (SD 2.2 cm). The most common subtype was IIa (n=59, 45.4%). Starting with the covariates of age, sex, ASA, prior EMR, prior biopsy at the same, and length of polyp, the logistic regression model reduced them to three: prior EMR, prior biopsy at the same site, and length. Univariate analysis of these three variables found that there was no significant difference with polyp length and SMI (P=0.147) and no significant association with prior EMR on SMI (RR=0.8 [95% CI 0.3 to 1.9]. The presence of prior biopsies at the same site of the lesions was significantly associated with SMI (RR=2.4 [95% CI 1.2 to 4.7])

Conclusions

We did not find that the Paris classification for type of polyp lesion did not correlate with the presence of submucosal invasion, nor did prior EMR, age, sex, or length of polyp. The presence of a prior biopsy, however, did in fact tend to predict submucosal invasion. Future work should aim to incorporate mortality data and response to treatment into the above analysis.

Funding Agencies

None
A158 DEVELOPMENT OF MODELS TO SUDY THE INTERACTION BETWEEN CANCER STEM CELLS AND THE MICROENVIRONMENT IN COLON CANCER
Authors: Sedeuil M G , Gonneaud A , Giroux V
Published: February 2024

Background

Colon cancer affects 1 in 15 people and is the 3rd deadliest cancer worldwide. The standard of care consists of surgical resection combined with 5-fluorouracil (5-FU) chemotherapy. However, relapses remain frequent due to a partial or complete loss of sensitivity to treatment, also known as chemoresistance. Over the last decades, studies have revealed the importance of intratumoral heterogeneity in this phenomenon, and in particular of two components: cancer stem cells (CSCs) and the microenvironment. CSCs are cells with a high capacity of self-renewal, potency (ability to give rise to different cell types) and resistance to anti-cancer treatments. The microenvironment, for its part, comprises all the components surrounding tumour cells, such as cancer-associated fibroblasts (CAFs). Although their respective importance in resistance has been well studied, it is important to better understand their respective modulation during resistance as well as their interactions.

Aims

Identify the specific changes occurring in CSCs and CAFs, as well as their interactions, during the induction of 5-FU resistance in colon cancer.

Methods

To achieve this goal, we are establishing 5-FU resistant models using organoid lines from colon cancer patients. First, we validated that parental organoids maintain their expected cellular heterogeneity by immunofluorescence. We also confirmed that our parental organoids are sensitive to 5-FU by measuring the survival through a WST1 assay.

Results

Indeed, we showed the presence of CSCs (ALDH1+) and proliferative cells (Ki67+), among others. With a baseline IC50 of 5µM, we concluded that they can be used to generate a 5-FU resistant line. In addition, our initial findings suggest that the conditioned media of CAF cultures decreases the sensitivity of parental organoids to 5-FU, emphasizing the need to study deeper the interaction between these two tumor components

Conclusions

In summary, our preliminary results suggest that the interaction between tumor cells and CAFs modulates the response to chemotherapy. We are currently exploring whether CSCs are particularly involved in this phenomenon. In addition, we are developing patient-derived xenograft models (PDX) sensitive or resistant to 5-FU in order to study in vivo the interactions between CAFs and CSCs. At the end, this project will provide a better understanding of the changes required for resistance, paving the way for new targeted therapies

Funding Agencies

Canada foundation for innovation, Canada Research Chairs
A159 MALIGNANT PERITONEAL MESOTHELIOMA: A CASE OF MISTAKEN IDENTITY
Authors: Seeraj A A , Cheung A
Published: February 2024

Background

In the Western hemisphere, cirrhosis is the most common cause of ascites. One of the least common causes is malignant peritoneal mesothelioma (MPM), which occurs in one in one million cases. MPM can be a diagnostic challenge due to its rarity and features that mimic other causes of ascites.

Aims

To describe a complex case of MPM, highlighting the diagnostic dilemma stemming from the subtleties of presentation, confounders in ascites diagnostic criteria, and indeterminate testing.

Methods

We performed a detailed retrospective chart review of a patient who presented with ascites. He was initially given the diagnosis of decompensated cirrhosis and eventually was diagnosed with MPM. He provided his consent for this case report.

Results

A 37-year-old male presented with progressive ascites and peripheral edema. He had no known exposure to asbestos and consumed 6 standard drinks a day for 2 years; with a prior history of 10 standard drinks a week for over 3 years. His physical examination was unremarkable for cardiac, renal or liver disease. His transthoracic echocardiogram and urinalysis were normal. Abdominal ultrasound showed features of liver cirrhosis with large-volume ascites and a FIB-4 score of 0.34, excluding advanced fibrosis Laboratory investigations including liver tests were normal; with a platelet count of 568 x 109/L. Viral, metabolic and autoimmune liver disease were excluded. A diagnostic paracentesis demonstrated a serum albumin-ascites gradient (SAAG) of 1.3 g/dL. Due to his history of alcohol misuse, imaging findings and high SAAG, he was diagnosed with alcohol-related cirrhosis.

His repeat abdominal ultrasound showed multiple liver nodules. Magnetic resonance imaging was done to investigate for hepatocellular carcinoma; revealing diffuse peritoneal carcinomatosis, cirrhosis and large-volume ascites. Investigations to identify the primary malignancy included a computed tomography chest, colonoscopy and EGD. His EGD was the only positive test; showing a 2cm submucosal gastric lesion with normal gastric mucosa pathology. An endoscopic ultrasound (EUS) with fine needle aspiration was then performed; the lesion appearance in keeping with a gastrointestinal stromal tumor (GIST). Pathology favored a diagnosis of poorly differentiated gastric carcinoma. Cytology was positive for malignancy, with the differential being mesothelioma or adenocarcinoma and a repeat SAAG was 1.0 g/dL. Given the discordances, an ultrasound-guided core biopsy was performed of the peritoneal lesions. Pathology revealed features of poorly differentiated epithelioid mesothelioma. A subsequent review of his gastric biopsies revealed similar cells in retrospect were in keeping with mesothelioma.

Conclusions

The presentation of MPM is not easily distinguishable from other causes of ascites. There must be a high degree of suspicion for malignant ascites in the face of inconsistent clinical and diagnostic findings.

Funding Agencies

None
A162 DEFINING INNATE IMMUNE CELL MECHANISMS UPON HELICOBACTER PYLORI MEDIATED TUMORIGENESIS
Authors: Supreme T , Kim T
Published: February 2024

Aims

Hypothesis: H. pylori interacts with eosinophils to inhibit degranulation, alter eosinophil gene expression and promote gastric tumorigenesis

Aim 1: Elucidate the mechanisms underlying the interactions between eosinophils and H. pylori.

Aim 2: Determine the role of eosinophils during H. pylori mediated gastric tumorigenesis.

Methods

Histological and immunofluorescent staining. Hemotoxilin and eosin staining is important to analyze gastric gland structure and parietal cell loss. Immunofluorescent staining is used to detect and localize specific antigens present in cells and cell membranes.

Gastric organoids: Gastric organoids are an important tool for modelling dissease. Gastric organoids generated from adult stem cells from gastric glands depend on growth factors that mimic tissue regeneration.

Bone marrow derived eosinophils: Bone marrow progenitor cells isolated from murine femur and tibia are easily converted into maturer eosinophils with the addition of cytokine interleukin-5.

Results

Addition of mouse derived eosinophils to gastric organoids significantly increases number of organoids.

To understand the relationship between eosinophils and gastric epithelial cell (GEC) growth, I designed a co-culture experiment that involved incubating mature eosinophils with gastric glands in an extracellular matrix. These findings revealed a significant increase in the number of gastric organoids per well when eosinophils were present compared to the gastric organoids without eosinophils. This observation supports the hypothesis that eosinophils may play a crucial role in promoting gastric tumorigenesis.

Exposure of mouse derived eosinophils to H. pylori significantly increases gastric organoid proliferation.

To explore the impact of stimulating eosinophils prior to incubation with GECs I incubated the eosinophils with H. pylori. As expected, there was a significant increase in the number of organoids per well with the addition of uninfected eosinophils. Interestingly, when H. pylori incubated eosinophils were added to the gastric glands, there was a significant increase in the number of gastric organoids per well compared to uninfected eosinophils.

Conclusions

My preliminary findings have indicated that eosinophils can promote gastric epithelial stem cell proliferation. These results led me to ask how treatment of eosinophils with H. pylori subsequently impacts gastric organoid growth and gastric stem cell proliferation. Interestingly, I found H. pylori treated eosinophils increase growth and gastric stem cell proliferation. These results support my hypothesis as increased proliferation is considered a hallmark of tumorigenesis. There little known about resident and inflammatory GI eosinophils and the role of eosinophils during tumorigenesis in unknown. A better understanding of the role eosinophils play can uncover novel mechanisms to be targeted for therapeutic intervention.

Funding Agencies

CIHR
A164 OPTIMIZING A PROVINCIAL SCREENING PROGRAM FOR DETECTION OF LYNCH SYNDROME
Authors: Winter R , Liu Y , Stone J , Rothenmund H , Chodirker B , Kim C , Klein J , Singh H
Published: February 2024

Background

Up to 30% of those with colorectal cancer (CRC) have an affected family member. Lynch syndrome (LS) is the most common inherited condition predisposing patients to CRC. LS is an autosomal dominant condition associated with microsatellite instability (MSI) and mutations in DNA mismatch repair (MMR) genes, and screening CRC cases ≤ age 70 can identify LS in a cost-effective manner. Manitoba launched Canada's first provincial reflex screening program for all CRC cases diagnosed ≤ age 70 using MMR immunohistochemistry (MMR-IHC) in 2017. Our prior 2022 study evaluating the program showed compliance rates of 89.4% for MMR-IHC reflex testing and a 75.8% overall referral rate of screen-positive cases to genetics. However, only 50% were referred directly by pathologists. Several modifications have since been implemented to enhance the program. These included providing feedback to pathologists, creating an “additional testing comment section” on synoptic pathology reports, and regular review of the pathology reports by a pathology assistant. Information materials were developed to encourage genetic testing among relatives.

Aims

Assess whether modifications to Manitoba’s universal screening protocol improved LS patient outcomes and determine any remaining factors to optimize. We specifically aimed to identify current compliance rates for MMR-IHC testing, the overall referral rate of screen-positive cases to genetics, uptake of genetic referrals and genetic testing as well as rate of cascade testing among relatives.

Methods

Data has been obtained by searching the provincial pathology database for “adenocarcinoma” in the colorectal specimen pathology reports. All specimens from 2022 and Q1/Q2 of 2023 were reviewed, meeting the criteria of: a) specimen from colon biopsy/excision containing the term “adenocarcinoma”, b) patient age ≤70 years, and c) missing MMR centralized by the IT/Pathology department.

Additionally, a random sample of cases categorized as “MMR performed” will be audited. We are in the process of reviewing genetic referrals, genetic uptake and the frequency of reminders triggered to each pathologist.

Results

Currently, a total of 1,308 colonic adenocarcinoma specimens (811 from 2022, 497 for 2023) have been reviewed. Appropriate MMR testing was missed in only 1.5% of cases (13/811 =1.6% missed in 2022, 7/497= 1.4% missed in 2023).

Conclusions

Current MMR testing rates for colonic adenocarcinoma specimens within the Manitoba LS screening program have reached a current compliance rate of 98.5%, a substantial improvement from the prior audit (89.4% previously). Further data collection and analysis is ongoing and will also be presented. The reported rates of compliance are the highest that have been reported from any jurisdiction. This study highlights the sustained efforts required to improve detection of LS.

Funding Agencies

None
A167 ASSESSMENT OF QUALITY OF LIFE AMONG CHILDREN WITH CELIAC DISEASE IN JORDAN
Authors: Altamimi E , Haj-Ahmad L , Alqaisi A
Published: February 2024

Background

Celiac disease has a profound impact on the daily lives of patients who are diagnosed with this chronic disease and affected by its myriad of clinical implications. Thus, health-related quality of life (HrQol) surveys proved invaluable in assessing children with this condition.

Aims

We aimed to assess HrQol of children with celiac disease in Jordan. In addition to the effect of gender, diet-restriction compliance compliance and the concomitant occurance of other chronic illnesses on the HrQol in our cohort.

Methods

A cross-sectional study of all children registered with the Celiac Disease Care Providers Society (CDPS) were asked to fill an online quality of life questionnaire. The Arabic version of the Kidscreen-52 questionnaire, with 10 domains was adopted. Data was analyzed using descriptive statistics and average T-scores across 10 health domains. Data was compared to previously published international norms.The sample was divided into four cohorts based on concomitant disorders, disease duration, adherence to gluten free diet (GFD), and growth issues. Independent sample t-tests, p-values, and Cohen's ds were determined for each cohort. Subcohorts were compared to each other.

Results

Out of 400 children registered with the society. 126(31.5%) patients responded. Male celiac patients performed worse in six health domains compared to the general population: moods and emotions, self-perception, bullying, psychological well-being, social support, and financial resources. The last three of which showed poorer performance in female celiacs too. Moods and emotions and self-perception were significantly worse in males with chronic disease and without GFD adherence. Females with growth issues performed worse in school environment and financial resources.

Conclusions

The study reveals a significant reduction in Hrqol in celiac patients compared to healthy individuals, a first in Jordan. This highlights the need for education initiatives for patients and physicians, as well as campaigns for national support for GFD. Further research is needed to identify other contributing factors and what interventions at community level should be taken.

Funding Agencies

None
A170 A RARE CASE OF CELIAC DISEASE WITH PULMONARY HEMOSIDEROSIS AND DILATED CARDIOMYOPATHY
Authors: Dessie E K
Published: February 2024

Background

Celiac disease (CD) is a primary disease of the intestine but patients also present with extra intestinal manifestations like iron deficiency anemia, dermatitis herpetiformis, selective IgA deficiency, thyroid disorders, diabetes mellitus and various connective tissue disorders but rarely with pulmonary hemosiderosis and dilated cardiomyopathy.

Aims

We present a rare case of CD associated with pulmonary hemosiderosis and dilated cardiomyopathy in a 10 year old child.

Methods

Patient interview and chart review was conducted. Literature reveiw was performed using pub med data base.

Results

A 10 year old presented with a 1 day of cough and hemoptysis. His past medical history includes Constipation and low percentile for weight and height. His first cousin is recently diagnosed with celiac disease, otherwise his family history is unremarkable. He is pale on exam and has a BMI of 13.64 which is ampersand:003C1% for age. He had fine crackles on bilateral lung fields but no signs of respiratory distress. His pericardium was active but no murmur or gallop. CXR showed cardiomegaly and Echo was suggestive of dilated cardiomyopathy. ECG was significant for LBBB. Chest CT showed bilateral confluent symmetric ground glass densities with possibility of pulmonary hemosiderosis. His blood work was significant for iron deficiency anemia, low selenium of 0.94umol/L and zinc 8.4umol/L. His antibody screen was positive for ANA, a tTGA of ampersand:003E4,965.5 and positive EMA. The cardiomyopathy and pulmonary hemosiderosis in this case are considered to be secondary findings as both have been reported in the context of celiac disease and patient was initiated on gluten free diet (GFD). Patient was blood transfused and kept on oral iron and multivitamins. He was also started on aldactazide 1 tab daily, 20mg twice daily enteresto and carvedilol 3.125mg twice daily as part of his heart failure management. At one month follow up, patient was having abdominal discomfort due to his constipation and follow up labs showed improvement of his anemia.

Conclusions

Patients with pulmonary hemosiderosis occuring with CD demonstrate improvement of their symptoms with GFD highlighting the importance of screening all pulmonary hemosiderosis patients for CD. Cardiomyopathy associated with celiac disease is also another very rare occurrence and only few studies have been reported so far.

In conclusion, although a rare occurrence, the association of CD with pulmonary hemosiderosis and cardiomyopathy has huge therapeutic implications emphasizing the need to have high index of suspicion and routine screening for CD among patients with pulmonary hemosiderosis and dilated cardiomyopathy.

Funding Agencies

The hospital for sick children/sick kids hospital
A172 A CLASSIC CASE OF WHIPPLE'S DISEASE
Authors: Hearn J , Webster D , Carpentier S
Published: February 2024

Background

Whipple’s disease is a systemic disorder caused by the Gram-positive bacillus Tropheryma whippelii. It is classically defined by the four cardinal clinical manifestations of arthralgias, weight loss, diarrhea and abdominal pain. Classic Whipple’s disease is considered extremely rare, with an estimated global incidence of 30 cases per year, though this may be an underestimate.

Aims

To present a case of classic Whipple’s disease, so as to raise awareness and clinical suspicion for this rare condition.

Methods

We performed a retrospective chart review of a case of classic Whipple’s disease diagnosed in Saint John, NB, in 2020.

Results

A 55-year-old female presented to hospital with intractable weakness and diarrhea. Her history was notable for several years of right leg weakness, myalgias and low-grade fevers. More acutely, she presented to hospital due to worsening secretory diarrhea resulting in 15kg weight loss. Initial investigations were remarkable for an elevated C-reactive protein. The patient was admitted for coordinated evaluation for possible rheumatologic and infectious causes. As part of that workup, colonoscopy was performed.

Colonoscopy revealed an abnormal ileum, with villi described as edematous with a mosaic pattern alternating between erythematous and “white tipped”. On histologic assessment, ileal biopsies showed macrophages with PAS-positive diastase resistant granules suspicious for Whipple’s disease. A follow-up esophagogastroduodenoscopy with duodenal biopsies was thus performed to gain further tissue for confirmatory testing. The duodenal mucosa was also noted to have a mosaic pattern with hypertrophic villi alternating between pale and erythematous in appearance. Duodenal biopsies were taken and sent for PCR testing. This testing was positive for T. whippelii, confirming the diagnosis of Whipple’s disease.

The patient was initiated on long-term antibiotic therapy with ceftriaxone transitioning to trimethoprim-sulfamethoxazole prior to discharge. She unfortunately re-presented one month post-discharge with recurrent fevers, malaise and arthralgias. Given suspicion that her disease may be resistant to trimethoprim-sulfamethoxazole, she was transitioned to doxycycline and hydroxychloroquine as second-line therapy. She clinically improved on this regimen, and was able to be de-escalated to long-term doxycycline monotherapy after one year. At a recent follow-up, nearly three years from her initial diagnosis, she was doing well with essentially no ongoing symptoms of her Whipple’s disease.

Conclusions

Whipple’s disease is a rare infection presenting with intractable diarrhea and abdominal discomfort. Our case highlights the excellent clinical response that can be achieved with successful diagnosis and management of this otherwise debilitating disease.

Funding Agencies

None
A174 TESTING FOR AND INCIDENCE OF CELIAC DISEASE AUTOIMMUNITY SAW SIGNIFICANT BUT TEMPORARY DECLINES DURING COVID-19 PANDEMIC
Authors: King J A , Coward S , Kaplan G G , Williamson T
Published: February 2024

Background

Celiac disease (CD) is an autoimmune disorder with various complications and long-term health risks. The COVID-19 pandemic affected the entire healthcare system—including screening for and diagnosing non-infectious conditions.

Aims

Determine how the COVID-19 pandemic affected the testing for, and incidence of, CD autoimmunity.

Methods

Using the population-based Alberta Medical Laboratory database, all tissue transglutaminase antibody tests (tTG-IgA) were identified in Alberta (April 2012 to March 2023). Incident cases of CD autoimmunity comprised of individuals newly positive for tTG-IgA between April 2015 and March 2023. Prevalent cases of CD were excluded based on previous tTG-IgA positivity and/or CD diagnosis codes in outpatient or inpatient settings. Average monthly percent changes and inflection points for testing and incidence rates were estimated using Joinpoint regression. Autoregressive integrated moving average models were performed to forecast rates if the pandemic had not occurred. Incidence rate ratios (IRRs) were estimated to compare a pre-pandemic era (April 2017 to March 2020) and a pandemic era (April 2020 to March 2023) overall and across subgroups.

Results

In the pandemic era, 311,971 tTG-IgA tests were performed on 284,882 unique individuals (21.1 per 1000 person-years (Table 1)). Testing decreased by 23.4% per month from February 2020 until May 2020 (Figure 1A). From June 2020 to August 2020, testing rates increased by 22.3% per month and then remained stable until the end of the study period. There were 4907 new cases of CD autoimmunity in the pandemic era, with an incidence of 36.3 per 100,000 person-years (Table 1). Incidence rates decreased by 14.1% per month from January 2020 until April 2020 (Figure 1B). Subsequently, incidence continued to rise by 2.0% per month from May 2020 until the end of the study period.

Conclusions

The COVID-19 pandemic appears to have had a minor impact on identifying potential CD. Future surveillance is needed to determine if the pandemic affected the diagnostic pathway to biopsy-confirmed CD through upper endoscopy procedures and any adverse outcomes individuals may have had from delayed diagnosis.

Table 1: Testing and incidence rates for CD autoimmunity in Alberta in pre-pandemic era (April 2017 to March 2020) and pandemic era (April 2020 to March 2023)

IRR=incidence rate ratio; CI=confidence interval

Figure 1: Testing (A) and incidence (B) rates for CD autoimmunity before and after the start of the COVID-19 pandemic

Funding Agencies

CAG, CIHRhttps://triangleprogram.org
A175 IMPACT OF THE COVID-19 PANDEMIC ON CANADIANS WITH CELIAC DISEASE
Authors: King J A , McAulay C , Secord M , Pinto-Sanchez M , Turner J , Gidrewicz D , Case S , Duerksen D
Published: February 2024

Background

The COVID-19 pandemic affected various healthcare services, including primary care and management of certain health conditions. There is limited data on how the pandemic impacted those with celiac disease (CD).

Aims

Explore the implications of the COVID-19 pandemic on CD diagnosis and management.

Methods

The State of Celiac Disease in Canada Survey was made available online by Celiac Canada in December 2022. Over 75 questions were included, covering diagnostic pathways, COVID-19 factors such as infection and vaccination, perceptions around COVID-19, and gluten-free food access during the pandemic. Analysis was restricted to those who responded to having CD, dermatitis herpetiformis, or gluten ataxia.

Results

A total of 6052 participants were included. A total of 2320 (38.3%) reported having tested positive for COVID-19 at some time during the pandemic. Among those with an infection at some point, 93.8% tested positive after already being diagnosed with CD. Just under 2% of those testing positive for COVID-19 required hospitalization, of which 10% were admitted to the intensive care unit. Vaccination against COVID-19 was reported by 4695 (77.6%) individuals, although 1157 (19.1%) did not provide a response to this specific question. This did not differ significantly by gender (p = 0.901), although it did across age groups (p ampersand:003C 0.001), with a mean age of 54.2 years who were vaccinated compared to a mean age of 45.7 years who were not vaccinated. 718 (11.9%) of individuals felt they were at higher risk of COVID-19 complications due to having CD; however, 1290 did not respond. Reported delays from symptoms to diagnosis did not increase among those diagnosed during the pandemic compared to those diagnosed before. Most respondents did not feel the pandemic made it more challenging to follow the gluten-free diet, and just over half (52.8%) did not feel it was harder to obtain or access gluten-free food during this time. However, almost three-quarters (73.4%) noted an increase in the cost of gluten-free food during the pandemic – this meant adjusting finances in other areas to afford gluten-free food (28.5%), changing the type of food purchased (19.3%), or accessing a food bank (0.7%).

Conclusions

A significant number of patients with CD reported COVID-19 infections, but less than 2% had serious outcomes. This survey identified gaps in our understanding of COVID-19 vaccination in patients with CD and highlighted some adverse impacts of the pandemic on the costs of gluten-free foods.

Funding Agencies

Celiac Canada (FKA Canadian Celiac Association)
A180 SYSTEMATIC REVIEW OF MACHINE LEARNING-BASED PREDICTIVE MODELS FOR CLOSTRIDIOIDES DIFFICILE INFECTION
Authors: Tariq R , Malik S , Khanna S
Published: February 2024

Background

Clostridioides difficile infection (CDI) is a significant healthcare-associated infection that poses a substantial burden on patients and healthcare systems. Despite extensive research, accurately predicting CDI incidence and its associated complications remains a challenge. Electronic health records (EHRs) contain a wealth of clinical data that could potentially aid in predicting CDI and its outcomes. Machine-learning (ML) models have emerged as promising tools in healthcare, offering the potential to harness this data and enhance our ability to predict CDI incidence and complications.

Aims

This systematic review aimed to evaluate the performance of machine-learning (ML) models in predicting CDI incidence and complications using clinical data from electronic health records.

Methods

We conducted a comprehensive search of databases up to September 2023, adhering to the PRISMA guidelines. Studies employing ML techniques for predicting CDI or its complications were included. The primary outcome was the type of and performance of ML models, assessed using the area under the receiver operating characteristic curve (AUROC).

Results

Twelve retrospective studies that evaluated CDI incidence or outcomes were included. The most commonly used ML models were random forest and Gradient Boosting. The AUROC ranged from 0.60 to 0.81 for CDI incidence, 0.59 to 0.80 for recurrence, and 0.64 to 0.88 for complication prediction. Advanced ML models demonstrated similar performance over traditional logistic regression in predicting CDI complication. However, there was notable heterogeneity in defining CDI and the different outcomes, such as incidence, recurrence, and complications, and a lack of external validation in many studies.

Conclusions

ML models show promise in predicting CDI incidence and outcomes. However, the observed heterogeneity in CDI definitions and the lack of real-world validation highlight challenges in clinical implementation. Future research should focus on external validation and use of standardized definitions across studies.

Funding Agencies

None

Microbiome & Microbial Therapy
A184 HCPE CONTRIBUTES TO THE HOST INFLAMMATORY RESPONSE TO HELICOBACTER PYLORI
Authors: Creuzenet C , Salloum N , Lester J , Takougoum J M , Carroll D , Patel K , Atanassov C , Bodet C , Burucoa C
Published: February 2024

Background

Helicobacter pylori (HP) colonizes chronically 50% of the world population, leading to gastric ulcers or cancers in 2-10 % of infections. Due to rising antibiotic resistance, curtailing HP-induced diseases requires the identification of new anti-HP molecules that can reduce HP viability or its ability to elicit inflammation. Amongst HP’s virulence factors are the Helicobacter Cysteine-rich Proteins (Hcp) that are secreted outside the bacteria and contain Sel-Like Repeats (SLR) which support protein / protein interactions involved in signal transduction across kingdoms. Several SLR-containing bacterial proteins including HcpA are involved in bacteria / host interactions. Thus, Hcps may affect HP’s virulence via interaction of their SLRs with host proteins.

Aims

We aim to elucidate the role of Hcps in HP’s virulence. Hcps were considered as immune decoys since anti-Hcp antibodies made in infected patients are unable to clear the infection. However, recent data suggest that Hcps interact with host components and may modulate the function of immune cells. However, their effects on gastric cells remain unknown and functional differences between Hcps remain to be explored.

Methods

This work uses knockout mutagenesis, interactions with gastric cells, transcriptomics, and microscopy.

Results

We focus on HcpE, the largest Hcp that may interact with many host proteins via its 9 SLRs motifs. We showed that HcpE is secreted outside HP in 2 lab strains and that ~ 30% of secreted HcpE was comprised in outer membrane vesicles that may deliver HcpE into eukaryotic cells by membrane fusion. We also showed that the DiSulfide Bond forming protein DsbK is essential for HcpE production and secretion. Here, we demonstrate the production and secretion of HcpE by clinical isolates in vitro, and its production in situ in infected patients. Using our HcpE and DsbK knockout mutants, we investigate the role of HcpE and other Hcps in interactions with human gastric cells in vitro and in ex vivo gastric explants, showing a role in inflammation activation. Finally, we demonstrate their role in murine gastric colonization and in murine splenocytes activation. Overall, our data show a role of Hcps in host / pathogen interactions largely due to immuno-modulatory functions and a role in gastric colonization, with a predominant role of HcpE over other Hcps.

Conclusions

The findings open up possibilities to use Hcps or the gate keeper DsbK that controls their production as novel therapeutic targets to alleviate the burden of HP-associated disease.This could benefit the ~6 million patients who develop gastric ulcers or cancers each year worldwide due to HP infection, also saving billions of annual health care costs.

Funding Agencies

Western University
A186 INFLAMMATION MODIFIES DOSE-DEPENDENT RESPONSES OF INTESTINAL ANTI-TUMOUR MICRORNAS TO CRANBERRY PROANTHOCYANIDIN AND ITS MICROBIAL METABOLITE 3-(4-HYDROXYPHENYL)-PROPIONIC ACID
Authors: Dimoff Z , Lofft Z , Liang F , Chen S , Paetau-Robinson I , Khoo C , Taibi A , Comelli E
Published: February 2024

Background

Cranberries are a rich source of proanthocyanidins (PAC), a type of polyphenol with anti-cancer properties. We previously found that PAC, along with its microbially-derived metabolite 3-(4-hydroxyphenyl)-propionic acid (HPPA), trigger unique regulatory responses of microRNAs (miRNAs) in intestinal epithelial cells including the upregulation of miR-146a-5p. Both miR-146a-5p and miR363-3p are anti-inflammatory and downregulate anti-tumorigenic signalling pathways such as the interleukin (IL)-17 and wingless-related integration site (Wnt) respectively. miR-146a-5p also attenuates IL-17-promoting cytokines levels (e.g., IL-6).

Aims

To determine if miR-146a-5p and miR-363-3p respond to different physiologically relevant concentrations of PAC and HPPA in inflammatory and non-inflammatory conditions.

Methods

Fully differentiated Caco-2BBe1 colonic epithelial cells were treated with two doses of PAC-enriched cranberry extract (50μg/ml, 100μg/ml), HPPA (5μg/ml, 10μg/ml), or with Dulbecco’s Modified Eagle Medium (DMEM; control) for 24 hours, followed by IL-1β (1ng/ml) or mock stimulation for three hours. Human IL-6 homogeneous time-resolved fluorescence (HTRF) kits were used to quantify IL-6 in cell supernatant. RNA was extracted and used for miRNA profiling using Nanostring technology. Statistical analysis was performed in R version 4.2.1 with the R-packages NanostringDiff, NanostringNorm, and Pheatmap.

Results

At homeostasis, 42 and 2 (miR-146a and miR363-3p) miRNAs, respectively, uniquely responded to increasing PAC or HPPA concentrations. In the inflammatory state, no miRNAs responded to increasing concentrations of PAC and HPPA. However, the expression of miR-363-3p increased (qampersand:003C0.001) in response to 50μg/ml of PAC + IL-1β but decreased in response to 5μg/ml of HPPA + IL-1β , and the expression of miR-146a-5p increased (qampersand:003C0.001) in response to 5μg/ml of HPPA + IL-1β, and 50μg/ml PAC + IL-1β. Predicted miRNA gene-pathway analysis revealed that miR-146a-5p, miR-363-3p, and the other 42 miRNAs commonly target pathways involved in the tumorigenesis of colorectal cancer such as mitogen-activated protein kinases (MAPK), hedgehog, and Wnt pathways. Though, in inflamed cells, only HPPA (5 or 10 μg/ml) attenuated IL-6 secretion (pampersand:003C0.05), which may be driven by increased expression of miR-146a-5p.

Conclusions

These findings suggest that cranberries proanthocyanidins and their metabolites affect miRNAs involved in cancer related pathways in different manners and concentrations, which may depend on the inflammatory status. The gut microbiota may be partially responsible for unlocking these effects.

Funding Agencies

Ocean Spray Cranberries, Inc. and the Natural Sciences of Engineering Research Council of Canada (NSERC)