Journal of the Canadian Association of Gastroenterology最新文献

{"title":"A164 OPTIMIZING A PROVINCIAL SCREENING PROGRAM FOR DETECTION OF LYNCH SYNDROME","authors":"R. Winter, Y Liu, J. Stone, H. Rothenmund, B. Chodirker, C Kim, J Klein, H Singh","doi":"10.1093/jcag/gwad061.164","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.164","url":null,"abstract":"Abstract 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","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"357 6","pages":"127 - 128"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139839503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A275 THE POTENTIAL MECHANISTIC ROLES OF SPHINGOLIPIDS IN HEALTHY FIRST-DEGREE RELATIVES OF PATIENTS WITH CROHN'S DISEASE","authors":"M. Xue, S Lee, A. Neustaeter, J SHAO, H. Huynh, A. Griffiths, D. Turner, K. Madsen, P. Moayyedi, H. Steinhart, A. Bitton, D. Mack, K. Jacobson, M. Ropeleski, M. Cino, C. Bernstein, R. Panaccione, B. Bressler, W. Turpin, K. Croitoru","doi":"10.1093/jcag/gwad061.275","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.275","url":null,"abstract":"Abstract Background Crohn's Disease(CD) features a complex etiology intertwining genetic, environmental, and immunological dimensions. Sphingolipids (SPs) are pivotal lipid molecules within cell membranes and various biological processes, including cell growth, apoptosis, and inflammatory responses. While our prior research identified SPs as significant risk factors for CD onset, their pre-clinical influence on CD risk biomarkers and potential role in pathogenesis remains unclear Aims To identify the relationship between SPs and established CD risk factors Methods We used samples from healthy first-degree relatives(FDRs), followed in a nested case-control cohort from the Crohn's Colitis Canada- Genes, Environment, Microbial(GEM) project, matching those who developed CD(n=77) with control FDRs(n=303) based on age, sex, follow-up time, and geographic location. 59 SPs were selected from serum metabolites measured via an untargeted metabolomics platform. We used partial Spearman correlation to identify relationships between SPs and CD risk factors: i)intestinal permeability via the urinary fractional excretion ratio of lactulose to mannitol(LMR); ii)gut subclinical inflammation using fecal calprotectin(FCP); iii)systemic inflammation with C-reactive protein(CRP); iv)microbiome composition through fecal 16S rRNA sequencing and v)serum protein profile using the Olink® Proximity Extension Assay platform. A two-sided qampersand:003C0.05 was considered significant Results We identified 38 positive correlations between CRP and SPs across various sub-pathways, including Ceramides, Sphingomyelins and Hexosylceramides(0.117≤rho≤0.342, 1.37×10−09≤q≤0.042). One SP Ceramide(d18:1/16:0) correlated positively with FCP(rho=0.201, q=0.012). Moreover, two SPs, N-palmitoyl-sphingosine (d18:1/16:0) and glycosyl-N-(2-hydroxynervonoyl)-sphingosine (d18:1/24:1(2OH)), correlationed with Peptoclostridium genus (rho=0.465 and -0.245, q=1.47×10−16 and 0.028 respectively). All SPs correlated with one or more proteins, most positively between Sphingosine-1-phosphate and non-receptor tyrosine kinase(rho=0.637, q=1.98 ×10−36) and most negatively between sphingadienine and Chymotrypsin-C protein(rho=-0.334, q=4.11×10−8). No significant correlations emerged between SPs and LMR Conclusions We identified correlations between SPs and CD risk factors. The correlation with CRP suggests SPs might contribute to systemic inflammatory pathways related to CD. Moreover, correlations with the bacterial taxa highlight SPs' potential role in regulating microbial composition. Extensive correlations with proteins emphasize the pivotal impact of SPs on their function. This study may offer new insights into CD prevention Funding Agencies CCC, CIHR","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"85 1","pages":"221 - 222"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139776743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A77 COMPLICATIONS OF DUODENAL DIVERTICULA: A SYSTEMATIC REVIEW ON CLINICAL PRESENTATION AND MANAGEMENT OF ENTEROLITH ILEUS SECONDARY TO DUODENAL DIVERTICULA FORMATION","authors":"C. J. Miranda, A. M. Carlson, N. Hossein-Javaheri, A. Aijaz, M H Ali, M Ismail","doi":"10.1093/jcag/gwad061.077","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.077","url":null,"abstract":"Abstract Background Duodenal diverticula (DD) are relatively common findings in the gastrointestinal (GI) tract with their presence noted in up to 20% of the population. Rarely, however, these diverticula predispose to enterolith formation which can lead to small bowel obstruction, a phenomenon termed “enterolith ileus”. Both surgical and non-surgical approaches have been espoused in tackling this complication but definitive literature on optimal management is lacking and is limited to scattered case reports and case series. With this phenomenon carrying significant morbidity and mortality, we have conducted a comprehensive review of all available case reports to summarize our understanding of this condition. Aims To investigate the prevalance and clinical presentation of enterolith ileus secondary to duodenal diverticula and their optimal management whether that be medical or surgical. Methods A comprehensive search of PubMed, OVID, CINAHL, and Cochrane databases up to February 2023 was conducted to identify all studies reporting clinical information on enterolith formation in DD leading to small bowel obstruction. Each article was qualitatively assessed, and relevant data were extracted from selected studies to determine clinical courses and optimal management. Results Our literature review identified 17 case reports of enterolith ileus secondary to DD. The mean age of the patients was 72 years (SD 11.43), with 59% of them being female. Three patients had previously undergone Roux-en-Y gastric bypass, while one patient had undergone a distal gastrectomy. The most common symptoms reported were abdominal pain, nausea, and vomiting (88%), followed by abdominal distension (47%). Dilated bowel loops was the most common finding on X-rays, while CT scans revealed signs of small bowel obstruction and DD with an endoluminal mass in most of the cases. Upper GI series was performed in five cases, revealing multiple duodenal diverticula. Despite initial conservative management, 16 out of 17 patients eventually required surgical intervention. Enteroliths were extracted via enterotomy in 14 out of 17 cases, while surgical resection of the bowel was performed in three cases due to suspicion of tumor or perforation. Conclusions Our findings highlight the importance of prompt diagnosis and management of DD leading to enterolith ileus, particularly in elderly patients and those with a history of gastric surgery. Surgical intervention is almost always required and therefore early recognition and intervention can help minimize the risk of morbidity and mortality associated with this condition. Funding Agencies None","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"16 7","pages":"53 - 54"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139777187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A232 TEMPORAL TRENDS IN RE-HOSPITALIZATION RATES AMONG PATIENTS WITH INFLAMMATORY BOWEL DISEASE IN THE POST-BIOLOGIC ERA","authors":"C. Dziegielewski, M. Pugliese, J. Begum, E. I. Benchimol, J. McCurdy, S. Murthy","doi":"10.1093/jcag/gwad061.232","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.232","url":null,"abstract":"Abstract Background Hospitalization for severe inflammatory bowel disease (IBD) flares or complications are a major source of morbidity and healthcare expenditure. Aims To assess temporal trends in 30-day and 90-day re-hospitalization rates among persons with Crohn’s disease (CD) and ulcerative colitis (UC) in the post-biologic era. Methods We conducted a population-based study of all non-elective IBD-related hospitalizations among patients with CD and UC in Ontario, Canada between April 1, 2002 and March 31, 2020. We identified individuals, admissions, and variables of interest from Ontario population health administrative datasets housed at IC/ES. We performed multivariable logistic regression analysis to evaluate the association between time period of hospitalization (2002-2007 vs. 2002-2007 vs. 2007-2012 for CD; 2004-2008 vs. 2008-2012 vs. 2012-2016 vs. 2016-2020 for UC) and rates of 30-day and 90-day re-hospitalization, adjusting for patient age, sex, co-morbidities, residential setting, income quintile, hospital type of initial admission, and clustering of hospital admissions within patients. We excluded patients with elective admissions or length of stay ampersand:003C24 hours, and those without continuous valid Ontario health care registration during the 90-day period following hospital discharge. Results There were 18,625 hospitalizations among 14,868 patients with CD, and 10,830 hospitalizations among 9,264 patients with UC. The 30-day re-hospitalization rate was 8.5% for patients with CD and 9.7% for patients with UC, while the respective 90-day re-hospitalization rates were 15.0% and 13.8%. For CD, re-admission rates differed across the 3 time periods (pampersand:003C0.0001 for 30-day and p=0.012 for 90-day). For UC, re-hospitalization rates differed across the 4 time periods for 30-day re-hospitalization (p=0.048), but not 90-day (p=0.080). There was a higher relative odds of CD-related re-hospitalization in 2002-2007 as compared to 2012-2017 (adjusted odds ratio [aOR] 1.32, 95% confidence interval [CI] 1.16-1.50 for 30-day; aOR 1.14, 95% CI [1.03-1.26] for 90-day). For UC, there was a higher relative odds of re-hospitalization in 2012-2016 as compared to 2016-2020 (aOR 1.26, 95% CI [1.05-1.52] for 30-day; aOR 1.22, 95% CI [1.04-1.43] for 90-day). Conclusions Up to 15% of patients with IBD in Ontario are re-admitted to hospital within 90 days of hospital discharge. The risk of re-hospitalization may have decreased over time in the post-biologic era. Our findings could be explained by changing access to inpatient and/or outpatient resources, improvements to medical and/or surgical care, shifting patient behaviour with respect to healthcare resource utilization, or residual confounding. These results require validation in other jurisdictions. Funding Agencies None","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"49 17","pages":"185 - 186"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139777363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A158 DEVELOPMENT OF MODELS TO SUDY THE INTERACTION BETWEEN CANCER STEM CELLS AND THE MICROENVIRONMENT IN COLON CANCER","authors":"M. Sedeuil, A. Gonneaud, V. Giroux","doi":"10.1093/jcag/gwad061.158","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.158","url":null,"abstract":"Abstract 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","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"43 12","pages":"122 - 123"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139778968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A190 HELICOBACTER PYLORI INDUCES AN AUTO-REACTIVE PHENOTYPE IN PINK1 DEFICIENT MICE THAT CORRELATES WITH MOTOR DYSFUNCTION","authors":"A. Kazanova, H. Bessaiah, J Sung, C. Gavino, J. Pei, S. Recinto, W. Miller, L. Burns, L Zhu, J. Stratton, S. Gruenheid","doi":"10.1093/jcag/gwad061.190","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.190","url":null,"abstract":"Abstract Background Parkinson’s disease (PD) is a chronic neurodegenerative disorder. Several genetic predispositions, including the PTEN-induced kinase 1 (PINK1) mutation, have been implicated in early onset family cases. Besides the loss of dopaminergic neurons in the brain, PD patients have a unique immune phenotype that includes increased inflammation, blood serum, brain levels of proinflammatory cytokines, brain infiltration with cytotoxic CD8 T cells, and loss of regulatory T cells (Treg) and their anti-inflammatory phenotype. The role of the gut microbiota and gastrointestinal infections are increasingly recognized as a cofactor in PD. One of pathogens associated with the risk of PD is Helicobacter pylori. The prevalence of this Gram-negative bacteria in PD patients is higher than in the general population and its eradication in PD patients improves motor function. Loss of the PD-associated PINK1 alters induced Treg function in vitro. We previously have shown that in PINK1 knock-out (KO) mice, gut infection with Gram-negative bacteria, Citrobacter rodentium, induces mitochondrial antigen presentation (MitAP) to the CD8 T cells that later infiltrate the brain. In this model, PINK1 KO mice develop a Parkinson-like L-DOPA-responsive motor phenotype after four C. rodentium infections. Aims Here we aimed to scrutinize potential role of the H. pylori infection in the induction of motor dysfunction and disbalanced immune tolerance in PINK1 KO mice. Methods In addition to standard behavioural testing, at 2- and 6-months post-infection we performed a multiplex cytokine analysis of gastric homogenates and spectral flow cytometry of gastric lamina propria, mesenteric lymph nodes, blood, spleen, and brain infiltrating immunocytes. As well as in vitro immunocytes response and function assays to H.pylori exposure in PINK1 KO and wild-type (WT) littermate controls. Results We show that infection with H. pylori causes a long-lasting inflammation in the stomach; and local and systemic immune phenotype that remains 6 months post-infection. This phenotype, though present in some WT infected mice, is higher in PINK1 KOs and similarly to PD patients includes a decrease in Treg proportion, FoxP3 downregulation in regulatory T cells, Gata3+ CD4 T cell loss, as well as increase of circulating mitochondrial antigen-specific CD8 T cells. Moreover, the immune phenotype in the H. pylori infected PINK1 KO mice correlates with motor dysfunction and CD8 T cell brain infiltration with no such association seen in the WT mice. Conclusions These results provide insight to the gut-immunity-brain axis in the pathogenesis of Parkinson’s disease, and further investigate the role of Gram-negative bacteria in the establishment of immune tolerance-autoreactivity balance. Funding Agencies ASAP","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"29 1","pages":"149 - 150"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139778980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A51 MICROBIALLY-MEDIATED IMPAIRMENT OF VAGAL AFFERENT NEURONAL EXCITABILITY IS OREXIN RECEPTOR DEPENDENT","authors":"S. Sachdev, A. Tashtush, T. Alward, D E Reed, A. Lomax","doi":"10.1093/jcag/gwad061.051","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.051","url":null,"abstract":"Abstract Background An impairment of vagally-mediated satiety signalling has been implicated in the caloric imbalance that leads to weight gain during obesity. Previous studies have suggested that a reduction in the excitability of vagal afferent neurons with cell bodies in nodose ganglia (NG) was responsible, but the cellular mechanisms are unclear. Host and bacterially derived mediators present in the small intestine and stool provide a physiologically relevant model to help elucidate the role luminal mediators play in modulating vagal afferent neuronal excitability. Aims We hypothesize that the microbiota of obese individuals and mice produce mediators that impair NG neuron excitability and satiety in mice. Methods Perforated patch clamp was used to measure the excitability of NG neurons following exposure to human and mouse fecal supernatants (FS), mouse jejunal supernatants (JS), and mice serum samples. Human FS were from ampersand:003E 5 healthy human donors or FS from ampersand:003E 5 obese donors. Mice FS, JS and serum samples were collected from ampersand:003E 5 obese mice fed a high-fat diet and ampersand:003E 5 control mice fed a normal diet. Results NG neurons incubated in FS from obese participants were significantly less excitable (rheobase was 30% higher and action potential discharge at 2x rheobase was 50% lower) than NG neurons exposed to FS from non-obese participants. NG neurons incubated in FS or JS from obese mice were also significantly less excitable (rheobase was 65% higher and action potential discharge at 2x rheobase was 50% lower) than NG neurons incubated with FS or JS from control mice. Lastly, NG neurons incubated with obese mouse serum were significantly less excitable (rheobase was 50% higher and action potential discharge at 2x rheobase was 80% lower) than NG neurons incubated with serum from control mice. We then attempted to identify mediators that may account for this inhibitory effect by using receptor antagonists that block GABA, ghrelin, and orexin signalling. Ghrelin and GABA receptor antagonists did not block the inhibitory effect of obese patients’ FS on NG neurons but the orexin receptor 1 antagonist (SB-334867;10µM) did. Following this, we incubated the orexin receptor 1 antagonist (SB-334867;10µM) on NG neurons incubated with mouse FS and JS and observed a similar blocking of inhibitory effects back to control values. Conclusions These findings suggest that the gut luminal contents of obese mice and humans contain an orexin receptor agonist that inhibits satiety and may contribute to over-eating. Funding Agencies CIHRNSERC","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"155 ","pages":"32 - 33"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139836539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A235 INFLAMMATORY BOWEL DISEASE AND PREECLAMPSIA: A PHYSICIAN SURVEY","authors":"Y. Hanna, P. Tandon, V. Huang","doi":"10.1093/jcag/gwad061.235","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.235","url":null,"abstract":"Abstract Background Preeclampsia is a disorder of pregnancy recognized as the second cause of maternal mortality worldwide. The association between IBD and preeclampsia remains unclear, but the significant comorbid profile, and lack of treatment aside from urgent delivery, make primary prevention a priority. Aspirin was shown to halve preeclampsia rates and is recommended for primary prevention for women at risk. Despite high-quality evidence supporting Aspirin use and its well tolerated side effect profile, studies in non-IBD patients have demonstrated a knowledge-to-practice gap. Aims While there are no studies reported in women with IBD, prescribing rates may be even lower in this population, given that it may be incorrectly perceived to increase the risk of an IBD flare. Understanding physician perceptions could allow for a targeted educational approach to increase patient and physician awareness of the indications for Aspirin prophylaxis and its safety profile. Methods This is a cross-sectional survey study assessing physician perceptions and Aspirin prescribing patterns for preeclampsia prevention conducted from Mount Sinai Hospital. Demographic information, information on perceptions of preeclampsia risk in pregnant women with IBD, and on the perceived clinical benefit and risk of Aspirin prescribing were collected. Results A total of 38 Canadian healthcare professionals (HCPs) (15 Gastroenterologists, 14 Obstetricians, 5 General Practitioners, 2 General Internists, 1 nurse practitioner, and 1 midwife) were surveyed. Most HCPs were practicing for over 10 years (71%). In total, 68% of HCPs were comfortable with pregnancy-specific management of IBD. Most HCPs correctly identified all comorbidities associated with a high risk of preeclampsia including a history of preeclampsia (95%), renal disease (87%), and autoimmune disease (68%). A total of 55% of HCPs believed that pregnant patients with IBD were at increased risk of placental related diseases, and 56% agreed that these patients were at increased risk of preeclampsia specifically. Thirty-five percent of HCPs believed that IBD in remission, in the absence of other risk factors, was an indication for Aspirin prophylaxis. More so, 45% believed that IBD, with poor disease control, was an indication. Only 8% of HCPs believed that Aspirin, when used for preeclampsia prevention, was associated with an IBD flare. In patients whom Aspirin prophylaxis was indicated, 77% agreed with its use, even in patients in whom disease control was poor. Finally, 63% agreed that the Aspirin dose should be 162 mg daily, and more than half (58%) agreed that the prescriber should be the patient’s obstetrician. Conclusions Most HCPs agreed that IBD was a risk factor for preeclampsia and that Aspirin prophylaxis was effective and safe for primary prevention. High quality studies are needed to evaluate risk of preeclampsia in IBD, especially in patients with active disease. Funding Agencies CAG","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"235 ","pages":"188 - 189"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139836653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A275 THE POTENTIAL MECHANISTIC ROLES OF SPHINGOLIPIDS IN HEALTHY FIRST-DEGREE RELATIVES OF PATIENTS WITH CROHN'S DISEASE","authors":"M. Xue, S Lee, A. Neustaeter, J SHAO, H. Huynh, A. Griffiths, D. Turner, K. Madsen, P. Moayyedi, H. Steinhart, A. Bitton, D. Mack, K. Jacobson, M. Ropeleski, M. Cino, C. Bernstein, R. Panaccione, B. Bressler, W. Turpin, K. Croitoru","doi":"10.1093/jcag/gwad061.275","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.275","url":null,"abstract":"Abstract Background Crohn's Disease(CD) features a complex etiology intertwining genetic, environmental, and immunological dimensions. Sphingolipids (SPs) are pivotal lipid molecules within cell membranes and various biological processes, including cell growth, apoptosis, and inflammatory responses. While our prior research identified SPs as significant risk factors for CD onset, their pre-clinical influence on CD risk biomarkers and potential role in pathogenesis remains unclear Aims To identify the relationship between SPs and established CD risk factors Methods We used samples from healthy first-degree relatives(FDRs), followed in a nested case-control cohort from the Crohn's Colitis Canada- Genes, Environment, Microbial(GEM) project, matching those who developed CD(n=77) with control FDRs(n=303) based on age, sex, follow-up time, and geographic location. 59 SPs were selected from serum metabolites measured via an untargeted metabolomics platform. We used partial Spearman correlation to identify relationships between SPs and CD risk factors: i)intestinal permeability via the urinary fractional excretion ratio of lactulose to mannitol(LMR); ii)gut subclinical inflammation using fecal calprotectin(FCP); iii)systemic inflammation with C-reactive protein(CRP); iv)microbiome composition through fecal 16S rRNA sequencing and v)serum protein profile using the Olink® Proximity Extension Assay platform. A two-sided qampersand:003C0.05 was considered significant Results We identified 38 positive correlations between CRP and SPs across various sub-pathways, including Ceramides, Sphingomyelins and Hexosylceramides(0.117≤rho≤0.342, 1.37×10−09≤q≤0.042). One SP Ceramide(d18:1/16:0) correlated positively with FCP(rho=0.201, q=0.012). Moreover, two SPs, N-palmitoyl-sphingosine (d18:1/16:0) and glycosyl-N-(2-hydroxynervonoyl)-sphingosine (d18:1/24:1(2OH)), correlationed with Peptoclostridium genus (rho=0.465 and -0.245, q=1.47×10−16 and 0.028 respectively). All SPs correlated with one or more proteins, most positively between Sphingosine-1-phosphate and non-receptor tyrosine kinase(rho=0.637, q=1.98 ×10−36) and most negatively between sphingadienine and Chymotrypsin-C protein(rho=-0.334, q=4.11×10−8). No significant correlations emerged between SPs and LMR Conclusions We identified correlations between SPs and CD risk factors. The correlation with CRP suggests SPs might contribute to systemic inflammatory pathways related to CD. Moreover, correlations with the bacterial taxa highlight SPs' potential role in regulating microbial composition. Extensive correlations with proteins emphasize the pivotal impact of SPs on their function. This study may offer new insights into CD prevention Funding Agencies CCC, CIHR","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"201 ","pages":"221 - 222"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139836753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A283 HETEROGENEITY OF TREATMENT RESPONSE TO BETA-BLOCKERS IN THE TREATMENT OF PORTAL HYPERTENSION RELATED TO CIRRHOSIS","authors":"M. Alsaeid, J. Abraldes","doi":"10.1093/jcag/gwad061.283","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.283","url":null,"abstract":"Abstract Background Non-selective beta-blockers (BB) improve clinical outcomes in patients with cirrhosis and portal hypertension. However, it has been suggested that only a proportion of patients treated with BB benefit from them. Indeed, patients who achieve a ampersand:003E20% reduction in Hepatic Venous Pressure Gradient (HVPG) with BB have an excellent prognosis, but only 30-50% achieve such response. This has been suggested as a reason for not using BB where no HVPG measurements are available. Aims In this study we aimed to quantify how heterogeneous is the response to BB in patients with cirrhosis, by analyzing trials in which the effects of BB on HVPG were compared with those of placebo. Methods For assessing the potential heterogeneity of treatment response to BB we conducted a meta-analysis of differences in variance between trial arms. The degree of heterogeneity of HVPG response to BB was quantified with the pooled variability ratio (VR) (SD of the HVPG at the end of the trial in the BB group divided by that in the placebo group). Results Our systematic search yielded 18 studies. Figure 1 shows a forest plot with the meta-analysis of the variability ratios (VR) in final HVPG. Pooled VR was 0.99 (95% CI 0.87-1.14). This indicates that there was no evidence for a higher average variability in the final HVPG in the beta-blocker treatment groups as compared to placebo groups, and hence there was no evidence to support that patients with cirrhosis exhibit a heterogeneous response to beta-blockers (i.e. there is no evidence to support that some patients responded to beta-blockers and others did not). Conclusions In conclusion, the analysis of RCTs comparing the HVPG response of beta-blockers with placebo in patients with cirrhosis does not suggest a heterogeneous hemodynamic response to beta-blockers. This, together with the fact that in most RCTs demonstrating the clinical benefits of beta-blockers treatment was not adjusted based on HVPG response, further supports the concept that there is no need to perform portal pressure measurements to guide treatment with beta-blockers. Funding Agencies None","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"178 ","pages":"228 - 229"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139836768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}