Journal of the Canadian Association of Gastroenterology最新文献

{"title":"A187 PROPHYLACTIC PHAGE TREATMENT ENHANCES SUB-THERAPEUTIC EFFICACY OF BUDESONIDE AGAINST E. COLI DRIVEN COLITIS IN MICE COLONIZED WITH A DEFINED MICROBIOTA","authors":"K. Jackson, H. Galipeau, A. Hann, M. Bording Jorgensen, B. Coombes, Z. Hosseinidoust, Eduardo Verdu","doi":"10.1093/jcag/gwad061.187","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.187","url":null,"abstract":"Abstract Background Patients with IBD are increasingly experiencing treatment failures on frontline therapies. While corticosteroids are an effective frontline intervention, 16% of patients fail to respond, and 20%–30% show only partial responses. Bacteriophages have recently garnered attention as a potential adjunctive therapy for IBD to target bacterial strains associated with IBD, including adherent-invasive Escherichia coli (AIEC). Aims Our aim was to determine whether prophylactic bacteriophage therapy could enhance the therapeutic efficacy of a sub-therapeutic dose of budesonide in a gnotobiotic mouse model of E. coli-driven colitis. Methods Adult germ-free C57BL/6 mice were co-colonized with altered Schaedler-like flora (ASF) plus E. coli NRG857c, a Crohn’s disease-associated bacterial isolate. Three weeks later, mice were treated with phage HER259 (1x109 PFU/dose; 0.1% bicarbonate) 3 times/ week or vehicle (PBS with 0.1% bicarbonate) 3 times/ week (n=5/group). Mice were then exposed to low-dose dextran sulfate sodium (2%; DSS) in drinking water for 5 days, followed by 2 days of water. All mice were administered a subtherapeutic dosage of 2ug/day of Budesonide halfway through DSS exposure to endpoint. Mice were monitored daily for weight loss, stool consistency, and fecal occult blood. At sacrifice, colon tissue was collected for histological analysis. Results Compared with budesonide treatment alone, prophylactic phage treatment, followed by a sub-therapeutic dose of budesonide, led to reduced stool consistency scores (p ampersand:003C0.001) and reduced presence of occult blood (p ampersand:003C 0.001). No difference in fecal E. coli load was observed between groups. At endpoint, the combined phage-budesonide treatment was associated with lower histological scores as compared with mice treated with budesonide alone (p ampersand:003C 0.01). Conclusions While underlying mechanisms remain elusive, our results suggest a beneficial effect of prophylactic phage intervention to the subsequent administration of a frontline immunosuppressive compound used to treat IBD. Future work will investigate the mechanisms by which adjunctive phage therapy can enhance existing therapies used to treats colitis, to better inform clinical guidelines. Funding Agencies CIHR","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"120 3","pages":"147 - 148"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139838708","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":"915 ","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":"139838741","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":"A296 ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY AND PRIMARY SCLEROSING CHOLANGITIS: A RETROSPECTIVE STUDY OF A HIGH-VOLUME PROGRAMME","authors":"K. Leung, M. Youssef, Y Xiao, C. Streutker, N. Calo, A. Gulamhusein, B. Hansen, G. May, J. Mosko, G. Hirschfield","doi":"10.1093/jcag/gwad061.296","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.296","url":null,"abstract":"Abstract Background Endoscopic retrograde cholangiopancreatography (ERCP) is a crucial component of care in primary sclerosing cholangitis (PSC). Aims In this retrospective study, we sought to characterize the clinical and procedural characteristics of PSC patients undergoing ERCP in a high-volume therapeutic endoscopy centre. Methods Using procedural codes and chart review from April 2011 to July 2021, PSC patients who underwent ERCP at St. Michael’s Hospital (SMH) were identified. Chart review of documentation was done to collect clinical attributes, procedural characteristics, pathology, and post-ERCP complications within 90 days. Descriptive statistics and regression analyses were conducted. Results There were 167 PSC patients included (69% male, 66% concurrent inflammatory bowel disease). Of 464 ERCPs performed, 64% were patients’ 2nd or more ERCP at SMH. When evaluating patient characteristics per ERCP procedure, median age was 45 yrs. (IQR 31-59), median duration of PSC diagnosis was 6.7 yrs (IQR 2.2-11.0), with cirrhosis diagnosed in 42%. Symptoms at ERCP were jaundice (56%), abdominal pain (43%), subjective fevers (30%) and pruritus (25%). Bloods pre-ERCP demonstrated median ALP 362 U/L (IQR 231-552) and median total bilirubin 76 µmol/L (IQR 29-141). Procedural indications were biliary obstruction (82%), cholangitis (31%) and concern for malignancy (22%). Procedural details are summarized in Figure 1. Stent insertion was associated with concern for malignancy (OR 2.87, 95%CI 1.81-4.55), previous stent insertion (OR 1.73, 95%CI 1.16-2.62) and elevated bilirubin (per unit increase in log[bilirubin] OR 1.53, 95%CI 1.23-1.92). Neoplastic pathology was noted in 20% of satisfactory cytology samples and 27% of biliary/bile duct biopsies, while 86% and 76% had reactive/inflammatory/atypical cells respectively. Post-ERCP complications within 90 days (ascertained in 423 ERCPs) was reported in one-third (127, 31%). The most common complications were biliary blockage (23%), post-ERCP cholangitis (15%), and stent failure (9.3%). Stent insertion was significantly associated with 90-day post-ERCP complications on multivariable analyses accounting for per patient clustering, sex, age, relevant stricture presence, stone removal, target location, symptoms, and pre-ERCP bilirubin level. Conclusions Patients with PSC who undergo ERCP have high disease burden. Stent insertion is associated with a sicker PSC phenotype with more obstruction (i.e., higher bilirubin, concern for malignancy); this may explain its association with higher 90-day post-ERCP complications. As this study is limited in its single centre retrospective nature, large-scale administrative data studies are needed to characterize and define optimal use of ERCP in the management of PSC. Figure 1. Procedural characteristics of 464 endoscopic retrograde cholangiopancreatographies in 167 patients with primary sclerosing cholangitis. Funding Agencies None","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"907 ","pages":"239 - 240"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139838745","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":"A142 PROGNOSTICATING FACTORS AND OUTCOMES OF EARLY ENDOSCOPIC EVALUATION IN ACUTE UPPER GASTROINTESTINAL BLEEDING","authors":"M. Saunders, H. Melchiorre, L. Schmanda, D. Savage, P. Zezos","doi":"10.1093/jcag/gwad061.142","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.142","url":null,"abstract":"Abstract Background Current guidelines recommend esophagogastroduodenal endoscopy (EGD) early (ampersand:003C24 hours after presentation) for all suspected acute upper gastrointestinal bleeds (AUGIB). Among referral centers providing advanced tiers of care to large regions, treatment is often delayed secondary to geographic constraints. Metropolitan centers meet early EGD recommendations in up to 87.5% of patients. Some centers limit endoscopy to the ICU setting outside of normal hospital operational times. There is currently no data assessing Canadian referral center endoscopic timing, including factors delaying AUGIB endoscopy and outcomes. Aims The aim of this study was to report the prevalence of early EGD in AUGIB at a Northern Ontario referral center. Factors associated with delayed EGD and poor outcomes associated with AUGIB were also evaluated. Methods Of 441 patients retrospectively identified with an ICD-10 discharge diagnosis of gastrointestinal hemorrhage from 2016–22, 327 patients met inclusion criteria. Patients were excluded if they were below the age of 18 years at the time of presentation, had chronic UGIB, or lower gastrointestinal hemorrhage. Results Pre-endoscopic risk stratification via GBS and clinical Rockall score was high at 10 and 3, respectively. There were 279 patients who received early EGD for AUGIB, of which 56% were male. The median (IQR) time to endoscopy was 27.4 (29.3) hours with early EGD achieved in 46% of presentations. A significantly greater proportion of patients presenting to hospital on the weekend (n=105) had delayed EGD (pampersand:003C0.0001; Phi effect size 0.45). Patients presenting at times when EGD was unavailable (n=157) also experienced delayed EGD (pampersand:003C0.05). regional patients did not experience a greater proportion of delayed EGD. In multivariate analysis, presentation on the weekend, higher CCI, absence of pre-existing evidence of liver cirrhosis, and absence of major stigmata of recent hemorrhage on EGD were independent predictors of delayed EGD (Nagelkerke R2 = 0.379, pampersand:003C0.0001). The odds ratio for receiving late EGD was 8.9 times greater (95% CI 3.7–21.3) for patients presenting on the weekend (pampersand:003C0.0001). Longer endoscopy wait time was significant correlated with higher pre-EGD blood transfusions and longer length of stay (pampersand:003C0.001). Delayed EGD did not increase all-cause 30-day mortality. Conclusions Prevalence of delayed EGD in AUGIB was markedly elevated and associated with hospital presentation during times of limited endoscopic capabilities. Outcomes of delayed GED included increased length of stay and higher blood transfusion rates. Funding Agencies NOAMA","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"526 1","pages":"109 - 110"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139838943","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":"A128 OPTIMIZED COMPUTER ASSISTED TECHNIQUE FOR INCREASING ADENOMA DETECTION DURING COLONOSCOPY: A RANDOMIZED CONTROLLED TRIAL","authors":"R. Djinbachian, M. Taghiakbari, A. Barkun, E. Medawar, B. Panzini, S. Sidani, J Liu, D. von Renteln","doi":"10.1093/jcag/gwad061.128","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.128","url":null,"abstract":"Abstract Background Efforts to improve colonoscopy have recently focused on improving adenoma detection interventions such as artificial intelligence (CADe) that have demonstrated improvements in Adenoma Detection Rates (ADR). Although studies have focused on implementation of one intervention at a time. Aims We evaluated an optimized computer assisted technique (CADopt) versus standard colonoscopy to improve ADR during colonosocopy. Methods A prospective randomized controlled trial was conducted enrolling adults (45–80 years) undergoing elective colonoscopy. Participants were randomized (1:1) to the intervention group (CADopt, and control group. In the CADopt group, endoscopists used a computer aided polyp detection combined with linked colour imaging, water exchange colonoscopy, and cecal retroflexion. In the control group, standard colonoscopy was performed. Primary outcome was Adenoma Detection Rate (ADR) in the intervention and control groups. Secondary outcomes included advanced ADR (AADR) and sessile serrated lesion detection rates (SDR). Results A total of 467 patients were recruited and randomized (CADopt group 229 patients, 50.2% female vs 238 patients, 48.3% female in the control group). ADR was 49.3% (95%CI 42.7-56.0) for the CADopt group vs 38.2% (95%CI 32.0-44.7) for the control group (p=0.016). AADR and SDR were 13.1% (95%CI 9.0-18.2) and 6.6% (95%CI 3.7-10.6) for the CADopt group versus 8.0% (95%CI 4.9-12.2), and 7.1% (95%CI 4.2-11.1) for the control group, respectively. Conclusions Using an optimized computer assisted technique led to significant improvements in ADR and a trend towards AADR improvements. Funding Agencies Fujifilm","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"767 ","pages":"97 - 98"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139838992","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":"A219 EARLY CANADIAN EXPERIENCE WITH BALLOON CRYOTHERAPY FOR BARRETT’S ESOPHAGUS","authors":"R Sullivan, A. Fazal, M Gupta, P. Belletrutti, C Wong","doi":"10.1093/jcag/gwad061.219","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.219","url":null,"abstract":"Abstract Background Balloon Cryotherapy (bCr) is a novel endoscopic treatment modality for Barrett’s esophagus (BE) associated dysplasia. Cryotherapy offers an additional approach, particularly in cases refractory to or with an anatomical impediment to radiofrequency ablation (RFA), currently first line in endoscopic eradiation therapy (EET). The use of bCr is new in Canada and it was introduced in Alberta in February 2023. Aims To present the early experience of bCr use for BE from a provincial Canadian cohort. Methods An Alberta health technology assessment approved bCr, which was then incorporated into the provincial BE treatment algorithm. Indications for bCr include: 1) RFA-refractory, 2) anatomical impediment to RFA, 3) need for concomitant biopsy/EMR, and 4) pain with RFA. All patients who underwent bCr for BE in Alberta from February to September 2023 at two tertiary care centers were included. Data on demographics, BE lesion characteristics, prior BE treatments, and bCr use are presented. Results During the 8-month period, 22 patients underwent a total of 32 bCr treatments. The median age was 68, with 77% of patients being male. At baseline, 81% had long-segment BE (≥3 cm), with a median maximal BE length of 7cm. The majority had baseline histology of high-grade dysplasia (HGD) (n=11, 50%), followed by low-grade dysplasia (LGD) (n=5, 22%), T1a (n=4, 18%), T1b (n=1, 4.5%), and intestinal metaplasia (IM) (n=1, 4.5%). All patients had previously received EET, with 77% undergoing a combination of EMR, RFA, APC, and/or ESD. Most had received RFA (n=18, 81%, median sessions=5) and EMR (n=13, 59%, median sessions=2). Some had prior APC (n=10, 45%, median sessions=1) and one had ESD. Prior to bCr, most patients had converted to short-segment (ampersand:003C3cm) BE (n=16, 72%), and histology was predominately IM (31%), followed by visible BE though no biopsy (27%), HGD (22%), T1a (13%), and LGD (4.5%). The primary indication for bCr was RFA-refractory BE (n=17, 77%), followed by anatomical impediment to RFA (n=4, 18%), and concomitant EMR (n=1, 4%). No procedures were aborted due to technical difficulties and there were no major adverse events such as perforation, bleeding, or pain requiring hospitalization. Among those with follow-up after a bCr session (n=19, 59%), one reported pain, two reported self-limited dysphagia, and one had a stricture requiring dilation. Of the 7 patients with post-bCr endoscopy, all had no dysplasia on the first set of biopsies (no IM, n=4; IM, n=2; indefinite for dysplasia, n=1). Conclusions Our early experience with bCr demonstrates there is a need for additional EET for BE. Cryotherapy, in accordance with gastroenterology society guidelines, is a promising next step in the BE algorithm. In our provincial cohort, bCr has shown technical success, and preliminary data suggests that it is safe and effective in ablating resistant BE segments. Funding Agencies None","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"505 2","pages":"173 - 174"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139839057","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":"A249 PARADOXICAL PSORIASIS FOLLOWING ANTI-TNFΑ THERAPY IN INFLAMMATORY BOWEL DISEASE AND ASSOCIATION WITH AN IL-23 RECEPTOR VARIANT: A PRELIMINARY REPORT","authors":"N. Natt, A Wilson","doi":"10.1093/jcag/gwad061.249","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.249","url":null,"abstract":"Abstract Background Patients with inflammatory bowel disease (IBD) who receive anti-tumor necrosis factor (TNF) α therapy are at risk of developing drug-related psoriatic skin lesions known as paradoxical psoriasis (PP). This is a severe unpredictable adverse drug event that often leads to discontinuation of anti-TNFα therapy. To date, there are no tools for identifying high-risk individuals. Variation in the IL-23 receptor (IL23R) gene has been linked to psoriasis onset and may be implicated in PP. Aims To evaluate the frequency of the IL23R variant (IL23R1142Gampersand:003EA) in anti-TNFα exposed IBD patients who develop PP versus those who do not. Clinical variables associated with PP development will also be assessed. Methods A case-control study is ongoing, including anti-TNFα-exposed adult IBD patients. Participants are divided based on the development of PP (cases n=11; controls n=48, identified to date, 500 additional patients will be screened). All participants were retrospectively genotyped for the occurrence of the IL23R1142Gampersand:003EA variant. Clinical variables and outcomes were assessed from the time of anti-TNFα exposure for at least one year of follow-up or to the time of anti-TNFα discontinuation. Results To date, we have included 59 adult IBD patients treated with infliximab or adalimumab. Eleven patients developed PP after a median duration of treatment of three months with anti-TNFα therapy. The most common presentations were guttate, plaque, and pustular psoriasis. Six patients had PP that involved 50% or more of their body surface area (BSA). Nine participants discontinued their anti-TNFα therapy due to PP. None of the cases had a personal or family history of psoriasis. PP patients were similar to controls with respect to age, sex, ethnicity, IBD type, disease duration, and concurrent immunomodulator use. The variant genotype occurred more frequently in PP patients compared to controls (54.5% vs. 4.2%, OR 27.6, 95%CI 4.3-145.4). Those with the variant genotype also had more extensive psoriasis compared to wildtypes (mean BSA 61% vs. 25%, p=0.045). Conclusions In this preliminary analysis, there was an increased frequency of the IL23R1142Gampersand:003EA variant in patients who developed PP compared to those who did not after anti-TNFα exposure. We did not identify any other clinical variables associated with development of PP. Interpretation of these results is limited by the small sample size. Completion of this study may help clarify the association between PP and the IL23R gene as well as other clinical risk factors implicated in PP development. Funding Agencies None","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"537 2","pages":"200 - 201"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139839152","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":"A101 TRENDS IN MEDICAID SPENDING FOR HEPATITIS C TREATMENT FROM 2012-2021","authors":"G. Malik, C H Tsai, S. Congly","doi":"10.1093/jcag/gwad061.101","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.101","url":null,"abstract":"Abstract Background Hepatitis C virus (HCV) infection is a pervasive disease that reduces quality and quantity of life. Medicaid is the largest health insurance program in the United States that provides coverage to individuals with low income including children, pregnant individuals, and people with disabilities. Due to the impact of HCV on individuals and the world goal for elimination of HCV by 2030, an analysis of healthcare costs attributed to hepatitis C medications is imperative to guide further policy and coverage changes. Aims To analyze Medicaid spending and utilization for hepatitis C treatment from 2012 to 2021 and provide a reflection on the impact it has on healthcare costs in the USA. Methods The Centers for Medicare & Medicaid Services public database was accessed to obtain Medicaid spending on Hepatitis C medications from 2012-2021. Data extracted included brand and generic drugs to treat HCV, total annual spending, total dosage units prescribed, total number of claims, and average spending per dosage unit and claim. Microsoft Excel was used for data analysis and creation of graphs. Results A total of 20 oral medications were included in this study. Total spending on all medications per year increased from $184 million in 2012 and peaked in 2016 at $3.3 billion. In 2021, the highest amount of Medicaid spending was on Mavyret ($658 million) followed by generic sofosbuvir-velpatasvir ($389 million) and Epclusa ($262 million). The total number of claims decreased from 135,542 in 2012 to 121,101 in 2021 with a peak in 2016 at 159,826. During the same time, the average spending per claim increased from 2012 ($6,518) to 2021 ($146,792). In 2021, the highest average spending per claim was seen with Harvoni ($30,941) followed by Sovaldi ($27,247), Vosevi ($23,877), and Epclusa ($22,917). In the same year, Mavyret had the greatest number of claims at 51,500 followed by generic sofosbuvir-velpatasvir (50,115), Epclusa (11,437), and Vosevi (2,177). Conclusions Despite the number of claims declining from 2012 to 2021, the average spending has increased due to the significant cost of HCV medications on Medicaid spending. The highest spending was noted to be with originator medications while generic formulations had the highest number of claims. Understanding the trends in spending on HCV medications can help guide insurance coverage changes for those depending on Medicaid. Lastly, shifting policies towards increased use of generic medications can help with increasing access and reducing costs to the population. Figure 1. Total annual spending per year in billions ($ USD, blue bars) and total number of claims (orange line) per year from 2012 to 2021. Funding Agencies None","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"428 5","pages":"73 - 74"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139839334","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":"A52 THE LGR5 ACTIVITY MODULATES CELL METABOLISM TO FAVOR WOUND HEALING","authors":"J. A. Acosta Montalvo, G. Arguin, S. Dagenais Bellefeuille, F. Gendron","doi":"10.1093/jcag/gwad061.052","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.052","url":null,"abstract":"Abstract Background The stem cell marker leucine-rich G-protein-coupled receptor-5 (LGR5) acts as an R-spondin (RSPO) signal transducer, facilitating WNT signaling to support tissue development and renewal. In GI diseases, LGR5+intestinal stem cells play a critical role in wound healing, while its expression by cancer stem cells correlates with cancer progression and chemoresistance. Surprisingly, only a handful of studies have investigated the functional role of LGR5 as a receptor. Demonstrating LGR5 receptor function and identifying signaling determinants will be a significant breakthrough in understanding stem cell biology under normal and pathological conditions. The project hypothesis is that LGR5 scaffolds the assembly of signaling complexes that modulate cell metabolism to accommodate cell fate, growth, and migration. Aims The project aims to characterize the molecular determinants linking LGR5 to cell metabolism and wound healing. Methods As a working model, recombinant LGR5 and mutant constructs were expressed in HEK293 cells. Wound healing was determined using scratch and single-cell tracking assays to measure cell migration. Cellular metabolism was measured using Seahorse assays complemented by metabolomic studies. Results Proteomic analysis revealed a rich LGR5 protein interactome associated with amino acid, glucose, purine metabolism, scaffold proteins (e.g., 14-3-3), and GPCR signaling. Using Seahorse assays, we showed that oxygen consumption and glycolysis were increased in LGR5-expressing cells, while metabolic profiling revealed enrichment in metabolites associated with glutamate, purine, pyrimidine metabolism, pentose phosphate pathway, glycolysis, and TCA cycle, among others. Finally, LGR5 expression promoted wound healing and a single cell's migration distance. Conclusions The results describe for the first time a functional role of LGR5 as a receptor, but foremost as an effector modulating cell metabolism. The findings may pave the way for new therapeutics targeting the LGR5 interactome to restore tissue homeostasis in diseases such as inflammatory bowel disease or to block cell adaptation and dissemination in the context of cancer. Funding Agencies CCCNSERC","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"363 4","pages":"33 - 34"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139839385","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":"A29 INVESTIGATING THE IMPACT OF PARKINSON’S DISEASE-ASSOCIATED GENES ON INTESTINAL HOMEOSTASIS","authors":"J. Pei, S. Recinto, A. MacDonald, A. Kazanova, C. Gavino, L. Trudeau, M. Desjardins, J. Stratton, S. Gruenheid","doi":"10.1093/jcag/gwad061.029","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.029","url":null,"abstract":"Abstract Background Intestinal epithelial cells (IECs) provide an essential physical barrier between harsh luminal contents and underlying host tissue. The maintenance of intestinal homeostasis must be intricately regulated through the proliferation and differentiation of intestinal stem cells (ISCs). Dysregulation of this system results in the loss of barrier function, causing pathologies in both intestinal and extra-intestinal diseases. While Parkinson’s Disease (PD) is primarily a neurodegenerative disorder, there is increasing evidence linking PD progression and gastrointestinal (GI) dysfunction. Constipation and increased bowel permeability are often observed years prior to development of motor dysfunction in PD, and people with inflammatory bowel disease are more likely to develop PD. Our group developed a model to investigate the role of the gut in PD, demonstrating that mice with genetic ablation of the PD-associated gene Pink1 exhibited motor phenotypes only when previously infected with Gram-negative Citrobacter rodentium intestinal bacteria. As Pink1 and other PD-associated genes are expressed in IECs, we hypothesize that PD-associated gene mutations directly affect the epithelium and impact early PD pathophysiology. Aims 1. Determine how Pink1 mutation affects the transcriptional profiles in IECs at steady state and in vivo C. rodentium infection. 2. Use colonoid systems to study the effect of Pink1 mutation on epithelial activity. Methods ScRNAseq was performed on IECs isolated from uninfected and infected Pink1 WT and KO mice, sacrificed at day 7 and 14 (early and peak infection) to elucidate transcriptional differences between epithelial lineages of each genotype. Additionally, colonoids were derived from primary mouse tissue and treated with lipopolysaccharide (LPS) to determine how Pink1 KO affects the inflammatory response of the epithelium. Results Our data revealed that Pink1 KO profoundly affected several epithelial lineages. ISCs from infected Pink1 KO mice had dysregulated cell cycle genes, transit amplifying cells showed dysregulated expression of tight junction genes, and enterocytes displayed dysregulation in oxidative damage and apoptotic genes. Preliminary data from colonoids showed that Pink1 KO mice, when stimulated with LPS, had altered pro-inflammatory cytokine gene expression. We are also evaluating colon motility differences between genotypes through transit time assays, counting fecal pellets per hour, and fecal water content. Conclusions In Pink1 KO IECs, there is indeed an altered cellular response upon infection, but more information is needed to decern the mechanistic role of IECs in PD. By investigating the role of PD genes in the GI tract, these studies carry important implications for understanding the initiation and progression of PD. Funding Agencies CIHR","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"392 4","pages":"15 - 16"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139839478","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}