Pub Date : 2024-02-14DOI: 10.1093/jcag/gwad061.314
M. K. Parvizian, D. Hurlbut, M. S. Rai
Abstract Background Pancreatic undifferentiated carcinoma with osteoclast-like giant cells (UCOGC) is a rare form of pancreatic cancer representing under 1% of cases. UCOGC is hypothesized to be a variant of pancreatic adenocarcinoma and while the pathophysiology is incompletely defined, it is felt to be an undifferentiated sarcomatoid carcinoma variant with chemotaxis of osteoclastic giant cells. Clinical, radiographic, or biochemical features do not reliably differentiate this from other tumors. Definitive diagnosis is made by histologic examination demonstrating non-neoplastic multinucleated osteoclastic giant cells (CD68 positive), mononuclear histiocytes, and neoplastic mononuclear cells. Aims To describe the case of a patient with UCOGC, highlighting key clinicopathologic features and management. Methods Case report and literature review. Results A 79-year-old man with atrial fibrillation on Xarelto presented with 4 months of abdominal pain, nausea, vomiting, and weight loss (22 kg). An MRI revealed a dilated main pancreatic duct and side branches with abrupt cutoff in the neck due to an ill-defined lesion. Endoscopic ultrasound confirmed a 36 mm hypoechoic ill-defined mass in the pancreatic neck. Biopsy performed with a 22-gauge needle with dry suction showed tissue fragments consistent with UCOGC (Figure 1). Unfortunately, the patient presented to hospital with worsened abdominal pain and nausea and was found to have new portal, superior mesenteric, and splenic vein thrombosis. His anticoagulant was changed to Dalteparin. A multidisciplinary cancer conference was held including input from experts in Toronto, and due to surrounding inflammation and new thrombosis he was not considered a surgical candidate at the time and neoadjuvant treatment with standard adenocarcinoma chemotherapy was planned. Unfortunately, the patient continued to decline and he was treated with palliative intent FOLFIRINOX for 2 cycles before opting for a medical assistance in dying procedure. Conclusions Treatment for UCOGC has not been well studied due to its rarity. Surgery is first-line therapy if appropriate based on patient status and cancer stage. The efficacy of chemotherapy and radiation is unclear but as a suspected adenocarcinoma variant, standard chemotherapy regimens are often used. Research is ongoing with an area of interest being PD-L1 inhibition due to high tumor PD-L1 positivity rates. Recognition of this rare entity is crucial due to its distinct diagnostic and therapeutic characteristics with more research needed to establish optimal therapy. Figure 1: Pathologic examination with HPS and CD68 stains demonstrating UCOGC Funding Agencies None
{"title":"A314 UNDIFFERENTIATED PANCREATIC CARCINOMA WITH OSTEOCLAST-LIKE GIANT CELLS: A CASE REPORT","authors":"M. K. Parvizian, D. Hurlbut, M. S. Rai","doi":"10.1093/jcag/gwad061.314","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.314","url":null,"abstract":"Abstract Background Pancreatic undifferentiated carcinoma with osteoclast-like giant cells (UCOGC) is a rare form of pancreatic cancer representing under 1% of cases. UCOGC is hypothesized to be a variant of pancreatic adenocarcinoma and while the pathophysiology is incompletely defined, it is felt to be an undifferentiated sarcomatoid carcinoma variant with chemotaxis of osteoclastic giant cells. Clinical, radiographic, or biochemical features do not reliably differentiate this from other tumors. Definitive diagnosis is made by histologic examination demonstrating non-neoplastic multinucleated osteoclastic giant cells (CD68 positive), mononuclear histiocytes, and neoplastic mononuclear cells. Aims To describe the case of a patient with UCOGC, highlighting key clinicopathologic features and management. Methods Case report and literature review. Results A 79-year-old man with atrial fibrillation on Xarelto presented with 4 months of abdominal pain, nausea, vomiting, and weight loss (22 kg). An MRI revealed a dilated main pancreatic duct and side branches with abrupt cutoff in the neck due to an ill-defined lesion. Endoscopic ultrasound confirmed a 36 mm hypoechoic ill-defined mass in the pancreatic neck. Biopsy performed with a 22-gauge needle with dry suction showed tissue fragments consistent with UCOGC (Figure 1). Unfortunately, the patient presented to hospital with worsened abdominal pain and nausea and was found to have new portal, superior mesenteric, and splenic vein thrombosis. His anticoagulant was changed to Dalteparin. A multidisciplinary cancer conference was held including input from experts in Toronto, and due to surrounding inflammation and new thrombosis he was not considered a surgical candidate at the time and neoadjuvant treatment with standard adenocarcinoma chemotherapy was planned. Unfortunately, the patient continued to decline and he was treated with palliative intent FOLFIRINOX for 2 cycles before opting for a medical assistance in dying procedure. Conclusions Treatment for UCOGC has not been well studied due to its rarity. Surgery is first-line therapy if appropriate based on patient status and cancer stage. The efficacy of chemotherapy and radiation is unclear but as a suspected adenocarcinoma variant, standard chemotherapy regimens are often used. Research is ongoing with an area of interest being PD-L1 inhibition due to high tumor PD-L1 positivity rates. Recognition of this rare entity is crucial due to its distinct diagnostic and therapeutic characteristics with more research needed to establish optimal therapy. Figure 1: Pathologic examination with HPS and CD68 stains demonstrating UCOGC Funding Agencies None","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"437 1","pages":"255 - 256"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139837026","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}
Pub Date : 2024-02-14DOI: 10.1093/jcag/gwad061.067
T. Afzaal, R. AlRamdan, H. Bualbanat, N. C. Howarth, G. Malhi, D. Hudson, I. ChinYee, A. Teriaky
Abstract Background Review of the literature identifies a rising trend in laboratory testing, with over 30% of tests estimated to be inappropriately repeated. Laboratory overutilization increases healthcare costs, and can lead to overdiagnosis, overtreatment and negative health outcomes. Indications for repeat Gamma Glutamyl Transferase (GGT) testing in adults are limited, particularly repeat testing within the same admission. Aims Our aim was to reduce the inappropriate ordering of repeat GGT testing by 25% for all inpatients at the London Health Sciences Centre (LHSC) over a one-year study period. Methods An interprofessional team was created to help engage relevant stakeholders, collect baseline data and reassess the indications for GGT testing. A combination of root cause analysis tools, specifically the Ishikawa diagram and Pareto chart, were employed to identify potential factors contributing to the overutilization of GGT testing. After prioritizing potential solutions, intervention bundles were developed, and Plan-Do-Study-Act (PDSA) cycles were created to target correctable factors. In PDSA cycle #1, the process started by eliminating GGT as a laboratory testing option in the three most commonly used admission order care sets. Considering the hierarchy of intervention effectiveness, PDSA cycle #2 involved implementing a computerized Clinical Decision Support (CDS) system to restrict the reordering of GGT tests within 72 hours of the same admission. Results Baseline data showed that in 2022, a total of 62,542 GGT tests were ordered, with an average of approximately 5,200 GGT tests ordered per month. Of these, 16.4% were ordered through the top 3 most prevalent admission order care sets, and around 25% of all GGT tests were repeats within 72 hours of admission. Referring to Figure 1, PDSA cycle #1 yielded no significant reduction in GGT testing. PDSA cycle #2 successfully reduced the proportion of repeat GGT tests ordered by 12% within two months of implementation, leading to an estimated annualized cost savings of approximately $37,440. Conclusions Our results establish the effectiveness of CDS systems in reducing laboratory testing overutilization, suggesting their superiority to individual care set targeting interventions, and emphasize the potential for cost-effective CDS development in contemporary healthcare. Funding Agencies None
{"title":"A67 REDUCING INAPPROPRIATE GAMMA-GLUTAMYL TRANSFERASE TESTING FOR INPATIENTS: A QUALITY IMPROVEMENT INITIATIVE IN LAB WASTE REDUCTION APPLYING THE MODEL FOR CONTINUOUS IMPROVEMENT","authors":"T. Afzaal, R. AlRamdan, H. Bualbanat, N. C. Howarth, G. Malhi, D. Hudson, I. ChinYee, A. Teriaky","doi":"10.1093/jcag/gwad061.067","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.067","url":null,"abstract":"Abstract Background Review of the literature identifies a rising trend in laboratory testing, with over 30% of tests estimated to be inappropriately repeated. Laboratory overutilization increases healthcare costs, and can lead to overdiagnosis, overtreatment and negative health outcomes. Indications for repeat Gamma Glutamyl Transferase (GGT) testing in adults are limited, particularly repeat testing within the same admission. Aims Our aim was to reduce the inappropriate ordering of repeat GGT testing by 25% for all inpatients at the London Health Sciences Centre (LHSC) over a one-year study period. Methods An interprofessional team was created to help engage relevant stakeholders, collect baseline data and reassess the indications for GGT testing. A combination of root cause analysis tools, specifically the Ishikawa diagram and Pareto chart, were employed to identify potential factors contributing to the overutilization of GGT testing. After prioritizing potential solutions, intervention bundles were developed, and Plan-Do-Study-Act (PDSA) cycles were created to target correctable factors. In PDSA cycle #1, the process started by eliminating GGT as a laboratory testing option in the three most commonly used admission order care sets. Considering the hierarchy of intervention effectiveness, PDSA cycle #2 involved implementing a computerized Clinical Decision Support (CDS) system to restrict the reordering of GGT tests within 72 hours of the same admission. Results Baseline data showed that in 2022, a total of 62,542 GGT tests were ordered, with an average of approximately 5,200 GGT tests ordered per month. Of these, 16.4% were ordered through the top 3 most prevalent admission order care sets, and around 25% of all GGT tests were repeats within 72 hours of admission. Referring to Figure 1, PDSA cycle #1 yielded no significant reduction in GGT testing. PDSA cycle #2 successfully reduced the proportion of repeat GGT tests ordered by 12% within two months of implementation, leading to an estimated annualized cost savings of approximately $37,440. Conclusions Our results establish the effectiveness of CDS systems in reducing laboratory testing overutilization, suggesting their superiority to individual care set targeting interventions, and emphasize the potential for cost-effective CDS development in contemporary healthcare. Funding Agencies None","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"17 4","pages":"45 - 46"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139837260","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}
Pub Date : 2024-02-14DOI: 10.1093/jcag/gwad061.094
S. Jiang, A. Zarrin, A. Walia, C. Galorport, W Xiong, R. Enns, E. Lam, N. Shahidi
Abstract Background Modality selection between cold snare resection (CSR) and endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) is largely predicated on the ability to differentiate between serrated and adenomatous histopathology. While optical evaluation has modest accuracy for diminutive polyps, performance has not been evaluated for large non-pedunculated colorectal polyps (LNPCPs). Aims To evaluate the performance of pre-resection optical evaluation to differentiate between serrated and adenomatous LNPCPs. Methods Consecutive patients ampersand:003E 18 years of age who underwent endoscopic resection for a LNPCP were enrolled in a prospective single center observation cohort study (clinicaltrials.gov ID: NCT05402696). Pre-resection optical evaluation was performed using high-definition white-light and narrow-band imaging (NBI) with or without near-focus. The Japanese NBI Expert Team (JNET) classification was used to differentiate between serrated (JNET I) vs. adenomatous (JNET IIA, IIB) LNPCPs. Traditional serrated adenomas (TSAs) and cancers were excluded from analysis. Sensitivity, specificity, and accuracy were used to evaluate optical evaluation performance. Results From 06/2022-09/2023, 266 patients underwent 282 procedures for a total of 335 LNPCPs. Median size was 30mm (IQR 20-40mm). Histopathology identified 215 (64.2%) adenomatous, 91 (27.2%) serrated, 16 (4.8%) cancerous, and 13 (3.9%) other LNPCPs; including 5 TSAs. Of the 91 serrated lesions, 90 (98.9%) were predicted as serrated; sensitivity, specificity, and accuracy were 98.90% (95% CI 94.03-99.97), 99.53% (95% CI 97.44-99.99), 99.35% (95% CI 97.66-99.92), respectively. Of the 215 adenomatous lesions, 213 (99.1%) were predicted as adenomatous; sensitivity, specificity, and accuracy were 99.07% (95% CI 96.68-99.89), 98.90% (95% CI 94.03-99.97), 99.02% (95% CI 97.16-99.80), respectively. Conclusions Optical evaluation demonstrates excellent performance characteristics to differentiate between serrated and adenomatous LNPCPs; therefore, empowering endoscopists to reliably apply a selective resection algorithm between CSR, EMR and ESD. Funding Agencies None
{"title":"A94 PRE-RESECTION OPTICAL EVALUATION RELIABLY DIFFERENTIATES BETWEEN SERRATED AND ADENOMATOUS LARGE NON-PEDUNCULATED COLORECTAL POLYPS","authors":"S. Jiang, A. Zarrin, A. Walia, C. Galorport, W Xiong, R. Enns, E. Lam, N. Shahidi","doi":"10.1093/jcag/gwad061.094","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.094","url":null,"abstract":"Abstract Background Modality selection between cold snare resection (CSR) and endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) is largely predicated on the ability to differentiate between serrated and adenomatous histopathology. While optical evaluation has modest accuracy for diminutive polyps, performance has not been evaluated for large non-pedunculated colorectal polyps (LNPCPs). Aims To evaluate the performance of pre-resection optical evaluation to differentiate between serrated and adenomatous LNPCPs. Methods Consecutive patients ampersand:003E 18 years of age who underwent endoscopic resection for a LNPCP were enrolled in a prospective single center observation cohort study (clinicaltrials.gov ID: NCT05402696). Pre-resection optical evaluation was performed using high-definition white-light and narrow-band imaging (NBI) with or without near-focus. The Japanese NBI Expert Team (JNET) classification was used to differentiate between serrated (JNET I) vs. adenomatous (JNET IIA, IIB) LNPCPs. Traditional serrated adenomas (TSAs) and cancers were excluded from analysis. Sensitivity, specificity, and accuracy were used to evaluate optical evaluation performance. Results From 06/2022-09/2023, 266 patients underwent 282 procedures for a total of 335 LNPCPs. Median size was 30mm (IQR 20-40mm). Histopathology identified 215 (64.2%) adenomatous, 91 (27.2%) serrated, 16 (4.8%) cancerous, and 13 (3.9%) other LNPCPs; including 5 TSAs. Of the 91 serrated lesions, 90 (98.9%) were predicted as serrated; sensitivity, specificity, and accuracy were 98.90% (95% CI 94.03-99.97), 99.53% (95% CI 97.44-99.99), 99.35% (95% CI 97.66-99.92), respectively. Of the 215 adenomatous lesions, 213 (99.1%) were predicted as adenomatous; sensitivity, specificity, and accuracy were 99.07% (95% CI 96.68-99.89), 98.90% (95% CI 94.03-99.97), 99.02% (95% CI 97.16-99.80), respectively. Conclusions Optical evaluation demonstrates excellent performance characteristics to differentiate between serrated and adenomatous LNPCPs; therefore, empowering endoscopists to reliably apply a selective resection algorithm between CSR, EMR and ESD. Funding Agencies None","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"7 2","pages":"67 - 67"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139837330","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}
Pub Date : 2024-02-14DOI: 10.1093/jcag/gwad061.257
A. Ricciuto, H. McKay, J. deBruyn, E. Crowley, P. Church, H. Huynh, A. Otley, A. Shaikh, W. El-Matary, E. Wine, T. Walters, A. Griffiths
Abstract Background Ustekinumab (UST) is an effective therapy for adults with moderate to severe Crohn’s disease (CD), but data concerning optimal dosing in children are sparse. Aims To examine real-world post-induction PK and efficacy in a prospective multicentre cohort study of paediatric CD (Canadian Children IBD Network (CIDsCaNN)). Methods Children 2-17 years-old with CD were eligible for this analysis if they received IV UST for treatment of luminal CD and had serum UST levels measured at week 8. Median with interquartile range (IQR) UST dose and serum trough levels at weeks 8 and 16 were compared between children ampersand:003C40 kg and ≥40 kg with Mann-Whitney U test. Clinical remission was defined as weighted Pediatric CD Activity Index (wPCDAI) ampersand:003C12.5. UST durability was compared between those with a week 8 serum UST level ampersand:003C5 versus ≥5 µg/mL (log-rank p-value). Results Between 21/04/2017 and 30/04/2023, 39 children were eligible (74% M; median age 13.5 (IQR 11.9-15.6) y; median weight 44.7 (IQR 30.4-55.0) kg, 12 children ampersand:003C40 kg; 84% bio-naïve). Median disease duration at UST start was 4 (IQR 1-17) months; CD location distal ileal ± limited cecal (18%), colonic (26%), ileocolonic (54%). Median follow-up duration was 10.0 (IQR 6.7-12.7) months. All children received UST IV induction (67% 260 mg, 18% 390 mg) followed by 90 mg SC every 8 weeks. Induction doses in mg per kg were higher in those ampersand:003C40 kg (median 9.11 (IQR 8.68-10.08)) compared to those ≥40 kg (5.77 (IQR 5.24-6.45) mg/kg), pampersand:003C0.001. Induction doses in mg per body surface area (BSA) in m2 were similarly higher in those ampersand:003C40 kg (median 251.66 (IQR 244.16-258.99) versus 195.15 (IQR 172.71-224.11) mg/m2, pampersand:003C0.001). Despite higher induction doses, week 8 trough levels were numerically lower in those ampersand:003C40 kg (median 4.32 (IQR 1.33-8.36) versus 6.96 (IQR 5.38-8.90) µg/mL, p=0.29). Week 16 serum UST levels were also numerically lower in ampersand:003C40 kg versus ≥40 kg (median 4.04 (IQR 1.92-6.98) versus 5.50 (IQR 3.17-8.27) µg/mL, p=0.57). Interval shortening during maintenance to every 4 weeks occurred in 7 children prior to week 16, and in 14 children prior to 6 months. By 4 months, 19 of 33 children with available data (56%) achieved clinical remission. Overall, 8/39 (21%) ceased UST. Those who discontinued UST had significantly lower week 8 levels than those who continued UST (median 3.52 (IQR 1.19-6.12) versus 7.15 (IQR 5.09-10.15) µg/mL, p=0.027). In survival analysis, week 8 trough level ampersand:003C5 µg/mL was associated with an increased risk of UST discontinuation (log-rank p=0.032) (Figure 1). Conclusions Higher UST concentration at week 8 is associated with greater drug durability. A higher BSA-based induction for children ampersand:003C40 kg is supported by higher serum drug levels and improved drug durability. Figure 1. Ustekinumab durability by week 8 serum drug level Fu
{"title":"A257 EARLY PROACTIVE THERAPEUTIC DRUG MONITORING WITH USTEKINUMAB THERAPY IN PAEDIATRIC CROHN’S DISEASE","authors":"A. Ricciuto, H. McKay, J. deBruyn, E. Crowley, P. Church, H. Huynh, A. Otley, A. Shaikh, W. El-Matary, E. Wine, T. Walters, A. Griffiths","doi":"10.1093/jcag/gwad061.257","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.257","url":null,"abstract":"Abstract Background Ustekinumab (UST) is an effective therapy for adults with moderate to severe Crohn’s disease (CD), but data concerning optimal dosing in children are sparse. Aims To examine real-world post-induction PK and efficacy in a prospective multicentre cohort study of paediatric CD (Canadian Children IBD Network (CIDsCaNN)). Methods Children 2-17 years-old with CD were eligible for this analysis if they received IV UST for treatment of luminal CD and had serum UST levels measured at week 8. Median with interquartile range (IQR) UST dose and serum trough levels at weeks 8 and 16 were compared between children ampersand:003C40 kg and ≥40 kg with Mann-Whitney U test. Clinical remission was defined as weighted Pediatric CD Activity Index (wPCDAI) ampersand:003C12.5. UST durability was compared between those with a week 8 serum UST level ampersand:003C5 versus ≥5 µg/mL (log-rank p-value). Results Between 21/04/2017 and 30/04/2023, 39 children were eligible (74% M; median age 13.5 (IQR 11.9-15.6) y; median weight 44.7 (IQR 30.4-55.0) kg, 12 children ampersand:003C40 kg; 84% bio-naïve). Median disease duration at UST start was 4 (IQR 1-17) months; CD location distal ileal ± limited cecal (18%), colonic (26%), ileocolonic (54%). Median follow-up duration was 10.0 (IQR 6.7-12.7) months. All children received UST IV induction (67% 260 mg, 18% 390 mg) followed by 90 mg SC every 8 weeks. Induction doses in mg per kg were higher in those ampersand:003C40 kg (median 9.11 (IQR 8.68-10.08)) compared to those ≥40 kg (5.77 (IQR 5.24-6.45) mg/kg), pampersand:003C0.001. Induction doses in mg per body surface area (BSA) in m2 were similarly higher in those ampersand:003C40 kg (median 251.66 (IQR 244.16-258.99) versus 195.15 (IQR 172.71-224.11) mg/m2, pampersand:003C0.001). Despite higher induction doses, week 8 trough levels were numerically lower in those ampersand:003C40 kg (median 4.32 (IQR 1.33-8.36) versus 6.96 (IQR 5.38-8.90) µg/mL, p=0.29). Week 16 serum UST levels were also numerically lower in ampersand:003C40 kg versus ≥40 kg (median 4.04 (IQR 1.92-6.98) versus 5.50 (IQR 3.17-8.27) µg/mL, p=0.57). Interval shortening during maintenance to every 4 weeks occurred in 7 children prior to week 16, and in 14 children prior to 6 months. By 4 months, 19 of 33 children with available data (56%) achieved clinical remission. Overall, 8/39 (21%) ceased UST. Those who discontinued UST had significantly lower week 8 levels than those who continued UST (median 3.52 (IQR 1.19-6.12) versus 7.15 (IQR 5.09-10.15) µg/mL, p=0.027). In survival analysis, week 8 trough level ampersand:003C5 µg/mL was associated with an increased risk of UST discontinuation (log-rank p=0.032) (Figure 1). Conclusions Higher UST concentration at week 8 is associated with greater drug durability. A higher BSA-based induction for children ampersand:003C40 kg is supported by higher serum drug levels and improved drug durability. Figure 1. Ustekinumab durability by week 8 serum drug level Fu","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"122 ","pages":"206 - 207"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139837343","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}
Pub Date : 2024-02-14DOI: 10.1093/jcag/gwad061.028
K. Mu, M. Xue, W. Turpin, K. Croitoru
Abstract Background Crohn's disease (CD) is a gastrointestinal disorder characterized by chronic inflammation. While increased oxidative stress is observed in established CD patients, it remains unknown whether a shift in redox status is present before the diagnosis of CD and whether it is correlated with changes in immune response and microbial composition. Our hypothesis is that oxidative stress plays a role in the development of CD, and it could be detected before the diagnosis of CD. Furthermore, it is likely to be correlated with systemic inflammation and alterations in gut microbiota composition. Aims We aimed to assess the relationship between the serum redox status-related indicators, specifically amino acids ratios, with risk of CD onset and if this is further association with systemic inflammation marker, and gut microbiota composition. Methods In the Genetic Environment Microbial Project (CCC-GEM), a cohort of first-degree relatives (FDRs) of CD patients was prospectively followed. Among them, we identified subjects who later developed CD, defined as pre-CD (n=69), and matched them at a 1:4 ratio with FDRs who remained disease-free (n=276). Serum levels at enrollment of cysteineglycine (reduced form) and cystineglycine (oxidized form) were quantified by mass spectrometry, and the cysteineglycine/cystineglycine ratio was used as an indicator of redox status. Conditional logistic regression assessed the association with CD, while partial Spearman regression evaluated its correlation with systemic inflammation, as indicated by c-reactive protein (CRP), and gut microbiota composition (determined by fecal 16S rRNA sequencing). Results A decrease in the ratio indicates a shift in redox status toward oxidative stress. The cysteineglycine/cystineglycine ratio was negatively associated with the likelihood of developing CD (coefficient = -0.6188; p =0.0146), and it was also negatively correlated with CRP levels (coefficient = -0.177; p =0.00095). A list of taxa belonging to the phyla Firmicutes and Actinobacteriota were positively correlated with cysteineglycine/cystineglycine ratio (p≤0.05). Conclusions This study is the first to report that when redox status shifts towards oxidative stress, as indicated by the cysteineglycine/cystineglycine ratio, the likelihood of CD increases. Furthermore, these markers also correlate with CRP levels and gut microbiota composition, indicating a loss of various taxa when the redox status shifts towards oxidative stress. Submitted on behalf of the CCC-GEM consortium. Funding Agencies CCC, CIHRHCT
摘要 背景 克罗恩病（CD）是一种以慢性炎症为特征的胃肠道疾病。虽然在已确诊的克罗恩病患者中观察到氧化应激增加，但氧化还原状态的变化是否在确诊克罗恩病之前就已存在，以及这种变化是否与免疫反应和微生物组成的变化相关，仍是未知数。我们的假设是，氧化应激在 CD 的发展过程中起着一定的作用，它可以在 CD 诊断前被检测到。此外，氧化应激还可能与全身炎症和肠道微生物群组成的改变有关。目的 我们旨在评估血清氧化还原状态相关指标（尤其是氨基酸比率）与 CD 发病风险之间的关系，以及这是否与全身炎症标志物和肠道微生物群组成有进一步关联。方法 在遗传环境微生物项目（CCC-GEM）中，我们对一组 CD 患者的一级亲属（FDRs）进行了前瞻性随访。在这些人中，我们发现了后来患上 CD 的受试者，他们被定义为 CD 前患者（69 人），并与仍未患病的 FDRs（276 人）按 1:4 的比例进行了配对。通过质谱法对入选时血清中半胱氨酸甘氨酸（还原型）和胱氨酸甘氨酸（氧化型）的水平进行量化，并将半胱氨酸甘氨酸/胱氨酸甘氨酸比值作为氧化还原状态的指标。条件逻辑回归评估了与 CD 的关联性，而部分斯皮尔曼回归评估了其与全身炎症（以 c 反应蛋白（CRP）和肠道微生物群组成（通过粪便 16S rRNA 测序确定）为指标）的相关性。结果 比值降低表明氧化还原状态转向氧化应激。半胱氨酸甘氨酸/胱氨酸甘氨酸比值与罹患 CD 的可能性呈负相关（系数 = -0.6188；P =0.0146），与 CRP 水平也呈负相关（系数 = -0.177；P =0.00095）。属于真菌门和放线菌门的一系列类群与半胱氨酸甘氨酸/胱氨酸甘氨酸比率呈正相关（p≤0.05）。结论 本研究首次报告了当氧化还原状态转向氧化应激时（如半胱氨酸甘氨酸/胱氨酸甘氨酸比率所示），发生 CD 的可能性会增加。此外，这些标记物还与 CRP 水平和肠道微生物群组成相关，表明当氧化还原状态转向氧化应激时，各种类群会减少。代表CCC-GEM联盟提交。资助机构 CCC、CIHRHCT
{"title":"A28 A SERUM REDOX STATUS-RELATED INDICATOR IS ASSOCIATED WITH THE RISK OF ONSET OF CROHN'S DISEASE","authors":"K. Mu, M. Xue, W. Turpin, K. Croitoru","doi":"10.1093/jcag/gwad061.028","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.028","url":null,"abstract":"Abstract Background Crohn's disease (CD) is a gastrointestinal disorder characterized by chronic inflammation. While increased oxidative stress is observed in established CD patients, it remains unknown whether a shift in redox status is present before the diagnosis of CD and whether it is correlated with changes in immune response and microbial composition. Our hypothesis is that oxidative stress plays a role in the development of CD, and it could be detected before the diagnosis of CD. Furthermore, it is likely to be correlated with systemic inflammation and alterations in gut microbiota composition. Aims We aimed to assess the relationship between the serum redox status-related indicators, specifically amino acids ratios, with risk of CD onset and if this is further association with systemic inflammation marker, and gut microbiota composition. Methods In the Genetic Environment Microbial Project (CCC-GEM), a cohort of first-degree relatives (FDRs) of CD patients was prospectively followed. Among them, we identified subjects who later developed CD, defined as pre-CD (n=69), and matched them at a 1:4 ratio with FDRs who remained disease-free (n=276). Serum levels at enrollment of cysteineglycine (reduced form) and cystineglycine (oxidized form) were quantified by mass spectrometry, and the cysteineglycine/cystineglycine ratio was used as an indicator of redox status. Conditional logistic regression assessed the association with CD, while partial Spearman regression evaluated its correlation with systemic inflammation, as indicated by c-reactive protein (CRP), and gut microbiota composition (determined by fecal 16S rRNA sequencing). Results A decrease in the ratio indicates a shift in redox status toward oxidative stress. The cysteineglycine/cystineglycine ratio was negatively associated with the likelihood of developing CD (coefficient = -0.6188; p =0.0146), and it was also negatively correlated with CRP levels (coefficient = -0.177; p =0.00095). A list of taxa belonging to the phyla Firmicutes and Actinobacteriota were positively correlated with cysteineglycine/cystineglycine ratio (p≤0.05). Conclusions This study is the first to report that when redox status shifts towards oxidative stress, as indicated by the cysteineglycine/cystineglycine ratio, the likelihood of CD increases. Furthermore, these markers also correlate with CRP levels and gut microbiota composition, indicating a loss of various taxa when the redox status shifts towards oxidative stress. Submitted on behalf of the CCC-GEM consortium. Funding Agencies CCC, CIHRHCT","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"75 1","pages":"15 - 15"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139837406","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}
Pub Date : 2024-02-14DOI: 10.1093/jcag/gwad061.133
S. Jiang, A. Zarrin, A. Walia, C. Galorport, W Xiong, R. Enns, E. Lam, N. Shahidi
Abstract Background Recurrence following endoscopic mucosal resection (EMR) historically occurs in approximately 15-20% of large (≥20 mm) non-pedunculated colorectal polyps (LNPCPs). Margin thermal ablation with snare-tip soft coagulation (STSC) of the post-EMR defect is an evidence-based modality to mitigate recurrence. However, international validation of margin thermal ablation outcomes is needed. Aims To evaluate the frequencies of endoscopic and histologic recurrence following margin thermal ablation with STSC for LNPCPs managed by EMR. Methods Consecutive patients ampersand:003E 18 years of age who underwent endoscopic resection for a LNPCP were enrolled in a prospective single center observation cohort study (clinicaltrials.gov ID: NCT05402696). Of those lesions which underwent successful EMR, margin STSC was applied systematically aiming to create at least a 2-3mm rim of completed ablated tissue (complete whitening). Recurrence was evaluated both endoscopically, using a standardized protocol for the post-EMR scar, and histologically. Results From 06/2022-09/2023, 335 LNPCPs were endoscopically resected, including 209 by EMR. Following successful EMR, 182 (87.1%) underwent margin STSC. Of these lesions, 49 LNPCPs in 46 patients were assessed at first surveillance colonoscopy. Margin STSC was complete for 44 (89.8%) lesions and incomplete for 5 (10.2%) due to difficult angulation/positioning (n=3) and ileocecal valve location (n=2). Median interval to first surveillance colonoscopy was 6 (IQR 6-7) months. There was no evidence of recurrence noted on endoscopy. Biopsy was performed in 44 (89.8%) with no evidence of histologic recurrence. Conclusions Thermal ablation of the defect margin with STSC effectively negates recurrence and should be considered standard of care following EMR. Funding Agencies None
{"title":"A133 MARGIN THERMAL ABLATION WITH SNARE-TIP SOFT COAGULATION EFFECTIVELY MITIGATES RECURRENCE AFTER ENDOSCOPIC MUCOSAL RESECTION OF LARGE NON-PEDUNCULATED COLORECTAL POLYPS","authors":"S. Jiang, A. Zarrin, A. Walia, C. Galorport, W Xiong, R. Enns, E. Lam, N. Shahidi","doi":"10.1093/jcag/gwad061.133","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.133","url":null,"abstract":"Abstract Background Recurrence following endoscopic mucosal resection (EMR) historically occurs in approximately 15-20% of large (≥20 mm) non-pedunculated colorectal polyps (LNPCPs). Margin thermal ablation with snare-tip soft coagulation (STSC) of the post-EMR defect is an evidence-based modality to mitigate recurrence. However, international validation of margin thermal ablation outcomes is needed. Aims To evaluate the frequencies of endoscopic and histologic recurrence following margin thermal ablation with STSC for LNPCPs managed by EMR. Methods Consecutive patients ampersand:003E 18 years of age who underwent endoscopic resection for a LNPCP were enrolled in a prospective single center observation cohort study (clinicaltrials.gov ID: NCT05402696). Of those lesions which underwent successful EMR, margin STSC was applied systematically aiming to create at least a 2-3mm rim of completed ablated tissue (complete whitening). Recurrence was evaluated both endoscopically, using a standardized protocol for the post-EMR scar, and histologically. Results From 06/2022-09/2023, 335 LNPCPs were endoscopically resected, including 209 by EMR. Following successful EMR, 182 (87.1%) underwent margin STSC. Of these lesions, 49 LNPCPs in 46 patients were assessed at first surveillance colonoscopy. Margin STSC was complete for 44 (89.8%) lesions and incomplete for 5 (10.2%) due to difficult angulation/positioning (n=3) and ileocecal valve location (n=2). Median interval to first surveillance colonoscopy was 6 (IQR 6-7) months. There was no evidence of recurrence noted on endoscopy. Biopsy was performed in 44 (89.8%) with no evidence of histologic recurrence. Conclusions Thermal ablation of the defect margin with STSC effectively negates recurrence and should be considered standard of care following EMR. Funding Agencies None","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"185 ","pages":"101 - 102"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139837413","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}
Pub Date : 2024-02-14DOI: 10.1093/jcag/gwad061.201
U. A. Salmi, C. Stallwood, khan Gastroenterology
Abstract Aims This is the first reported case of bleeding from an aorto-esophageal fistula as a consequence of ischemic esophageal ulceration post esophageal variceal banding. Methods A 46-year-old male presented with epigastric pain for one-week, which was not associated with fever, jaundice, or symptoms of GI bleed. He was hemodynamically stable with an unremarkable exam and basic labs. He underwent a CT scan which showed chronic portal vein thrombosis extending from the main portal vein into the superior mesenteric vein and evidence of portal hypertension, along with massive esophageal varices. Anticoagulation was not started due to risk of GI bleed. Upper endoscopy confirmed the presence of three columns of large esophageal varices in the distal and mid esophagus, the largest was 3 cm in size. There was no stigmata of recent bleeding and no gastric varices. Seven bands were applied. CT abdomen was repeated on the seventh day of admission, showing extension of portal vein thrombosis. As such, the thrombosis team started a low dose of anticoagulation. (dalteparin 7500 IU). He tolerated it well and showed no signs of bleeding prior to discharge. The day after discharge, the patient presented again with an episode of melena. Examination was remarkable for tachycardia, hypotension and melena. Hemoglobin was stable. Patient was admitted with impression of upper GI bleed most likely secondary to post banding ulcer. He was started on medical therapy. Anticoagulation was held. Next day, the patient had an episode of hematemesis with large amount of blood and clots. Emergent upper endoscopy showed active bleeding in the distal esophagus. Further examination showed a full-thickness, 7 mm defect in the lower esophagus with fresh red blood emptying from it into the esophagus (Figure 1). Thoracic surgery was consulted and suspected a perforated esophageal ulceration at the site of previous banding, with an aorto-esophageal fistula. Patient deteriorated immediately and passed away. The cause of death was cardiac arrest secondary to acute blood loss anemia. Results AEF is a recognized cause of upper GI bleeding with a high mortality rate. While rare, it can occur secondary to ischemic esophageal ulcer post EV banding. Conclusions This is the first reported case of an aorto-esophageal fistula as a consequence esophageal variceal band ligation. While extremely rare, this complication should be considered as a potentially fatal complication of variceal banding, especially in the setting of a diseased or previously repaired aorta.
{"title":"A201 AORTO-ESOPHAGEAL FISTULA AS A COMPLICATION OF ESOPHAGEAL VARICEAL BANDING","authors":"U. A. Salmi, C. Stallwood, khan Gastroenterology","doi":"10.1093/jcag/gwad061.201","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.201","url":null,"abstract":"Abstract Aims This is the first reported case of bleeding from an aorto-esophageal fistula as a consequence of ischemic esophageal ulceration post esophageal variceal banding. Methods A 46-year-old male presented with epigastric pain for one-week, which was not associated with fever, jaundice, or symptoms of GI bleed. He was hemodynamically stable with an unremarkable exam and basic labs. He underwent a CT scan which showed chronic portal vein thrombosis extending from the main portal vein into the superior mesenteric vein and evidence of portal hypertension, along with massive esophageal varices. Anticoagulation was not started due to risk of GI bleed. Upper endoscopy confirmed the presence of three columns of large esophageal varices in the distal and mid esophagus, the largest was 3 cm in size. There was no stigmata of recent bleeding and no gastric varices. Seven bands were applied. CT abdomen was repeated on the seventh day of admission, showing extension of portal vein thrombosis. As such, the thrombosis team started a low dose of anticoagulation. (dalteparin 7500 IU). He tolerated it well and showed no signs of bleeding prior to discharge. The day after discharge, the patient presented again with an episode of melena. Examination was remarkable for tachycardia, hypotension and melena. Hemoglobin was stable. Patient was admitted with impression of upper GI bleed most likely secondary to post banding ulcer. He was started on medical therapy. Anticoagulation was held. Next day, the patient had an episode of hematemesis with large amount of blood and clots. Emergent upper endoscopy showed active bleeding in the distal esophagus. Further examination showed a full-thickness, 7 mm defect in the lower esophagus with fresh red blood emptying from it into the esophagus (Figure 1). Thoracic surgery was consulted and suspected a perforated esophageal ulceration at the site of previous banding, with an aorto-esophageal fistula. Patient deteriorated immediately and passed away. The cause of death was cardiac arrest secondary to acute blood loss anemia. Results AEF is a recognized cause of upper GI bleeding with a high mortality rate. While rare, it can occur secondary to ischemic esophageal ulcer post EV banding. Conclusions This is the first reported case of an aorto-esophageal fistula as a consequence esophageal variceal band ligation. While extremely rare, this complication should be considered as a potentially fatal complication of variceal banding, especially in the setting of a diseased or previously repaired aorta.","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"78 4","pages":"158 - 159"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139837596","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}
Pub Date : 2024-02-14DOI: 10.1093/jcag/gwad061.088
H. Guo, K. Bishay, Z. Meng, Y. Ruan, D. Brenner, N. Forbes
Abstract Background Endoscopic retrograde cholangiopancreatography (ERCP) is a widely utilized procedure for diagnosing and managing various biliary and pancreatic disorders. Despite its established effectiveness, ERCP is associated with a total adverse event (AE) rate exceeding 10%. However, existing literature lacks a comprehensive synthesis of incidence rates pertaining to specific or overall AEs following ERCP procedures. Aims We performed separate systematic reviews and meta-analyses of (1) data from randomized controlled trials (RCTs) and (2) data from observational studies to evaluate the incidence of AEs following ERCPs in adult patients. Methods Two separate systematic literature searches were conducted to identify ERCP AE rates in RCTs and observational studies published between 2000 and 2021, inclusive. Abstracts underwent independent assessment to identify studies for full-text review and subsequent data extraction. DerSimonian and Laird random effects meta-analyses were applied to determine pooled incidence rates of individual post-ERCP AEs, accompanied by 95% confidence intervals (CIs). The Newcastle-Ottawa Scale (NOS) and Risk of Bias 2 (ROB2) tool were used for quality assessment of observational studies and RCTs respectively. Results Our analysis incorporated 242 RCTs and 143 observational studies. Among RCTs, the pooled incidences of post-ERCP pancreatitis (PEP) in patients with native and non-native papillae were 6.9% (CI 6.2% to 7.6%) and 6.1% (CI 5.3% to 7.1%), respectively. In observational studies, the pooled PEP incidences were 5.0% (CI 4.0% to 6.1%) for patients with native papillae and 4.2% (CI 3.6% to 4.8%) for patients with non-native papillae. The incidences of bleeding for patients with native papillae were 1.6% (CI 1.3% to 2.0%) and 2.2% (CI 1.2% to 3.9%) in RCTs and observational studies, respectively. The incidences of perforation for patients with native papillae were 0.3% (CI 0.2% to 0.4%) in RCTs and 0.5% (CI 0.3% to 0.7%) in observational studies. The incidence of cholangitis was 1.4% (CI 1.1% to 1.9%) in RCTs and 1.1% (CI 0.7% to 1.7%) in observational studies. Conclusions This meta-analysis offers comprehensive insights into the incidence of ERCP-associated AEs from 2000 to 2021, both in idealized study settings where procedures are performed by experts, and in ‘real world’ settings. More precise estimates of ERCP-related AEs can help facilitate patient consent, manage appropriate patient expectations, and enhance peri-procedural care. Funding Agencies None
{"title":"A88 ADVERSE EVENTS ASSOCIATED WITH ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY: A SYSTEMATIC REVIEW AND META-ANALYSIS","authors":"H. Guo, K. Bishay, Z. Meng, Y. Ruan, D. Brenner, N. Forbes","doi":"10.1093/jcag/gwad061.088","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.088","url":null,"abstract":"Abstract Background Endoscopic retrograde cholangiopancreatography (ERCP) is a widely utilized procedure for diagnosing and managing various biliary and pancreatic disorders. Despite its established effectiveness, ERCP is associated with a total adverse event (AE) rate exceeding 10%. However, existing literature lacks a comprehensive synthesis of incidence rates pertaining to specific or overall AEs following ERCP procedures. Aims We performed separate systematic reviews and meta-analyses of (1) data from randomized controlled trials (RCTs) and (2) data from observational studies to evaluate the incidence of AEs following ERCPs in adult patients. Methods Two separate systematic literature searches were conducted to identify ERCP AE rates in RCTs and observational studies published between 2000 and 2021, inclusive. Abstracts underwent independent assessment to identify studies for full-text review and subsequent data extraction. DerSimonian and Laird random effects meta-analyses were applied to determine pooled incidence rates of individual post-ERCP AEs, accompanied by 95% confidence intervals (CIs). The Newcastle-Ottawa Scale (NOS) and Risk of Bias 2 (ROB2) tool were used for quality assessment of observational studies and RCTs respectively. Results Our analysis incorporated 242 RCTs and 143 observational studies. Among RCTs, the pooled incidences of post-ERCP pancreatitis (PEP) in patients with native and non-native papillae were 6.9% (CI 6.2% to 7.6%) and 6.1% (CI 5.3% to 7.1%), respectively. In observational studies, the pooled PEP incidences were 5.0% (CI 4.0% to 6.1%) for patients with native papillae and 4.2% (CI 3.6% to 4.8%) for patients with non-native papillae. The incidences of bleeding for patients with native papillae were 1.6% (CI 1.3% to 2.0%) and 2.2% (CI 1.2% to 3.9%) in RCTs and observational studies, respectively. The incidences of perforation for patients with native papillae were 0.3% (CI 0.2% to 0.4%) in RCTs and 0.5% (CI 0.3% to 0.7%) in observational studies. The incidence of cholangitis was 1.4% (CI 1.1% to 1.9%) in RCTs and 1.1% (CI 0.7% to 1.7%) in observational studies. Conclusions This meta-analysis offers comprehensive insights into the incidence of ERCP-associated AEs from 2000 to 2021, both in idealized study settings where procedures are performed by experts, and in ‘real world’ settings. More precise estimates of ERCP-related AEs can help facilitate patient consent, manage appropriate patient expectations, and enhance peri-procedural care. Funding Agencies None","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"17 1","pages":"62 - 63"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139837622","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}
Pub Date : 2024-02-14DOI: 10.1093/jcag/gwad061.231
F. Diaz, R. Belaghi, T. Walters, E. Chea, D. Friedland, E. Wine, C. Deslandres, H. Huynh, J. deBruyn, D. Mack, A. Otley, A. Ricciuto, E. I. Benchimol, M. Carroll, P. Church, N. Carman, A. Shaikh, A. Griffiths, W. El-Matary
Abstract Background The effectiveness of combining biologics for pediatric inflammatory bowel disease (IBD) is under-investigated. Aims To evaluate the effectiveness of dual biologic therapy in children with IBD. Methods Children and adolescents ampersand:003C 17 years old with IBD enrolled in the Canadian Children IBD Network (CIDsCANN) who received any biologic therapy were included. Patients were classified as cases if they received two biologics simultaneously, and controls if they were switched from one biologic to another. All cases and controls who met inclusion criteria were analyzed. Baseline demographic and disease-specific data were collected. The primary outcome was clinical activity indices at the end of the 1-year period following the start of dual biologic therapy or the switch to a different biologic. The Wilcoxon signed rank test (for continuous variables) and the Fisher exact test (for nominal variables) were used to compare demographic data. A multivariable Cox proportional hazard model was used to infer about disease activity reduction between the two groups. p ampersand:003C 0.05 was used to determine statistical significance. Results Twenty-six cases and 194 controls fulfilled the inclusion criteria. Demographic and disease-specific data are summarized in Table 1. The most common combination was ustekinumab with vedolizumab in 11 (42.3%) patients; while the most common first biologic in the control group was infliximab (104, 54.1%) and the second was ustekinumab (109, 56.2%). The most common indication for the biologic therapy addition or switch was unsatisfactory clinical response. No differences between cases and controls in reductions of disease activity indices were seen at the end of the 1-year period (Figure 1). Conclusions In children with IBD, dual biologic therapy was not more effective than switching from one biologic to another. We are currently investigating the safety of this approach. Baseline data Dual biologic (n=26) Control (n=194) Sex Male 18 (69%) 103 (53%) Female 8 (31%) 91 (47%) Age at diagnosis (years) Mean (SD) 10.9 (3.11) 11.5 (3.46) Diagnosis Ulcerative colitis 12 (46%) 107 (55%) Crohn's disease 14 (54%) 87 (45%) Disease duration (years) Mean (SD) 4.47 (2.43) 4.34 (2.31) Baseline disease activity index PUCAI mean (SD) 25.0 (21.3) 25.3 (23.8) PCDAI mean (SD) 29.0 (22.2) 29.3 (23.0) Proportion of patients with 10- and 20-point reduction in clinical activity indices at the end of the 1-year period Funding Agencies None
{"title":"A231 EFFECTIVENESS OF DUAL BIOLOGIC THERAPY IN PEDIATRIC INFLAMMATORY BOWEL DISEASE: A MULTICENTRE CANADIAN STUDY","authors":"F. Diaz, R. Belaghi, T. Walters, E. Chea, D. Friedland, E. Wine, C. Deslandres, H. Huynh, J. deBruyn, D. Mack, A. Otley, A. Ricciuto, E. I. Benchimol, M. Carroll, P. Church, N. Carman, A. Shaikh, A. Griffiths, W. El-Matary","doi":"10.1093/jcag/gwad061.231","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.231","url":null,"abstract":"Abstract Background The effectiveness of combining biologics for pediatric inflammatory bowel disease (IBD) is under-investigated. Aims To evaluate the effectiveness of dual biologic therapy in children with IBD. Methods Children and adolescents ampersand:003C 17 years old with IBD enrolled in the Canadian Children IBD Network (CIDsCANN) who received any biologic therapy were included. Patients were classified as cases if they received two biologics simultaneously, and controls if they were switched from one biologic to another. All cases and controls who met inclusion criteria were analyzed. Baseline demographic and disease-specific data were collected. The primary outcome was clinical activity indices at the end of the 1-year period following the start of dual biologic therapy or the switch to a different biologic. The Wilcoxon signed rank test (for continuous variables) and the Fisher exact test (for nominal variables) were used to compare demographic data. A multivariable Cox proportional hazard model was used to infer about disease activity reduction between the two groups. p ampersand:003C 0.05 was used to determine statistical significance. Results Twenty-six cases and 194 controls fulfilled the inclusion criteria. Demographic and disease-specific data are summarized in Table 1. The most common combination was ustekinumab with vedolizumab in 11 (42.3%) patients; while the most common first biologic in the control group was infliximab (104, 54.1%) and the second was ustekinumab (109, 56.2%). The most common indication for the biologic therapy addition or switch was unsatisfactory clinical response. No differences between cases and controls in reductions of disease activity indices were seen at the end of the 1-year period (Figure 1). Conclusions In children with IBD, dual biologic therapy was not more effective than switching from one biologic to another. We are currently investigating the safety of this approach. Baseline data Dual biologic (n=26) Control (n=194) Sex Male 18 (69%) 103 (53%) Female 8 (31%) 91 (47%) Age at diagnosis (years) Mean (SD) 10.9 (3.11) 11.5 (3.46) Diagnosis Ulcerative colitis 12 (46%) 107 (55%) Crohn's disease 14 (54%) 87 (45%) Disease duration (years) Mean (SD) 4.47 (2.43) 4.34 (2.31) Baseline disease activity index PUCAI mean (SD) 25.0 (21.3) 25.3 (23.8) PCDAI mean (SD) 29.0 (22.2) 29.3 (23.0) Proportion of patients with 10- and 20-point reduction in clinical activity indices at the end of the 1-year period Funding Agencies None","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"167 ","pages":"184 - 185"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139837682","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}
Pub Date : 2024-02-14DOI: 10.1093/jcag/gwad061.024
A. Gilliland, Y Chen, D. Tertigas, M. Surette, B. Bressler, B. Vallance
Abstract Background Inflammatory bowel disease (IBD) pathobionts are commensal microbes with pathogenic potential that may cause or exacerbate IBD symptoms. Some pathobionts (ex. Escherichia coli) reside at low levels in the lumen of a healthy gut but can rapidly grow in the inflamed colons of ulcerative colitis (UC) patients. To promote disease, these pathobionts must cross the colonic mucus barrier (comprised of MUC2) that separates the epithelium from luminal microbes. It is currently unclear how bacterial pathobionts cross the mucus barrier of UC patients. Aims Using healthy and UC patient biopsy-derived colonic organoids (colonoids) and an air liquid interface (ALI) monolayer model, we investigated how the UC-isolated E. coli pathobiont p19A crosses the mucus barrier. Methods Apical out healthy and UC patient biopsy-derived colonoids were infected with p19A to confirm this pathobiont exerts direct cytopathic effects on human colonocytes. Sequencing p19A’s genome, we found it contains two mucus degrading proteins (mucinases). Healthy human and UC colonoids, as well as mouse colonoids, were used to generate mucus-producing ALI monolayers. To detect p19A-mediated mucus degradation, concentrated p19A supernatant was incubated with ALI-derived mucus and degraded MUC2 proteins were detected by protein gel and MUC2 Western blot. MUC2 glycosylation was analyzed by protein gel and PAS staining. ALI monolayers were infected with p19A to evaluate mucus degradation and p19A localization by immunostaining. Results The UC-isolated pathobiont p19A infected and exerted cytotoxic effects on apical out healthy and UC patient colonoids. By day 14, ALI monolayers were differentiated and covered by a thick mucus layer as assessed using brightfield microscopy. Mucus removed for mucinase assays was replenished within 7 days. p19A harbours proteins capable of degrading human ALI-, but not mouse ALI-derived mucus, in vitro, suggesting the presence of host-specific mucinases. Mucus produced by UC ALI monolayers showed reduced glycosylation and increased degradation both over time and by p19A proteins. Day 21 ALI-monolayers infected with p19A for 18 hours exhibited overt mucus degradation allowing p19A to infect the underlying epithelium. Conclusions Patient-derived ALI monolayers produce a thick mucus layer that can be used to study pathobiont-mucus interactions. The UC pathobiont p19A disrupts apical out organoids and produces proteins that degrade ALI-derived mucus in vitro, with UC mucus being more susceptible to degradation than mucus from healthy controls. The results from our model suggest a potential mechanism for pathobiont-mediated mucosal barrier disruption in UC patients. Patient-derived ALI monolayer (blue/white) produces a thick mucus layer (green) that can be degraded by the pathobiont p19A (red). Funding Agencies CCC, CIHR
摘要 背景 炎症性肠病（IBD）致病菌是具有致病潜能的共生微生物，可引起或加重 IBD 症状。一些病原菌（如大肠杆菌）在健康肠道内腔中的存活水平较低，但在溃疡性结肠炎（UC）患者的炎性结肠中却能迅速生长。这些病原菌必须穿过将上皮细胞与管腔微生物隔开的结肠粘液屏障（由 MUC2 组成），才能促进疾病的发生。目前还不清楚细菌致病菌是如何穿过 UC 患者的粘液屏障的。目的 我们利用健康和 UC 患者活检获得的结肠器官组织（结肠组织）和气液界面（ALI）单层模型，研究了 UC 分离出的大肠杆菌病原菌 p19A 如何穿过粘液屏障。方法 用 p19A 感染健康结肠和 UC 患者活检提取的结肠组织，以证实这种病原菌对人类结肠细胞产生直接的细胞病理效应。通过对 p19A 的基因组测序，我们发现它含有两种粘液降解蛋白（粘蛋白酶）。我们用健康人和加州大学结肠细胞以及小鼠结肠细胞来生成产生粘液的 ALI 单层细胞。为了检测 p19A 介导的粘液降解，将浓缩的 p19A 上清液与 ALI 衍生的粘液孵育，并通过蛋白凝胶和 MUC2 Western 印迹检测降解的 MUC2 蛋白。通过蛋白凝胶和 PAS 染色分析 MUC2 糖基化。用 p19A 感染 ALI 单层细胞，通过免疫染色法评估粘液降解和 p19A 定位情况。结果 UC 分离出的病原体 p19A 感染了健康结肠和 UC 患者结肠的顶端，并对其产生了细胞毒性作用。到第 14 天，ALI 单层细胞开始分化，并被厚厚的粘液层覆盖，这是用明视野显微镜评估的结果。p19A 含有能在体外降解人 ALI 而非小鼠 ALI 衍生粘液的蛋白质，这表明存在宿主特异性粘蛋白酶。UC ALI 单层产生的粘液显示，随着时间的推移和 p19A 蛋白的作用，糖基化减少，降解增加。第 21 天 ALI 单层细胞感染 p19A 18 小时后，粘液降解明显，p19A 得以感染下层上皮细胞。结论 患者来源的 ALI 单层细胞会产生厚厚的粘液层，可用于研究病原体与粘液之间的相互作用。UC 病原体 p19A 会破坏顶端的器官组织，并在体外产生降解 ALI 衍生粘液的蛋白质，与健康对照组的粘液相比，UC 粘液更容易被降解。我们的模型结果表明了 UC 患者病原体介导的粘膜屏障破坏的潜在机制。患者来源的ALI单层（蓝/白）产生的厚粘液层（绿色）可被病原体p19A（红色）降解。资助机构 CCC、CIHR
{"title":"A24 AN ULCERATIVE COLITIS-ISOLATED PATHOBIONT CAN DEGRADE MUCUS PRODUCED BY UC PATIENT-DERIVED COLONOIDS","authors":"A. Gilliland, Y Chen, D. Tertigas, M. Surette, B. Bressler, B. Vallance","doi":"10.1093/jcag/gwad061.024","DOIUrl":"https://doi.org/10.1093/jcag/gwad061.024","url":null,"abstract":"Abstract Background Inflammatory bowel disease (IBD) pathobionts are commensal microbes with pathogenic potential that may cause or exacerbate IBD symptoms. Some pathobionts (ex. Escherichia coli) reside at low levels in the lumen of a healthy gut but can rapidly grow in the inflamed colons of ulcerative colitis (UC) patients. To promote disease, these pathobionts must cross the colonic mucus barrier (comprised of MUC2) that separates the epithelium from luminal microbes. It is currently unclear how bacterial pathobionts cross the mucus barrier of UC patients. Aims Using healthy and UC patient biopsy-derived colonic organoids (colonoids) and an air liquid interface (ALI) monolayer model, we investigated how the UC-isolated E. coli pathobiont p19A crosses the mucus barrier. Methods Apical out healthy and UC patient biopsy-derived colonoids were infected with p19A to confirm this pathobiont exerts direct cytopathic effects on human colonocytes. Sequencing p19A’s genome, we found it contains two mucus degrading proteins (mucinases). Healthy human and UC colonoids, as well as mouse colonoids, were used to generate mucus-producing ALI monolayers. To detect p19A-mediated mucus degradation, concentrated p19A supernatant was incubated with ALI-derived mucus and degraded MUC2 proteins were detected by protein gel and MUC2 Western blot. MUC2 glycosylation was analyzed by protein gel and PAS staining. ALI monolayers were infected with p19A to evaluate mucus degradation and p19A localization by immunostaining. Results The UC-isolated pathobiont p19A infected and exerted cytotoxic effects on apical out healthy and UC patient colonoids. By day 14, ALI monolayers were differentiated and covered by a thick mucus layer as assessed using brightfield microscopy. Mucus removed for mucinase assays was replenished within 7 days. p19A harbours proteins capable of degrading human ALI-, but not mouse ALI-derived mucus, in vitro, suggesting the presence of host-specific mucinases. Mucus produced by UC ALI monolayers showed reduced glycosylation and increased degradation both over time and by p19A proteins. Day 21 ALI-monolayers infected with p19A for 18 hours exhibited overt mucus degradation allowing p19A to infect the underlying epithelium. Conclusions Patient-derived ALI monolayers produce a thick mucus layer that can be used to study pathobiont-mucus interactions. The UC pathobiont p19A disrupts apical out organoids and produces proteins that degrade ALI-derived mucus in vitro, with UC mucus being more susceptible to degradation than mucus from healthy controls. The results from our model suggest a potential mechanism for pathobiont-mediated mucosal barrier disruption in UC patients. Patient-derived ALI monolayer (blue/white) produces a thick mucus layer (green) that can be degraded by the pathobiont p19A (red). Funding Agencies CCC, CIHR","PeriodicalId":508018,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":"75 3","pages":"13 - 14"},"PeriodicalIF":0.0,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139837799","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}
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