Pub Date : 2023-03-01DOI: 10.1093/jcag/gwac036.109
M. Rai, L. Hookey, R. Bechara
Abstract Background Colonoscopy and polypectomy reduce colorectal cancer incidence and mortality, but is also associated with adverse events, including bleeding. Postpolypectomy delayed bleeding (PPDB) after EMR of large colorectal polyps (≥2cm) has an incidence of 2.6-9.7%. Tranexamic acid is a member of a class of drugs called antifibrinolytic agents. It reduces fibrinolysis by slowing down the conversion of plasminogen to plasmin, which may prevent bleeding. Purpose The goal of this pilot study is to assess the feasibility of using tranexamic acid after EMR of large (≥2 cm) non-pedunculated colorectal polyps (LNPCPs) to prevent PPDB. Method This was a single center feasibility study conducted at the Kingston Health Sciences Center from March 2021 to September 2021. Patients referred for removal of a ≥2cm LNPCP and those who were referred for a positive fecal immunochemical test were approached for consideration of inclusion. Patients with INR ≥ 1.5, platelets <50, higher risk of risk of thromboembolic events (atrial fibrillation on anticoagulation, history of stroke, TIA, pulmonary embolism, deep vein thrombosis hypercoagulable state, mechanical heart valve on anticoagulation, myocardial infarction in the last twelve months), pregnancy or undergoing ESD were not included. Coagulation of submucosal vessels after polypectomy by snare tip coagulation or forceps was performed if thought necessary by the endoscopist. Clipping could be performed only where there was concern for perforation. Intraprocedural bleeding was recorded and managed at the discretion of the endoscopist. After the procedure was completed, 1 gram of TXA in 100mL of normal saline (NS) was infused over a 10-minute interval. The participants received tranexamic acid 1 gram PO TID to be taken for 5 days after the procedure. A post procedure day 5, 14 and 30 phone call was conducted with participants to monitor study drug compliance and adverse events. Result(s) A total of 25 patients were enrolled with a mean polyp size of 3 cm. Baseline patient and polyp characteristics are presented in table 1. 90% of eligible patients approached consented to be in the study. Procedure details are presented in table 2. Intraprocedural bleeding occurred in 7 patients (28%) and all of these were treated with soft coagulation. 2 patients had clipping for muscle injury. All 25 patients received IV TXA post procedure. 16 patients (64%) took every dose of the prescribed pills. 21 patients (84%) took at least 80% of the prescribed TXA pills. 1 patient presented with post polypectomy bleeding. All patients completed the day 30 follow up phone call. There were no adverse events. Image Conclusion(s) TXA to prevent postpolypectomy delayed bleeding (PPDB) was feasible to use with no adverse events reported. All patients received IV TXA post procedure and completed 30 day follow up. However, only 64% of patients took every scheduled dose of medication. A randomized controlled study will be needed to see if TX
{"title":"A109 TRANEXAMIC ACID TO PREVENT BLEEDING AFTER ENDOSCOPIC RESECTION OF LARGE COLORECTAL POLYPS: A PILOT PROJECT","authors":"M. Rai, L. Hookey, R. Bechara","doi":"10.1093/jcag/gwac036.109","DOIUrl":"https://doi.org/10.1093/jcag/gwac036.109","url":null,"abstract":"Abstract Background Colonoscopy and polypectomy reduce colorectal cancer incidence and mortality, but is also associated with adverse events, including bleeding. Postpolypectomy delayed bleeding (PPDB) after EMR of large colorectal polyps (≥2cm) has an incidence of 2.6-9.7%. Tranexamic acid is a member of a class of drugs called antifibrinolytic agents. It reduces fibrinolysis by slowing down the conversion of plasminogen to plasmin, which may prevent bleeding. Purpose The goal of this pilot study is to assess the feasibility of using tranexamic acid after EMR of large (≥2 cm) non-pedunculated colorectal polyps (LNPCPs) to prevent PPDB. Method This was a single center feasibility study conducted at the Kingston Health Sciences Center from March 2021 to September 2021. Patients referred for removal of a ≥2cm LNPCP and those who were referred for a positive fecal immunochemical test were approached for consideration of inclusion. Patients with INR ≥ 1.5, platelets <50, higher risk of risk of thromboembolic events (atrial fibrillation on anticoagulation, history of stroke, TIA, pulmonary embolism, deep vein thrombosis hypercoagulable state, mechanical heart valve on anticoagulation, myocardial infarction in the last twelve months), pregnancy or undergoing ESD were not included. Coagulation of submucosal vessels after polypectomy by snare tip coagulation or forceps was performed if thought necessary by the endoscopist. Clipping could be performed only where there was concern for perforation. Intraprocedural bleeding was recorded and managed at the discretion of the endoscopist. After the procedure was completed, 1 gram of TXA in 100mL of normal saline (NS) was infused over a 10-minute interval. The participants received tranexamic acid 1 gram PO TID to be taken for 5 days after the procedure. A post procedure day 5, 14 and 30 phone call was conducted with participants to monitor study drug compliance and adverse events. Result(s) A total of 25 patients were enrolled with a mean polyp size of 3 cm. Baseline patient and polyp characteristics are presented in table 1. 90% of eligible patients approached consented to be in the study. Procedure details are presented in table 2. Intraprocedural bleeding occurred in 7 patients (28%) and all of these were treated with soft coagulation. 2 patients had clipping for muscle injury. All 25 patients received IV TXA post procedure. 16 patients (64%) took every dose of the prescribed pills. 21 patients (84%) took at least 80% of the prescribed TXA pills. 1 patient presented with post polypectomy bleeding. All patients completed the day 30 follow up phone call. There were no adverse events. Image Conclusion(s) TXA to prevent postpolypectomy delayed bleeding (PPDB) was feasible to use with no adverse events reported. All patients received IV TXA post procedure and completed 30 day follow up. However, only 64% of patients took every scheduled dose of medication. A randomized controlled study will be needed to see if TX","PeriodicalId":17263,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47776137","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 : 2023-03-01DOI: 10.1093/jcag/gwac036.013
S. Tandon, J. Stefanolo, L. Russell, M. D. L. Paz Temprano, S. Niveloni, Eduardo Verdu, D. Armstrong, B. Lebwohl, D. Leffler, J. Tye-Din, A. Day, C. Olano, V. López, L. Uzcanga, E. Madaria, M. Montoro Huguet, S. Vivas, A. Rodríguez-Herrera, G. Makharia, D. Sanders, J. Zeitz, C. Mulder, C. Ciacci, F. Valerio, M. Pinto-Sanchez
Abstract Background Patients with celiac disease (CeD) reported increased COVID-19 vaccine hesitancy due to a fear of adverse events (AEs). However, the risk of AEs post-COVID-19 vaccination in patients with CeD is unknown. Purpose To assess whether the rate of common side effects (SEs) and AEs due to COVID vaccines are higher in patients with CeD compared to a non-CeD population. Method We conducted a collaborative international cross-sectional study in 16 countries between April 2022 and July 2022. An online survey was distributed to patients with CeD through patients’ local societies, and to non-CeD from the general population in each country through social media posts, word-of-mouth, and through academic institutions. We collected data on participant demographics, medical conditions, CeD diagnosis, GFD adherence, history of COVID-19 vaccinations (type and doses) and self-reported SEs and AEs post-COVID-19 vaccine. SEs included pain/swelling at the site, fatigue, fever, chills, nausea and/or headaches. AEs included thrombosis, myocarditis, anaphylactic reaction, and hospitalization related to the vaccine. Logistic regression models were used to assess predictors such as CeD diagnosis, age, gender, vaccine type and comorbidities on the likelihood of reporting SEs and AEs post-vaccine. Result(s) : A total of 17,795 participants completed the survey, 13,638 with CeD (median age of 45[27]) and 4,157 non-CeD controls (median age of 43[20]). There were no significant differences in sex between CeD and controls. Overall, CeD patients had similar odds of SEs compared with non-CeD individuals (aOR=1.02;95% CI=0.92-1.14). SEs were slightly increased only in the second dose of the vaccine in the CeD population compared to non-CeD individuals (aOR= 1.35; 95% CI=1.19-1.53). The most common reported SEs in CeD and controls were pain/swelling at the injection site (29% vs 23 %, p< 0.0001) and fatigue (29% vs 24%, p<0.0001). The odds of SEs were higher with Moderna Spikevax, AstraZeneca/Oxford and Johnson and Johnson vaccines than after the Pfizer vaccine (p< 0.0001). The overall rate of AEs post-vaccine was similar between patients with CeD and non-CeD individuals (aOR= 1.29; 95% CI= 0.89-1.87). Overall, female gender, older age, GFD adherence, respiratory conditions, obesity and receiving immunosuppressive medications increased the odds of SEs, while only age and a history of allergies increased the odds of AEs. Conclusion(s) In this large international study, patients with CeD reported similar rates of SEs and AEs post-COVID vaccine compared to non-CeD individuals. This information is highly relevant as it addresses the main concern leading to COVID-19 vaccine hesitancy in CeD patients. Disclosure of Interest None Declared
{"title":"A13 THE RATE OF ADVERSE EVENTS AFTER COVID-19 VACCINATION IS SIMILAR IN PATIENTS WITH CELIAC DISEASE AND NON-CELIAC POPULATION: RESULTS OF A LARGE INTERNATIONAL CROSS-SECTIONAL STUDY","authors":"S. Tandon, J. Stefanolo, L. Russell, M. D. L. Paz Temprano, S. Niveloni, Eduardo Verdu, D. Armstrong, B. Lebwohl, D. Leffler, J. Tye-Din, A. Day, C. Olano, V. López, L. Uzcanga, E. Madaria, M. Montoro Huguet, S. Vivas, A. Rodríguez-Herrera, G. Makharia, D. Sanders, J. Zeitz, C. Mulder, C. Ciacci, F. Valerio, M. Pinto-Sanchez","doi":"10.1093/jcag/gwac036.013","DOIUrl":"https://doi.org/10.1093/jcag/gwac036.013","url":null,"abstract":"Abstract Background Patients with celiac disease (CeD) reported increased COVID-19 vaccine hesitancy due to a fear of adverse events (AEs). However, the risk of AEs post-COVID-19 vaccination in patients with CeD is unknown. Purpose To assess whether the rate of common side effects (SEs) and AEs due to COVID vaccines are higher in patients with CeD compared to a non-CeD population. Method We conducted a collaborative international cross-sectional study in 16 countries between April 2022 and July 2022. An online survey was distributed to patients with CeD through patients’ local societies, and to non-CeD from the general population in each country through social media posts, word-of-mouth, and through academic institutions. We collected data on participant demographics, medical conditions, CeD diagnosis, GFD adherence, history of COVID-19 vaccinations (type and doses) and self-reported SEs and AEs post-COVID-19 vaccine. SEs included pain/swelling at the site, fatigue, fever, chills, nausea and/or headaches. AEs included thrombosis, myocarditis, anaphylactic reaction, and hospitalization related to the vaccine. Logistic regression models were used to assess predictors such as CeD diagnosis, age, gender, vaccine type and comorbidities on the likelihood of reporting SEs and AEs post-vaccine. Result(s) : A total of 17,795 participants completed the survey, 13,638 with CeD (median age of 45[27]) and 4,157 non-CeD controls (median age of 43[20]). There were no significant differences in sex between CeD and controls. Overall, CeD patients had similar odds of SEs compared with non-CeD individuals (aOR=1.02;95% CI=0.92-1.14). SEs were slightly increased only in the second dose of the vaccine in the CeD population compared to non-CeD individuals (aOR= 1.35; 95% CI=1.19-1.53). The most common reported SEs in CeD and controls were pain/swelling at the injection site (29% vs 23 %, p< 0.0001) and fatigue (29% vs 24%, p<0.0001). The odds of SEs were higher with Moderna Spikevax, AstraZeneca/Oxford and Johnson and Johnson vaccines than after the Pfizer vaccine (p< 0.0001). The overall rate of AEs post-vaccine was similar between patients with CeD and non-CeD individuals (aOR= 1.29; 95% CI= 0.89-1.87). Overall, female gender, older age, GFD adherence, respiratory conditions, obesity and receiving immunosuppressive medications increased the odds of SEs, while only age and a history of allergies increased the odds of AEs. Conclusion(s) In this large international study, patients with CeD reported similar rates of SEs and AEs post-COVID vaccine compared to non-CeD individuals. This information is highly relevant as it addresses the main concern leading to COVID-19 vaccine hesitancy in CeD patients. Disclosure of Interest None Declared","PeriodicalId":17263,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46868280","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 : 2023-03-01DOI: 10.1093/jcag/gwac036.146
R. Winter, A. Ilnyckyj
Abstract Background We report a case of a benign gastric ulcer (GU) complicated by gastrojenunal (GJ) fistulization which healed with proton-pump inhibitor (PPI) therapy. It presented in an elderly malnourished patient. Purpose To highlight this rare complication of benign peptic ulcer disease, as only 13 similar cases are reported. Additionally, our case is one of the few demonstrating medical treatment can effectively heal both the ulcer and GJ fistula, thus obviating the need for surgery. Method A detailed chart review was conducted to summarize all salient clinical data. Using PubMed database, a comprehensive literature review identified similar cases using MeSH terms such as “gastrojejunal”, “fistula”, and “ulcer” under the case report filter. Result(s) An 83-year-old previously healthy woman presented with four weeks of weakness, abdominal pain, and nausea. She denied any overt GI bleeding or NSAID use. Physical exam demonstrated cachexia (36.6kg) with benign abdominal and rectal examinations. Initial workup revealed anemia (hemoglobin of 38g/L), iron deficiency, hypoalbuminemia (20g/L) and depleted B12 (108pmol/L). She was started on IV pantoprazole and transfused 3 units of red cells. A gastroscopy revealed a giant, penetrating gastric ulcer at the lesser curvature. The ulcer base showed protruding tissue consistent with a segment of intestine (Figure 1 - left image). Examination to the distal duodenum was normal. Biopsies of the ulcer edge were negative for neoplasia. Urease testing of antrum and body samples were negative. CT scan demonstrated a 3.1 cm gastric ulcer with a linear tract communicating with the proximal jejunum, confirming the endoscopic impression. Surgical consultation was obtained; conservative treatment was advised given her age and cachexia. Calorie intake was optimized and the patient commenced twice daily PPI. She rapidly gained 7 kg in the community, accompanied by normalization of albumin (33g/L) and B12 (293 pmol/L) levels. Hemoglobin remained stable near 100g/L after initial transfusion. At month three, repeat gastroscopy was performed. The ulcer and fistula had completely healed. (Figure 1 - right image). Image Conclusion(s) Gastro-enteric fistulas complicating benign ulcers are rare. When described, other sites, such as gastroduodenal, are more common. Direct gastrojejunal fistulization is less favorable due to the anatomy of the mesentery. The literature reports only 13 gastrojejunal fistulas complicating benign ulcers. In other cases, unique risk factors are reported (malignancy, prior gastric surgery). Only 3 of 13 reported cases resolved with medication alone. The overwhelming majority required surgery. Notably, many of the case reports pre-date the introduction of proton-pump inhibitors. The etiology of our patient’s ulcer was benign but remains undefined. ASA use was excluded on history, and H. pylori sampling was negative. We speculate profound malnutrition placed her at risk for poor healing and thus c
{"title":"A146 BENIGN GASTRIC ULCER COMPLICATED BY GASTROJEJUNAL FISTULA FORMATION HEALED WITH PROTON-PUMP INHIBITOR","authors":"R. Winter, A. Ilnyckyj","doi":"10.1093/jcag/gwac036.146","DOIUrl":"https://doi.org/10.1093/jcag/gwac036.146","url":null,"abstract":"Abstract Background We report a case of a benign gastric ulcer (GU) complicated by gastrojenunal (GJ) fistulization which healed with proton-pump inhibitor (PPI) therapy. It presented in an elderly malnourished patient. Purpose To highlight this rare complication of benign peptic ulcer disease, as only 13 similar cases are reported. Additionally, our case is one of the few demonstrating medical treatment can effectively heal both the ulcer and GJ fistula, thus obviating the need for surgery. Method A detailed chart review was conducted to summarize all salient clinical data. Using PubMed database, a comprehensive literature review identified similar cases using MeSH terms such as “gastrojejunal”, “fistula”, and “ulcer” under the case report filter. Result(s) An 83-year-old previously healthy woman presented with four weeks of weakness, abdominal pain, and nausea. She denied any overt GI bleeding or NSAID use. Physical exam demonstrated cachexia (36.6kg) with benign abdominal and rectal examinations. Initial workup revealed anemia (hemoglobin of 38g/L), iron deficiency, hypoalbuminemia (20g/L) and depleted B12 (108pmol/L). She was started on IV pantoprazole and transfused 3 units of red cells. A gastroscopy revealed a giant, penetrating gastric ulcer at the lesser curvature. The ulcer base showed protruding tissue consistent with a segment of intestine (Figure 1 - left image). Examination to the distal duodenum was normal. Biopsies of the ulcer edge were negative for neoplasia. Urease testing of antrum and body samples were negative. CT scan demonstrated a 3.1 cm gastric ulcer with a linear tract communicating with the proximal jejunum, confirming the endoscopic impression. Surgical consultation was obtained; conservative treatment was advised given her age and cachexia. Calorie intake was optimized and the patient commenced twice daily PPI. She rapidly gained 7 kg in the community, accompanied by normalization of albumin (33g/L) and B12 (293 pmol/L) levels. Hemoglobin remained stable near 100g/L after initial transfusion. At month three, repeat gastroscopy was performed. The ulcer and fistula had completely healed. (Figure 1 - right image). Image Conclusion(s) Gastro-enteric fistulas complicating benign ulcers are rare. When described, other sites, such as gastroduodenal, are more common. Direct gastrojejunal fistulization is less favorable due to the anatomy of the mesentery. The literature reports only 13 gastrojejunal fistulas complicating benign ulcers. In other cases, unique risk factors are reported (malignancy, prior gastric surgery). Only 3 of 13 reported cases resolved with medication alone. The overwhelming majority required surgery. Notably, many of the case reports pre-date the introduction of proton-pump inhibitors. The etiology of our patient’s ulcer was benign but remains undefined. ASA use was excluded on history, and H. pylori sampling was negative. We speculate profound malnutrition placed her at risk for poor healing and thus c","PeriodicalId":17263,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48786030","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 : 2023-03-01DOI: 10.1093/jcag/gwac036.024
J. Pei, S. J. Recinto, A. MacDonald, C. Gavino, L. Trudeau, M. Desjardins, J. Stratton, S. Gruenheid
Abstract Background Intestinal epithelial cells (IECs) provide an essential physical barrier between harsh luminal contents and underlying host tissue. The maintenance of intestinal homeostasis in this rapidly renewing tissue 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 dysfunction. For instance, constipation and increased bowel permeability are frequently observed years prior to development of motor dysfunction in PD, people with inflammatory bowel disease are more likely to develop PD, and a positive correlation exists between gastrointestinal infections and PD incidence. Our group recently 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. Purpose Investigate the impact of Pink1 and other PD-associated genes in IECs under steady state and infection. Method Single-cell RNA sequencing was performed on IECs isolated from Pink1 WT and KO mice, at steady state and following in vivo C. rodentium infection. Mice were sacrificed at an early timepoint of infection (day 6) to elucidate transcriptional differences between epithelial lineages of each genotype. Additionally, ex vivo colonoids were derived from primary mouse tissue and treated with lipopolysaccharide (LPS) to determine how PINK1 loss-of-function affects the inflammatory response of the epithelium. Result(s) Our data revealed that loss-of-function of PINK1 profoundly affected the ISC compartment and several epithelial lineages. Specifically, ISCs from infected Pink1 KO mice demonstrated differentially regulated proliferative and cell cycle genes, while transit amplifying cells showed dysregulated expression of tight junction genes, and enterocytes displayed differentially expressed oxidative damage and apoptotic genes. Preliminary data from colonoids showed that Pink1 KO mice, when stimulated with LPS, had increased pro-inflammatory cytokine gene expression. Conclusion(s) In Pink1 KO intestinal epithelial cells, there is indeed an altered cellular response upon infection in vivo and LPS treatment ex vivo. However, more information is needed to decern the mechanistic role of IECs in PD. By investigating the role of PD genes in the gastrointestinal tract, these studies carry important implications for understanding the initiation and progression of PD. Disclosure of Inter
{"title":"A24 INVESTIGATING THE IMPACT OF PARKINSON’S DISEASE-ASSOCIATED GENES ON INTESTINAL HOMEOSTASIS","authors":"J. Pei, S. J. Recinto, A. MacDonald, C. Gavino, L. Trudeau, M. Desjardins, J. Stratton, S. Gruenheid","doi":"10.1093/jcag/gwac036.024","DOIUrl":"https://doi.org/10.1093/jcag/gwac036.024","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 in this rapidly renewing tissue 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 dysfunction. For instance, constipation and increased bowel permeability are frequently observed years prior to development of motor dysfunction in PD, people with inflammatory bowel disease are more likely to develop PD, and a positive correlation exists between gastrointestinal infections and PD incidence. Our group recently 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. Purpose Investigate the impact of Pink1 and other PD-associated genes in IECs under steady state and infection. Method Single-cell RNA sequencing was performed on IECs isolated from Pink1 WT and KO mice, at steady state and following in vivo C. rodentium infection. Mice were sacrificed at an early timepoint of infection (day 6) to elucidate transcriptional differences between epithelial lineages of each genotype. Additionally, ex vivo colonoids were derived from primary mouse tissue and treated with lipopolysaccharide (LPS) to determine how PINK1 loss-of-function affects the inflammatory response of the epithelium. Result(s) Our data revealed that loss-of-function of PINK1 profoundly affected the ISC compartment and several epithelial lineages. Specifically, ISCs from infected Pink1 KO mice demonstrated differentially regulated proliferative and cell cycle genes, while transit amplifying cells showed dysregulated expression of tight junction genes, and enterocytes displayed differentially expressed oxidative damage and apoptotic genes. Preliminary data from colonoids showed that Pink1 KO mice, when stimulated with LPS, had increased pro-inflammatory cytokine gene expression. Conclusion(s) In Pink1 KO intestinal epithelial cells, there is indeed an altered cellular response upon infection in vivo and LPS treatment ex vivo. However, more information is needed to decern the mechanistic role of IECs in PD. By investigating the role of PD genes in the gastrointestinal tract, these studies carry important implications for understanding the initiation and progression of PD. Disclosure of Inter","PeriodicalId":17263,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48693110","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 : 2023-03-01DOI: 10.1093/jcag/gwac036.123
R. Djinbachian, M. Taghiakbari, C. Haumesser, M. Zarandi-Nowroozi, M. Abou-Khalil, S. Sidani, J. Liu, B. Panzini, D. von Renteln
Abstract Background Accurate polyp size measurement is important for guideline conforming choice of polypectomy techniques and subsequent surveillance interval assignments. Some endoscopic tools (forceps or endoscopic rulers [ER]) exist to help with visual size estimation. A virtual scale endoscope (VSE) has been developed that allows superimposing a virtual measurement scale during live endoscopies. Purpose Our aim was to evaluate the performance of VSE when compared to ER and forceps-based measurement. Method We conducted a randomized trial to evaluate the relative accuracy of size measurement of simulated colorectal polyps when using: VSE, ER, and forceps. Six endoscopists performed 60 measurements randomized at a 1:1:1 ratio using each method. Primary outcome was relative accuracy in polyp size measurement. Secondary outcomes included misclassification of sizes at the 5, 10, and 20mm thresholds. Result(s) A total of 360 measurements were performed. The relative accuracy of biopsy forceps, ER, and VSE was 78.9% (95%CI=76.2-81.5), 78.4% (95%CI=76.0-80.8), and 82.7% (95%CI=80.8-84.8). VSE had significantly higher accuracy compared to biopsy forceps (p=0.02) and ER (p=0.006). VSE misclassified a lower percentage of polyps >5mm as ≤5mm (9.4%) compared to forceps (15.7%) and ER (20.9%). VSE misclassified a lower percentage of ≥20mm polyps as <20mm (8.3%) compared with forceps (66.7%) and ER (75.0%). 25.6%, 25.5%, and 22.5% of polyps ≥10mm were misclassified as <10mm with ER, forceps, and VSE, respectively. Conclusion(s) VSE had significantly higher relative accuracy in measuring polyps compared to ER or forceps assisted measurement. VSE improves correct classification of polyps at clinically important size thresholds. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest R. Djinbachian: None Declared, M. Taghiakbari: None Declared, C. Haumesser: None Declared, M. Zarandi-Nowroozi: None Declared, M. Abou-Khalil: None Declared, S. Sidani: None Declared, J. Liu: None Declared, B. Panzini: None Declared, D. von Renteln Grant / Research support from: Daniel von Renteln is supported by a “Fonds de Recherche du Québec Santé” (FRQS) career development award and has received research funding from ERBE, Ventage, Pendopharm, Fujifilm, and Pentax., Consultant of: Boston Scientific and Pendopharm,
背景准确的息肉大小测量对于息肉切除技术的指导选择和随后的监测间隔分配是重要的。一些内窥镜工具(钳或内窥镜尺子[ER])存在，以帮助视觉大小估计。一种虚拟尺度内窥镜(VSE)已经开发出来，可以在实时内窥镜检查中叠加虚拟测量尺度。我们的目的是评估VSE与ER和基于钳的测量相比的性能。方法我们进行了一项随机试验，评估使用VSE, ER和钳时模拟结肠息肉大小测量的相对准确性。6名内窥镜医师使用每种方法按1:1:1的比例随机进行60次测量。主要结果是息肉大小测量的相对准确性。次要结局包括5、10和20mm阈值的大小分类错误。结果共进行了360次测量。活检钳、ER和VSE的相对准确度分别为78.9% (95%CI=76.2-81.5)、78.4% (95%CI=76.0-80.8)和82.7% (95%CI=80.8-84.8)。与活检钳(p=0.02)和ER (p=0.006)相比，VSE具有更高的准确性。与钳(15.7%)和ER(20.9%)相比，VSE将bb0 mm息肉误诊为≤5mm的比例较低(9.4%)。VSE将≥20mm息肉误诊为<20mm的比例(8.3%)低于钳(66.7%)和ER(75.0%)。≥10mm的息肉，分别有25.6%、25.5%和22.5%被ER、钳和VSE误分类为<10mm。结论VSE测量息肉的相对准确度明显高于ER或钳辅助测量。VSE提高了临床上重要的息肉大小阈值的正确分类。请在以下适用框中确认所有资助机构的利益披露:R. Djinbachian:未申报，M. Taghiakbari:未申报，C. Haumesser:未申报，M. Zarandi-Nowroozi:未申报，M. Abou-Khalil:未申报，S. Sidani:未申报，J. Liu:未申报，B. Panzini:未申报，D. von RentelnDaniel von Renteln获得了“职业发展基金会”(FRQS)职业发展奖的支持，并获得了ERBE、Ventage、Pendopharm、Fujifilm和Pentax的研究资助。，波士顿科学与Pendopharm顾问，
{"title":"A123 COMPARING SIZE MEASUREMENT OF SIMULATED COLORECTAL POLYPS WHEN USING A NOVEL VIRTUAL SCALE ENDOSCOPE, ENDOSCOPIC RULER OR FORCEPS: A BLINDED RANDOMIZED TRIAL","authors":"R. Djinbachian, M. Taghiakbari, C. Haumesser, M. Zarandi-Nowroozi, M. Abou-Khalil, S. Sidani, J. Liu, B. Panzini, D. von Renteln","doi":"10.1093/jcag/gwac036.123","DOIUrl":"https://doi.org/10.1093/jcag/gwac036.123","url":null,"abstract":"Abstract Background Accurate polyp size measurement is important for guideline conforming choice of polypectomy techniques and subsequent surveillance interval assignments. Some endoscopic tools (forceps or endoscopic rulers [ER]) exist to help with visual size estimation. A virtual scale endoscope (VSE) has been developed that allows superimposing a virtual measurement scale during live endoscopies. Purpose Our aim was to evaluate the performance of VSE when compared to ER and forceps-based measurement. Method We conducted a randomized trial to evaluate the relative accuracy of size measurement of simulated colorectal polyps when using: VSE, ER, and forceps. Six endoscopists performed 60 measurements randomized at a 1:1:1 ratio using each method. Primary outcome was relative accuracy in polyp size measurement. Secondary outcomes included misclassification of sizes at the 5, 10, and 20mm thresholds. Result(s) A total of 360 measurements were performed. The relative accuracy of biopsy forceps, ER, and VSE was 78.9% (95%CI=76.2-81.5), 78.4% (95%CI=76.0-80.8), and 82.7% (95%CI=80.8-84.8). VSE had significantly higher accuracy compared to biopsy forceps (p=0.02) and ER (p=0.006). VSE misclassified a lower percentage of polyps >5mm as ≤5mm (9.4%) compared to forceps (15.7%) and ER (20.9%). VSE misclassified a lower percentage of ≥20mm polyps as <20mm (8.3%) compared with forceps (66.7%) and ER (75.0%). 25.6%, 25.5%, and 22.5% of polyps ≥10mm were misclassified as <10mm with ER, forceps, and VSE, respectively. Conclusion(s) VSE had significantly higher relative accuracy in measuring polyps compared to ER or forceps assisted measurement. VSE improves correct classification of polyps at clinically important size thresholds. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest R. Djinbachian: None Declared, M. Taghiakbari: None Declared, C. Haumesser: None Declared, M. Zarandi-Nowroozi: None Declared, M. Abou-Khalil: None Declared, S. Sidani: None Declared, J. Liu: None Declared, B. Panzini: None Declared, D. von Renteln Grant / Research support from: Daniel von Renteln is supported by a “Fonds de Recherche du Québec Santé” (FRQS) career development award and has received research funding from ERBE, Ventage, Pendopharm, Fujifilm, and Pentax., Consultant of: Boston Scientific and Pendopharm,","PeriodicalId":17263,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45064278","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 : 2023-03-01DOI: 10.1093/jcag/gwac036.114
M. R. Fujiyoshi, Y. Fujiyoshi, N. Gimpaya, R. Bechara, T. Jeyalingam, N. Calo, N. Forbes, Ryan Basith Fasih Khan, M. Atalla, A. Toshimori, Y. Shimamura, M. Tanabe, J. Mosko, H. Inoue, S. Grover
Abstract Background Magnification endoscopy and magnification narrow-band imaging are image enhanced endoscopy technologies that may allow for the diagnosis of advanced neoplasia in the GI tract on the basis of imaging characteristics. Recently, the Unified Magnifying Endoscopic Classification (UMEC) has been developed, which unified the criteria for the esophagus, stomach, and colon. UMEC divides optical diagnosis into one of the three categories: non-neoplastic, intramucosal neoplasia, and deep submucosal invasive cancer. Purpose The objective of this study is to educate North American endoscopists on the use of the UMEC schema, and to ascertain performance of the UMEC framework among North American endoscopists. Method Using UMEC, five North American endoscopists (>1000 procedures) without prior training in magnifying endoscopy independently diagnosed previously collected endoscopic image set of the esophagus, stomach, and colon. The endoscopists were trained on the use of UMEC via an eleven-minute training video with exemplars of each element of UMEC from esophagus, stomach, and colon. All endoscopists were blinded to white-light and non-magnifying NBI findings as well as histopathological diagnosis. The diagnostic performance of UMEC was assessed while using the gold standard histopathology as a reference. Result(s) A total of 299 gastrointestinal lesions (77 esophagus, 92 stomach, and 130 colon) were assessed using UMEC. For esophageal squamous cell carcinoma, the sensitivity, specificity, and accuracy for all 5 endoscopists ranged from 65.2% (95% CI: 50.9–77.9) to 87.0% (95% CI: 75.3–94.6), 77.4% (95% CI: 60.9–89.6) to 96.8% (95% CI: 86.8–99.8), and 75.3% to 87.0%, respectively. For gastric adenocarcinoma, the sensitivity, specificity, and accuracy for all 5 endoscopists ranged from 94.9% (95% CI: 85.0–99.1) to 100%, 52.9% (95% CI: 39.4–66.2) to 92.2% (95% CI: 82.7–97.5), and 73.3% to 93.3%, respectively. For colorectal adenocarcinoma, the sensitivity, specificity, and accuracy for all 5 endoscopists ranged from 76.2% (95% CI: 62.0–87.3) to 83.3% (95% CI: 70.3–92.5), 89.7% (95% CI: 82.1–94.9) to 97.7% (95% CI: 93.1–99.6), and 86.8% to 90.7%, respectively. Image Conclusion(s) UMEC is a simple and practical classification that can be used to introduce and educate endoscopists to magnification narrow-band imaging and optical diagnosis. Please acknowledge all funding agencies by checking the applicable boxes below CAG Disclosure of Interest M. R. A. Fujiyoshi Grant / Research support from: 2022 CAG/AbbVie Education Research Grant, Y. Fujiyoshi: None Declared, N. Gimpaya: None Declared, R. Bechara: None Declared, T. Jeyalingam: None Declared, N. Calo: None Declared, N. Forbes: None Declared, R. Khan: None Declared, M. Atalla: None Declared, A. Toshimori: None Declared, Y. Shimamura: None Declared, M. Tanabe: None Declared, J. Mosko: None Declared, H. Inoue: None Declared, S. Grover: None Declared
{"title":"A114 UNIFIED MAGNIFYING ENDOSCOPIC CLASSIFICATION (UMEC) FOR GASTROINTESTINAL LESIONS: A NORTH AMERICAN EDUCATION STUDY","authors":"M. R. Fujiyoshi, Y. Fujiyoshi, N. Gimpaya, R. Bechara, T. Jeyalingam, N. Calo, N. Forbes, Ryan Basith Fasih Khan, M. Atalla, A. Toshimori, Y. Shimamura, M. Tanabe, J. Mosko, H. Inoue, S. Grover","doi":"10.1093/jcag/gwac036.114","DOIUrl":"https://doi.org/10.1093/jcag/gwac036.114","url":null,"abstract":"Abstract Background Magnification endoscopy and magnification narrow-band imaging are image enhanced endoscopy technologies that may allow for the diagnosis of advanced neoplasia in the GI tract on the basis of imaging characteristics. Recently, the Unified Magnifying Endoscopic Classification (UMEC) has been developed, which unified the criteria for the esophagus, stomach, and colon. UMEC divides optical diagnosis into one of the three categories: non-neoplastic, intramucosal neoplasia, and deep submucosal invasive cancer. Purpose The objective of this study is to educate North American endoscopists on the use of the UMEC schema, and to ascertain performance of the UMEC framework among North American endoscopists. Method Using UMEC, five North American endoscopists (>1000 procedures) without prior training in magnifying endoscopy independently diagnosed previously collected endoscopic image set of the esophagus, stomach, and colon. The endoscopists were trained on the use of UMEC via an eleven-minute training video with exemplars of each element of UMEC from esophagus, stomach, and colon. All endoscopists were blinded to white-light and non-magnifying NBI findings as well as histopathological diagnosis. The diagnostic performance of UMEC was assessed while using the gold standard histopathology as a reference. Result(s) A total of 299 gastrointestinal lesions (77 esophagus, 92 stomach, and 130 colon) were assessed using UMEC. For esophageal squamous cell carcinoma, the sensitivity, specificity, and accuracy for all 5 endoscopists ranged from 65.2% (95% CI: 50.9–77.9) to 87.0% (95% CI: 75.3–94.6), 77.4% (95% CI: 60.9–89.6) to 96.8% (95% CI: 86.8–99.8), and 75.3% to 87.0%, respectively. For gastric adenocarcinoma, the sensitivity, specificity, and accuracy for all 5 endoscopists ranged from 94.9% (95% CI: 85.0–99.1) to 100%, 52.9% (95% CI: 39.4–66.2) to 92.2% (95% CI: 82.7–97.5), and 73.3% to 93.3%, respectively. For colorectal adenocarcinoma, the sensitivity, specificity, and accuracy for all 5 endoscopists ranged from 76.2% (95% CI: 62.0–87.3) to 83.3% (95% CI: 70.3–92.5), 89.7% (95% CI: 82.1–94.9) to 97.7% (95% CI: 93.1–99.6), and 86.8% to 90.7%, respectively. Image Conclusion(s) UMEC is a simple and practical classification that can be used to introduce and educate endoscopists to magnification narrow-band imaging and optical diagnosis. Please acknowledge all funding agencies by checking the applicable boxes below CAG Disclosure of Interest M. R. A. Fujiyoshi Grant / Research support from: 2022 CAG/AbbVie Education Research Grant, Y. Fujiyoshi: None Declared, N. Gimpaya: None Declared, R. Bechara: None Declared, T. Jeyalingam: None Declared, N. Calo: None Declared, N. Forbes: None Declared, R. Khan: None Declared, M. Atalla: None Declared, A. Toshimori: None Declared, Y. Shimamura: None Declared, M. Tanabe: None Declared, J. Mosko: None Declared, H. Inoue: None Declared, S. Grover: None Declared","PeriodicalId":17263,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48147829","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 : 2023-03-01DOI: 10.1093/jcag/gwac036.041
L. Khendek, V. Molina, N. Laverdure, K. Abukasm, S. Khullar, M. Lachaud, J. DuBois, D. Dal Soglio, J. Miró, A. Fournier, M. Paganelli
Abstract Background Non-invasive assessment of Fontan Associated Liver Disease (FALD) is of interest, but studies have yielded inconsistent results about the correlation of severity of disease with laboratory values and imaging. Transient elastography (TE) is a non-invasive imaging modality used commonly for liver stiffness measurement (LSM) and in Fontan patients it is hypothesized to reflect not only liver fibrosis but also venous congestion. Purpose To better define the potential role of TE for non-invasive assessment of the severity of FALD. Method This was a retrospective study conducted on patients’ medical records at CHU Sainte-Justine Hospital. Patients less than 18 years of age with FALD who had at undergone at least one LSM by TE between 1998-2021 were included. The relationship between LSM and liver function tests, hepatic ultrasound findings (including a cirrhosis score), cardiac catheterization results and histological fibrosis scores were analyzed. The impact of interventions during cardiac catherization on LSM were also studied. Result(s) A total of 54 patients (36 boys and 18 girls) with FALD were studied. Median age at Fontan surgery was 4.6 years (IQR 4.0 ─ 5.4 years). Higher LSM values significantly correlated with longer time from Fontan, higher total and direct bilirubin and GGT levels, higher INR, longer APTT, lower Factor V, and lower absolute lymphocyte count. Greater LSM was also significantly associated with the presence of heterogenous parenchymal echogenicity, irregular liver contours and greater ultrasonographic cirrhosis scores. Higher TE values were significantly correlated with higher wedged hepatic venous pressure and Fontan pressure. After catherization interventions that addressed stenoses, there was a statistically significant reduction in mean LSM (24.9±3.63 kPa vs 15.8±4.6 kPa, p=0.005). After closure of significant pulmonary collaterals, mean LSM tended to increase, but this difference did not reach statistical significance (19.1±1.9 kPa vs 24.6±3.5 kPa, p=0.2). At liver biopsy, significant direct correlation was found between LSM and the grade of sinusoidal fibrosis and LSM. TE with values >20 kPa were found to have higher grades of sinusoidal fibrosis, while values <20kPa had higher grades of sinusoidal dilatation. Conclusion(s) This study showed that TE allows to identify patients with higher cholestatic parameters, more severe liver fibrosis at biopsy and sonographic signs suggestive of cirrhosis. Moreover, it confirmed that liver congestion significantly contributes to LSM values. Interestingly, catheter interventions addressing pulmonary stenoses led to the improvement of TE measurements, giving hope for the reduction of hepatic venous congestion in these patients, which might have an effect on their FALD. Finally, the LSM threshold of 20 kPa could be useful clinically as a value above which fibrosis is likely to be significant, while if below could indicate a greater contribution from hepatic congesti
背景Fontan相关性肝病(FALD)的无创评估引起了人们的兴趣，但关于疾病严重程度与实验室值和影像学的相关性，研究结果不一致。瞬时弹性成像(TE)是一种非侵入性成像方式，通常用于肝刚度测量(LSM)，在Fontan患者中，它不仅可以反映肝纤维化，还可以反映静脉充血。目的更好地确定TE在无创评估FALD严重程度中的潜在作用。方法对朱棣文圣贾斯汀医院的患者病历进行回顾性研究。年龄小于18岁的FALD患者在1998-2021年间至少接受过一次TE LSM。分析LSM与肝功能检查、肝脏超声检查结果(包括肝硬化评分)、心导管检查结果和组织学纤维化评分之间的关系。我们还研究了心导管期间干预措施对LSM的影响。结果共研究了54例FALD患者，其中男36例，女18例。Fontan手术的中位年龄为4.6岁(IQR 4.0 ~ 5.4岁)。较高的LSM值与较长的Fontan时间、较高的总胆红素和直接胆红素及GGT水平、较高的INR、较长的APTT、较低的Factor V和较低的绝对淋巴细胞计数显著相关。LSM越大，实质回声不均匀、肝脏轮廓不规则和肝硬化超声评分也越高。较高的TE值与较高的楔形肝静脉压和Fontan压显著相关。导管介入治疗狭窄后，平均LSM降低有统计学意义(24.9±3.63 kPa vs 15.8±4.6 kPa, p=0.005)。重要肺侧枝关闭后，平均LSM有升高的趋势，但差异无统计学意义(19.1±1.9 kPa vs 24.6±3.5 kPa, p=0.2)。肝活检发现LSM与肝窦纤维化和LSM的分级有显著的直接相关性。值bbb20 kPa的TE有较高程度的窦性纤维化，值<20kPa的TE有较高程度的窦性扩张。结论(5)本研究表明，TE可以识别出胆汁淤积参数较高、活检时肝纤维化较严重以及提示肝硬化的超声征象的患者。进一步证实肝脏充血对LSM值有显著影响。有趣的是，针对肺狭窄的导管干预导致TE测量的改善，为减少这些患者的肝静脉充血带来了希望，这可能对他们的FALD有影响。最后，20 kPa的LSM阈值在临床上可能是有用的，因为超过该值，纤维化可能很明显，而低于该值则可能表明肝充血的贡献更大。请勾选以下适用的方框，确认所有资助机构
{"title":"A41 FONTAN ASSOCIATED LIVER DISEASE: THE ROLE OF TRANSIENT ELASTOGRAPHY IN CHILDREN AND ADOLESCENTS","authors":"L. Khendek, V. Molina, N. Laverdure, K. Abukasm, S. Khullar, M. Lachaud, J. DuBois, D. Dal Soglio, J. Miró, A. Fournier, M. Paganelli","doi":"10.1093/jcag/gwac036.041","DOIUrl":"https://doi.org/10.1093/jcag/gwac036.041","url":null,"abstract":"Abstract Background Non-invasive assessment of Fontan Associated Liver Disease (FALD) is of interest, but studies have yielded inconsistent results about the correlation of severity of disease with laboratory values and imaging. Transient elastography (TE) is a non-invasive imaging modality used commonly for liver stiffness measurement (LSM) and in Fontan patients it is hypothesized to reflect not only liver fibrosis but also venous congestion. Purpose To better define the potential role of TE for non-invasive assessment of the severity of FALD. Method This was a retrospective study conducted on patients’ medical records at CHU Sainte-Justine Hospital. Patients less than 18 years of age with FALD who had at undergone at least one LSM by TE between 1998-2021 were included. The relationship between LSM and liver function tests, hepatic ultrasound findings (including a cirrhosis score), cardiac catheterization results and histological fibrosis scores were analyzed. The impact of interventions during cardiac catherization on LSM were also studied. Result(s) A total of 54 patients (36 boys and 18 girls) with FALD were studied. Median age at Fontan surgery was 4.6 years (IQR 4.0 ─ 5.4 years). Higher LSM values significantly correlated with longer time from Fontan, higher total and direct bilirubin and GGT levels, higher INR, longer APTT, lower Factor V, and lower absolute lymphocyte count. Greater LSM was also significantly associated with the presence of heterogenous parenchymal echogenicity, irregular liver contours and greater ultrasonographic cirrhosis scores. Higher TE values were significantly correlated with higher wedged hepatic venous pressure and Fontan pressure. After catherization interventions that addressed stenoses, there was a statistically significant reduction in mean LSM (24.9±3.63 kPa vs 15.8±4.6 kPa, p=0.005). After closure of significant pulmonary collaterals, mean LSM tended to increase, but this difference did not reach statistical significance (19.1±1.9 kPa vs 24.6±3.5 kPa, p=0.2). At liver biopsy, significant direct correlation was found between LSM and the grade of sinusoidal fibrosis and LSM. TE with values >20 kPa were found to have higher grades of sinusoidal fibrosis, while values <20kPa had higher grades of sinusoidal dilatation. Conclusion(s) This study showed that TE allows to identify patients with higher cholestatic parameters, more severe liver fibrosis at biopsy and sonographic signs suggestive of cirrhosis. Moreover, it confirmed that liver congestion significantly contributes to LSM values. Interestingly, catheter interventions addressing pulmonary stenoses led to the improvement of TE measurements, giving hope for the reduction of hepatic venous congestion in these patients, which might have an effect on their FALD. Finally, the LSM threshold of 20 kPa could be useful clinically as a value above which fibrosis is likely to be significant, while if below could indicate a greater contribution from hepatic congesti","PeriodicalId":17263,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47140186","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 : 2023-03-01DOI: 10.1093/jcag/gwac036.004
R. S. Deshpande, B. E. Callejas Pina, R. Peng, J. A. Sousa, A. Wang, R. Panaccione, D. McKay
Abstract Background With cellular immunotherapy, the individuals’ medication could ablate (or enhance) any therapeutic benefit of the transferred cells. Murine and human macrophages activated with IL-4 (i.e., M(IL4)) improve wound healing and reduce the severity of disease in murine models of colitis. Advancing the position that autologous M(IL4) could be a novel approach to IBD, a critical question arises: will concurrent medication impact the M(IL4)s anti-colitic effect? To address this, we tested if prednisolone, a synthetic, anti-inflammatory glucocorticoid used to induce remission in IBD flares,impacts human M(IL4) phenotype and function. Purpose To determine if prednisolone suppresses or enhances a human M(IL4) phenotype as defined by canonical marker molecules and wound healing and anti-colitic activities. Method Macrophages were differentiated from the blood monocytes of healthy volunteers using M-CSF (7 days) and treated with GMP-grade IL-4 (10 ng/mL, 48h) ± a 24h treatment with prednisolone (1μg/mL). Subsequently, conditioned medium was collected for TGFb measurement by ELISA and for use in a T84 epithelial cell in vitro wound healing assay. Retrieved M(IL4) and M(IL4,pred.) were characterized by mRNA expression of CD206 (mannose receptor), RAMP1 (CGRP receptor), and CD14 (LPS co-receptor). One million murine bone marrow-derived M(IL4) or M(IL4,pred.) were injected into BALB/c mice 48h prior to intra-rectal DNBS (3mg), and colitis was assessed 72h-post DNBS. Result(s) Human M(IL4)s displayed increased mRNA expression of CD206 and RAMP1, and reduced CD14 compared to M(0), with the CD206 and RAMP1 being further increased by prednisolone treatment. M(IL4,pred.) produced more TGF-β than M(IL4) upon LPS stimulation [363 ± 30 vs. 241 ± 24 pg/ml, n= 4, p<0.05], which would predict an enhanced wound healing capacity. Stimulated M(IL4,pred.) produced more IL-10 than M(IL4). Furthermore, murine M(IL4,pred.) retained an anti-colitic capacity comparable to M(IL4) as determined by disease activity score in the DNBS model. Conclusion(s) Human M(IL4)s subsequently exposed to the potent immunomodulatory glucocorticoid, prednisolone show increased expression of phenotypic markers and increased output of TGFb and IL-10. Crucially M(IL4,pred.) retained an anti-colic effect in the murine DNBS model of colitis. Interpreting these data, we suggest that the anti-colitic effect of M(IL4) immunotherapy would not be adversely offset by the individuals concomitant use of steroids. Our preliminary findings support pursuing M(IL4) transfers as a novel approach to the management of IBD. Please acknowledge all funding agencies by checking the applicable boxes below Other Please indicate your source of funding; Helmsley Charitable Trust Disclosure of Interest None Declared
{"title":"A4 PREDNISOLONE, A GLUCOCORTICOID WIDELY USED FOR TREATMENT OF IBD, ENHANCES A HUMAN INTERLEUKIN-4-ACTIVATED MACROPHAGE PHENOTYPE","authors":"R. S. Deshpande, B. E. Callejas Pina, R. Peng, J. A. Sousa, A. Wang, R. Panaccione, D. McKay","doi":"10.1093/jcag/gwac036.004","DOIUrl":"https://doi.org/10.1093/jcag/gwac036.004","url":null,"abstract":"Abstract Background With cellular immunotherapy, the individuals’ medication could ablate (or enhance) any therapeutic benefit of the transferred cells. Murine and human macrophages activated with IL-4 (i.e., M(IL4)) improve wound healing and reduce the severity of disease in murine models of colitis. Advancing the position that autologous M(IL4) could be a novel approach to IBD, a critical question arises: will concurrent medication impact the M(IL4)s anti-colitic effect? To address this, we tested if prednisolone, a synthetic, anti-inflammatory glucocorticoid used to induce remission in IBD flares,impacts human M(IL4) phenotype and function. Purpose To determine if prednisolone suppresses or enhances a human M(IL4) phenotype as defined by canonical marker molecules and wound healing and anti-colitic activities. Method Macrophages were differentiated from the blood monocytes of healthy volunteers using M-CSF (7 days) and treated with GMP-grade IL-4 (10 ng/mL, 48h) ± a 24h treatment with prednisolone (1μg/mL). Subsequently, conditioned medium was collected for TGFb measurement by ELISA and for use in a T84 epithelial cell in vitro wound healing assay. Retrieved M(IL4) and M(IL4,pred.) were characterized by mRNA expression of CD206 (mannose receptor), RAMP1 (CGRP receptor), and CD14 (LPS co-receptor). One million murine bone marrow-derived M(IL4) or M(IL4,pred.) were injected into BALB/c mice 48h prior to intra-rectal DNBS (3mg), and colitis was assessed 72h-post DNBS. Result(s) Human M(IL4)s displayed increased mRNA expression of CD206 and RAMP1, and reduced CD14 compared to M(0), with the CD206 and RAMP1 being further increased by prednisolone treatment. M(IL4,pred.) produced more TGF-β than M(IL4) upon LPS stimulation [363 ± 30 vs. 241 ± 24 pg/ml, n= 4, p<0.05], which would predict an enhanced wound healing capacity. Stimulated M(IL4,pred.) produced more IL-10 than M(IL4). Furthermore, murine M(IL4,pred.) retained an anti-colitic capacity comparable to M(IL4) as determined by disease activity score in the DNBS model. Conclusion(s) Human M(IL4)s subsequently exposed to the potent immunomodulatory glucocorticoid, prednisolone show increased expression of phenotypic markers and increased output of TGFb and IL-10. Crucially M(IL4,pred.) retained an anti-colic effect in the murine DNBS model of colitis. Interpreting these data, we suggest that the anti-colitic effect of M(IL4) immunotherapy would not be adversely offset by the individuals concomitant use of steroids. Our preliminary findings support pursuing M(IL4) transfers as a novel approach to the management of IBD. Please acknowledge all funding agencies by checking the applicable boxes below Other Please indicate your source of funding; Helmsley Charitable Trust Disclosure of Interest None Declared","PeriodicalId":17263,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44421458","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 : 2023-03-01DOI: 10.1093/jcag/gwac036.092
C. S. Liu, Z. X. Lin, K. Kroeker
Abstract Background Although tremendous strides have been made in the participation of women in medicine, female continues to be underrepresented in leadership positions and higher-level academic medicine. An important factor in determining career advancement in academic medicine is the quality and quantity of an individual’s scholarly publications. To date, no study has looked at female authorship in gastroenterology (GI) randomized control trials (RCTs), which remains the gold standard for evaluating intervention effectiveness. Purpose The primary outcome is to assess female authorship in gastroenterology randomized control trials from 2011 to 2021, and the secondary outcome is to assess female authorship within GI subspecialty RCT publications. Method In this observational study, the gender of the first and last author of gastroenterology RCTs from January 1, 2011 to December 31, 2021 was assessed. Python (v3.8.12) was used to extract publication data from PubMed. A validated algorithm, genderize.io, was used to determine gender. Author first names that cannot be determined by the algorithm were manually searched on publicly-available profiles. Result(s) A total of 5690 original gastroenterology RCTs were included from January 1, 2011 to December 31, 2021. The gender of the first and senior authors of the papers was determined for 5668 (99.6%) first authors and 5656 (99.4%) senior authors. Overall, 1937 (34.1%) of the first authors and 1138 (20.0%) of senior authors were female. There was an increase in the proportion of female first authors over the past decade, from 25.4% in 2011 to 37.8% in 2021 (p<0.05). For senior authors, there was a more gradual increase in female authorship from 14.2% in 2011 to 21.6% in 2021 (p<0.05). (Figure 1) Within GI subspecialties, 612 RCTs were included for inflammatory bowel disease, 1143 RCTs were included for hepatology, and 1856 RCTs were included for therapeutic endoscopy from January 1, 2011 to December 31, 2021. Further analysis will be performed to determine the gender trend for GI subspecialties. Image Conclusion(s) Female authorship in gastroenterology RCTs has increased from 2011 to 2021, although the rate of senior authorship has increased to a slower extent compared to first authors. Across all years, female authorship in gastroenterology RCTs has been lower than males. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared
{"title":"A92 FEMALE AUTHORSHIP IN GASTROENTEROLOGY RANDOMIZED CONTROL TRIALS: 2011 - 2021","authors":"C. S. Liu, Z. X. Lin, K. Kroeker","doi":"10.1093/jcag/gwac036.092","DOIUrl":"https://doi.org/10.1093/jcag/gwac036.092","url":null,"abstract":"Abstract Background Although tremendous strides have been made in the participation of women in medicine, female continues to be underrepresented in leadership positions and higher-level academic medicine. An important factor in determining career advancement in academic medicine is the quality and quantity of an individual’s scholarly publications. To date, no study has looked at female authorship in gastroenterology (GI) randomized control trials (RCTs), which remains the gold standard for evaluating intervention effectiveness. Purpose The primary outcome is to assess female authorship in gastroenterology randomized control trials from 2011 to 2021, and the secondary outcome is to assess female authorship within GI subspecialty RCT publications. Method In this observational study, the gender of the first and last author of gastroenterology RCTs from January 1, 2011 to December 31, 2021 was assessed. Python (v3.8.12) was used to extract publication data from PubMed. A validated algorithm, genderize.io, was used to determine gender. Author first names that cannot be determined by the algorithm were manually searched on publicly-available profiles. Result(s) A total of 5690 original gastroenterology RCTs were included from January 1, 2011 to December 31, 2021. The gender of the first and senior authors of the papers was determined for 5668 (99.6%) first authors and 5656 (99.4%) senior authors. Overall, 1937 (34.1%) of the first authors and 1138 (20.0%) of senior authors were female. There was an increase in the proportion of female first authors over the past decade, from 25.4% in 2011 to 37.8% in 2021 (p<0.05). For senior authors, there was a more gradual increase in female authorship from 14.2% in 2011 to 21.6% in 2021 (p<0.05). (Figure 1) Within GI subspecialties, 612 RCTs were included for inflammatory bowel disease, 1143 RCTs were included for hepatology, and 1856 RCTs were included for therapeutic endoscopy from January 1, 2011 to December 31, 2021. Further analysis will be performed to determine the gender trend for GI subspecialties. Image Conclusion(s) Female authorship in gastroenterology RCTs has increased from 2011 to 2021, although the rate of senior authorship has increased to a slower extent compared to first authors. Across all years, female authorship in gastroenterology RCTs has been lower than males. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared","PeriodicalId":17263,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43525182","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 : 2023-03-01DOI: 10.1093/jcag/gwac036.157
R. Sullivan, J. Jones, C. Williams, E. Kilfoil, D. Macintosh, M. Stewart
Abstract Background Population-based colorectal cancer (CRC) screening programs aim to minimize disparities in CRC rates through universal access. However, Canadian CRC mortality rates remain inversely associated with socioeconomic status and rural residence. In the United States some racialized groups have higher rates of advanced adenomas and CRC. Little is known about pre-cancerous findings or CRC mortality amongst racialized groups in Canada because race and ethnicity data are not routinely collected. Purpose To determine whether FIT-positive colonoscopy incident adenomas and CRC differ on the basis of sex, race, and regional population density in a provincial CRC screening program. Method In this retrospective cohort study drawn from the Nova Scotia Colon Cancer Prevention Program database, we identified adults who had a positive FIT from 2011 to 2021. This report describes incident adenomas and CRC, stratified by sex, race (white vs. racialized groups), and regional population density (urban vs. rural). Racialized groups included those who self-identified as Black/African Canadian, Asian, Middle Eastern and Indigenous. Urban was defined as population centers with more than 5000 individuals. Colonoscopy findings were categorized as no findings, low-risk adenoma (LRA), high-risk adenoma (HRA), or CRC. Comparison between categorical variables was performed with a chi-square test and a t-test for continuous variables. P-value <0.05 was considered significant. Result(s) 41,209 adults (mean age 63.9) had a positive FIT and 34,636 went on to have a colonoscopy offered by the screening program. The FIT-positive colonoscopy participation rate was 84%. Of the 16% overall with a positive FIT but no screening program colonoscopy, 83% had a program consultation but did not proceed with endoscopy for unspecified reasons, 9% declined, and 8.2% are unknown. The overall rate of CRC was 2.4% (n=825) and the adenoma-detection rate was 60.4% (n=20,932). CRC (mean age 65.4) and HRA (mean age 64.6) were associated with older age (p <0.01). Males were more likely to have HRA (38.4% of males) or LRA (26.6% of males) identified compared to females, and females were more likely to have no colonoscopy findings (47.8% of females). CRC was more likely to be identified in urban (2.8%) than rural sub-populations (2.0%). No difference in adenomas or CRC incident rates were noted between white and racialized sub-groups. Image Conclusion(s) This analysis of a provincial CRC screening program suggests that males and urban sub-populations had more high-risk findings during FIT-positive colonoscopies. In the first reported Canadian data, incident rates of adenomas and CRC were similar in white and racialized sub-groups. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared
{"title":"A157 FIT-POSITIVE COLONOSCOPY FINDINGS IN NOVA SCOTIA STRATIFIED BY SEX, RACE, AND REGIONAL POPULATION DENSITY","authors":"R. Sullivan, J. Jones, C. Williams, E. Kilfoil, D. Macintosh, M. Stewart","doi":"10.1093/jcag/gwac036.157","DOIUrl":"https://doi.org/10.1093/jcag/gwac036.157","url":null,"abstract":"Abstract Background Population-based colorectal cancer (CRC) screening programs aim to minimize disparities in CRC rates through universal access. However, Canadian CRC mortality rates remain inversely associated with socioeconomic status and rural residence. In the United States some racialized groups have higher rates of advanced adenomas and CRC. Little is known about pre-cancerous findings or CRC mortality amongst racialized groups in Canada because race and ethnicity data are not routinely collected. Purpose To determine whether FIT-positive colonoscopy incident adenomas and CRC differ on the basis of sex, race, and regional population density in a provincial CRC screening program. Method In this retrospective cohort study drawn from the Nova Scotia Colon Cancer Prevention Program database, we identified adults who had a positive FIT from 2011 to 2021. This report describes incident adenomas and CRC, stratified by sex, race (white vs. racialized groups), and regional population density (urban vs. rural). Racialized groups included those who self-identified as Black/African Canadian, Asian, Middle Eastern and Indigenous. Urban was defined as population centers with more than 5000 individuals. Colonoscopy findings were categorized as no findings, low-risk adenoma (LRA), high-risk adenoma (HRA), or CRC. Comparison between categorical variables was performed with a chi-square test and a t-test for continuous variables. P-value <0.05 was considered significant. Result(s) 41,209 adults (mean age 63.9) had a positive FIT and 34,636 went on to have a colonoscopy offered by the screening program. The FIT-positive colonoscopy participation rate was 84%. Of the 16% overall with a positive FIT but no screening program colonoscopy, 83% had a program consultation but did not proceed with endoscopy for unspecified reasons, 9% declined, and 8.2% are unknown. The overall rate of CRC was 2.4% (n=825) and the adenoma-detection rate was 60.4% (n=20,932). CRC (mean age 65.4) and HRA (mean age 64.6) were associated with older age (p <0.01). Males were more likely to have HRA (38.4% of males) or LRA (26.6% of males) identified compared to females, and females were more likely to have no colonoscopy findings (47.8% of females). CRC was more likely to be identified in urban (2.8%) than rural sub-populations (2.0%). No difference in adenomas or CRC incident rates were noted between white and racialized sub-groups. Image Conclusion(s) This analysis of a provincial CRC screening program suggests that males and urban sub-populations had more high-risk findings during FIT-positive colonoscopies. In the first reported Canadian data, incident rates of adenomas and CRC were similar in white and racialized sub-groups. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared","PeriodicalId":17263,"journal":{"name":"Journal of the Canadian Association of Gastroenterology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43589957","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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