bluuebunny/crossref_metadata_2025 huggingface dataset:
A124 PERORAL ENDOSCOPIC MYOTOMY IS THE PREFERRED TREATMENT FOR PATIENTS WITH SYMPTOMATIC ZENKER’S DIVERTICULUM
Authors: Hasan M , Buduhan G , Liu R , Tan L , Srinathan S , Kidane B
Published: March 2023

Background

Zenker’s diverticulum (ZD) is a mucosal herniation at the pharyngoesophageal junction presenting with dysphagia, regurgitation and aspiration. While open surgical myotomy (OSM) is the conventional treatment option, select patients can undergo myotomy using endoscopic techniques.

Purpose

Evidence on third-space flexible endoscopy with myotomy is lacking, especially in North America. We aimed to assess the safety and efficacy of peroral endoscopic myotomy (POEM) for symptomatic ZD.

Method

Retrospective cohort study was performed of consecutive patients undergoing OSM and POEM completed in a tertiary hospital from 2010-2020. Only patients with accessible electronic medical records and at least 3 months of follow-up were included in this study. Data collected included: demographics, comorbidities, ZD characteristics, clinical and patient-reported outcomes.

Result(s)

14 patients underwent OSM and 18 patients underwent POEM. 10 of the patients undergoing POEM were considered for but were not able to get stapled endoscopic myotomy, the most common reasons were related to the technical limitations (ZD size too small, unable to hyper-extend neck, unable to position suspension laryngoscope). There were no significant differences between groups in age (p=0.35), BMI (p=0.38), Charlson comorbidity index (p=0.26) and size of ZD (p=0.92). Length of stay was significantly lower for POEM (0.4 vs. 3.1, p<0.01). Complications were more common and severe with OSM (36%, n=5) versus POEM (11%, n=2). The only complications post-POEM were contained esophageal perforations. Complications post-OSM included esophageal perforations requiring open cervical drainage, surgical site infections, recurrent laryngeal nerve injury/paresis, esophageal strictures requiring multiple dilatations. All patients undergoing POEM had 100% technical success with post-treatment barium esophagogram showing 100% resolution of obstruction/hang-up. The median follow-up time post-POEM was 11 months. Over the follow-up period there was a significant improvement of patient-reported outcomes, with a mean decrease of Eckardt score (4.7 to 1.1, p<0.001) and mean increase of Dakkak-Watson score (20.7 to 41, p<0.001). Only one patient had persistent ongoing symptoms of dysphagia post-POEM and was subsequently diagnosed with ineffective esophageal motility on high resolution manometry.

Conclusion(s)

POEM is a minimally invasive treatment option for ZD with high treatment success as well as reduced length of stay and complications. It is less invasive than OSM, more versatile than stapled endoscopic myotomy and is less prone to technical limitations.

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None

Disclosure of Interest

None Declared
A130 ENDOSCOPIC ULTRASOUND GUIDED THROMBIN INJECTION: A NOVEL TECHNIQUE IN THE MANAGEMENT OF RECURRENT UPPER GASTROINTESTINAL BLEEDING CAUSED BY GASTRODUODENAL ARTERY PSEUDOANEURYSMS
Authors: Chin Koon Siw K , Kundra A , Chatterjee A
Published: March 2023

Background

Gastroduodenal artery (GDA) aneurysm is a rare vascular condition that is potentially life-threatening. It is associated with significant morbidity and mortality and most often encountered in patients with chronic pancreatitis. Other etiologies including atherosclerosis, peptic ulcer disease, alcohol abuse, cholecystectomy and absence of celiac axis, have been reported. False and true GDA aneurysms account for about 1.5% of all visceral artery aneurysms however are associated with a risk of rupturing and hemorrhage up to 75%. Mainstay of GDA aneurysm management involves aneurysm repair with open surgery with vessel ligation or endovascular repair with coil embolization or stent placement, depending on the patient’s comorbidities and overall hemodynamic stability. The use of percutaneous thrombin injection via computed tomography (CT) and ultrasound has also been described in the literature and is being increasingly used to promote clot formation and pseudoaneurysm occlusion as a less invasive option.

Purpose

To present a case of endoscopic ultrasound guided thrombin injection as an effective and safe management strategy for GDA pseudoaneurysms.

Method

At this time, there are limited data in the literature on endoscopic ultrasound guided thrombin injection for pseudoaneurysms. To our knowledge, this is the first case report describing a patient with recurrent gastrointestinal bleeding from a duodenal ulcer, who had undergone multiple endoscopic and angiographic procedures, with subsequent development of a gastroduodenal pseudoaneurysm unrelated to pancreatitis which was successfully managed by occluding the pseudoaneurysm with thrombin injection under endoscopic ultrasound guidance. EUS guided thrombin injection is a viable alternative to traditional interventional radiology guided thrombin injection for management of pseudoaneurysms.

Result(s)

In clinic follow-up three weeks after thrombin injection, our patient continued to do clinically well, without abdominal pain or symptoms. Repeat CT angiogram demonstrated the GDA pseudoaneurysm had remained thrombosed, indicating successful endoscopic obliteration. He had no further signs of gastrointestinal bleeding.

Conclusion(s)

EUS guided thrombin injection is a novel approach that has been presented as an option in the management of bleeding gastroduodenal pseudoaneurysms, especially when radiology guided or surgical options are higher risk or have previously failed. The paucity of available data highlights the need for ongoing clinical studies comparing the different therapeutic strategies that can effectively and safely manage these rare but life-threatening vascular entities.

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None

Disclosure of Interest

None Declared
A139 ONE OF THESE THINGS IS NOT LIKE THE OTHER: A CURIOUS CASE OF DISCORDANT ENDOSCOPIC OPTICAL EVALUATION
Authors: Aboalfaraj N T , Shahidi N , Tomaszewski M , Jiang S , Xiong W
Published: March 2023

Background

Optical evaluation has become the cornerstone of early gastrointestinal neoplasia management as it informs therapeutic decisions between minimally invasive endoscopic resection techniques and surgery.

Purpose

We report an unusual case of a subepithelial gastric inlet patch (GIP) with optical evaluation mimicking early squamous neoplasia

Method

Case Presentation:

A 74-year-old male was referred for epigastric discomfort. On esophagogastroduodenoscopy, a 10-mm GIP was identified at 23cm from the incisors. Furthermore, a 15-mm polypoid lesion was identified at 25cm from the incisors on the contralateral wall. On optical evaluation, it was believed to be atypical but suspicious for squamous neoplasia (Figure 1). Histopathology of the lesion revealed a stratified squamous epithelium with an underlying focus on glandular mucosa. After a multidisciplinary team review, endoscopic submucosal dissection was performed, given the atypical optical characteristics of the lesion.

Result(s)

Histopathology of the lesion identified subepithelial gastric cardia-type mucosa with focal extension into the muscularis mucosae, most consistent with a subepithelial GIP. No neoplasia was identified.

Image

Conclusion(s)

We describe an unusual case of subepithelial GIP. With the widespread availability of high-definition endoscopes equipped with image-enhanced endoscopy, this case highlights the optical characteristics of this likely underappreciated endoscopic finding.

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None

Disclosure of Interest

None Declared
A151 OSEPHAGEAL VARICEAL RECURRENCE 4 YEARS BEYOND ENDOSCOPIC BAND LIGATION IN HEPATITIS C PATIENTS WHO ACHIEVED SUSTAINED VIROLOGICAL RESPONSE WITH ORAL DIRECT ACTING ANTIVIRAL THERAPIES
Authors: Abdel-Samiee M , Abdelsameea E , Badran A
Published: March 2023

NOT PUBLISHED AT AUTHOR’S REQUEST

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None

Disclosure of Interest

None Declared

GASTROINTESTINAL ONCOLOGY
A153 PYCRL LACTYLATION AS A POTENTIAL REGULATOR OF CANCER STEM CELL METABOLISM IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA (ESCC)
Authors: Douchin J , Nogueira de Almeida L G , Gonneaud A , Boisvert F -M , Dufour A , Giroux V
Published: March 2023

Background

Patients with esophageal malignancy have a 5-year survival rate of only 14% in Canada. This high mortality rate is due to three factors: late diagnosis, difficulty in surgically removing the tumor because of its localization, and treatment resistance. Resistance can be developed after prolonged exposure to anti-cancer drugs and/or radiation. Indeed 30% of patients will not respond to treatment or will relapse. Resistance has been mainly ascribed to the presence of cancer stem cells (CSCs) inside the tumor. However, no treatment specifically directed against CSCs is available to patients.

Purpose

Thus, targeting CSCs is a promising strategy to improve the survival of patients with esophageal squamous cell carcinoma (ESCC), the most common type of esophageal cancer worldwide. Therefore, a better understanding of the molecular mechanisms occurring during long-term exposure to cancer treatments is imperative.

Method

Herein, we developed an unbiased approach to identify new players in chemotherapy and radiotherapy resistance development in ESCC. We established radio- (R), chemo- (C), and radiochemo-resistant (RC) human ESCC cell lines using prolonged exposure to radiation and/or chemotherapeutic agent 5-FU, respectively.

Result(s)

The enrichment in CSCs in all treated cell lines was demonstrated by an increase of ALDH1high cells and CD24high/CD44high cells in flow cytometry. We then used a proteomic approach to identify new players in treatment resistance. Interestingly, pathway analysis pointed out to alterations in energy metabolism as well as amino acid metabolism. Seahorse assays showed that resistant cell lines have a lower respiration rate than control cells, while glycolysis remains unchanged. To further characterize these metabolic changes, we performed an unbiased metabolomic study and confirmed a decrease in amino acid levels such as proline, in resistant cell lines. Recently, metabolic regulation has been linked to a new post-translational modification, lactylation. Proteomic data were re-analyzed looking for lactylated protein and found, amongst others, PYCRL, an enzyme implicated in proline biosynthesis, as one of the most differentially lactylated proteins in treated cell lines compared to control. PYCRL lactylation was confirmed using immuno-fluorescence colocalization and immuno-precipitation. Lastly, using AlphaFold, preliminary results point toward the importance of PYCRL lactylation impairing PYCRL homomultimerization.

Conclusion(s)

To conclude, our results suggest an important role of proline metabolism following long-term treatment in ESCC. This study is a first step toward the identification of new targets to fight treatment resistance in ESCC patients.

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CAG, CIHR, Other

Please indicate your source of funding;

FRQ

Disclosure of Interest

None Declared
A163 INFECTION WITH HYMENOLEPIS DIMINUTA ELICITS A TH2 IMMUNITY AND ALLEVIATES DNBS-COLITIS IN A MOUSE MODEL WITH MINIMAL INTESTINAL MICROBIOTA
Authors: Li S , Wang A , McKay D M
Published: March 2023

Background

Immunocompetent mice infected with the rat tapeworm Hymenolepis diminuta are protected from dinitrobenzene sulphonic-acid (DNBS)-induced colitis that was accompanied by the increased relative abundance of short-chain fatty acid (SCFA)-producing bacteria and fecal SCFA levels at 8 days post-infection (dpi). These changes were not observed in antibiotic-treated BALB/c mice or germ-free mice. To further characterize the host-parasite-microbiota interaction in the control of colitis, experiments have been conducted in a reductionist system in which the H. diminuta anti-colitic response was tested in mice colonized with 12 commensal bacteria representing the major five phyla of the mouse gut.

Purpose

To identify key bacterial species and microbe-derived mediators involved in the H. diminuta-induced protection from DNBS-induced colitis.

Method

OligoMM12 (Oligo-Mouse-Microbiota) mice (n=4-8/group) were infected with 10 viable antibiotic-treated H. diminuta cysticercoids eight days prior to challenge with DNBS (3mg, i.r.). Mice were monitored daily and necropsied 72h post-DNBS. Disease was assessed by a macroscopic disease activity score, colon length and histopathology on H&E sections of mid-colon. Production of IL-4, -5, -10 and -13 by concanavalin-A treated spleen cells by ELISA was used as an index of successful helminth infection.

Result(s)

OligoMM12 mice treated with DNBS developed acute colitis, with 3/8 mice requiring humane euthanization, while all mice infected with H. diminuta survived the DNBS challenge. Successful infection was confirmed by statistically significant increases in splenic output of the Th2-cytokines in response to mitogenic stimulation and efficient expulsion of the worms burden by 11 dpi. The severity of DNBS-induced colitis was reduced in H. diminuta-infected mice (n=4), although additional experiments are required to confirm the statistical significance of these data.

Conclusion(s)

Reproducible DNBS-induced colitis in mice with the simplified OligoMM12 consortium of bacteria and reduced disease in H. diminuta-infected mice has created a model by which the participation of exact bacterial groups or species in H. diminuta-induced suppression of colitis can be tested. This is of translational value, since the failure of helminth therapy in IBD could be predicated by dysbiosis in the patient, and therefore potentially overcome by combination therapy of ‘probiotic’ and helminth.

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CIHR, Other

Please indicate your source of funding;

NSERC-CGS D, Eyes High doctoral Recruitment Scholarship

Disclosure of Interest

None Declared
A171 INTESTINAL INTERFERON-LAMBDA RECEPTOR 1 EXPRESSION AND RESPONSES ARE SIGNIFICANTLY DECREASED IN PEDIATRIC INFLAMMATORY BOWEL DISEASE PATIENTS
Authors: Ogungbola O , Mahmood R , Bittorf K , Nguyen N , El-Matary W , Wine E , Tyrrell L , Armstrong H , Santer D
Published: March 2023

Background

While interferon-lambdas (IFN-λs) were initially discovered for their role in antiviral immunity at mucosal barriers such as the lung and gut, there are many unanswered questions for how IFN-λs uniquely dampen inflammatory immune responses. In mouse colitis models, IFN-λs were shown to play a significant role in promoting epithelial barrier integrity and mucosal healing. Microbes present in the gut naturally induce IFN-λs, but how chronic inflammation, such as in patients with inflammatory bowel diseases (IBD), affects IFN-λ biology has not been well studied, especially in humans.

Purpose

Here, we tested the hypothesis that children with active, more severe IBD would present with lower intestinal IFN-λR levels and IFN-λ responses which could contribute to IBD pathology through exacerbated inflammation, decreased mucosal healing and impaired barrier function.

Method

We screened 14 novel antibodies to find the optimal clone that accurately stains the unique IFN-λ receptor subunit (IFN-λR1) protein in human intestinal tissue and IFN-λR1 levels were quantified by immunohistochemistry and flow cytometry in biopsy samples from children without IBD, Crohn’s disease, or ulcerative colitis (n=35 total). Fresh patient biopsies (ascending colon or terminal ileum) were also treated in media +/- IFN-λ for 24hrs using our novel ex vivo biopsy assay and changes in gene expression were quantified by RT-qPCR. Intestinal washes were also collected and microbes profiled by shotgun metagenomics.

Result(s)

We identified 2 new antibodies that accurately stained human cell lines and immune cells known to express IFN-λR1 protein (gut epithelial cells and B cells). We found that IFN-λ receptor (IFN-λR) levels are significantly reduced in gut epithelial and immune cells within pediatric IBD intestinal tissue, even at non-inflamed sites (p<0.01, 30-50% reduction) and this was even more pronounced when comparing moderate/severe disease compared to children with no disease activity. This led to lower IFN-λ responsiveness in IBD compared to non-IBD biopsies when investigating IFN-stimulated gene expression (p<0.05, up to 7-fold reduction). Paired patient gut microbe analyses identified specific species that correlated with changes in IFN-λ receptor expression.

Conclusion(s)

Together, our findings demonstrate pediatric IBD patients may be less able to induce critical IFN-λ-mediated antimicrobial responses and protective anti-inflammatory pathways. This work supports the goal to restore and promote IFN-λ responses as a novel therapeutic strategy for pediatric IBD.

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Other

Please indicate your source of funding;

Children's Hospital Research Institute of Manitoba

Disclosure of Interest

None Declared
A194 IMPACT OF SUPPRESSOR OF CYTOKINE SIGNALING 1 (SOCS1) EXPRESSION IN INTESTINAL EPITHELIAL CELLS ON THE GUT MICROBIOTA
Authors: Leon L M , Marrero Cofino G , Delannoy A , Placet M , Geha S , Verdú E F , Fortier L -C , Menendez A , Saucier C
Published: March 2023

NOT PUBLISHED AT AUTHOR’S REQUEST

Disclosure of Interest

None Declared
A208 REAL WORLD EVIDENCE ANALYSIS WITH ADALIMUMAB BIOSIMILAR, MSB 11022, REPORTED WITH PATIENT CARE PROGRAM
Authors: Cheung S , Heidari P , Truong D
Published: March 2023

Background

Injection site reactions (ISR), including injection site pain (ISP) are common adverse events reported with drugs administrated via subcutaneous injections. In clinical trials, the rates of ISR of adalimumab and adalimumab biosimilars range from 3% to 22.8% with citrate-buffer formulations, and from 1.7% to 16.6% with acetate-buffered and other formulations.

Purpose

The objective of this study is to evaluate ISR of adalimumab biosimilar, MSB 11022, in real world setting.

Method

Patients with immune mediated inflammatory diseases (IMIDs) enrolled with patient care program (PSP), and received at least one dose of adalimumab biosimilar, MSB 11022, were followed up. Incidences of injection site reactions, including injection site pain, burning sensation, bruise, erythema, hemorrhage, pruritus, and/or swelling were documented through unsolicited and solicited (outgoing following up calls with patients after their first injection through PSP contacts) reports. The data were collected between April 2021 and July 2022, and the rates of ISRs were assessed.

Result(s)

There were 2812 patients that met criteria through data collection period, with 219 cases of ISR. More than 99% of case reports were through solicited contacts, i.e., through case-manager follow up calls. Overall, rate of injection site reaction is 7.8% in patients with IMIDs treated with adalimumab biosimilar, MSB 11022. The rates of ISRs reported by disease are as follows: 6.8% of patients with Crohn's disease, 8.7% with ulcerative colitis, 8.8% with rheumatoid arthritis, 6.5% with psoriatic arthritis, 7.8% ankylosing spondylitis, 6.1% uveitis, 8.3% with hidradenitis suppurativa, and 11.1% of juvenile rheumatoid arthritis.

Conclusion(s)

Real world data provided evidence that ISR rate of adalimumab biosimilar, MSB 11022, is within the ranges of clinical trial data of adalimumab with citrate-buffer, and other formulations. As far as we know, this is the first real world evidence reported for ISR among adalimumab biosimilars with IMID patients.

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None

Disclosure of Interest

None Declared
A232 RISK OF TOTAL METACHRONOUS ADVANCED NEOPLASIA AT SURVEILLANCE COLONOSCOPY AFTER DETECTION OF SERRATED LESIONS: A MATCHED COHORT STUDY
Authors: Djinbachian R , Lafontaine M -L , Anderson J C , Pohl H , Dufault T , Boivin M , Bouin M , von Renteln D
Published: March 2023

Background

Serrated lesions (SLs), including sessile serrated lesions (SSL) and traditional serrated adenomas (TSA) have become subject of increased interest for their role as CRC precursors.

Purpose

Study aim was to evaluate the risk to develop total metachronous advanced neoplasia (T-MAN) at follow-up in patients with index SL compared to a matched cohort without SL.

Method

Patients 45-74y with SLs were identified through pathology database search. SL patients were matched 2:1 by sex; age; synchronous polyps (high-risk adenoma [HRA], low-risk adenoma [LRA], no-adenoma); timing of index, to patients without SL. Primary outcome was risk of T-MAN (advanced adenoma or high-risk SL) at follow-up. Secondary outcomes included risk of T-MAN stratified by synchronous polyps and SL characteristics.

Result(s)

1425 patients were included (475 patients, 642 SLs; 950 controls (mean follow-up 2.9 vs 3.9y). The SL group had greater risk of T-MAN compared to the non-SL group [Hazard-ratio (HR)=6.12 (95%confidence-interval (CI)3.91-9.58)]. Patients with SL+HRA had higher risk of T-MAN compared to HRA alone [HR=2.62 (95%CI 1.45-4.71)], as well as patients with SL+LRA compared to LRA alone [HR=7.03 (95%CI 2.78-18.44)], and SL without adenoma compared to no-adenoma [HR=14.87 (95%CI 6.51-33.95)]. Presence of proximal SSL (HR=9.30), large SSL (HR=17.87) and proximal large SSL (HR=24.99), but not distal SSL, was associated with greater risk for T-MAN.

Conclusion(s)

Patients with SLs are at greater risk for developing T-MAN regardless of synchronous adenomas. Patients with SL and HRA, and those with large or proximal SSLs appear to be at greatest risk for T-MAN.

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Other

Please indicate your source of funding;

ACG

Disclosure of Interest

R. Djinbachian Grant / Research support from: Grant from the American College of Gastroenterology for the conduction of this project, M.-L. Lafontaine: None Declared, J. Anderson: None Declared, H. Pohl: None Declared, T. Dufault: None Declared, M. Boivin: None Declared, M. Bouin: 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,
A245 A TERTIARY CENTRE REVIEW OF PORTO-SYSTEMIC SHUNTS: AN INCREASINGLY IMPORTANT TOOL IN LIVER DISEASE MANAGEMENT
Authors: Malik S , Hirschfield G , Jaberi A
Published: March 2023

Background

Portal hypertensive complications arising from chronic liver disease are increasingly prevalent. Radiologically placed porto-systemic shunts are used successfully to address complications such as ascites and recurrent variceal bleeding.

Purpose

We sought, with approval from ethics to electronically chart review the UHN experience for TIPSS (transjugular intrahepatic porto-systemic shunt) and DIPS (direct intrahepatic porto-caval shunt) over time.

Method

We employed a search strategy focused on radiologic databases, to identify UHN patients who had received a porto-systemic shunt insertion over three decades between January 1, 1990, to September 14, 2021. A total of 238 UHN patients that had a shunt imaged, re-assessed, or inserted were included in this retrospective electronic chart review. Demographic information was recorded at baseline. Data pertaining to clinical outcomes of portal hypertension such as refractory ascites, recurrent gastrointestinal bleeding and ESLD progression was recorded at baseline, 1 month, 3 months and 6 months post-shunt insertion. HVPG was recorded pre-shunt and post-shunt insertion. Transplant-free survival and post-operative complications was also assessed. Patients were followed until death or liver transplant.

Result(s)

Out of 238 patients confirmed, 219 had a TIPSS insertion and 19 a DIPS insertion. The average age at time of shunt was 55.1 ± 8.4 years. 53.7% (n=128) of patients were male. Indications for portosystemic shunt placement included refractory ascites (n=141), recurrent gastrointestinal bleeding (n=73), hydrothorax (n=10), hepatorenal syndrome (n=8), and portal vein thrombosis (n=4). Etiology of disease was categorized as alcohol-associated liver disease (n=107), non-alcohol associated fatty liver disease (n=36), viral hepatitis (n=27), autoimmune hepatitis (n=38) and vascular liver disease (n=20). Relevant events noted post procedure included hepatic encephalopathy (n=34), hydrothorax (n=17), vascular (including stent) thrombosis (n=17) and renal failure (n=4). 12 months post-shunt insertion 2.5% (n=6) of patients had died or received liver transplant; of these 1.7% (n=4) were transplanted. HPVG fell consistently post-procedure: 15.6 ± 1.5mmHg pre-shunt to 5.9 ± 1.2mmHg post-shunt. There was no observable increase in MELD-Na score in the first month post-shunt. Temporal trends showed that more patients aged 50 to 69, and more female patients, are now receiving shunt insertion than at the initiation of the chart review.

Image

Conclusion(s)

Portosystemic shunt placement in the form of TIPSS or DIPS insertion is an increasingly common and effective treatment for portal hypertension in patents with advanced liver disease at UHN.

Disclosure of Interest

None Declared
A264 ORAL IRON SUPPLEMENTATION SHAPES THE RECOVERY OF GUT THE MICROBIOTA AND PROMOTES CARCINOGENESIS IN THE APCMIN/+ MOUSE MODEL
Authors: Cuisiniere T , Oliero M , Hajjar R , Calvé A , Fragoso G , Santos M M
Published: March 2023

Background

Colorectal cancer (CRC) induces anemia in a large proportion of patients and is usually treated with oral iron supplementation. Surgery, the main treatment for CRC, is routinely accompanied by prophylactic antibiotics to avoid infection. Moreover, the concomitance of oral iron supplementation and antibiotics treatment is highly prevalent in general population. However, the combined effect of antibiotics and high luminal iron concentration in the gut on the microbiota and intestinal homeostasis remains unknown.

Purpose

This study sought to identify possible deleterious effects of the recovery from antibiotics exposure of the gut microbiota under oral iron supplementation.

Method

In order to assess the effects of luminal iron on the recovery of the gut microbiota, WT mice were subjected to antibiotic treatment with different concentrations of dietary iron. Then, to explore potential deleterious effects of this setup on CRC promotion and progression mediated by the human CRC gut microbiota, CRC model ApcMin/+ mice were subjected to antibiotics prior to gavage with fecal samples from anemic CRC patients, then fed different concentrations of dietary iron. The composition of the gut microbiota and its recovery after these interventions were assessed in stool samples by 16S rRNA. Gut microbiota functions were inferred by using the PICRUSt2, and short chain fatty acid (SCFA) concentration in feces were assessed by liquid-chromatography mass spectrometry. CRC progression and promotion were assessed by tumour counts and immunohistochemistry.

Result(s)

Recovery from antibiotics under high luminal iron concentration shifted the gut microbiota toward a Bacteroidetes phylum-dominant composition. Three bacterial species characterized as CRC initiators were significantly more abundant. Nitrogen, pentose phosphate, cyanoamino acid metabolisms were higher after recovery under oral iron supplementation. Antibiotic exposure induced a long-term increase in SCFAs linked to gut inflammation, propionate and succinate. For mice under high luminal iron concentration, they showed a lack of recovery in baseline levels of butyrate, a SCFA that inhibits cancer cell proliferation in the gut. In addition, an increase in CRC burden and progression were found in ApcMin/+ mice receiving fecal sample from patients and oral iron supplementation.

Conclusion(s)

Gut microbiota recovery from antibiotic exposure under oral iron supplementation is frequent in CRC patients, but is also common in the general population. This study identifies possible deleterious effects of the concomitance of these two disruptive agents of the gut microbiota on the CRC progression.

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Other

Please indicate your source of funding;

NSERC, ICM

Disclosure of Interest

None Declared
A268 RESOLUTION RATES IN OPEN-LABEL VERSUS RANDOMIZED CONTROLLED TRIALS FOR MICROBIOTA RESTORATION FOR RECURRENT CLOSTRIDIOIDES DIFFICILE INFECTION: AN UPDATED META-ANALYSIS
Authors: Tariq R , Pardi D S , Khanna S
Published: March 2023

Background

Microbiota restoration is highly effective to treat recurrent Clostridioides difficile infection (CDI) in observational studies (cure rates >90%) but efficacy in controlled clinical trials appears lower.

Purpose

We performed an updated meta-analysis to assess the efficacy of microbiota restoration for recurrent CDI in open-label registered prospective clinical trials compared to randomized controlled trials (RCTs).

Method

A systematic search of Embase, Web of Science and Scopus was performed up to June 2022 to identify studies of interest. Clinical trials of microbiota restoration for recurrent CDI with clinical resolution with one dose as the primary outcome were included. We calculated both unweighted and weighted pooled resolution rates (UPR and WPR) with 95% confidence intervals (CI).

Result(s)

Eighteen studies (9 RCTs and 9 open-label trials) with 1149 CDI patients were included. Of the patients treated with microbiota restoration, 881 experienced symptom resolution (UPR 77%%; WPR 79%, 95% CI, 72%-85%). There was significant heterogeneity among studies with an I2of 86%. Analysis of trials with a control arm (non-microbiota restoration) revealed CDI resolution in 357 of 496 patients (UPR 72%; WPR 73%, 95% CI 63%-82%) with microbiota restoration. Among the 9 open-label clinical trials, CDI resolution was seen in 524 of 653 patients after initial microbiota restoration (UPR 80%; WPR 84%, 95% CI 74%-92%). Comparison of resolution rates between RCTs and open-label trials revealed a lower cure rate in RCTs compared to open-label trials (WPR 73% vs 84%, p<0.0001).

Analysis of the 10 trials with non-microbiota restoration revealed CDI resolution in 201 of 397 patients with antibiotics (WPR 52%, 95% CI 43%-60%). There was significant heterogeneity among the included studies with an I2of 61%. Comparison of cure rates with microbiota restoration vs antibiotics showed higher cure rate with microbiota restoration (WPR 73%, [95% CI 63%-82%] vs 52% [95% CI, 43%-60%]; p<0.0001). There were no serious adverse events reported.

Conclusion(s)

Microbiota restoration in a randomized controlled setting leads to lower resolution rates compared to open label and observational settings, likely due to stricter definitions and inclusion criteria. Resolution rates in open label studies were similar to observational studies.

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None

Disclosure of Interest

None Declared
A273 INCREASING THE REPRESENTATION OF INDIANS IN MICROBIOME RESEARCH: HOW DOES THEIR GUT MICROBIOME DIFFER?
Authors: D'Aloisio L D , McComb C , Shetty V , Ballal M , Ghosh S , Gibson D L
Published: March 2023

Background

During the 1900s when industrialization was on the rise in western countries, inflammatory bowel disease (IBD) began to present itself and continually increase over the decades. Now, newly industrialized countries such as India are following this same pattern, and with a population reaching over one billion, India is projected to have one of the highest IBD prevalence worldwide. Furthermore, pediatric diagnoses of IBD are more frequently reported in India and in Indian children living in Canada, suggesting this disease may present differently in those of Indian descent. While the etiology of IBD remains unclear, a gut microbiome that is no longer symbiotic with its host is a key player. However, Indians are one of the least represented in microbiome research, therefore we cannot accurately assess the role of their gut microbiome in IBD. To effectively understand the nature of IBD in Indians, we must first define their gut microbiome.

Purpose

Our study characterizes the microbiome of Indians living in India to explore how it differs from Canadians of European descent.

Method

Stool samples from healthy volunteers (ages 18-55) were collected from Indians in India and Euro-Canadians in Kelowna, BC. Microbial DNA was extracted for 16S sequencing on the Illumina MiSeq platform and QIIME2 was used for microbiome analysis.

Result(s)

We will discuss the similarities and differences comparing the gut microbiome of Indians to Euro-Canadians, further highlighting the need for more microbiome research of this demographic.

Conclusion(s)

Our research aims to increase representation of Indians in microbiome research in the hopes of improving our knowledge of the predispositions to IBD, which will aid in the information required to develop effective preventive measures. With elevated risk for IBD in Indians residing in Canada, future studies should also aim to analyze if the gut microbiome in Indians change as they migrate and adopt the westernized lifestyle.

Disclosure of Interest

None Declared
A279 EVIDENCE OF TRANSIENT RECEPTOR POTENTIAL MELASTATIN 3 (TRPM3) CHANNEL SENSITIZATION IN A MOUSE MODEL OF COLITIS
Authors: King J W , Bennett A S W , Wood H , Baker C , Reed D E , Lomax A E
Published: March 2023

Background

Abdominal pain is a primary symptom of inflammatory bowel disease (IBD). Opioids provide relief from IBD-associated pain, but they are addictive and associated with excess mortality in IBD patients. Thus, there is a need to develop novel therapeutics for IBD-associated pain. The mechanosensitive ion channel, transient receptor potential melastatin 3 (TRPM3) is upregulated in sensory neurons innervating inflamed tissue and contributes to pain from inflamed joints and cystitis. However, TRPM3’s role in abdominal pain has not been investigated.

Purpose

To evaluate whether TRPM3 contributes to abdominal pain using a mouse model of colitis.

Method

We used ratiometric Ca2+ imaging and extracellular afferent nerve recording to determine the effects of pharmacological activation or inhibition of TRPM3 on T13-L5 dorsal root ganglia (DRG) neurons and lumbar splanchnic nerves, respectively. Increased intracellular Ca2+ indicates neuronal excitation. Furthermore, the effects of TRPM3 activation in neurons and nerves from healthy mice and mice with dextran sulphate sodium-induced colitis were compared.

Result(s)

The TRPM3 agonists, CIM-0216 (0.1-10µM) and pregnenolone sulphate sodium (PSS; 1-300µM), concentration-dependently increased intracellular Ca2+ concentration in mouse DRG neurons and this was blocked using the TRPM3 inhibitor isosakuranetin (5µM; p<0.0001, Mann-Whitney Test). CIM-0216 (5µM)-induced increases in intracellular Ca2+ were significantly larger in neurons from mice with colitis (326±16% of baseline) compared to neurons from healthy mice (257±13% of baseline; p<0.01, Kruskal-Wallis with Dunn’s Multiple Comparison Test). The percentage of neurons responding to CIM-0216 was significantly increased in mice with colitis compared to healthy mice (79% vs 62%; p<0.001, Fischer’s Exact Test). Similarly, the percentage of neurons responding to PSS from mice with colitis was increased compared to healthy mice; however, this did not reach statistical significance (75% vs 70%, p=0.351, Fischer’s Exact Test). Furthermore, CIM-0216 (20µM)-induced change in the basal firing of lumbar splanchnic nerves was significantly increased in mice with colitis (1.23±0.24Hz) compared to healthy mice (0.60±0.14Hz, p<0.05, unpaired t-test).

Conclusion(s)

TRPM3 activation excited DRG neurons and lumbar splanchnic nerves and these excitatory effects were augmented in mice with colitis.

Disclosure of Interest

None Declared
A287 HOME PARENTERAL NUTRITION FOR INDIVIDUALS WITH SHORT BOWEL SYNDROME SECONDARY TO CROHN’S DISEASE VERSUS OTHER ETIOLOGIES: A PROSPECTIVE COHORT STUDY
Authors: Sasson A N , Noelting J , Schwenger K , Armstrong D , Raman M , Duerksen D , Whittaker S , Lu Y , Jurewitsch B , Gramlich L , Ananthakrishnan A , Allard J
Published: March 2023

Background

Individuals with short bowel syndrome (SBS) have reduced intestinal absorptive capacity and many require home parenteral nutrition (PN) support. One of the common causes of SBS is secondary to intestinal resections in the management of Crohn’s disease (CD). Complication rates and survival in SBS secondary to CD on PN versus other etiologies remains unknown.

Purpose

To determine whether patients with SBS secondary to CD versus SBS secondary to other etiologies on home PN, have increased risk of hospitalizations and complications including central line associated bloodstream infection (CLABSI) and venous thromboembolism and whether there is a difference in overall survival between groups.

Method

This is a multicentre prospective cohort study using the Canadian Home Parenteral Nutrition (HPN) Registry on individuals with defined SBS separated into two cohorts: 1) Patients with SBS secondary to Crohn’s disease vs. 2) Patients with SBS secondary to other aetiologies (trauma, surgical complication, vascular event, volvulus, malignancy). Patient characteristics and clinical factors are presented as mean (standard deviation) for continuous variables and as frequency (percentage) for categorical variables. Comparison between groups (SBS CD vs SBS other) were performed using 2-sample t-test for continuous variables and Chi-square or Fisher exact tests when appropriate for categorical variable. Survival probabilities will be estimated using the Kaplan-Meier method.

Result(s)

The study included a total of 379 patients with short bowel syndrome on home PN. There are 170 (45%) patients with SBS secondary to CD and 209 (55%) patients with SBS from other secondary causes. The average age of those with CD is 52 and 65% female patients. The average age of those with other causes of SBS is 56 with similar percentage of female patients (65%). There were significant differences in baseline medications with higher use of immunosuppressant therapy (39% vs. 7%, p<0.001) in those with CD. There was no significant difference in total number of hospitalizations, hospitalizations related to PN and CLABSI.

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Conclusion(s)

Individuals with SBS secondary to CD do not appear to be at increased risk of central line infections or hospitalizations compared those with SBS from other causes.

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Disclosure of Interest

None Declared
Recent Douglas-fir Mortality in the Klamath Mountains Ecoregion of Oregon: Evidence for a Decline Spiral
Authors: Bennett Max , Shaw David C , Lowrey Laura
Published: March 2023

Recent increases in Douglas-fir (Psuedotsuga menziesii var. menziesii) mortality in the Klamath Mountains ecoregion raise concerns about the long-term resilience of Douglas-fir in the ecoregion and increased potential for uncharacteristic wildfire. We used data from the USDA Forest Service Aerial Detection Survey and ninety-six field plots to explore the relationships between physiographic and climate variables and Douglas-fir mortality. Our results provide strong evidence for a decline spiral in which Douglas-fir growing on hot, dry sites (predisposing factor) are further stressed by drought (inciting factor) and are then exploited by the flatheaded fir borer (Phaenops drummondi) and other secondary biotic agents (contributing factors), resulting in decline and mortality. At the landscape scale, Douglas-fir mortality increased as average annual precipitation declined and average climatic water deficit increased. We developed a risk score integrating several environmental variables associated with drought and heat stress to predict the likelihood and intensity of mortality at the stand scale.
Optometric Brain Injury Curriculum in Federal Residency Training Programs: A Consensus Report
Authors: Jackson Kevin M , Merezhinskaya Natalya , Mallia Rita K , Barker II Felix M
Published: March 2023

Introduction

Brain injury often impacts the visual system. Diagnosis and treatment of visual system problems related to brain injury is a field with less settled science and more variation in practice than most specialty fields. Most optometric brain injury residency programs are in federal clinics (VA and DoD). A consensus core curriculum has been created that will allow some consistency while facilitating program strengths.

Materials and Methods

Kern’s curriculum development model and a focus group of subject matter experts were used to reach consensus in producing a core curriculum to provide a common framework for brain injury optometric residency programs.

Results

A common high-level curriculum was developed with educational goals through consensus.

Conclusions

In a relatively new subspeciality without a firm foundation of settled science, a common curriculum will help provide a common framework to facilitate clinical and research progress in this field. The process sought out expertise and community building to help improve the adoption of this curriculum. This core curriculum will provide a framework for educating optometric residents in the diagnosis, management, and rehabilitation of patients with visual sequelae because of brain injury. It is intended to ensure that appropriate topics are covered while allowing for flexibility according to each program’s strengths and resources.
A case of Behçet’s-like disease associated with trisomy 8–positive myelodysplastic syndrome carrying MEFV E148Q variant presented with periodic fever
Authors: Ishikawa Yukiko , Sasaki Ryo , Ishiwata Akira , Hatakeyama Shuji , Matsumura Masami , Sato Takeo
Published: March 2023

Behçet’s-like disease, which incompletely fulfils the criteria of Behçet’s disease, is often associated with trisomy 8–positive myelodysplastic syndrome (MDS). We report a case of an 82-year-old man with these conditions carrying the E148Q variant of MEFV gene who presented with periodic fever. The patient presented with joint pain, muscle pain, and episodes of periodic fever every 2 weeks for the past 3 months. On admission, painful erythema and fever were observed. Colonoscopy revealed erosion in the caecum and ascending colon. The patient had bicytopenia, and a bone marrow biopsy showed findings compatible with trisomy 8–positive unclassifiable MDS. Because the patient incompletely fulfilled the criteria for Behçet’s disease, he was diagnosed with Behçet’s-like disease associated with trisomy 8–positive MDS. Positron emission tomography–computed tomography performed during the fever revealed multiple muscle lesions consistent with the sites of pain. To examine the cause of the periodic fever attacks, MEFV gene was analysed, and the results revealed an E148Q variant. Steroids were ineffective against periodic fever attacks. A daily dose of 0.5 mg colchicine was prescribed, but the effect was minimal, probably, because of the insufficient dose due to renal dysfunction. Based on the diagnosis of atypical familial Mediterranean fever, canakinumab was added, which partially mitigated the periodic fever. This case suggests the importance of ruling out MDS when physicians see an elderly patient who present with Behçet’s-like disease. Although the significance of the E148Q variant in the pathogenesis of periodic fever remains controversial, it may act as a disease modifier in accordance with trisomy 8–positive MDS.
Magnetoelectric effect generated through electron transfer from organic radical to metal ion
Authors: Liu Xiaolin , Liu Qiang , Zhao Haixia , Zhuang Guilin , Ren Yanping , Liu Tao , Long Lasheng , Zheng Lansun
Published: March 2023

Magnetoelectric (ME) materials induced by electron transfer are extremely rare. Electron transfer in these materials invariably occurs between the metal ions. In contrast, ME properties induced by electron transfer from an organic radical to a metal ion have never been observed. Here, we report the ME coupling effect in a mononuclear molecule-based compound [(CH3)3NCH2CH2Br][Fe(Cl2An)2(H2O)2] (1) [Cl2An = chloranilate, (CH3)3NCH2CH2Br+ = (2-bromoethyl)trimethylammonium]. Investigation of the mechanism revealed that the ME coupling effect is realized through electron transfer from the Cl2An to the Fe ion. Measurement of the magnetodielectric (MD) coefficient of 1 indicated a positive MD of up to ∼12% at 103.0 Hz and 370 K, which is very different from that of ME materials with conventional electron transfer for which the MD is generally negative. Thus, the current work not only presents a novel ME coupling mechanism, but also opens a new route to the synthesis of ME coupling materials.
Trends inStreptococcus pneumoniaeAntimicrobial Resistance in US Children: A Multicenter Evaluation
Authors: Mohanty Salini , Feemster Kristen , Yu Kalvin C , Watts Janet A , Gupta Vikas
Published: March 2023

Background

Antimicrobial resistance (AMR) poses a significant challenge for treating pneumococcal disease. This study assessed AMR trends in Streptococcus pneumoniae from US children.

Methods

We evaluated antibiotic resistance, defined as facility antimicrobial susceptibility reports of intermediate/resistant, in 30-day nonduplicate S pneumoniae isolates from children (<18 years of age) with invasive (blood or cerebrospinal fluid/neurological) or noninvasive (respiratory or ear/nose/throat) isolates at 219 US hospital inpatient/outpatient settings in the BD Insights Research Database (January 2011–February 2020). We used descriptive statistics to characterize the percentage of antimicrobial-resistant isolates and generalized estimating equations to assess variations in resistance over time.

Results

Of 7605 S pneumoniae isolates analyzed, 6641 (87.3%) were from noninvasive sources. Resistance rates were higher in noninvasive versus invasive isolates. Isolates showed high observed rates of resistance to ≥1 drug class (56.8%), ≥2 drug classes (30.7%), macrolides (39.9%), and penicillin (39.6%) and significant annual increases in resistance to ≥1 drug class (+0.9%), ≥2 drug classes (+1.8%), and macrolides (+5.0%).

Conclusions

Among US children over the last decade, S pneumoniae isolates showed persistently high rates of resistance to antibiotics and significant increases in ≥1 drug class, ≥2 drug classes, and macrolide resistance rates. Efforts to address AMR in S pneumoniae may require vaccines targeting resistant serotypes and antimicrobial stewardship efforts.