bluuebunny/crossref_metadata_2025_split huggingface dataset:
A268 1 YEAR FOLLOW-UP OF PEDIATRIC ULCERATIVE COLITIS USING INTESTINAL ULTRASOUND
Authors: Thornton S , Isaac D , Hudson A , MacKay D , Kuc A , Carroll M W , Wine E , Huynh H 
Published: February 2024

Abstract

Background
Intestinal ultrasound (IUS) is an emerging tool that offers a non-invasive method for monitoring inflammatory bowel disease in pediatric patients, with increasing popularity worldwide. Assessment of IUS for monitoring pediatric Ulcerative Colitis (UC) has been previously limited to small samples of patients with no long-term follow up.

Aims
This project aims to utilize intestinal ultrasound assessments obtained at routine time points to determine changes in IUS parameters within 12 months of study enrollment in newly diagnosed children with UC, and their relationship to biochemical markers, clinical assessments, and endoscopic findings.

Methods
Pediatric patients with suspected ulcerative colitis were prospectively enrolled through the Edmonton Pediatric IBD Clinic. Participants underwent IUS, clinical assessments, bloodwork for biomarkers, and fecal calprotectin (FCP) testing at baseline, 1-, 3-, 6-, and 12-month visits, as well as endoscopy at baseline and 6-12 months. In each IUS assessment, the bowel wall thickness (BWT), presence of hyperemia, abnormal haustrations, and fat wrapping was determined in 4 bowel segments (right, transverse, descending, and sigmoid colon). The Pediatric Ulcerative Colitis Activity Index (PUCAI) scores and Ulcerative Colitis Intestinal Ultrasound Scores (UC-IUS) were calculated at each visit.

Results
42 patients (55% male) were included. Median UC-IUS total scores and BWT alone improved in all bowel segments over the study period. For the most affected bowel segment for all patients, median percent reduction of BWT was 39.6%, 34.2%, 33.7%, and 42.5%, at the 1-, 3-, 6-, and 12-month assessment respectively. The biggest decrease in UC-IUS scores and BWT occurred with the initiation of therapy between baseline and 1-month. UC-IUS scores significantly correlated with endoscopy at 12-months, clinical assessments at all time points, and biochemical markers of disease at all time points over the 12-month study period (pampersand:003C0.05). BWT measurement alone also had significant correlation with endoscopy at 12 months; clinical assessment at 1-, 3-, and 6-months; and with biochemical markers at every time point (pampersand:003C0.05). Patients with inflammatory bowel markers (indicated by elevated FCP (ampersand:003E250)) at 12-months were found to have significantly thicker BWT and UC-IUS scores at 3- and 6-months.

Conclusions
BWT and UC-IUS performed well in pediatric patients with newly-diagnosed UC, with UC-IUS scores and BWT measurements alone correlating significantly with endoscopic, clinical, and biochemical disease activity over the 12-month study period. BWT alone performed similarly to total UC-IUS scores. This data suggests that IUS can offer a non-invasive method to monitor long-term pediatric UC disease severity.

Funding Agencies
TRIANGLE, WCHRI, Stollery Children's Hospital Foundation.
A269 SEX-DEPENDENT EFFECT OF PANCREASTATIN INHIBITION ON COLON MUCOSAL INTEGRITY IN HOMEOSTATIC CONDITION
Authors: Tshikudi D M , Hitchinson H , Hesampour F , Ghia J 
Published: February 2024

Abstract

Background
Sex bias in inflammatory bowel disease (IBD)-associated colorectal cancer (CRC) epidemiology is well known. Pancreastatin (PST), an epithelial cells-derived peptide overexpressed in IBD patients, regulates the endoplasmic reticulum (ER) and survival signalling involved in CRC. Pancreastatin inhibitor 8 (PSTi8), an inhibitor of PST, showed promising anti-inflammatory effects in IBD male mice model. However, no data exists regarding PST’s role in colon mucosal regeneration and epithelium maintenance.

Aims
Here, we investigated the impact of PSTi8 treatment on colonic epithelial cells in male and female mice under homeostatic conditions.

Methods
Male and female C57BL/6 mice were treated with PSTi8 (2.5mg/mL/kg, i.r.) or PBS for six days. Epithelial cells’ proliferation (Ki67) and differentiation (cytokeratin-20) were measured by immunofluorescence. Genetic markers for differentiated epithelial cells (goblet Muc2 and Tuft Dclk1), stem cells (fast-cycling Lgr5, reserve Hopx and fetal-like Ly6a), stem cell regulator (BMP4), epithelial cells lineage commitment (Atoh1, Hes1, Gfl1), ER activation (ATF6), and apoptosis (CHOP) were tested by qRT-PCR.

Results
PSTi8 treatment decreased epithelial cell proliferation in both sexes. The inhibition of PST lowered the differentiation of epithelial cells and mucus production and increased tuft cell gene expression in females but not in male mice. In females, PSTi8 treatment increased fast-cycling stem cells but lower reserve and fetal-like stem cells in both sexes. In addition, PST inhibition significantly downregulated BMP4, which regulates epithelial cell differentiation, in females while not altering its expression in males. In contrast, PSTi8 treatment significantly increased transcription factors regulating epithelial cells' self-renewal and lineage commitments Hes1 and GFI1 in females but decreased Atoh1 in both sexes. PST inhibition enhanced gene expression of ER stress molecules ATF6 and CHOP in female and ATF6 in male mice. CHOP remained unaltered by PST inhibition in males.

Conclusions
PSTi8 alters colonic epithelial regeneration, differentiation, and thus maintenance in a sex-dependent manner.

Funding Agencies
CIHRChildren’s Hospital Research Institute of Manitoba (CHRIM)/Research Manitoba
A270 RISK FACTORS FOR COLORECTAL NEOPLASIA DEVELOPMENT IN INFLAMMATORY BOWEL DISEASE PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS: A CASE-CONTROL STUDY
Authors: van Lierop L , Derks M , te Groen M , Tran C , Lytvyak E , Montano Loza A , Hoentjen F 
Published: February 2024

Abstract

Background
Patients with inflammatory bowel disease (IBD) and concomitant primary sclerosing cholangitis (PSC-IBD) have a 25-year cumulative risk of up to 50% to develop colorectal neoplasia (CRN). Mucosal inflammation is an important driver of CRN development in IBD, but it is unknown whether this also applies to PSC-IBD patients.

Aims
We aimed to assess the impact of active mucosal inflammation per colonic segment and endoscopic remission on CRN risk.

Methods
This is a single-center case-control study, including cases with PSC-IBD with CRN, and controls with PSC-IBD without CRN. Exclusion criteria were a CRN diagnosis prior to IBD or PSC diagnosis, familial CRC syndromes, and insufficient endoscopic follow-up (ampersand:003C2 available colonoscopy reports, and for cases, ampersand:003C2 available endoscopy reports before CRN diagnosis). Data was collected on demographics, IBD and PSC disease characteristics, and IBD medication use. Data from all available colonoscopy and sigmoidoscopy reports between 2002 and 2023, including endoscopic and histologic disease severity, disease extent, and CRN lesions, was collected. The primary outcome was a diagnosis of CRN, secondary outcomes included CRN grade and location, inflammatory burden per colonic segment harboring CRN, and colonic surgery.

Results
We included 247 PSC-IBD patients (163 ulcerative colitis, 80 Crohn’s disease) with a median follow-up of 6.3 years (IQR: 4.1-12.6) and 6 endoscopic procedures (IQR: 4.0-8.0). Median disease duration was 19 years for IBD (IQR: 11.0-26.0) and 13 years for PSC (IQR: 7.0-18.0). In 50 cases a total of 113 CRN lesions were observed, of which 11 (10%) were advanced CRN (aCRN; HGD or CRC). 23 patients (45%) were diagnosed with ampersand:003E 1 lesion while 45 lesions (40%) were identified in the right-sided colon, 27 (24%) in the transverse colon, 28 (25%) in the left-sided colon, and 10 (9%) in the rectum (3 lesions unknown). Endoscopic remission was observed in 24 cases (48%) during the 2 endoscopies prior to lesion detection vs. in 83 controls (42%) for their last 2 endoscopies. Of all CRN lesions, 39 (35%) were found in a colonic segment with confirmed previous endoscopic and/or histologic inflammation during the 1-2 endoscopies prior to lesion detection (31 low-grade and 8 aCRN). Of the 32 patients who underwent (sub)total colectomy or proctocolectomy, 20 (63%) had an indication due to CRN diagnosis. Mortality was 13% (n=32) during follow-up.

Conclusions
The risk for CRN and associated colectomy is high in PSC-IBD. Active mucosal inflammation preceded CRN in the affected colonic segment in only 35% of the lesions. Future expansion and additional analysis of our cohort will focus on the impact of persistent endoscopic remission and impact of biologic therapy on CRN risk in PSC-IBD.

Funding Agencies
None
A271 EFFECT OF ANTI-TNF AGENTS ON DNA METHYLATION IN PERIPHERAL BLOOD OF PATIENTS WITH INFLAMMATORY BOWEL DISEASE
Authors: Venner J , Francis J , Rumore J , Sargent M , Jones M , Bernstein C 
Published: February 2024

Abstract

Background
Despite the success and ongoing use of tumor necrosis factor inhibitors (TNFi) in the treatment of inflammatory bowel disease (IBD), there are no predictors of response to therapy. While much research has gone into understanding genetic risks for IBD, less work has been done exploring epigenetic associations with treatment. Hence, we wondered whether epigenetic changes were associated with failure of TNFi in IBD.

Aims
Describe the association of TNFi response with DNA methylation in patients with IBD.

Methods
Participants ≥18 years with IBD (N=169) were selected from the Inflammation, Microbiome, and Alimentation: Gastro-Intestinal and Neuropsychiatric Effects (IMAGINE) Strategy for Patient Oriented Research (SPOR) Network. At enrollment participants completed a questionnaire that included their disease diagnosis, therapy, smoking history, and disease activity using the validated IBD Symptom Inventory (IBDSI). Patients provided whole blood samples that were processed for and run on Illumina DNA methylation arrays.

Results
The 169 patients were in three treatment groups: TNFi naïve (N=98, never exposed to an anti-TNF agent), TNFi responder (N=32, inactive disease on anti-TNF agent), and TNFi nonresponder (N=39, active disease not on any biologic at time of enrollment). The mean symptom score (SIBDSI) was different across the three groups (pampersand:003C0.001): TNFi nonresponders having a higher SIBDSI (24 ± 6.1) than the TNFi naïve (9.1 ± 5.5) or responder (8.3 ± 4.3) treatment groups. Relative proportions of leukocyte populations were estimated using DNA methylation. CD4 and CD8 T cell and B cell counts were higher (pampersand:003C0.05) in the nonresponders and responders versus TNFi naïve group. Neutrophil counts were lower (pampersand:003C0.05) in the TNFi nonresponders and responders compared to the TNFi naïve group (Figure 1). There was a trend towards increased epigenetic estimates of age acceleration (pampersand:003E0.05) in nonresponders versus responders and TNFi naïve patients, likely driven by disease activity (data not shown). Epigenome-wide analysis of the three groups revealed 16 CpGs for responder versus naïve (e.g. CDK5 regulatory subunit-associated protein 1-like 1 (CDKAL1), and two CpGs for nonresponders versus responders (Table 1). This includes a CpG for guanine nucleotide-binding protein subunit gamma-2 (GNG2) that was shared between the two comparisons.

Conclusions
Exposure to TNFi is associated with changes in peripheral leukocyte populations independent of response to treatment, indicating a TNFi effect. This implies that anti-TNF treatment is having some effect on patients even if there is clinical nonresponse. Differentially expressed CpGs implicates possible markers of response to treatment, particularly CDKAL1, a gene that has been associated with TNFi response in psoriasis.

Funding Agencies
Guts and Roses Charity
A275 THE POTENTIAL MECHANISTIC ROLES OF SPHINGOLIPIDS IN HEALTHY FIRST-DEGREE RELATIVES OF PATIENTS WITH CROHN'S DISEASE
Authors: Xue M , Lee S , Neustaeter A , SHAO J , Huynh H , Griffiths A , Turner D , Madsen K , Moayyedi P , Steinhart H , Bitton A , Mack D , Jacobson K , Ropeleski M , Cino M , Bernstein C , Panaccione R , Bressler B , Turpin W , Croitoru K 
Published: February 2024

Abstract

Background
Crohn's Disease(CD) features a complex etiology intertwining genetic, environmental, and immunological dimensions. Sphingolipids (SPs) are pivotal lipid molecules within cell membranes and various biological processes, including cell growth, apoptosis, and inflammatory responses. While our prior research identified SPs as significant risk factors for CD onset, their pre-clinical influence on CD risk biomarkers and potential role in pathogenesis remains unclear

Aims
To identify the relationship between SPs and established CD risk factors

Methods
We used samples from healthy first-degree relatives(FDRs), followed in a nested case-control cohort from the Crohn's Colitis Canada- Genes, Environment, Microbial(GEM) project, matching those who developed CD(n=77) with control FDRs(n=303) based on age, sex, follow-up time, and geographic location. 59 SPs were selected from serum metabolites measured via an untargeted metabolomics platform. We used partial Spearman correlation to identify relationships between SPs and CD risk factors: i)intestinal permeability via the urinary fractional excretion ratio of lactulose to mannitol(LMR); ii)gut subclinical inflammation using fecal calprotectin(FCP); iii)systemic inflammation with C-reactive protein(CRP); iv)microbiome composition through fecal 16S rRNA sequencing and v)serum protein profile using the Olink® Proximity Extension Assay platform. A two-sided qampersand:003C0.05 was considered significant

Results
We identified 38 positive correlations between CRP and SPs across various sub-pathways, including Ceramides, Sphingomyelins and Hexosylceramides(0.117≤rho≤0.342, 1.37×10−09≤q≤0.042). One SP Ceramide(d18:1/16:0) correlated positively with FCP(rho=0.201, q=0.012). Moreover, two SPs, N-palmitoyl-sphingosine (d18:1/16:0) and glycosyl-N-(2-hydroxynervonoyl)-sphingosine (d18:1/24:1(2OH)), correlationed with Peptoclostridium genus (rho=0.465 and -0.245, q=1.47×10−16 and 0.028 respectively). All SPs correlated with one or more proteins, most positively between Sphingosine-1-phosphate and non-receptor tyrosine kinase(rho=0.637, q=1.98 ×10−36) and most negatively between sphingadienine and Chymotrypsin-C protein(rho=-0.334, q=4.11×10−8). No significant correlations emerged between SPs and LMR

Conclusions
We identified correlations between SPs and CD risk factors. The correlation with CRP suggests SPs might contribute to systemic inflammatory pathways related to CD. Moreover, correlations with the bacterial taxa highlight SPs' potential role in regulating microbial composition. Extensive correlations with proteins emphasize the pivotal impact of SPs on their function. This study may offer new insights into CD prevention

Funding Agencies
CCC, CIHR
A276 A SYSTEMATIC REVIEW OF THE ASSOCIATION BETWEEN EOSINOPHILIC ESOPHAGITIS AND INFLAMMATORY BOWEL DISEASE
Authors: Yanofsky R P , Jogendran R , Hoxha T , Pathak A , Orchanian-Cheff A , Tandon P 
Published: February 2024

Abstract

Background
Inflammatory bowel disease (IBD) and eosinophilic esophagitis (EoE) are chronic inflammatory conditions of the gastrointestinal tract. IBD and EoE have been linked to other autoimmune conditions. There has been conflicting evidence on whether these two diseases are associated.

Aims
The purpose of the current study is to perform a systematic review evaluating the incidence of co-existing IBD and EoE. To determine whether the relationship between IBD and EOE is unique for autoimmune conditions, we also evaluated the relationship between other autoimmune conditions such as rheumatoid arthritis and atopic dermatitis and EOE.

Methods
A comprehensive search strategy was conducted on July 10, 2023 using MESH terms for eosinophilic esophagitis and IBD, autoimmune disorders or connective tissue disorders in Ovid MEDLINE; Ovid Embase; Cochrane Database of Systematic Reviews (Ovid); and Cochrane Central Register of Controlled Trials (Ovid). The primary outcome was defined as the frequency of concomitant IBD and EOE compared to the frequency of IBD alone. Secondary outcomes included the frequency of concomitant autoimmune conditions and EOE compared the frequency of the autoimmune condition alone, as well as the examination of clinical, biomarker, and endoscopic outcomes of patients with concomitant IBD and EOE compared to patients with IBD alone.
Five independent reviewers participated in study selection applying eligibility criteria and selecting studies for inclusion. Duplicate items were removed and title and abstracts screening occurred. Any publication deemed potentially relevant by was carried forward to the full-text review. Discrepancies were resolved by consensus.

Results
Our systematic search identified 2144 potential studies. After screening titles, we were left with 268 studies. Following full text review, 50 studies remained which included 9 articles and 19 abstracts on IBD and EOE, and 8 articles and 14 abstracts on other autoimmune conditions and EOE.
The 9 articles on IBD and EOE consisted of 6 retrospective cohort, 1 prospective cohort, 1 case-control and 1 case series study. 8 of the studies were conducted in the United States and 1 was conducted in Italy. There were 4 studies on adult populations, 4 studies on pediatric populations, and 1 study in both. There was a total of 133,451,249 patients evaluated, the majority being from one study (n=133,308,339 patients). The number of concomitant IBD and EOE patients per study ranged from 5 to 3506 patients and the number of IBD patients without EOE ranged from 33 to 701,601 patients. In the general population, the number of EOE patients alone per study ranged from 33 to 102,048. Completion of data extraction and statistical analysis is ongoing.

Conclusions
There may be an association between IBD and EOE. Further data analysis is ongoing.

Funding Agencies
None
A279 WHY LIVER TRANSPLANT RECIPIENTS DIE: A QUALITY ASSURANCE REVIEW
Authors: Aboalfaraj N , Talab R , Marquez V , Chahal D , Hussaini T , Dmitriew M , Yoshida E 
Published: February 2024

Abstract

Background
Liver transplant techniques have significantly advanced over time, enhancing patient survival rates. In 2022, 99 liver transplants were performed in British Columbia (BC), ranking second in organ transplants. In BC, mortality rates for liver transplant recipients are 9.4% at one year, 15.6% at three years, 21% at five years, and 31% at ten years. However, a knowledge gap exists about the causes of post-transplant deaths in BC. This study aims to explore the primary mortality causes among these recipients over the last decade.

Aims
This study aims to investigate the leading causes of mortality among liver transplant recipients in British Columbia between 2013 and 2023. The objective is to identify areas for improvement and to develop strategies to decrease mortality rates.

Methods
We conducted a retrospective observational study including all patient deaths among liver transplant recipients in BC between January 1, 2013, to August 31, 2023. Secondary data from the BC Transplant database were used for this analysis.

Results
Over a ten-year period, 320 deaths were recorded in liver transplant recipients in BC. On average, patients were 53.5±12.96 years. Additionally, 60% of these individuals were male. Deaths occurred, on average, 8.6 ± 8.05 years after the patients received their transplants. Malignancy emerged as the primary cause of death, representing 24.7% of all fatalities. Together, multi-organ failure (12.5%), sepsis (11.3%), and cardiovascular issues (6.9%) made up close to one-third of the total deaths. Thirty-one patients (9.7%) died due to liver-related causes. The most common causes of graft loss were hepatitis C recurrence (6/31) and allograft rejection (8/31). Unfortunately, the cause of death was unknown in a significant proportion of patients (67/320), with nearly one-third (10/31) of all liver-related mortalities lacking a clear documented etiology.

Conclusions
Our study elucidated the causes of death in liver transplant recipients in British Columbia over the past decade. Cancer-related mortality, multi-organ failure, sepsis, cardiovascular events, and liver allograft failure were among the most common causes of death in this patient population. Hepatitis C recurrence and allograft rejection were common etiologies for liver-related mortality. The significant proportion of patients with undetermined or undocumented causes of death is of concern. These findings underscore the necessity for enhanced oncological surveillance, rigorous patient evaluation, and a potential re-evaluation of post-transplant care, especially in managing infections and cardiovascular health. The substantial "unknown" causes of death emphasize a need for better data capture provincially.

Funding Agencies
None
A291 ANA-NEGATIVE AUTOIMMUNE HEPATITIS IN A 30-YEAR-OLD FEMALE: A DIAGNOSTIC CHALLENGE
Authors: Islam A H , Mortuza R , Arab J 
Published: February 2024

Abstract

Background
Autoimmune Hepatitis (AIH) is a chronic liver condition arising from the immune system's attack on liver cells. Its diagnosis is typically supported by the presence of autoantibodies, notably ANA. However, cases have been identified where AIH occurs in the absence of these conventional serologic markers. Prior studies have reported that ANA-negative AIH patients showed more acute presentations and higher frequencies of histologic acute hepatitis compared to those with positive autoimmune serology. As such, ANA-negative subset of patients presents a diagnostic challenge but highlights the evolving understanding of autoimmune processes in liver diseases.

Aims
To detail the clinical presentation, investigative measures, and treatment approach in a an otherwise healthy 30-year-old female diagnosed with ANA-negative autoimmune hepatitis.

Methods
The diagnostic approach included clinical symptomatology, biochemical tests, imaging via abdominal ultrasound, and histopathological evidence from an ultrasound-guided liver biopsy

Results
The patient presented initially with epigastric pain, jaundice, and pruritus over two weeks. Blood tests revealed acute hepatitis: ALT at 2723 U/L[JA1] , AST at 1428 U/L, and hyperbilirubinemia at 503 μmol/L, with GGT and ALP remaining normal. An abdominal ultrasound presented a typical liver morphology and biliary system. Initial autoimmune liver disease panels, including ANA, and viral hepatitis screenings, returned negative results. Furthermore, the patient's medication and drug history provided no additional clues for drug-induced aetiologies. For more conclusive diagnostics, an US-guided liver biopsy was performed during the admission revealing moderate acute hepatitis characterized by both interface hepatitis and lobular inflammation, prompting the suspicion for ANA-negative AIH. Initiating prednisone treatment (40 mg daily) based on clinical and biopsy evidence led to a significant reduction in liver enzymes and bilirubin. By the time of her discharge, her primary residual symptoms were mildly controlled jaundice and pruritus. She was transitioned to a tapering dose of prednisone, and Azathioprine was later added to her regimen. Subsequent close follow up revealed complete resolution of her symptoms. Notably, a 7-month follow-up unveiled a previously undetected AIH marker: ASMA with a titre of 1:80.

Conclusions
ANA-negative AIH, as showcased in this case, emphasizes the importance of a thorough and iterative diagnostic approach. Traditional serological markers may not always be present, necessitating reliance on a combination of clinical presentations and histopathology. Regular follow-ups and periodic re-evaluations are essential. This approach is crucial for pinpointing the diagnosis, guiding effective therapeutic interventions, and ultimately ensuring positive outcomes for patients navigating complex autoimmune liver conditions.

Funding Agencies
None