bluuebunny/crossref_metadata_2025_split huggingface dataset:
A67 CASE REPORT: A RARE CASE OF MALAKOPLAKIA
Authors: Bray S D , Myette J , Stueck A , Petropolis H 
Published: February 2025

Abstract

Background
Malakoplakia is a rare chronic granulomatous inflammatory condition first described in the literature in 19021. It is thought to be a result of impaired macrophages ability to completely digest and kill bacteria, resulting in phagocytosed bacteria accumulating in macrophages calcifying overtime. Malakoplakia can affect all organs of the body and is four-times more likely to affect females2. It most commonly occurs within the genitourinary tract with the gastrointestinal tract being the second most common site.

Aims
The literature regarding malakoplakia of the rectum is limited and rare3.

Methods
This 39-year-old immunosuppressed male with a history of three renal transplants receiving tacrolimus and chronic prednisone found to have rectal malakoplakia. He was referred to gastroenterology for symptoms of constipation and iron deficiency anemia. A colonoscopy was completed which demonstrated 4-rectal polyps, each at an estimated size of 5 mm which were removed by cold snare.

Results
The rectal polyps were sent for histological analysis and demonstrated expansion of cells into the lamina propria. Cells were mostly epithelioid histiocytes with some admixed neutrophils, lymphocytes, and plasma cells, but infiltration did not destroy the mucosal architecture or crypts. Some of the histiocytes contain pale, round intracytoplasmic structures with concentric layering, consistent with Michaelis-Gutmann bodies. CD68 confirmed infiltrating cells were macrophages, confirming a diagnosis of rectal malakoplakia (Figure 1).

Conclusions
He was seen in follow-up in Gastroenterology clinic and his symptoms of constipation, did not appear to be contributory towards this incidental finding of malakoplakia. Furthermore, infectious disease was involved in this patient’s care for consideration of antimicrobial therapy, but a decision was made to treat conservatively and monitor for any new gastrointestinal symptoms. This patient is followed by gastroenterology and booked for repeat colonoscopy in 6-months for follow-up to determine if these lesions can be eradicated through polypectomy.
1. Liu, Xiangyu, et al. “Rectal malakoplakia mimicking advanced rectal cancer: A case report.” Heliyon 9.10 (2023).
2. Wang, Zhenting, and Jiannan Ren. “Clinical analysis of renal failure caused by malakoplakia: a case report and literature review.” Frontiers in Medicine 9 (2022): 770731.
3. Achufusi, T. G., Jessamy, K., Chebaya, P., & Rawlins, S. (2020). Rectal malakoplakia. Proceedings (Baylor University. Medical Center), 33(3), 389–390.

Funding Agencies:
A72 INFLUENCE OF THE MICROBIOME ON DENDRITIC CELL FUNCTION
Authors: Miller W L , Kazanova A , Brouillard-Galipeau M , Gavino C , Gruenheid S 
Published: February 2025

Abstract

Background
The intestinal microbiome educates the immune system, in part through signaling in antigen- presenting cells including dendritic cells (DCs). Germ-free mice exhibit DC deficiency, migration impairment, and priming dysfunction, implying a relationship between microbiota and DC function. Naturally acquired, endemic Helicobacter species (H. spp.) such as H. hepaticus are common in many mouse colonies, whereas some facilities are Helicobacter-free.

Aims
Although they do not cause overt disease in most immune-competent mouse strains, we hypothesized that H. spp. could be a source of low-level inflammation, resulting in immune reprogramming and leading to phenotypic differences between H. spp.-positive and H. spp.- negative mice.

Methods
We generated bone marrow-derived dendritic cells (BMDCs) from H. spp.-positive mice and from genetically identical mice rendered H. spp.-free through mouse rederivation. BMDCs were stimulated for 6 hours (or not) with ultra-pure lipopolysaccharide (LPS). We measured expression of molecules MHC-I and MHC II (Signal 1 of antigen presentation) and CD80, CD86 and PD-L1 (Signal 2), the “activating” epigenetic mark of trimethylation at lysine 3 of histone 4 (H3K4me3) and metabolic changes via flow cytometry. Multiplex ELISA was used to measure secreted cytokines (Signal 3) and in vitro methods were used to assay BMDC antigen presentation. Bulk RNA sequencing of BMDCs was performed to further understand microbiome-linked changes in BMDC phenotype.

Results
Surface expression of molecules related to Signal 1 and Signal 2 of antigen presentation were increased both at steady state and after LPS stimulation in BMDCs derived from H. spp.-positive in comparison with H. spp.-free mice and this correlated with the abundance of H3K4me3. The presence or absence of H. spp. also altered metabolic phenotype of BMDCs upon LPS stimulation.

Conclusions
The presence of Helicobacter in the gut microbiome influences BMDC phenotype and may alter BMDC function. We anticipate epigenetic changes involved in BMDC phenotypic and functional changes, which will require in-depth epigenetic profiling. Future directions also include fecal microbiota transplant experiments and Helicobacter infection models followed by BMDC characterization using our established pipeline.

Funding Agencies
None
A81 GASTROINTESTINAL ADVERSE EVENTS ASSOCIATED WITH GLUCAGON-LIKE PEPTIDE-1 (GLP-1) AGONISTS IN OVERWEIGHT PATIENTS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Verma Y , Gimpaya N , Tran W , Sondawle R , Sinanian G , Tham D , Grover S 
Published: February 2025

Abstract

Background
Glucagon-Like Peptide-1 (GLP-1) agonists are widely prescribed for managing type 2 diabetes and have recently gained attention for their potential in promoting weight loss in obese patients. The off-label use of certain GLP-1 agonists for weight loss has been steadily increasing, raising concerns about their safety in non-diabetic patients. Although the gastrointestinal (GI) side effects of GLP-1 agonists are well-documented in diabetic populations, their impact on overweight or obese individuals has not been systematically analyzed.

Aims
To systematically review and analyze the incidence, severity, and types of GI adverse events (AEs) associated with the use of GLP-1 agonists in overweight or obese patients (BMI: &gt;25 kg/m2)

Methods
We conducted a systematic search across five databases, including PubMed, Ovid MEDLINE, Embase, Web of Science, and Scopus. Studies were restricted to randomized controlled trials (RCTs) involving GLP-1 agonists whose primary indication was obesity and whose primary outcome was weight loss. Studies that did not report adverse events were excluded. Adverse events were extracted using their preferred terms from the Medical Dictionary for Regulatory Activities (MedDRA). A meta-analysis was performed to pool the relative risk (RR) of GI AEs using the random effects model. A meta-regression was also performed.

Results
A total of 42 studies (n = 23318 patients) met the inclusion criteria. GLP-1 agonists showed an increased risk of nausea (RR 2.77; 95% CI 2.50–3.10; p &lt; 0.001), diarrhea (RR 2.01; 95% CI 1.78–2.01; p &lt; 0.001), and constipation (RR 2.13; 95% CI 1.90–2.38; p = 0.05) when compared to placebo. The incidence of nausea was higher in those with lower average BMI (coefficient: 3.88; p = 0.005). Additionally, we found no difference between GLP-1 agonists and placebo in the risk of cholelithiasis, cholecystitis, and biliary dyskinesia (RR 1.62; 95% CI 1.22–2.17; p = 0.99).

Conclusions
Our study found that obese patients are at an increased risk of experiencing nausea, diarrhea and constipation when using GLP-1 agonists compared to placebo. Gallbladder disorders showed no difference in risk. For obese patients, lower average BMI may increase the likelihood of experiencing nausea.

FIgure 1. Forest plot indicating relative risk for nausea in obese patients treated with GLP-1 agonists. Error bars represent 95% confidence intervals.

Funding Agencies
None
A82 DIETARY PROTEIN COMPOSITION ALTERS INTESTINAL INFLAMMATION AND MTOR ACTIVATION
Authors: Rondeau L E , Muppidi P , Da Luz B , Kan K , Dang R , Wang X , Caminero A 
Published: February 2025

Abstract

Background
Environmental factors, notably changes in diet and microbiota composition, have been identified as key contributors to the development of inflammatory bowel diseases (IBD). The prevalence of IBD is on the rise, particularly in industrialized nations with populations consuming western-style diets rich in fat and protein. While total and animal protein intake have been associated with IBD, their specific impact on intestinal inflammation remains poorly understood. Branch-chain amino acids found in different protein source possess bioactive properties and can interact with the mechanistic target of rapamycin (mTOR), a cellular growth regulator that controls autophagy and inflammation. Given the observed mTOR hyperactivation in IBD patients, coupled with its correlation with exacerbated colitis severity in murine models, a comprehensive exploration into the relationship between dietary protein intake, mTOR activation, autophagy, and intestinal inflammation is warranted.

Aims
To study the influence of high protein and animal protein diets on mTOR activation, autophagy, and intestinal inflammation in mouse models of colitis.

Methods
Specific pathogen free C57BL/6 mice were fed a high protein diet (HPD; 40% casein), animal meat protein diet (APD; 14% mixed protein), or control diet (CD; 14% casein), for three weeks prior to tissue collection (N=6 per diet) or experimental colitis induction (N=8 per diet). Experimental colitis was induced using dextran sulfate sodium in drinking water (DSS; 2.5% w/v) or colonic administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS; 2%). DSS was provided ad libitum for five days, followed by two days of water recovery before tissue collection. Rapamycin (10 mg/kg/day) was provided intraperitoneally to a subset of mice as an mTOR inhibitor. mTOR activation and autophagy markers were assessed by western blot (WB) of mTOR substrates and autophagy proteins in colon tissue extracts pre- and post-colitis. Apoptotic cells in colon cross sections were quantified by TUNEL. Susceptibility to colitis was assessed by histologic analysis of distal colon sections, weight loss, and clinical scores. Inflammatory gene transcripts were quantified in colon tissue by Nanostring.

Results
DSS and TNBS exposure in mice fed the HPD and APD led to greater weight loss, tissue damage, inflammatory gene signaling, diarrhea, and stool blood. HPD and APD increased mTOR activation (phosphorylation of mTOR and S6 ribosomal kinase) compared to CD. Autophagy proteins were downregulated, and apoptotic cells were increased in intestinal tissue of HPD- and APD-fed mice, before colitis. Inhibition of mTOR with rapamycin restored autophagy and reduced colitis severity.

Conclusions
Protein quantity, source, and BCAA content optimization is crucial for determining inflammation, mTOR activation, and autophagy in mouse models of colitis.

Funding Agencies
CAG, CCC, CIHR
A83 PLANT-BASED ENTERAL NUTRITION: A POTENTIAL METHOD OF SECRETION MANAGEMENT IN A PALLIATIVE PATIENT WITH PROGRESSIVE MYOTONIC DYSTROPHY — A CASE REPORT
Authors: Nap Hill E F , Broening J , Sasson S , Ou G 
Published: February 2025

Abstract

Background
Degenerative neuromuscular conditions such as myotonic dystrophy is characterized by oropharyngeal dysfunction leading to reduced ability to eat orally and clear respiratory secretions. Enteral nutrition (EN) is often required in these patients but aspiration pneumonia remains a concern. Dairy-based EN are commonly used, but evidence suggests that casein digestion may stimulate mucin production in respiratory tissues, increasing secretions (Bartley 2010).
McClanahan et al. (2019) showed that switching patients to plant-based EN improved gastrointestinal outcomes and reduced medication use in chronically ill, tube-fed children. Viall et al. (1990) found soy-based EN led to fewer gastrointestinal issues, such as vomiting and gastric residuals, compared to casein-based EN. Goelen et al. (2021) also reported that plant-based EN resulted in faster gastric emptying compared to casein-based EN, which could reduce secretion-related complications.

Aims
To describe nutrition management in a palliative patient with myotonic dystrophy with recurrent aspiration pneumonia.

Methods
Case report.

Results
A patient with myotonic dystrophy type 1, was admitted with viral respiratory infection resulting in respiratory failure and prolonged hospitalization with marked deterioration in respiratory and swallowing functions. A nasogastric and then percutaneous gastrostomy feeding tubes were placed but feeding regimens remained suboptimal (50% caloric provision) due to recurrent aspiration pneumonia. A transgastric jejunal feeding tube was then placed without much clinical improvement despite trying various enteral feeding formula (including high-protein and high-calorie formulations) and maximal anti-secretory management as per palliative care team. Aggressive feeding was in line with patient’s goals of care after much discussion, so nutrition team was consulted for recommendations.
Patient was switched to plant-based EN due to concerns that dairy protein stimulated secretions. Patient experienced a reduction in secretion thickness and fewer aspiration events. Goal EN rate was achieved.

Conclusions
This case highlights the potential benefits of plant-based EN in managing secretions and reducing aspiration risk in a patient with progressive myotonic dystrophy. Transition from dairy-based to a plant-based alternative led to better secretion control, fewer aspirations, and reduced antibiotics. While this is a single case, the findings align with evidence that plant-based EN may improve gastrointestinal outcomes and alleviate secretion-related complications. Further studies are needed to explore the efficacy of plant-based EN in broader patient populations and its role in managing secretions and aspiration pneumonia.

Funding Agencies
None
A84 THE USE OF PHYTASE TO ENHANCE DIETARY IRON AND ZINC ABSORPTION - A SCOPING REVIEW
Authors: Hirota S , Adamidi N , Chondrou T , Lygouras D , Androutsos O , Svolos V 
Published: February 2025

Abstract

Background
Phytic acid is abundant in plant-based diets and acts as a micronutrient inhibitor for humans and non-ruminant animals. Phytases are enzymes that break down phytic acid, releasing micronutrients and enhancing their bioavailability, particularly iron and zinc. Deficiencies in iron and zinc are common in patients with the inflammatory bowel diseases and in those in developing countries consuming phytic acid-rich diets.

Aims
This literature review aimed to summarize findings from human intervention studies on the interactions between phytic acid, phytase and micronutrient bioavailability.

Methods
An extensive PubMed search (01/01/1990 to 08/02/2024) was conducted using MeSH terms (phytic acid, phytase, IP6, “inositol hexaphosphate,” micronutrient, magnesium, calcium, iron, zinc). Eligible studies included human intervention trials investigating the bioavailability of micronutrients following a) phytase supplementation, b) consumption of phytic acid-rich foods, or c) consumption of dephytinised foods. In-vitro, animal, cross-sectional, and non-English studies were excluded.

Results
3055 articles were identified. After title and full-text review 40 articles were eligible. Another 2 were identified after cross-checking reference lists from included papers, resulting in 42 included articles. Most studies exploring the efficacy of exogenous phytase (9 of 11, 82%) or the efficacy of food dephytinisation (11 of 14, 79%) presented augmented iron and zinc bioavailability. In agreement to this, most phytic acid-rich food feeding studies (13 of 17, 77%) showed compromised iron and zinc bioavailability.

Conclusions
Strong evidence supports decreased iron and zinc bioavailability in phytic acid-rich diets and the improvement potential with phytase interventions. Further studies are needed in larger populations.

Funding Agencies
None
A92 MULTIFACETED STRIDE II-BASED MONITORING FOR INFLAMMATORY BOWEL DISEASE ADVANCED THERAPY STARTS
Authors: Parsons D , MacKay S A , Hoque S , Hoentjen F , Dieleman L , Gozdzik M , Kroeker K , Wong K , McMullen T , Peerani F , Halloran B 
Published: February 2025

Abstract

Background
Inflammatory bowel disease (IBD) outreach monitoring has been shown to be cost-effective and reduce healthcare utilization. IBD STRIDE-II guidelines recommend monitoring patient-reported outcomes (PRO’s), biomarkers (e.g., fecal calprotectin (FCP), C-reactive protein (CRP)), and endoscopy to determine if patients achieve defined therapeutic targets. Previous monitoring in the literature has focused on PRO’s alone, which risks undertreating asymptomatic inflammation in spite of elevated flare and colorectal cancer risk. We designed a protocol to closely monitor biomarkers and PRO’s.

Aims
We aimed to assess STRIDE-II based clinical response and facilitate responsive disease management for new advanced therapy start patients.

Methods
Patients complete 24 weeks of outreach monitoring. PRO’s are obtained on days 0, 3, and 7, and every 2 weeks thereafter. Serum labs are collected at baseline and weeks 4, 8, 12, 16, and 24. FCP is collected at baseline and weeks 8, 16, and 24. Medication adherence is assessed at baseline and weeks 12 and 24. Endoscopy is booked 6-12 months from the start date. Treating gastroenterologists receive granular clinical reports summarizing results, the date of last IBD review, and last flare.

Results
75 protocol patients on the following therapies: ustekinumab (n = 31), risankizumab (n = 17), tofacitinib (n = 14), upadacitinib (n = 10), vedolizumab (n = 2), and infliximab (n = 1) were monitored in our protocol so far. 51 patients (68.0%) had failed 1+ prior advanced therapies and 13 (17.3%) had prior IBD surgery. 7 (9.3%) were switched from their initial agent before 24 weeks due to lack of response. 1 (1.3%) had an adverse drug event. 64 patients (85.3%) complied with all FCP collections and 73 (97.3%) completed 95+% of PRO’s. Per STRIDE-II definitions, 47 patients (62.7%) demonstrated clinical response during the protocol and 25 (33.3%) achieved remission by 24 weeks. 15 (20.0%) received steroid courses, 9 (12.0%) presented to an emergency department, and 5 (6.7%) were hospitalized for IBD during monitoring.

Conclusions
Our proactive monitoring protocol provided granular real-world clinical response data to treating physicians. Patients were highly compliant with serial PRO, FCP, and serum labs collection. The protocol facilitates responsive disease management and may lead to treatment-specific monitoring recommendations. In future, we will compare protocol patients to standard of care managed patients to learn if the protocol reduces healthcare utilization and improves patient outcomes and quality of life.

Funding Agencies
None
A105 TRANSITION TO ADULTHOOD THROUGH COACHING AND EMPOWERMENT (TRACE): A FEASIBILITY RCT
Authors: Beaudoin K , McKean H , Nsamenang S , Bortolin K , Cellucci T , Dowhaniuk J , Heale L , Issenman R M , Pai N , Sherlock M , Zachos M , Beattie K , Batthish M , Prowse K 
Published: February 2025

Abstract

Background
Pediatric patients with chronic disease face challenges during the transition to adult care, including psychosocial and emotional stressors, as well as worsening disease.

Aims
Transition to Adulthood through Coaching and Empowerment (TRACE) assessed the feasibility of conducting a virtual transition coaching randomized controlled trial for adolescent patients and collected preliminary clinical outcomes.

Methods
Individuals aged 16-17 diagnosed with inflammatory bowel disease or juvenile idiopathic arthritis from the pediatric gastroenterology (GI) or rheumatology clinics at McMaster Children’s Hospital were recruited. Participants were randomized into control or Transition Coach Intervention (TCI) groups. TCI participants received 8 virtual coaching sessions; 6 with a child life specialist and 2 with a clinical psychologist. Electronic questionnaires were completed at baseline, 8 months, and 11 months. Feasibility outcomes, patient demographics, transition readiness, and quality of life were recorded. Descriptive statistics summarized feasibility outcomes and outcomes by group.

Results
Of all participants (n=27), 67% were male, and the mean (SD) age was 16.8 (0.5) years. The recruitment rate was 58% and 38% for the GI and rheumatology clinics, respectively. The overall dropout rate was 7%. All TCI participants attended at least 6/8 sessions, and 63% of participants had a complete data set (Table I). Figure 1 shows baseline and 8-month follow-up data for preliminary clinical outcomes, such as transition readiness and quality of life, which will inform the design of a future randomized controlled trial.

Conclusions
The TRACE study aims to show that a virtual TCI trial is feasible. Based on preliminary responses to this transition intervention, we plan to conduct a large-scale, randomized controlled trial.
Table I: Feasibility outcomes. (n=14 control group, n=13 TCI group, n=27 total). JIA = juvenile idiopathic arthritis, IBD = inflammatory bowel disease, TCI = transition coach intervention

Figure 1. Transition-Q and Peds-QL scores at baseline and 8-month follow-up. (n=13 for the control group, n=8 for the baseline TCI group; n=8 for the 8-month follow-up control group, and n=6 for the 8-month follow-up TCI group). F/U = follow-up, TCI = transition coach intervention
Funding Agencies: HAHSO