bluuebunny/crossref_metadata_2025_split huggingface dataset:
A63 FIRST REPORTED PEDIATRIC CASES OF SEWER WORKER’S DISEASE
Authors: Swatski M D , Issenman R M 
Published: February 2025

Abstract

Background
Sewer worker’s disease, often recognized as a workplace hazard for sewer workers, has never been described in pediatric subjects.

Aims
We report a case series of two siblings who developed chronic nasopharyngeal discharge, sore throat, diarrhea and irritability secondary to airborne supersaturation of E. Coli from an improperly vented household septic tank.

Methods
Case Series- Retrospective Chart and Literature Review

Results
The affected subjects were a six year old boy and his three year old sister. The boy presented with chronic diarrhea. The girl presented with six to eight watery stools per day and nocturnal stooling. Parents reported that both children also had a chronic purulent nasal discharge and complained of sore throats. Her parents also endorsed anorexia along with increased fussiness. Both siblings had been treated with metronidazole for Giardia Lamblia five years earlier. Repeat examination of stool for ova & parasites was negative. CBC and D-xylose were normal. Both children underwent upper GI endoscopy. Biopsy was normal in one and diffuse duodenal inflammation was noted in the second child. A heavy growth of E. Coli was cultured from the nares of both children.
The children both slept in a basement bedroom. Their father had installed a toilet in the basement 18 months prior to their presentation. The babysitter and the patient’s grandmother both developed similar symptoms after spending prolonged periods of time in the bedroom. Their symptoms resolved when they were away from the house. The mother recalled “a sewer” smell that had been present in the basement since her husband had installed a basement toilet. Professional inspection noted that the absence of a ”stack” to properly vent the toilet which was directly connected to the home septic tank. This left the basement air supersaturated with E. Coli. All the children’s symptoms resolved after the basement toilet was removed and the related drain sealed.
It is presumed that the growth of E. Coli as well as exposure to sewer gas was responsible for their ENT and GI symptoms. Lundholm, M. et al. describe how sewer worker’s symptoms including skin disorders and diarrhea were directly related to the concentration of airborne gram-negative bacilli.
As these children’s symptoms were directly related to exposure to an improperly vented sewage system and immediately resolved following corrective action, the most likely explanation was supersaturation. This should prompt Pediatricians to take a broader environmental history, particularly when multiple patients develop symptoms which are similar in character and time of onset.

References
Lundholm, M., & Rylander, R. (1983). Work related symptoms among sewage workers. Occupational and Environmental Medicine, 40(3), 325-329.

Conclusions
When confronted with a cluster of common symptoms in uncommon places, physicians should consider the possibility of environmental diseases.

Funding Agencies
None
A71 SUBGROUP ANALYSIS OF CANADIAN PARTICIPANTS IN PUNCH CD3-OLS: A PHASE 3 OPEN-LABEL CLINICALSTUDY TO EVALUATE THE SAFETY AND EFFICACY OF FECAL MICROBIOTA, LIVE-JSLM, IN ADULTS WITH RECURRENT CLOSTRIDIOIDES DIFFICILE INFECTION
Authors: Steiner T S , Louie T , Kao D , Smyth D , Guthmueller B , Jason T , Elliott S N , Srivastava S , Lee C 
Published: February 2025

Abstract

Background
Fecal microbiota, live-jslm (RBL) is the first United States (US) Food and Drug Administration-approved, single-dose, microbiota-based live biotherapeutic product to prevent recurrent Clostridioides difficile infection (rCDI) in adults following standard-of-care (SOC) antibiotics. In a prospective phase 3, open-label study (PUNCH CD3-OLS; NCT03931941) conducted in the US and Canada, RBL demonstrated a 73.8% treatment success rate at 8 weeks and a 91.0% sustained clinical response rate through 6 months.

Aims
To evaluate the safety and efficacy of RBL in Canadian participants in PUNCH CD3-OLS.

Methods
PUNCH CD3-OLS participants were aged ≥18 years with documented rCDI and confirmed use of SOC antibiotics. Participants with comorbidities including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and immunocompromising conditions due to disease and/or medications were permitted to enroll. A single dose of RBL was rectally administered within 24–72h of SOC antibiotic completion. The primary endpoint was the number of participants with RBL- or administration-related treatment-emergent adverse events (TEAEs). Secondary endpoints included treatment success at 8 weeks and sustained clinical response at 6 months after RBL administration.

Results
Of the 697 participants who received RBL, 117 were Canadian. Participants in Canada were mostly White (91.5%) and female (70.1%) with a mean (SD) age of 61.3 years (17.38). Twenty participants (17.1%) were hospitalized for their qualifying episode. Participants’ medical histories included IBD (unspecified, [1.7%, n=2]; Crohn’s disease, [6.0%, n=7]; ulcerative colitis, [5.1%, n=6]), IBS (6.8%, n=8), and mild-to-moderate immunocompromising conditions (7.7 %, n=9). TEAEs through 8 weeks after RBL administration were reported by 59.8% of participants; most were gastrointestinal (48.7%, n=57) and mild-to-moderate in severity. Serious TEAEs were reported by 5.1% of participants within 8 weeks of RBL administration. At 8 weeks, 75.2% of participants (88/117) had treatment success; of those, 90.9% (80/88) had a sustained clinical response at 6 months. Demographics, safety, and efficacy outcomes were similar for participants in the US.

Conclusions
RBL was safe and efficacious for preventing rCDI among Canadian participants from PUNCH CD3-OLS, the largest study of a live microbiota-based therapy conducted to date.

Funding Agencies
NRCFerring Pharmaceuticals
A73 MICROBIAL CONTRIBUTION TO THE RISK OF FUTURE CROHN’S DISEASE: STRATIFICATION BY SUBCLINICAL INFLAMMATION LEVELS MEASURED BY FECAL CALPROTECTIN
Authors: LI Q , Turpin W , Olivera Sendra P , Xue M , Griffiths A , Panaccione R , Dieleman L , Steinhart A , Jacobson K , Lee S , Croitoru K 
Published: February 2025

Abstract

Background
Crohn’s disease (CD) prevalence is rising globally, but its pathogenesis remains unclear. Our group found specific microbes predict future CD risk in healthy first-degree relatives (FDR), whereas high fecal calprotectin (FCP) level (&gt;100ug/g) was also significantly associated with a 6-fold higher risk of CD onset. However, the influence of FCP on how microbial communities contribute to CD risk remains unknown. Understanding microbial interactions with gut inflammation may offer insights into CD onset.

Aims
This study investigates how microbial composition and function contribute to CD risk in healthy in association with their baseline FCP levels.

Methods
Healthy FDRs from the CCC-GEM Project were followed for CD onset. Using baseline stool samples, microbial compositions were analyzed with 16S rRNA sequencing and functional predictions with PICRUSt2. Cox PH models assessed relationships between microbiome composition, functional pathways, and CD risk stratified by high or low levels of subclinical inflammation, defined by FCP with a cut-off of 100 ug/g (FCP&gt;100 and FCP&lt;100, respectively). q&lt;0.1 was considered statistically significant.

Results
We followed 3430 FDRs for a median of 7.7 years, among which 76 developed CD. In the subgroup with FCP&gt;100 a higher abundance of Ruminococcus torques group, an undefined Ruminococcus genus, and Romboutsia were significantly associated with an increased risk of CD. In contrast, Oscillospiraceae family was consistently associated with a lower CD risk in both FCP&gt;100 and FCP&lt;100 subgroups.
Microbial functional pathways analysis revealed that peptidoglycan-N-acetylmuramic acid deacetylase, 4’-phosphopantetheinyl transferase, and iron(III) transport system ATP-binding protein were consistently associated with a decreased risk of CD in both FCP&gt;100 and FCP&lt;100 subgroups. However, pathways including Flagellar motor switch protein FliN and Carboxynorspermidine decarboxylase were associated with increased risk of CD, but only in the FCP&gt;100 subgroup. In contrast, geranylgeranyl diphosphate synthase and heat shock protein HspR were associated with increased CD risk in the FCP&lt;100 subgroup.

Conclusions
The microbial contribution to CD risk in healthy FDRs may vary depending on baseline FCP levels. Specific taxa and functional pathways were identified as contributors to CD risk in FDRs in the presence or absence of intestinal inflammation. Notably, the Oscillospiraceae family was consistently associated with a decreased risk of CD, highlighting its potential as a therapeutic target in the pre-clinical phase of CD.

Funding Agencies
None
A74 IMPACT OF INDOLE-3-PROPIONIC ACID ON BACTERIAL INVASION POTENTIAL OF KLEBSIELLA STRAINS ISOLATED FROM PEDIATRIC ULCERATIVE COLITIS PATIENTS
Authors: Arjomand Fard N , Aujla H , Stuart L , Cheng C C , Elhenawy W , Perry T , Wine E 
Published: February 2025

Abstract

Background
Indole-3-propionic acid (IPA), a tryptophan metabolite produced by microbes, has demonstrated beneficial effects, including reversing dysbiosis, balancing bacterial populations, and reducing inflammation. However, the mechanisms behind these effects and their impact on pathogenic microbes remain unclear. This study aimed to evaluate the effects of IPA on bacterial invasion in vitro, using potential pathobionts (Klebsiella variicola and Klebsiella quasipneumoniae) isolated from non-inflamed sections of the colon in pediatric ulcerative colitis (UC) patients.

Aims
We hypothesized that IPA could reduce virulence traits, promoting a more homeostatic environment, which could lower inflammation in pediatric UC patients.

Methods
Caco-2 cells (colonic epithelial cell line) were infected with Klebsiella strains, with or without 0.5 mM IPA. Bacterial invasion was assessed via gentamicin protection assay, and qPCR measured Interleukin-8, IL-10, and TNF-α expression in infected cells. Transepithelial electrical resistance (TEER) assay evaluated barrier integrity, and qPCR analyzed the expression of bacterial virulence genes, including entB (siderophores), manC (capsule), and hcp1 (type VI secretion) in IPA-treated and untreated cultures. Additionally, siderophore production was quantified using a Chrome-Azurol Sulfonate (CAS) assay, and Anthony’s stain visualized the bacterial capsule.

Results
IPA-treated Caco-2 cells showed significantly reduced bacterial invasion, with further reductions when bacteria were also exposed to IPA. qPCR revealed a significant decrease in IL-8 expression in IPA-treated cells during infection. IL-10 levels decreased non-significantly, and TNF-α expression showed variable results. A trend toward improved tight junction integrity was observed in the TEER assay with IPA treatment, although no significant differences were detected. IPA treatment increased the expression of entB, manC, and hcp1 genes, except for K. variicola, where manC expression remained unchanged. IPA significantly reduced the capsule thickness of K. variicola and resulted in a significant reduction in K. quasipneumoniae siderophore production.

Conclusions
IPA reduces bacterial invasion and modulates immune responses in Caco-2 cells infected with Klebsiella pathobiont strains. It decreases the virulence of K. quasipneumoniae by targeting siderophore production and diminishes the virulence of K. variicola by reducing capsule formation, suggesting its potential as an anti-virulence agent against these pathobionts. These findings highlight IPA’s potential as an immunomodulatory agent for managing IBD. However, further research is needed into other Klebsiella virulence pathways and host-microbiota interactions.

Funding Agencies
CIHRWCHRI
A85 PATTERN OF SEMAGLUTIDE PRESCRIPTION IN A REAL-WORLD PATIENT COHORT
Authors: Farahvash A , Lee M , Jain R , Jaakkimainen L 
Published: February 2025

Abstract

Background
The weight-loss effects of semaglutide has been studies in many randomized controlled trials. However, real-world data on its use is limited, particularly in the Canadian healthcare setting.

Aims
This study aims to explore the pattern of semaglutide prescription and associated outcomes in an academic family medicine practice in Canada.

Methods
We conducted a retrospective study of patients at the Sunnybrook Hospital family health team in Toronto, Ontario. Patients aged ≥18 years who were prescribed semaglutide between January 2018 and April 2024 were included. Baseline demographics and follow-up safety and efficacy measures were collected up to 16 months after semaglutide initiation.

Results
Of the 9930 rostered patients, 368 (3.71%) were prescribed semaglutide during the study period. The average age of patients who were prescribed semaglutide was 57.7±14.1 years and 63.3% were female. The average BMI was 36.6±7.84 kg/m2 and 189 patients (51.4%) had diabetes. The indication for semaglutide prescription was weight-loss for 206 patients (56.0%), diabetes for 118 patients (32.1%), and both weight-loss and diabetes for 39 patients (10.6%). We observed that since 2018, there has been a growing number of family physicians prescribing semaglutide compared to endocrinologists. In 2023 and 2024, over 80% of all semaglutide prescribers for our patients were family physicians, and endocrinologists were in the minority. Despite being prescribed semaglutide, 20 patients (5.4%) did not initiate the medication and 66 (17.9%) discontinued it within 16 months. Reasons for discontinuation included gastrointestinal adverse effects (26/66, 39.4%), difficulty in access (30/66, 54.5%), and perceived lack of response (6/66, 9.1%).
Baseline and follow up weights were recorded for 211 patients (57.3%). Mean weight-loss was 7.36%. Mean weight-loss by 16 months was significantly greater in patients without diabetes (8.83% vs. 6.18%, p=0.003) and in females (8.30% vs. 5.90%, p=0.009), although there were more females without diabetes compared to males. The mean HbA1c at follow-up was 6.5±1.1%, which represents a significant reduction of 10.7% from baseline (p &lt;0.001).

Conclusions
Our analysis of a real-world cohort of patients who used semaglutide demonstrated its wight-loss effects, particularly in those without diabetes. Understanding the demographics of patients using semaglutide and its potential effects will help inform future prescription practices.

Funding Agencies
None
A86 DIETARY BIOMARKERS OF ULTRA-PROCESSED FOODS: A NARRATIVE REVIEW
Authors: Armstrong T S , Chappell K , Ajibulu L J , Wong K 
Published: February 2025

Abstract

Background
The rapidly increasing prevalence of ultra-processed foods (UPFs) in global diets necessitates a more comprehensive understanding of this food group’s effects on health and disease. Nutritional biomarkers are critical for developing this understanding, as they provide an objective assessment of the body’s response to UPF intake.

Aims
This study aimed to assemble a comprehensive list of the current clinical biomarkers of ultra-processed foods, then categorize them and evaluate their links to disease states and health.

Methods
This narrative review assessed the findings of eight studies, all of which focused on the biomarkers of ultra-processed foods and were identified via a systematic search of the literature that included stringent criteria. Pertinent information was extracted and summarized from these studies, with a primary focus on the biomarkers identified and an exploration of some of these biomarkers’ connections with disease.

Results
Based on the data extracted from the eight included studies, we categorized ultra-processed food biomarkers into organic acids (including amino acids), lipids/lipid-like molecules, xenobiotic food components (specifically associated with UPFs), and other molecular compounds (dietary oxysterols, nucleotides, proteins, etc). Via correlations between these four categories and diseases, biomarkers of ultra-processed foods were found to be associated with inflammatory mechanisms, as well as a variety of pathologies including intestinal disorders, atherosclerosis, chronic kidney disease, and others.

Conclusions
The usefulness of our review lies in its narrative format and succinct accumulation of information pertinent to ultra-processed food analysis, while also reinforcing the detrimental impacts of this food group on health and nutrition. These findings emphasized the importance of future studies concerning ultra-processed foods and food processing techniques, while providing a succinct summary of the current biomarkers of ultra-processed foods in relevant literature.
Funding Agencies:
A90 ASSESSMENT OF A MULTI-COMPONENT QUALITY IMPROVEMENT INTERVENTION TO IMPROVE DIAGNOSTIC YIELD FROM ENDOSCOPIC ULTRASOUND-GUIDED FINE NEEDLE ASPIRATION BIOPSY OF SOLID MASS LESIONS
Authors: Sandha G , Khan S , Mathura P , Puttagunta L , Girgis S , Thiesen A , Zhang J , Nilsson J , Wasilenko S , Zepeda-Gomez S 
Published: February 2025

Abstract

Background
A chart audit to review endoscopic ultrasound (EUS)-fine needle aspiration biopsy (FNAB) of solid mass lesions from 01/2022-12/2022 identified a diagnostic yield of 75%. To improve this, a quality improvement intervention including increasing the number of needle passes to 3/case, improving needle pass documentation in endoscopy reports, reducing the number of individuals making cytology slides, and using formalin as transport medium for cell block preparation instead of saline was developed and trialed for 9 months.

Aims
To assess intervention impact on improving the diagnostic yield of EUS-FNAB of solid mass lesions.

Methods
Three endoscopists were provided targeted education and a chart audit was completed for all patients undergoing EUS-FNAB of solid mass lesions from 01/2024-09/2024. Descriptive statistics were completed. Only a definite diagnosis, as confirmed on histological examination, was considered when calculating the diagnostic yield.

Results
A total of 183 patients (112 M, 71 F), mean age 63±13 years (range 12-88 years), underwent 198 EUS-FNABs by 3 endoscopists (who made cytology slides, ensured transport medium and completed documentation). Pancreatic masses were the most common (122/198, 62%). A 22-gauge FNAB needle was used in 194/198 (98%) cases. A total of 420 needle passes were performed for 191 patient cases (mean 2.2/case) compared with mean of 1.9/case pre-intervention. Documentation improved, 7 cases (3.5%) did not have the number of needle passes specified compared with 51 cases (26%) pre-intervention. Tissue samples were transported in formalin for histology in 197 cases, on cytology slides in 165 cases, and in formalin for cell block preparation in 42 cases, similar to pre-intervention. Overall, a definite diagnosis was achieved in 156/198 cases (79%) compared with 149/200 (75%) in the pre-intervention year. Stratifying for needle passes, a definite diagnosis was achieved in 20/36 (56%), 69/87 (79%), 56/63 (89%), and 5/5 (100%) cases that had 1, 2, 3, and &gt;3 needle passes, respectively. The number of passes was seen to independently impact diagnostic yield regardless of type of solid mass, endoscopist, type/size of needle used, and whether or not tissue was provided for cell block preparation.

Conclusions
Although we did not reach our goal of 3 needle passes per case, documentation and the number of tissue samples transported in formalin improved. The results suggest 3 or more needle passes per case may improve diagnostic yield and attempts should be made to avoid performing single needle pass FNAB.

Funding Agencies
None
A91 OUTCOMES OF PATIENTS WITH PRIOR BIOLOGIC INTOLERANCE ARE BETTER THAN THOSE WITH BIOLOGIC FAILURE IN CLINICAL TRIALS OF INFLAMMATORY BOWEL DISEASE
Authors: Samnani S , Wong E , Hamam H , Dulai P , Marshall J , Jairath V , Reinisch W , Narula N 
Published: February 2025

Abstract

Background
Inflammatory bowel disease (IBD) trials often stratify patients by prior biologic exposure, including prior biologic failure or intolerance.

Aims
This study aimed to assess clinical outcomes in IBD patients with prior biologic failure versus intolerance treated with ustekinumab or vedolizumab.

Methods
A post-hoc analysis of ulcerative colitis (UC) and Crohn’s disease (CD) clinical trials for ustekinumab (UNITI, UNIFI) and vedolizumab (GEMINI-1, GEMINI-2) was performed. Clinical response, clinical remission, and endoscopic improvement (for UC) were compared among biologic naïve, biologic-failure, and biologic intolerant patients. Statistical analyses, including chi-square tests and logistic regression, were performed.

Results
1178 UC and 1439 CD patients received either ustekinumab or vedolizumab. In UC, biologic intolerant patients exhibited higher clinical response (54.7% vs. 38.8%, aOR 1.87 [95% CI 0.93-3.73]), clinical remission (25.0% vs. 11.0%, aOR 2.84 [95% CI 1.47-5.49]), and endoscopic improvement (40.6% vs. 24.8%, aOR 2.76 [95% CI 1.28-5.94]) compared to biologic failure, with outcomes similar to biologic naïve patients. In biologic-intolerant CD patients, clinical response was similar between prior biologic failure and intolerance (34.2% vs 32.8%), but after adjustment for potential confounders, biologic intolerance was associated with higher odds of clinical response (aOR: 1.67, 95% CI 1.09-2.55), with no significant difference observed for clinical remission (aOR: 1.48, 95% CI 0.88-2.49).

Conclusions
Improved treatment outcomes were generally observed in patients with biologic intolerance compared to failure, especially in UC, where outcomes were similar to biologic naïve patients. Future clinical trials should meticulously differentiate prior biologic failure versus intolerance to mitigate potential bias.

Funding Agencies
None