Introduction

The prevalence of pathogenic APC and biallelic MUTYH mutations, in patients with 10 to 19 cumulative colorectal adenomas (CRA), is stated to be 5% and 4%, respectively. ESGE and NCCN suggest referring patients with ≥10 CRA to genetic counseling, limiting direct testing to patients with ≥20 CRA. USMSTF states that patients with multiple CRA should be considered for genetic testing. BSG recommends testing all patients under 60 years-of-age with ≥10 CRA, and over 60 only patients with family history of colorectal cancer (FHC) or polyposis. Predictors are needed to further select patients and maximize the diagnostic yield.

Aims & Methods

Aim: To assess the prevalence and predictors of pathogenic APC and MUTHY mutations in patients with 10-19 lifetime adenomas to the date of the genetic test.
Methods: We retrospectively included all patients undergoing screening for APC and MUTYH mutations, in our center since 2010. Patients undergoing family screening or with a history of colorectal cancer (CRC) were excluded. Endoscopic, histological, and family history data was collected.

Results

​96 patients (36%) presented with 10-19 cumulative adenomas. Patients were on average 64,45 (±9,33) years and 78.1% were male. FHC was present in 21,8%, diminishing to 19,7% when considering first-degree relatives only and to 4,2% applying ESGE familiar-CRC definition. On average patients had 5 advanced adenomas (size ≥10mm, tubulovillous/villous histology or with high-grade dysplasia) and 66.7% had ≥10 CRA on a single colonoscopy. No patients were found to have pathogenic mutations of the APC and MUTYH genes.

Conclusion

Despite a combined expected prevalence of 7-12/100 patients, and the high presence of risk factors in our cohort, no pathogenic mutations were found. ESGE and NCCN criteria would have led to the referral of 96 patients to genetic counseling and BSG recommendations would trigger 42 genetic tests. We question the prevalence of these mutations in the Portuguese population and the cost-effectiveness of testing patients with 10-19 cumulative CRA.

Introduction

We evaluated celiac disease (CeD)-related symptoms and comorbidities in two US healthcare databases after CeD diagnosis according to the presence/absence of CeD-related symptoms or comorbidities before diagnosis.

Aims & Methods

This matched case–control study used data from two US healthcare databases: 1) MarketScan^® Commercial and Medicare Supplemental database (collection period: 2002−2023); 2) Optum Clinformatics^® Data Mart (Optum CDM; collection period: 2007−2023). Patients with CeD had ≥ 1 inpatient or ≥ 2 outpatient International Classification of Diseases (ICD)-9 or -10 codes (579.0 and K90.0, respectively) at any time during the collection period. Patients were matched in a 1:5 ratio with controls without CeD (no CeD ICD-9/-10 codes at any time during data collection) for age at diagnosis, sex, region, and diagnosis year. All individuals had continuous medical and pharmacy enrollment for 2 years pre/post CeD diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) for symptoms/comorbidities after CeD diagnosis were estimated by generalized multivariate logistic regression comparing cases vs matched controls stratified by those with (persistent) or without (new-onset) the relevant symptom/comorbidity pre-diagnosis. Symptoms assessed included abdominal pain, bloating, diarrhea, headache, nausea/vomiting, and tiredness. Comorbidities assessed included depression/anxiety, irritable bowel syndrome (IBS), and iron deficiency anemia (IDA).

Results

The numbers of CeD cases and controls were 39,814 and 198,961 in MarketScan, and 18,357 and 91,754 in Optum CDM, respectively. In both databases, CeD diagnosis was significantly positively associated with having CeD-related symptoms/comorbidities 2 years after CeD diagnosis regardless of pre-diagnosis status; and the strengths of associations were greater among patients with new-onset than with persistent symptoms/comorbidities after CeD diagnosis.
In MarketScan, the ORs (95% CI) in patients with new-onset symptoms were highest for bloating (7.98 [7.32–8.71]), diarrhea (6.83 [6.48–7.19]), and nausea/vomiting (3.75 [3.49–4.04]), and in those with new-onset comorbidities for IBS (8.30 [7.65–9.00]), IDA (6.35 [5.94–6.79]), and depression/anxiety (2.12 [2.04–2.20]). The ORs (95% CI) in patients with persistent symptoms were 2.47 (1.86–3.27) for bloating, 2.47 (2.21–2.76) for diarrhea, and 2.46 (2.05–2.96) for nausea/vomiting, and in those with persistent comorbidities were 1.38 (1.16–1.64) for IBS, 1.93 (1.70–2.18) for IDA, and 1.42 (1.34–1.51) for depression/anxiety.
In Optum CDM, the ORs (95% CI) in patients with new-onset symptoms were highest for bloating (6.15 [5.56–6.80]), diarrhea (5.85 [5.48–6.24]), and nausea/vomiting (3.38 [3.08–3.70]), and in those with new-onset comorbidities for IBS (6.17 [5.56–6.85]), IDA (5.31 [4.89–5.77]), and depression/anxiety (2.10 [1.99–2.21]). The ORs (95% CI) in patients with persistent symptoms were 2.25 (1.70–2.97) for bloating, 2.51 (2.22–2.84) for diarrhea, and 2.77 (2.23–3.43) for nausea/vomiting, and in those with persistent comorbidities were 1.40 (1.15–1.71) for IBS, 2.54 (2.17–2.97) for IDA, and 1.50 (1.38–1.62) for depression/anxiety.

Conclusion

CeD diagnosis was significantly associated with having CeD-related symptoms/comorbidities 2 years after CeD diagnosis, with greater associations among patients with new-onset symptoms/comorbidities than those with persistent symptoms/comorbidities. These results emphasize the clinical burden of CeD and the need for improved treatment options.

Disclosure

FZ has served as a speaker for Werfen and a consultant for Takeda. MA, SM, VG, SG, IP, NC, and DAL are employees and shareholders of Takeda Development Center Americas, Inc. and receive stock or stock options. BL has nothing to disclose.

Introduction

Dientamoeba fragilis is a protozoan of the human digestive tract, yet its pathogenic role remains poorly understood. Fecal microbiota transplantation (FMT) provides a useful model for investigating the potential pathogenicity and transmission of this protist from donor to recipient. Donor selection is highly stringent, and the presence of D. fragilis is subject to controversy as an exclusion criterion [1-4].

Aims & Methods

This study aimed to determine the prevalence of D. fragilis in both FMT donors and recipients and to evaluate its potential impact on the efficacy and safety of FMT as a treatment for recurrent Clostridioides difficile infection (rCDI). This single-center, longitudinal cohort study analyzed stool samples from FMT donors and recipients at three time points: pre-treatment and at 2 and 8 weeks post-FMT. All samples were negative for D. fragilis on direct microscopy and were retrospectively tested using real-time (RT-PCR). CDI cure rates, gastrointestinal adverse events (AE), and serious adverse events (SAE) were assessed prospectively.

Results

A total of 53 FMT were administered to 47 different patients, with 23 of 53 (43%) derived from D. fragilis-positive donor stool (4 out of 10 donors, 40%). One recipient tested positive before FMT (1/47, 2.1%). Among 22 patients initially negative for D. fragilis who received stool from D. fragilis-positive donors, four (18.2%) tested positive on day 15 post-FMT and remained positive at week 8. None of the recipient with D. fragilis-negative FMT was tested positive. No significant differences in efficacy, AE, or SAE were observed between recipients of FMT from D. fragilis-positive versus -negative donors, even in severely immunocompromised patients. No SAE could be attributed to FMT.

Conclusion

This study suggests that D. fragilis can be transmitted through FMT without significant clinical impact in terms of efficacy and safety. These findings argue for reconsidering the exclusion of positive donors and support the lack of pathogenicity of D. fragilis.

References

1. Hall LM, Munasinghe VS, Vella NGF, Ellis JT, Stark D. Observations on the transmission of Dientamoeba fragilis and the cyst life cycle stage. Parasitology 2024 ; 151:337–345.
2. Cacciò SM. Molecular epidemiology of Dientamoeba fragilis. Acta Trop 2018 ; 184:73–77.
3. Shasha D, Grupel D, Treigerman O, et al. The clinical significance of Dientamoeba fragilis and Blastocystis in human stool—retrospective cohort study. Clin Microbiol Infect 2024 ; 30:130–136.
4. Terveer EM, Gool T van, Ooijevaar RE, et al. Human Transmission of Blastocystis by Fecal Microbiota Transplantation Without Development of Gastrointestinal Symptoms in Recipients. Clin Infect Dis 2019 ; 71:2630–2636.