Introduction

Functional defecation disorders are causes of obstructive defecation due to alteration in the coordination of abdominal contraction and anal relaxation. Four manometric patterns of dyssynergic defecation (DD) have been described, such that in type I and III there is an alteration of anal relaxation with adequate rectal propulsion, and in types II and IV rectal propulsion fails. According to the Rome IV criteria, the diagnosis of DD requires confirmation with two tests of anorectal function, with the most commonly used being high-resolution anorectal manometry (HRAM) and the balloon expulsion test (BET). Within the manometric parameters, the rectoanal gradient (RAG) appears to be the most useful.

Aims & Methods

To evaluate the clinical characteristics of patients according to patterns of DD defecation and to establish the cutoff point of the RAG and relaxation percentage (RP) that allows predicting balloon expulsion or not.
A total of 960 high-resolution anorectal manometries (HRAMs) performed from January 2021 to April 2024 were reviewed, including 337 patients with DD (35%). Prior to performing the HRAM, epidemiological and clinical data of the patients were collected. Although retrospectively reviewed, all data were prospectively collected. HRAM was performed with solid-state catheters (Medtronic). For BET a balloon (Matla Systems S.L) was filled with 50 mL of water was used under conditions of privacy while sitting on a toilet. Values of 60 seconds or less were considered normal.

Results

Included were 337 patients with a mean age of 61.7 ± 13.9 years. Among them, 226 (67.1%) were female. The diagnosis of DD was confirmed with an altered BET in 96 (28.5%) of the patients. In the remaining cases, the diagnosis of DD was inconclusive.
The epidemiological and clinical characteristics are described in table 1. The presence of associated structural causes was observed in all groups: 102 cases (42.7%) in types I-III; and 52 patients (53.6%) in types II-IV. The frequency for rectal hyposensitivity was 47.5%, and it was similar in both groups: 112 cases (46,6%) in types I-III, and in 48 cases (49,5%) in types II-IV.
The Area Under the Curve (AUC) for RAG was 0.738 (95% CI 0.682 - 0.794), identifying a cut-off value for RAG of -34.1 with an estimated sensitivity of 81.3% and specificity of 57.3% (figure 1). The AUC for RP was 0.544 with a cutoff point of 5.5% (95% CI 0.476 - 0.611), demonstrating low sensitivity (62,5%) and specificity (52,7%) (figure 2).

Conclusion

The frequency of DD diagnosed by HRAM is high (35% in our series), being more common in women. The high coexistence of structural causes, which can give a false manometric pattern of DD, is noteworthy. In types II and IV (rectal propulsion disorders), the diagnosis was confirmed by the failure to expel the balloon more frequently than in types I and III. Rectal hyposensitivity is very frequent in these patients. So far, the Rectoanal Gradient (RAG) is the best parameter of HRAM to evaluate DD. A value below -34 mmHg allows reasonably discriminating whether patients will expel the balloon or not.

Disclosure

No conflict of interests

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.

Introduction

The therapeutic landscape for ulcerative colitis (UC) is rapidly evolving, with an increasing number of biologic agents available.

Aims & Methods

This systematic review and meta-analysis synthesised randomised controlled trials (RCTs) data on biologic therapies for achieving key endoscopic and histologic endpoints in moderate to severe UC. A systematic search of MEDLINE, EMBASE, Cochrane Library, Web of Science and grey literature was conducted through November 2024. Separate meta-analyses were performed for induction and maintenance. A random-effects model was used to estimate relative risks (RR), with 95% confidence intervals (CI) and confidence in estimates was evaluated with the GRADE approach (Grading of Recommendation Assessment, Development and Evaluation).

Results

We included 40 RCTs (13 therapies , 14,369 patients). Thirty-two trials provided data in induction phase and twenty-eight in maintenance phase. During induction phase, all biologic therapies except for mirikizumab and filgotinib 100 mg demonstrated superiority over placebo (RR 2.02, 95% CI:1.76–2.31, I²=72%) for endoscopic improvement. Upadacitinib showed the highest efficacy (RR 5.53, 95% CI: 3.78-8.09). In biologic-naive patients and in patients with no previous biologic failure status upadacitinib 30mg had the highest efficacy (RR 4.07, 95% CI:2.69-6.16). In biologic-exposed patients or those with previous biologic failure, upadacitinib 30mg also showed the greatest benefit (RR 10.52, 95% CI:4.55-24.34). For induction of mucosal healing, all interventions were superior to placebo (RR 2.95, 95% CI:2.11–4.13,I²=61%), except for filgotinib 100 mg. Risankizumab showed the highest efficacy (RR 10.25, 95% CI:2.49-42.11). In maintenance phase, all therapies showed superiority over placebo for endoscopic improvement. Upadacitinib showed the highest efficacy (RR 4.18, 95% CI: 2.79–6.27). In biologic-naïve patients or those without prior biologic failure, all interventions—except filgotinib 100 mg and vedolizumab—were significantly superior to placebo, with etrasimod showing the highest efficacy (RR 3.12, 95% CI: 1.79–5.43). Among biologic-exposed patients or those with prior biologic failure, upadacitinib, mirikizumab, ustekinumab, etrasimod, tofacitinib, and risankizumab 180 mg were significantly superior to placebo. Upadacitinib showed the highest efficacy (RR 7.58, 95% CI: 3.42–16.8). For mucosal healing all therapies were superior to placebo, except for risankizumab. Upadacitinib showed the highest efficacy (RR 4.01 ,95% CI: 1.81–8.87). In biologic-naïve patients or those without prior biologic failure, only etrasimod, mirikizumab, upadacitinib 30 mg and subcutaneous infliximab were significantly superior to placebo, with upadacitinib showing the highest efficacy (RR 3.02, 95% CI: 1.18–7.71). Among biologic-exposed patients or those with prior biologic failure, only etrasimod, mirikizumab, and upadacitinib were significantly superior to placebo, with etrasimod demonstrating the highest efficacy (RR 9.45, 95% CI: 1.31–68.36).

Conclusion

Biologic and small-molecule therapies demonstrated substantial efficacy in achieving key endoscopic and histologic endpoints in moderate to severe UC. Upadacitinib consistently showed the highest efficacy across both induction and maintenance phases. Stratified analyses revealed enhanced response rates in biologic-naïve patients, supporting early initiation of advanced therapies. Our findings highlight the importance of individualised treatment strategies and the urgent need for standardised endpoint definitions to enhance comparability across future trials.