Introduction

Ulcerative colitis (UC) is a chronic inflammatory bowel disease marked by relapsing symptoms and significant impact on quality of life, with current therapies often limited by suboptimal efficacy or adverse effects. Interleukin-12/23p40 (IL-12/23p40) antagonists have emerged as targeted treatments due to their role in modulating key inflammatory pathways, yet the class-wide efficacy and safety of these agents remain uncertain.

Aims & Methods

To evaluate the effectiveness and safety of IL-12/23p40 antagonists in moderate to severe UC, a systematic review, meta-analysis, and trial sequential analysis were conducted. Databases including PubMed, Embase, Cochrane Central, and ClinicalTrials.gov were searched in December 2024 to identify randomized controlled trials (RCTs) comparing IL-12/23p40 antagonists to placebo. Outcomes included clinical and endoscopic remission and response, adverse events, and additional endpoints such as histologic healing, symptomatic relief, and glucocorticoid-free remission. Risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) were pooled using a random-effects model in R software.

Results

Nine RCTs enrolling 3,808 patients in the induction phase and 1,734 in the maintenance phase were included [1–6]. IL-12/23p40 antagonists significantly improved clinical remission during induction (21.8% vs. 8%; RR 2.63, 95% CI 2.05–3.36, p < 0.001) and maintenance (46.8% vs. 23%; RR 1.99, 95% CI 1.63–2.44, p < 0.001), and clinical response (induction: RR 1.94, 95% CI 1.70–2.20, p < 0.001; maintenance: RR 1.51, 95% CI 1.34–1.69, p < 0.001). Endoscopic remission (induction: RR 2.36, 95% CI 1.63–3.41, p < 0.001; maintenance: RR 1.96, 95% CI 1.63–2.37, p < 0.001) and endoscopic response were also significantly improved. Notably, prior biologic or JAK inhibitor failure was linked to higher induction remission rates (RR 3.74, 95% CI 1.60–8.76, p = 0.002), with meta-regression confirming this association (p = 0.008), suggesting enhanced remission in previously treatment-resistant patients. Additionally, IL-12/23p40 antagonists improved histologic, endoscopic, and mucosal healing (RR 2.49; 95% CI 2.01–3.08, p < 0.001), symptomatic remission (RR 2.16, 95% CI 1.66–2.82, p < 0.001), and quality of life as measured by the IBDQ score (MD 16.3, 95% CI 12.2–20.4, p < 0.001). Moreover, IL-12/23p40 antagonists demonstrated a favorable safety profile in both the induction and maintenance phases. During induction, they were associated with a significantly lower risk of serious adverse events (RR 0.40, 95% CI 0.27–0.69, p < 0.001). No significant differences were observed compared to placebo in the overall incidence of adverse events (induction: RR 0.97, 95% CI 0.90–1.04, p = 0.38; maintenance: RR 0.95, 95% CI 0.87–1.03, p = 0.22), headache (induction: RR 1.17, 95% CI 0.82–1.68, p = 0.39; maintenance: RR 1.29, 95% CI 0.60–2.78, p = 0.51), or nasopharyngitis (induction: RR 1.09, 95% CI 0.67–1.76, p = 0.73; maintenance: RR 1.07, 95% CI 0.77–1.50, p = 0.68).

Conclusion

IL-12/23p40 antagonists demonstrate superior efficacy compared to placebo in inducing and maintaining clinical and endoscopic remission in patients with moderate to severe UC, with a favorable safety profile and potential benefits even among biologic-experienced populations. These results support the use of IL-12/23p40 antagonists as an effective and well-tolerated treatment option in the management of UC.

References

1. Louis E, Schreiber S, Panaccione R, Bossuyt P, Biedermann L, Colombel JF, et al. Risankizumab for Ulcerative Colitis: Two Randomized Clinical Trials. JAMA. 2024 Sep 17;332(11):881–97.
2. D’Haens G, Dubinsky M, Kobayashi T, Irving PM, Howaldt S, Pokrotnieks J, et al. Mirikizumab as Induction and Maintenance Therapy for Ulcerative Colitis. N Engl J Med. 2023 Jun 29;388(26):2444–55.
3. Rubin DT, Allegretti JR, Panés J, Shipitofsky N, Yarandi SS, Huang KHG, et al. Guselkumab in patients with moderately to severely active ulcerative colitis (QUASAR): phase 3 double-blind, randomised, placebo-controlled induction and maintenance studies. Lancet. 2024 Dec 17;S0140-6736(24)01927-5.
4. Peyrin-Biroulet L, Allegretti JR, Rubin DT, Bressler B, Germinaro M, Huang KHG, et al. Guselkumab in Patients With Moderately to Severely Active Ulcerative Colitis: QUASAR Phase 2b Induction Study. Gastroenterology. 2023 Dec;165(6):1443–57.
5. Sandborn WJ, Ferrante M, Bhandari BR, Berliba E, Feagan BG, Hibi T, et al. Efficacy and Safety of Mirikizumab in a Randomized Phase 2 Study of Patients With Ulcerative Colitis. Gastroenterology. 2020 Feb;158(3):537-549.e10.
6. Sands BE, Sandborn WJ, Panaccione R, O’Brien CD, Zhang H, Johanns J, et al. Ustekinumab as Induction and Maintenance Therapy for Ulcerative Colitis. N Engl J Med. 2019 Sep 26;381(13):1201–14.

Introduction

Non-alcoholic fatty liver disease (NAFLD) is a significant public health concern. Social media (SoMe) is increasingly popular in lower-middle-income countries and can potentially influence perceptions and understanding of illness. Approximately one-third of Sri Lanka's population uses SoMe for health information. We assessed the quality of NAFLD-related content on SoMe.

Aims & Methods

This observational, cross-sectional study aimed to assess the accuracy, completeness and quality of SoMe content relating to NAFLD across Facebook, YouTube, TikTok, Instagram and X (Twitter) from Sri Lanka, in Sinhala, English, and Tamil languages. Posts containing keywords related to NAFLD published between January 2005 to December 2024 were evaluated. Specialist gastroenterologists independently reviewed the content using standardized scales for accuracy (0-3), completeness (0-5), and global quality score (GQS) (0-5). Posts were categorized by source profile [healthcare institution (HI), healthcare professional (HP), alternative healthcare professionals (AHP), non-healthcare person (NHP), or undisclosed identity (UI)] and content type [health education (HEd), health promotion (HProm), HEd and HProm or product endorsement]. User interactions (likes, shares, views) were also analyzed and correlated with reviewer scores.

Results

The analysis included 289 SoMe posts [158 (54.7%) YouTube, 101 (34.9%) Facebook, 14 (4.8%) TikTok, 11 (3.8%) X, 5 (1.7%) Instagram] relating to NAFLD in three languages [214 (74.0%) Sinhala, 54 (18.7%) Tamil, 21 (7.3%) English]. Posts from UI (36.0%) and NHP (26.0%) comprised the majority of content sources. HP (22.1%), AHP (14.2%), and HI (1.7%) represented the remainder. HProm (61.9%) was the predominant content type followed by HEd and HProm (17.6%), HEd alone (11.8%), and product endorsement (8.7%).
The mean accuracy score was 1.78/3(59.3%), with significant differences between sources (HP: 2.35/3(78.5%), AHP: 1.53/3(51.0%), NHP:1.65/3(55.1%), UI: 1.63/3(54.3); p<0.001). Completeness scores averaged 2.1/5(42%), with content in English scoring higher [2.52/5(50.4%)] than Sinhala [2.05/5(40.97%)] and Tamil [2.17/5(43.33%)]. GQS averaged 2.4/5(48.4%). 82% of posts were classified as "Rotten" (<60% composite reviewer score for accuracy, completeness, and global quality). Content quality by platform was compared using ANOVA (mean) and Kruskal-Wallis (median) tests. Posts on Facebook and YouTube showed significantly higher completeness and GQS compared to other platforms (p<0.05).
User interaction analysis was conducted using both Pearson’s and Spearman’s correlation tests. There were no significant correlations observed between accuracy, completeness, or GQS and views or likes. Inter-reviewer variation was assessed using ANOVA and non-parametric tests. There was no statistically significant inter-reviewer variation in scoring patterns, indicating consistency within reviewer groups.

Conclusion

The majority of the SoMe content was from NHP sources. HP delivered the most accurate content. Facebook and YouTube emerged as platforms with relatively higher-quality content compared to others. Overall accuracy, completeness and GQS remained suboptimal across platforms. Most posts (82%) failed to meet adequate quality standards. Notably, user engagement metrics did not correlate with content quality. These findings highlight the need for improved quality control measures and health literacy initiatives to enhance the reliability of information regarding NAFLD on SoMe platforms.

Disclosure

All authors confirm no conflicts of interests to declare.

Introduction

Non-invasive biomarkers that enable accurate diagnosis, patient stratification, and therapy monitoring in irritable bowel syndrome (IBS) are still lacking in clinical practice. Volatile organic compounds (VOCs) produced by the host metabolism, inflammatory processes, and the gut microbiota are present in exhaled breath and have recently gained attention as promising biomarker candidates. Prior research (Van Malderen et al. (2020)) demonstrated that breath VOC profiling could accurately distinguish IBS patients from healthy controls using multicapillary column/ion‑mobility spectrometry (MCC/IMS).

Aims & Methods

The present study aimed to assess the potential of high-resolution gas chromatography-quadrupole time‑of‑flight mass spectrometry (GC-QTOF-MS) profiling of breath VOCs to define distinct compound classes that enhance the mechanistic understanding of breath-based biomarkers in IBS. To this end, breath samples from 12 IBS patients and 11 healthy controls were collected, together with matched ambient air samples and were analyzed using GC-QTOF-MS. Breath samples were corrected by background subtraction and least‑absolute‑shrinkage‑and‑selection‑operator (LASSO) regression was applied with leave‑one‑out cross‑validation (LOOCV) to identify discriminative VOC signatures. The feature set was subsequently filtered to exclude sporadically detected VOCs and compounds of exogenous (non-host) origin. Finally, the remaining VOCs were mapped to putative pathways.

Results

IBS patients had a mean ± SD age of 36 ± 15.3 years, compared with 56 ± 15.4 for the healthy controls. The male-to-female ratio was 3:9 in the IBS cohort and 5:6 among the healthy controls. Within the IBS group, 7 patients had diarrhea-predominant IBS, 4 had constipation-predominant IBS, and 1 had mixed-type IBS. The LASSO regression model, validated with LOOCV, demonstrated high discriminative performance in differentiating IBS patients from healthy controls, with the corresponding model metrics in Table 1. Furthermore, the feature selection identified a panel of discriminative VOCs - predominantly alkanes, aldehydes, and ketones - that were up-regulated in the IBS breath profiles. These elevated compound classes could putatively be linked to mechanisms relevant to IBS pathophysiology, including altered microbial metabolism, increased oxidative stress, and low-grade inflammation.

Table 1: Model metrics

Conclusion

Volatomic breath profiling in IBS, shows great potential for discriminating IBS from healthy controls and for defining clinically relevant biomarkers composed of specific VOCs. Nonetheless, the limited sample size might risk model overfitting and introduces uncertainty in the estimates. Further research including larger, confounder-controlled cohorts is necessary, along with the targeted validation of the identified VOCs to further confirm their mechanistic role in IBS.

References

Van Malderen K, Hanning N, Lambrechts H, Haverhals T, Van Marcke S, Ceuleers H, De Man JG, De Winter BY, Lamote K, De Schepper HU. Volatile organic compound profiling as a potential biomarker in irritable bowel syndrome: A feasibility study. Front Med (Lausanne). 2022 Aug 4;9:960000. doi: 10.3389/fmed.2022.960000. PMID: 35991639; PMCID: PMC9388331.

Introduction

Advances in non-celiac wheat sensitivity (NCWS) have proved that it should be considered a protean condition in which several potential triggers [e.g. gluten, wheat amylase-trypsin inhibitors, etc.] might determine an intestinal mucosal damage with increased permeability and exposure of foods/microbial peptides to immune cells (1,2), resulting in both a local and systemic inflammatory activation responsible for its gastrointestinal and extraintestinal manifestations (3,4). Up to 75% of NCWS subjects complain of multiple foods hypersensitivities (MFH) (5). These patients usually have clinical, immunological and histological features similar to wheat allergy patients, although without positive gluten/wheat IgE assays, allowing to hypothesize the existence of a non-IgE mediated hypersensitivity. In addition, several studies have reported an association between atopic diseases and NCWS.

Aims & Methods

This study aimed to define the presence and features of atopic diseases and other hypersensitivities (primarily food allergies/intolerances) in NCWS compared with celiac disease (CD) and irritable bowel syndrome/functional dyspepsia (IBS/FD) and to analyze a possible correlation between these diseases and NCWS clinical manifestations. This retrospective, multicenter study included NCWS patients diagnosed by double-blind placebo-controlled challenge with wheat. Their clinical, laboratory and histology data at diagnosis (i.e. before the start of a wheat-free diet) were analyzed and compared to control subjects with CD and IBS/FD. Specific allergology data, other than clinical/laboratory features typical of NCWS, were collected and analyzed: family and personal history of atopic diseases, type of allergens responsible, positivity of skin prick tests (SPT), patch tests and total and food-specific IgE.

Results

Atopic disease prevalence was higher in NCWS (32.8%) than in CD (19.3%) and IBS/FD (21.5%) (P=.001 for both). Similarly, NCWS subjects had a higher frequency of MFH (39.8%) and self-reported milk intolerance (SRMI) (65.9%) compared to the controls (P <.001 for both). Allergic asthma, either alone (P=.03) or associated with allergic rhinitis (P=.005), was more prevalent in NCWS compared to IBS/FD, which was more often associated with allergic conjunctivitis (P=.004) or allergic rhinitis alone (P=.02). Graminaceae hypersensitivity and nickel allergic contact dermatitis (Ni-ACD) were more frequent in patients with NCWS (70.1% and 17.8%) vs both CD (48.7% and 9.4%, P=.03 and P=.01, respectively) and IBS/FD (50.8% and 6.7%, P=.01 and P<.001, respectively). On multiple logistic regression analysis, a coexistent atopic disease (OR 1.481), MFH (OR 3.882) and SRMI (OR 2.259) were associated with the NCWS diagnosis. NCWS subjects with atopy compared to those without more frequently had Ni-ACD (P<.001) and SRMI (P=.03), positive patch test (P<.001), SPT for foods (P=0.001) and both total and food-specific serum IgE (P=.02 and P=.002, respectively). On multiple logistic regression analysis, positivity to patch test (OR 2.955), SPT for foods (OR 5.799), and food-specific serum IgE (OR 3.101) were confirmed as differentiating the 2 subgroups.

Conclusion

NCWS subjects have a higher frequency of atopic disease, MFH and SRMI compared to both CD and IBS/FD ones. These conditions could be expression of an underlying hypersensitivity milieu characterizing NCWS and might be of support in the differential diagnosis between NCWS and functional gastrointestinal disorders, if inserted into a broader diagnostic panel.

References

1) Zevallos VF, Raker V, Tenzer S, Jimenez-Calvente C, Ashfaq-Khan M, Rüssel N, et al. Nutritional Wheat Amylase-Trypsin Inhibitors Promote Intestinal Inflammation via Activation of Myeloid Cells. Gastroenterology. 2017;152:1100-1113.e12.
2) Uhde M, Ajamian M, Caio G, De Giorgio R, Indart A, Green PH, et al. Intestinal cell damage and systemic immune activation in individuals reporting sensitivity to wheat in the absence of coeliac disease. Gut. 2016;65:1930–7.
3) Volta U, De Giorgio R, Caio G, Uhde M, Manfredini R, Alaedini A. Nonceliac Wheat Sensitivity. Gastroenterol Clin North Am. 2019;48:165–82.
4) Catassi C, Elli L, Bonaz B, Bouma G, Carroccio A, Castillejo G, et al. Diagnosis of Non-Celiac Gluten Sensitivity (NCGS): The Salerno Experts’ Criteria. Nutrients. 2015;7:4966–77.
5) Carroccio A, Mansueto P, Iacono G, Soresi M, D’Alcamo A, Cavataio F, et al. Non-Celiac Wheat Sensitivity Diagnosed by Double-Blind Placebo-Controlled Challenge: Exploring a New Clinical Entity. American Journal of Gastroenterology. 2012;107:1898–906.

Disclosure

This study is funded by the European Union - Next Generation EU, Mission 4, Component 1 CUP B53D23031860001, Project Code: P2022Z9RZY_001.

Introduction

Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction affecting 5 to 10% of the population, combining chronic abdominal pain and altered bowel transit. Its varied and complex mechanisms make management difficult and can be responsible for impaired quality of life. Patient education is recommended for managing chronic diseases. As part of a patient education program, the first step is to assess patients' knowledge and needs by conducting a shared educational assessment. Experiments conducted in various countries have shown that therapeutic patient education (TPE) can be effective, reducing severity, improving quality of life, and reducing care seeking. These studies have also shown that patients often have a lack of knowledge and/or misconceptions about IBS (1).

Aims & Methods

This study aimed to assess the baseline knowledge level of patients enrolled in a patient education program. Patients with IBS were selected for participation in a TPE program following a multidisciplinary day hospital for IBS. All patients had to have seen a general practitioner and/or a gastroenterologist outside the team without sufficient improvement in their condition. The TPE was based on a document developed in collaboration with a patient organisation (APSSII). This program was divided into five 1-hour sessions (training and discussion time) conducted by different professionals (neurogastroenterologists, clinical psychologist, dietitian) covering the following points:
1) understanding my illness (epidemiology, diagnosis, mechanisms),
2) talking about my illness and expressing my needs (interaction with loved ones, work, doctor, school, rights and support);
3) organizing my daily life, improving my quality of life (impact of IBS on QoL, work, exercise, intimate life);
4) taking advantage of different treatments and care options (placebo, adverse effects, symptomatic and long-term treatment, alternative treatments);
5) the role of eating and diets (balanced diet, lactose-free, gluten-free, low-FODMAP, food allergies, risks of diets). Before the start of each session, questionnaires testing participants' knowledge on the session topic were completed.

Results

From November 2023 to September 2024, 135 questionnaires completed by 43 patients with IBS were included. 70% were women, mean age 45 ± 18 years, subtypes based on IBS transit: IBS-C 55%, IBS-D 33%, IBS-M 12%, with a mean severity (IBS-SSS) of 331 ± 72 points, EQ5D health score of 50 ± 21. Among the most common misconceptions, 25% believed that a diagnosis by endoscopy was possible, 48% believed the disease could be complicated by IBD, and 13% by colon cancer. Regarding treatments, 11% of patients believed that the placebo effect only concerned medications, 58% believed that faecal microbiota transplantation could currently be offered in clinical routine for IBS care, 78% believed that hypnotherapy was only effective if you believe in it, and 68% believed that multi-strain probiotics were more effective than single-strain ones.

Conclusion

This study, conducted in France on patients with moderate or severe forms of IBS, shows a highly variable level of knowledge about their disease depending on the questions, with some significant misconceptions that need to be addressed. These results justify the implementation of therapeutic education for these patients. A study is underway to verify the improvement in patients' knowledge and the existence of a positive impact of this strategy on symptom severity and quality of life.

References

(1) Halpert et al. What Patients Know About Irritable Bowel Syndrome (IBS) and What They Would Like to Know. National Survey on Patient Educational Needs in IBS and Development and Validation of the Patient Educational Needs Questionnaire (PEQ). Am J Gastroenterol 2007; 102:1972-82.

Disclosure

Nothing to disclose