Publications

INTRODUCTION: Patients with Inflammatory Bowel Disease (IBD) experience Irritable Bowel Syndrome (IBS)-like symptoms more frequently than the general population. The impact of IBS-like symptoms on the clinical course of IBD remains uncertain.

METHODS: In a prospective cohort of patients with quiescent IBD, as defined by endoscopic remission, IBS-like symptoms were measured using the IBS-Symptom Severity Scale (IBS-SSS) at the time of endoscopy to define IBD patients with no IBS-like symptoms (IBS-SSS <75), mild IBS-like symptoms (IBS-SSS 75-175), and moderate-severe IBS-like symptoms (IBS-SSS >175). The primary outcome was total IBD-related healthcare utilization (HCU), while secondary outcomes included time to unscheduled/acute HCU and treatment failure among patients on biologics.

RESULTS: Among 114 patients with quiescent IBD, 53 had no IBS-like symptoms, 43 had mild IBS-like symptoms, and 18 had moderate-severe IBS-like symptoms. The median follow-up time was 3.5 years and was comparable among groups (p=0.330). Patients with mild or moderate-severe IBS-like symptoms had a higher total number of HCU events than patients without IBS-like symptoms (median (IQR): 8 (6-13) vs. 12 (9-15) vs 7 (5-11), respectively, p=0.042). After adjusting for IBD type and biologic therapy at baseline multivariable Cox proportional hazards regression analysis identified mild (HR: 3.6; 95%CI): 1.1-11.7; p=0.029) and moderate/severe (HR: 6.2; 95%CI: 1.8-21.3, p=0.004) IBS-like symptoms associated with unscheduled/acute HCU. Treatment failure did not differ by presence of IBS-like symptoms.

DISCUSSION: IBS-like symptoms in IBD are associated with increased HCU but not treatment failure. These findings suggest that IBS-like symptom burden in IBD is clinically meaningful, may drive healthcare seeking, and warrants targeted treatment within IBD care models.

Irritable bowel syndrome (IBS) is one of the most prevalent disorders of gut-brain interaction, characterized by recurrent abdominal pain or abdominal discomfort associated with altered bowel habits in the absence of identifiable structural disease. IBS affects  4-11% of the global population and is associated with substantial healthcare utilization, impaired quality of life and considerable socioeconomic burden. IBS is increasingly recognized as a heterogeneous condition caused by dysregulated bidirectional communication within the gut-brain axis. Altered gastrointestinal motility, visceral hypersensitivity, epithelial barrier dysfunction, neuroimmune activation, gut microbiome and metabolome changes, central pain amplification, stress and autonomic dysregulation, and sex-related biological influences underlie pathophysiological mechanisms. IBS can develop after a gastrointestinal infection and can frequently co-occur with other disorders of gut-brain interaction, chronic pain conditions, psychological disorders and organic gastrointestinal disorders such as inflammatory bowel disease and coeliac disease. Diagnosis relies on a positive symptom-based approach using the Rome V criteria, supported by clinical assessment and limited testing to exclude differential diagnoses. Management focuses on improving symptoms and quality of life through an individualized, stepwise approach that involves patient education, dietary interventions, pharmacological therapies and gut-brain behaviour therapies. Emerging biomarkers, multi-omics approaches, digital health tools and precision medicine strategies may enable mechanism-based diagnosis and targeted treatment in the future.

BACKGROUND: The use of dual advanced therapy is increasing among patients with overlapping immune-mediated diseases. This is particularly relevant in patients with inflammatory bowel disease (IBD) and eosinophilic esophagitis (EoE), where dupilumab may be added to an existing IBD-directed biologic regimen. However, real-world safety data regarding concomitant dupilumab and advanced immune-modifying therapies commonly used in IBD remain limited.

METHODS: We performed a retrospective cohort study using the All of Us Research Program Controlled Tier dataset. Adults receiving advanced immune-modifying therapies commonly used in IBD, including biologics, Janus kinase inhibitors, and sphingosine-1-phosphate receptor modulators, were categorized by documented dupilumab exposure. Participants designated as dual-exposed were required to have documented overlap between dupilumab and advanced therapy, with the index date defined as the first date of concurrent exposure. Outcomes evaluated included hospitalization, emergency department (ED) utilization, and selected infectious outcomes, including pneumonia, sepsis, cellulitis, and herpes zoster, identified using standardized diagnosis codes.

RESULTS: Among 4605 participants receiving advanced immune-modifying therapies, 21 (0.5%) had documented dupilumab exposure, of whom 12 (57.1%) had overlapping treatment periods and comprised the concurrent-therapy cohort. These participants were compared with 4458 individuals receiving advanced immune-modifying therapy alone. There were 2 versus 900 selected infectious outcomes, 3 versus 2111 hospitalizations, and 3 versus 2198 emergency department visits in the concurrent-therapy and comparator groups, respectively. Concurrent dupilumab exposure was not associated with statistically significant differences in rates of selected infectious outcomes (IRR, 2.87; 95% CI 0.35-10.40; P = 0.16), hospitalization (IRR, 1.50; 95% CI 0.31-4.40; P = 0.46), or emergency department utilization (IRR, 1.65; 95% CI 0.34-4.82; P = 0.44).

CONCLUSIONS: Concomitant dupilumab exposure among patients receiving advanced immune-modifying therapies commonly used in IBD was uncommon but was not associated with statistically significant differences in rates of selected infectious outcomes, hospitalization, or emergency department utilization in this national real-world cohort. Although limited by the small number of dual-exposed participants, these findings provide preliminary real-world data and support further investigation in larger disease-specific populations, particularly among patients with overlapping IBD and EoE, in whom the present study was not sufficiently powered to draw definitive conclusions regarding comparative safety.

OBJECTIVE: Inflammatory bowel disease (IBD) is increasingly diagnosed in older adults, but data from Latin America remain limited. This study aimed to compare the clinical, phenotypic and therapeutic characteristics of elderly and non-elderly adults with IBD in Brazil.

METHODS: This cross-sectional study included adults with confirmed Crohn's disease (CD) or ulcerative colitis (UC) attending an IBD clinic in Brazil. Patients were stratified as elderly (≥60 years) or non-elderly (<60 years); elderly individuals were further categorised according to age at diagnosis (<60 years vs ≥60 years). Clinical, therapeutic and frailty-related data were collected from medical records and structured interviews. The primary outcome was biologic therapy use.

RESULTS: 450 patients were included in the study (115 elderly, 335 non-elderly). UC was more common among the elderly patients (77.4% vs 56.7%, p<0.001). Elderly patients had higher comorbidity scores (2.6 vs 0.3 for CD; 2.6 vs 0.4 for UC; p<0.001) and greater polypharmacy (21.7% vs 3.3%, p<0.001) but similar disease activity (CD: Harvey-Bradshaw Index <5, 92.2% vs 79.3%; UC: Mayo Score <2, 88.6% vs 78.3%). They received fewer biologics (26.1% vs 43.6%, p=0.001) and immunosuppressants (22.6% vs 47.5%, p<0.001). Among elderly patients, immunosuppressant use was lower in those diagnosed at ≥60 years (2.9% vs 30.9%, p=0·001). Most elderly patients (82.3%) were robust according to the Clinical Frailty Scale.

CONCLUSION: Elderly patients were less likely to receive biologic and immunosuppressive therapy despite similar disease activity and had substantially greater comorbidity burden and polypharmacy. These findings suggest that therapeutic decisions in older adults should incorporate frailty and comorbidity assessment to support individualised age-adapted management.

INTRODUCTION: Colorectal cancer (CRC) is a common cause of cancer-related mortality. While overall incidence has declined, certain populations - particularly younger patients - have experienced a rise. This suggests a more complex risk profile than the dichotomous average vs high risk delineated in guidelines. Risk is currently largely characterized by polyp and family history; however, many additional variables contribute to risk.

AREAS COVERED: We synthesize the available data (Pubmed database, focus on article updates in the past 10 years) on non-modifiable and modifiable risk factors for CRC. We explore how these factors could affect screening and surveillance decisions in otherwise average-risk individuals. We then suggest strategies for personalized approaches to CRC screening, explore the role of shared decision making with patients, and highlight future directions for CRC screening.

EXPERT OPINION: Our understanding of CRC risk must become increasingly more nuanced to adequately serve, screen, and surveil our patients. Precision medicine offers a pathway to accomplish this, but will require significant research to accurately measure risk, and the ability to adapt risk models as our data evolves. This undertaking grows evermore relevant as medicine becomes increasingly personalized and shared decision making becomes the mainstay of counseling between physicians and patients.

Biologics targeting TNF-α, IL-23, or IL-17 clear psoriatic plaques effectively, yet lesions recur at the same anatomical sites upon treatment withdrawal. This is not a failure of potency but of target: the tissue-encoded immune memory that sustains site-specific relapse remains largely inaccessible to systemic cytokine blockade. This perspective proposes a design-first framework for skin-targeted RNA nanomedicines that translates this biological insight into concrete engineering requirements. Five immune nodes, tissue-resident memory T cells (TRM), regulatory T cells, dendritic cells, stromal-vascular niches, and cutaneous neuroimmune circuits, sustain psoriatic persistence across defined compartments of the plaque, and each is, in principle, addressable through RNA payloads delivered via dissolvable polymer microneedle arrays. The framework is organised around three design dimensions: where payloads must be deposited, what molecular instructions they must carry, and when delivery must be sequenced across a three-phase temporal model of suppression, tolerisation, and maintenance. A translational roadmap addresses regulatory classification, chemistry-manufacturing-and-controls, psoriasis-specific immunotoxicology, and adaptive within-patient trial designs anchored to mechanistic biomarkers. The framework is presented as a design hypothesis grounded in mechanistic evidence; empirical validation in human psoriatic skin is outlined as the next translational step.

BACKGROUND AND AIMS: The role of therapeutic drug monitoring (TDM) in optimizing vedolizumab (VDZ) therapy for Crohn's disease (CD) and ulcerative colitis (UC) remains unclear. Prior evidence was limited by small sample size and heterogeneous endpoints. We synthesized the available evidence on the association of VDZ trough concentrations with clinical and endoscopic remission.

METHODS: Following PRISMA 2020 guidelines, we searched the literature from inception to April 2026 for studies reporting VDZ trough concentrations stratified by remission status in CD and UC. Outcomes were clinical remission (CR) and endoscopic remission (ER). Pooled mean differences (MDs) were estimated using random-effects models with restricted maximum likelihood estimation; heterogeneity was quantified using I2 statistic.

RESULTS: Twenty-three studies (6,753 patients) met inclusion criteria; 18 contributed to quantitative synthesis. Higher VDZ trough concentrations were strongly associated with ER in UC (MD 4.86 μg/mL, 95% CI 2.75-6.98; p < 0.0001; I2 = 0.0%). Higher concentrations were also associated with CR in UC (MD 3.18 μg/mL; p = 0.025) and CD (MD 3.08 μg/mL; p < 0.0001), although these clinical-remission estimates were statistically heterogeneous; no association was observed for ER in CD (MD 1.40 μg/mL; p = 0.453). Pooled remission-associated concentrations were presented descriptively and supported maintenance targets of ≥13-15 μg/mL in UC and ≥10-12 μg/mL in CD.

CONCLUSIONS: Higher VDZ trough concentrations were associated with remission, most robustly for endoscopic remission in UC. As these associations are largely cross-sectional, they may reflect reverse causation rather than a dose-response relationship. Prospective interventional trials are required before proactive TDM can be recommended.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs), such as semaglutide, are highly effective treatments for obesity and type 2 diabetes but are often associated with gastrointestinal side effects including delayed transit times through the gastrointestinal tract. We present a non-invasive breath test to measure oral-cecal transit time (OCTT) in mice that could be readily translated to clinical studies. Current methods for measuring OCTT are limited by invasiveness, terminal procedures, anesthesia, radioactive tracers, or stress-induced influence on the outcomes. Here we demonstrate that 13C-labeled mannitol is metabolized by murine cecal microbiota, producing measurable 13CO₂ in exhaled breath. Using indirect calorimetry combined with real-time measurement of the 13C/12C ratio, this approach provides a highly granular, non-invasive method to measure OCTT in mice. This technique is performed in unrestrained freely moving animals while enabling high-throughput measurements performed longitudinally. The method improves experimental rigor and reproducibility and provides a valuable tool for studying gastrointestinal physiology and the effects of pharmacologic therapies.

BACKGROUND AND AIMS: Acute severe ulcerative colitis (ASUC) is a life-threatening manifestation of ulcerative colitis. Diagnosis typically relies on the 1955 Truelove and Witts criteria. These do not incorporate treatment history with steroids or modern advanced therapies. This Delphi panel gathered expert opinion regarding potential criteria and approaches for diagnosing ASUC in contemporary practice, including current outpatient treatment with corticosteroids/advanced therapy.

METHODS: European, North-American and Asia-Pacific gastroenterologists participated in a four-round Delphi panel and consensus meeting, forming the Refined Evaluation Framework and INvEstigations for Diagnostics in ASUC (REFINED-ASUC) Working Group. Consensus was defined as ≥70% agreement/disagreement for Likert-scale, or ≥70% homogeneity for single-/multiple-choice responses.

RESULTS: Panelists agreed there is unmet need for ASUC criteria in contemporary practice. Consensus was obtained that ASUC diagnosis could be based around 3 'major' (C-reactive protein (CRP) ≥2 x upper limit of normal (ULN), ≥6 bowel movements/24 hours, ≥50% bowel movements with visible blood/24 hours) plus ≥2 'minor' criteria (low albumin, increased heart rate, nocturnal bowel movements, low hemoglobin, increased body temperature, or elevated leukocyte count) in patients treated with advanced therapy/corticosteroids. Patients on high-dose corticosteroids constitute a subgroup requiring different thresholds (CRP ≥1 x ULN, ≥33% bowel movements with visible blood/24 hours). Similar principles were agreed for untreated patients but without achieving consensus. Panelists agreed endoscopy should confirm ASUC diagnosis and exclude cytomegalovirus infection, and radiologic investigations to support excluding toxic megacolon.

CONCLUSIONS: This consensus provides new diagnostic criteria for ASUC in the modern therapeutic era, that can be applied to patients already in receipt of outpatient treatments. These criteria include additional clinical and laboratory parameters, for validation in prospective studies.