Publications

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.

Liver damage in autoimmune hepatitis (AIH) is perpetrated by T-effector lymphocytes that are not adequately restrained by regulatory T cells (Tregs). The goal of AIH treatment is to control inflammation and induce disease remission through administration of immunosuppressive drugs including corticosteroids, azathioprine, and, in difficult-to-treat cases, mycophenolate mofetil or tacrolimus (TAC). Despite TAC being a potent immunosuppressant, its use has been hampered by a narrow therapeutic window and systemic toxicity. In this study, we have tested the effects of lipid-core nanoformulations encapsulating TAC (NC-TAC) as a novel drug delivery system that would enable potentially favorable immunomodulatory effects compared with unencapsulated TAC. NC-TAC properties were assessed in vitro, in CD4 T cells and Tregs isolated from the peripheral blood of AIH patients and controls; and in vivo through a model of T cell-mediated liver injury induced by Concanavalin-A (Con-A) in NOD/scid/gamma mice, pre-emptively reconstituted with human CD4 T lymphocytes. Compared to unencapsulated TAC, NC-TAC favored a regulatory phenotype in CD4 T cells of AIH patients, enhanced the suppressive function and preserved AIH Treg phenotype in the presence of an inflammatory stimulus. Systemic administration of NC-TAC ameliorated liver injury in vivo, as indicated by decreased ALT levels, reduced lymphocyte infiltration on histology, and an increased frequency of intrahepatic CD4+FOXP3+ lymphocytes. NC-TAC could therefore be considered as a novel drug delivery system to be possibly explored for the treatment of AIH, having a beneficial immunomodulatory profile and effectively favoring Treg immune responses.

BACKGROUND: Biologic therapies for patients with inflammatory bowel disease (IBD) were approved via large randomized controlled trials (RCTs) with strict criteria for patient enrollment. As newer IBD medications are approved, ongoing assessment is necessary to determine whether RCT eligibility criteria are too restrictive or adequately reflect real-world practice. Here, we investigate the trial-eligibility and clinical outcomes of patients with ulcerative colitis (UC) started on vedolizumab (VDZ) and ustekinumab (UST) therapy.

METHODS: This single-center retrospective cohort study at a large academic IBD referral center included patients with UC who received a new prescription for UST or VDZ between January 2020 and June 2023. The primary outcome assessed whether patients met trial eligibility using the inclusion and exclusion criteria from the UNIFI and GEMINI-1 RCTs. We also assessed treatment failure between the trial-eligible and ineligible groups.

RESULTS: Only 19/168 (11.3%) of patients with UC (n = 85 receiving VDZ; n = 83 receiving UST) were trial-eligible. The most common reasons for ineligibility were prior biologics and inadequate wash-out periods, the use of topical therapy, medical comorbidities and ongoing treatment with high doses of prednisone. Treatment failure was numerically higher in trial-ineligible compared to trial-eligible patients, though this difference was not statistically significant.

CONCLUSION: Most patients initiated on UST or VDZ would not have qualified for inclusion in their respective RCTs, largely due to current treatments. Revising trial eligibility criteria may be warranted to improve external validity and enable recruitment of a more diverse study population representative of real-world patients.

An intramural duodenal hematoma (IDH) is an uncommon clinical entity that can be an adverse event of therapeutic esophagogastroduodenoscopy (EGD). Herein, we present a case of a 60-year-old man who presented to the hospital with vomiting, diarrhea, and overt gastrointestinal bleeding with melena and small-volume hematemesis. EGD was pursued and revealed a bleeding duodenal ulcer that was therapeutically intervened upon to achieve hemostasis. After endoscopy, his hospital course was complicated by an intramural duodenal hematoma, which presented with abdominal pain and worsening anemia without recurrent overt gastrointestinal bleeding. After consultation with interventional radiology and surgery, he ultimately improved with supportive care and was discharged home without further endoscopic or procedural intervention. An IDH is an uncommon gastrointestinal pathology that should be considered after endoscopy in the setting of abdominal pain and anemia without overt bleeding. Conservative management often leads to successful outcomes, but multidisciplinary care should be considered in the setting of further adverse events.