Helena Tavares de Sousa

Background: Advanced therapies have revolutionized inflammatory bowel disease (IBD) management, but primary non-response and secondary loss of response remain clinical challenges across all mechanisms of action. This topical review aims to offer evidence-based current practice positions for therapy optimization across all available advanced therapies. Methods: A panel of gastroenterologists performed a literature review on optimization of IBD advanced therapies (anti-tumour necrosis factor agents, vedolizumab, anti-IL-12/23 and anti-IL-23 agents, and small molecules) and formulated current practice positions that were approved in consensus. Conclusions: Strategies to reduce treatment failures, maximize drug persistence, and achieve optimal clinical benefit, including therapeutic drug monitoring and dose optimization, have become standard components of modern IBD care; however, this may vary according to the current evidence for each specific drug.

Introduction: Ulcerative colitis (UC) and Crohn’s disease (CD) are inflammatory bowel diseases (IBDs) characterised by chronic inflammation of the digestive tract. Patients with IBD often present a suboptimal disease control due to the limited efficacy of current treatments and inadequate disease management. A suboptimal disease control is often associated with poor quality of life (QoL) and a higher economic burden. The objective of this study was to assess the proportion of suboptimal disease control in daily clinical practice, the associated impact on QoL, and the economic burden in patients with UC and CD in Portugal. Methods: This was a non-interventional, multicentre study, wherein clinician-reported outcomes, patient-reported outcomes, and retrospective data were collected from medical chart review from May 17, 2022, to October 17, 2022, in five hospital centres in Portugal. The primary outcomes of this study were to estimate: (1) the proportion of CD and UC patients with suboptimal disease control, according to the STRIDE-II based recommendations, and (2) the associated impact on QoL of optimal and suboptimal controlled CD or UC. Results: Of 130 patients included (67 with CD and 63 with UC), 56.7% of CD and 31.7% of UC patients were reported to have suboptimal disease control according to STRIDE-II based recommendations. Notably, 82.1% and 54.0% of the patients with CD and UC were currently on targeted immunomodulator (TIM). Patients with CD and UC and suboptimal disease control showed an impaired QoL compared to those with optimal control. Mean annual healthcare costs were substantially higher among patients with CD with optimal control and patients with UC with suboptimal control. Conclusion: Despite the high rate of treatment with TIM, a considerable proportion of patients with IBD had a suboptimal disease control, indicating a substantial disease burden. Ensuring effective disease management of these patients is crucial as a suboptimal disease control may negatively affect the patient’s long-term clinical outcomes and QoL.

Background: Endoscopy‐related musculoskeletal injuries (ERIs) are a major occupational hazard, impacting career longevity and personal well‐being.Objective: This systematic review and meta‐analysis aimed to update and expand on previous findings by assessing prevalence, risk factors and management of ERIs among endoscopists.Methods: Following PRISMA guidelines, we systematically searched MEDLINE, Web of Science and Scopus for relevant studies published since the last comprehensive review. A manual search of the references of relevant manuscripts was also performed. Outcomes of interest included the prevalence of ERIs, common pain syndromes, risk factors, and preventive or treatment strategies. Studies' quality was assessed using the National Institutes of Health (NIH) Quality Assessment Tool.Results: Thirty studies were included, incorporating data from 7646 gastrointestinal endoscopists. The pooled career‐long prevalence of overall ERI was 62.5% (CI 52.6–71.8, I² = 98%), including pain (67.5%; CI 46.4%–85.6%; I² = 98%) and numbness (12.4%; 95% CI 6.6%–19.7%; I² = 98%) syndromes. Among pain syndromes, the most affected areas were the hand (28.2%; CI 19.2%–38.2%; I² = 99%), lower back (27.3%; CI 20.1%–35.2%; I² = 97%), thumb (27.1%; CI 18.9%–37.7%; I² = 99%) and neck (25.7%; CI 19.3%–32.7%; I² = 98%). Higher procedural volume, years in practice and female gender were consistently reported as risk factors for ERIs.Concerning therapy, 41.8% of endoscopists used medications (CI 31.2%–52.8%; I² = 94%), while 28.2% engaged in physical therapy (CI 18.2%–39.5%; I² = 96%). Sick leave was reported by 13.8% of endoscopists (CI 7.9%–20.9%; I² = 94%). Practice modifications to manage ERIs included adjusting monitor (45.5%, CI 22.2%–69.9%; I² = 96%) and table (32.4%, CI 14.5%–53.5%; I² = 97%) height, but also reducing the number of cases per endoscopy session (14.6%; CI 10.4%–19.4%; I² = 72%).Conclusion: ERIs are highly prevalent among international gastrointestinal endoscopists, and are linked to procedural volume, years in practice, and gender. Ergonomic training and workplace adaptations are essential to mitigate risks and support career sustainability.Trial Registration: PROSPERO Registration: CRD42024534349

Background: The Montreal classification has been widely used in Crohn's disease since 2005 to categorize patients by the age of onset (A), disease location (L), behavior (B), and upper gastrointestinal tract and perianal involvement. With evolving management paradigms in Crohn's disease, we aimed to assess the performance of gastroenterologists in applying the Montreal classification. Methods: An online survey was conducted among participants at an international educational conference on inflammatory bowel diseases. Participants classified 20 theoretical Crohn's disease cases using the Montreal classification. Agreement rates with the inflammatory bowel diseases board (three expert gastroenterologists whose consensus rating was considered the gold standard) were calculated for gastroenterologist specialists and fellows/specialists with ≤ 2 years of clinical experience. A majority vote < 75% among participants was considered a notable disagreement. The same cases were classified using three large language models (LLMs), ChatGPT‐4, Claude‐3, and Gemini‐1.5, and assessed for agreement with the board and gastroenterologists. Fleiss Kappa was used to assess within‐group agreement. Results: Thirty‐eight participants from five countries completed the survey. In defining the Montreal classification as a whole, specialists (21/38 [55%]) had a higher agreement rate with the board compared to fellows/young specialists (17/38 [45%]) (58% vs. 49%, p = 0.012) and to LLMs (58% vs. 18%, p < 0.001). Disease behavior classification was the most challenging, with 76% agreement among specialists and fellows/young specialists and 48% among LLMs compared to the inflammatory bowel diseases board. Regarding disease behavior, within‐group agreement was moderate (specialists: k = 0.522, fellows/young specialists: k = 0.532, LLMs: k = 0.577; p < 0.001 for all). Notable points of disagreement included: defining disease behavior concerning obstructive symptoms, assessing disease extent via video capsule endoscopy, and evaluating treatment‐related reversibility of the disease phenotype. Conclusions: There is significant inter‐rater disagreement in applying the Montreal classification, particularly for disease behavior in Crohn's disease. Improved education or revisions to phenotype criteria may be needed to enhance consensus on the Montreal classification.

Background and aims: Predicting the treatment outcomes of biological therapies is an unmet need in Crohn's Disease. In this study, we explored the potential of serum neutrophil‐related biomarkers to predict infliximab therapeutic results and disease progression in Crohn's Disease patients, over a 2‐year period, in a real‐world setting.Methods: The study included 100 asymptomatic Crohn's Disease patients in the IFX maintenance phase from the prospective, observational, multicenter DIRECT study. Patients were categorized according to a composite outcome reflecting progression that included surgery, hospitalizations, new fistulae, abscess or stricture, and drug treatment escalation. Serum neutrophil elastase, lipocalin‐2, lactoferrin, and resistin (non‐neutrophil control) were analyzed via multiplex magnetic bead assays at multiple touchpoints. Fecal calprotectin was assessed by ELISA.Results: Over up to 2 years of follow‐up, serum biomarkers did not differentiate between the composite outcome groups, whereas fecal calprotectin was significantly higher in patients with worse outcomes. During the infliximab maintenance phase, there was a significant, sustained reduction of neutrophil elastase (p < 0.001), lipocalin‐2 (p < 0.001), and lactoferrin (p < 0.001), but not of resistin, despite stable neutrophil levels. Correlations between NE and NGAL levels were strong (Pearson correlations 0.75–0.85); all other correlations were of small magnitude.Conclusion: Our real‐world data do not support using serum neutrophil elastase, lipocalin‐2, or lactoferrin concentrations as predictors of treatment outcomes or disease evolution in infliximab ‐treated Crohn's Disease patients. On the other hand, the sustained decrease in biomarkers over time suggests that neutrophil stabilization might be an additional infliximab mechanism of action.

Introduction: Food-related quality of life (FR-QoL) has been shown to be an important patient-reported outcome in inflammatory bowel disease (IBD). We aimed to translate and validate a Portuguese version of the FR-QoL-29. Methods: This was a case-control cross-sectional study undertaken at a tertiary hospital. After obtaining the original authors’ authorization, both forward and backward translations of the original FR-QoL-29 were performed by bilingual researchers. After an IBD expert’s revision and the input of a small group of patients, a final version was obtained. Portuguese IBD patients were prospectively recruited from the outpatient clinic of a tertiary hospital and completed the questionnaire at two timepoints (0 and 4 weeks). Reliability (internal consistency, test-retest, and intraclass correlation [ICC]), validity (content and convergent validity, and hypothesis testing using Spearman’s correlations), and responsiveness (Student t tests) were analysed. Results: 239 patients (mean age 50.1 [SD = 15.3 years], 56.5% female) and 87 (36.4%) patients answered the questionnaire at the first and second timepoints, respectively; 126 controls answered the questionnaire. Overall, the FR-QoL-29-Portuguese showed excellent internal consistency (Cronbach’s α = 0.97) and good test-retest reliability (ICC = 0.78 [95% CI: 0.64–0.85]). FR-QoL moderately correlated with health-related quality of life, measured by the SIBDQ-PT (R = 0.49; p < 0.05). Lastly, the questionnaire revealed appropriate responsiveness when patients reported an overall improvement in general well-being (mean improvement 25.88 [SD = 32.50]; p < 0.05). Discussion/Conclusions: We present an adaptation and validation of the FR-QoL-29 tool for Portuguese IBD patients. The FR-QoL-29-Portuguese is a reliable and valid tool shown to be responsive to changes in general well-being.

In this review, we will describe the importance of fibrosis in inflammatory bowel disease (IBD) by discussing its distinct impact on Crohn’s disease (CD) and ulcerative colitis (UC) through their translation to histopathology. We will address the existing knowledge on the correlation between inflammation and fibrosis and the still not fully explained inflammation-independent fibrogenesis. Finally, we will compile and discuss the recent advances in the noninvasive assessment of intestinal fibrosis, including imaging and biomarkers. Based on the available data, none of the available cross-sectional imaging (CSI) techniques has proved to be capable of measuring CD fibrosis accurately, with MRE showing the most promising performance along with elastography. Very recent research with radiomics showed encouraging results, but further validation with reliable radiomic biomarkers is warranted. Despite the interesting results with micro-RNAs, further advances on the topic of fibrosis biomarkers depend on the development of robust clinical trials based on solid and validated endpoints. We conclude that it seems very likely that radiomics and AI will participate in the future non-invasive fibrosis assessment by CSI techniques in IBD. However, as of today, surgical pathology remains the gold standard for the diagnosis and quantification of intestinal fibrosis in IBD.

Background: Timely stratification of Crohn's disease (CD) is essential for patients' management. The use of noninvasive accurate biomarkers is key to monitor treatment and to pursue mucosal healing, the ultimate treatment endpoint in CD.Objective: We aimed to evaluate the performance of readily available biomarkers and develop risk matrices to predict CD progression.Methods: Data from 289 CD patients receiving infliximab (IFX) maintenance therapy for 2 years was collected; those patients were included in DIRECT, a prospective multicenter observational study. Disease progression was evaluated using two composite outcomes incorporating clinical and drug‐related factors, the first including IFX dose and/or frequency adjustments. Univariate and multivariable logistic regressions were used to calculate the odds ratios (OR) and to develop risk matrices.Results: The isolated presence of anemia at least once during follow‐up was a significant predictor of disease progression (OR 2.436 and 3.396 [p ≤ 0.001] for composite outcomes 1 and 2, respectively) regardless of confounding factors. Isolated highly elevated C‐reactive protein (CRP; >10.0 mg/L) and fecal calprotectin (FC; >500.0 μg/g) in at least one visit were also significant predictors, while milder elevations (3.1–10.0 mg/L and 250.1–500.0 μg/g) were only relevant when detected in at least two visits (consecutive or not). The combination of biomarkers in risk matrices had good ability to predict progression; patients simultaneously presenting anemia, highly elevated CRP and FC at least once had 42%–63% probability of achieving the composite outcomes.Conclusion: The combined evaluation of hemoglobin, CRP, and FC in at least one time point and their incorporation into risk matrices seems to be the optimal strategy for CD management, as data from additional visits did not meaningfully influence the predictions and may delay decision‐making.

Introduction: Evidence supporting transmural remission (TR) as a long‐term treatment target in Crohn's disease (CD) is still unavailable. Less stringent but more reachable targets such as isolated endoscopic (IER) or radiologic remission (IRR) may also be acceptable options in the long‐term.Methods: Multicenter retrospective study including 404 CD patients evaluated by magnetic resonance enterography and colonoscopy. Five‐year rates of hospitalization, surgery, use of steroids, and treatment escalation were compared between patients with TR, IER, IRR, and no remission (NR).Results: 20.8% of CD patients presented TR, 23.3% IER, 13.6% IRR and 42.3% NR. TR was associated with lower risk of hospitalization (odds‐ratio [OR] 0.244 [0.111–0.538], p < 0.001), surgery (OR 0.132 [0.030–0.585], p = 0.008), steroid use (OR 0.283 [0.159–0.505], p < 0.001), and treatment escalation (OR 0.088 [0.044–0.176], p < 0.001) compared to no NR. IRR resulted in lower risk of hospitalization (OR 0.333 [0.143–0.777], p = 0.011) and treatment escalation (OR 0.260 [0.125–0.540], p < 0.001), while IER reduced the risk of steroid use (OR 0.442 [0.262–0.745], p = 0.002) and treatment escalation (OR 0.490 [0.259–0.925], p = 0.028) compared to NR.Conclusions: TR improved clinical outcomes over 5 years of follow‐up in CD patients. Distinct but significant benefits were seen with IER and IRR. This suggests that both endoscopic and radiologic remission should be part of the treatment targets of CD.