Mohamed Attauabi

Background and aims: Treatment efficacy in Crohn's disease (CD) may vary according to disease location. We aimed to evaluate the long-term efficacy of biological and small molecule therapies in moderate-to-severe luminal CD stratified by CD location. Design: We conducted a systematic review and Bayesian network meta-analysis (NMA) of randomized controlled trials (RCTs) in adults (aged ≥18 years) with moderate-to-severe CD (Crohn’s Disease Activity Index [CDAI] 220-450), identified through PubMed, Embase, and CENTRAL to August 12, 2025. Predefined outcomes included clinical remission (CDAI < 150) and endoscopic response (≥50% reduction in Simple Endoscopic Score-CD (SES-CD) at week 52 (range, 44-56 weeks), stratified by Montreal disease location and trial design. Results: Eighteen RCTs (including 4697 patients) evaluating adalimumab, infliximab, vedolizumab, ustekinumab, mirikizumab, risankizumab, guselkumab, and upadacitinib were included. Clinical remission rates were lowest in isolated ileal disease, and only guselkumab regimens (200 mg/100 mg: relative risk, 3.4 [95% CI, 1.3-8.9]) were statistically superior to placebo for maintenance of clinical remission at week 52. In isolated colonic disease, upadacitinib 30 mg ranked highest in re-randomized trials and with significant location-dependent differences (efficacy ratio [EF] for colonic vs ileal is 4.6 [95% CI, 1.7-12.6], EF for ileocolonic vs ileal is 3.45 [95% CI, 1.2-9.6]), consistent with endoscopic response rates. No location-dependent differences were observed for other agents. Conclusion: Relative efficacy of advanced therapies in luminal CD varied by disease location. These findings support consideration of disease location in personalized treatment decision-making to improve clinical outcomes.

Background and Aims: Ulcerative colitis (UC) is a chronic inflammatory bowel disease with a relapsing course and significant morbidity. In outpatients with moderate‐to‐severe UC assessment of treatment response is often delayed, limiting timely treatment optimisation. Intestinal ultrasonography (IUS) is a noninvasive point‐of‐care modality with high correlation to endoscopic activity. Early changes in bowel wall thickness (BWT) may predict treatment response in hospitalised patients with acute severe UC, but prospective validation in the outpatient setting is lacking. This study aims to evaluate whether early changes in IUS parameters, particularly BWT, can predict treatment response and the need for treatment escalation in outpatients initiating systemic corticosteroids, biologics or small molecules. Methods: This is a prospective, nonrandomised, double‐blinded and multicentre study conducted across seven Nordic inflammatory bowel disease centres. Outpatients with moderate‐to‐severe UC extending beyond the rectum, initiating systemic corticosteroids or advanced therapy, will be included. IUS will be performed at baseline and repeated at day 2 ± 1, day 7 ± 1, day 90 ± 14 and at week 52 ± 4 using standardised protocols and evaluated by central reading. Clinical indices, biomarkers, endoscopy and patient‐reported outcomes will be collected and correlated with IUS longitudinally. The primary endpoint is the association between early changes in BWT on days 2 and 7 and treatment escalation at 3 and 12 months. Secondary and exploratory endpoints include remission outcomes, time to response, quality of life and integration of multiomics data. Results: Results are pending; recruitment is planned from March 2026 to February 2028. Discussion: This multicentre double‐blinded study will prospectively evaluate early IUS as a noninvasive predictor of treatment response in outpatients with moderate‐to‐severe UC. The design enables rapid point‐of‐care assessment of therapeutic efficacy and results will allow for an individualised, dynamic and treat‐to‐target management approach. Key strengths include standardised IUS protocols, blinded evaluations, integration of endoscopic, biochemical and multiomics data, and the creation of an image repository that enables future artificial intelligence applications. Limitations of this study includes the observational design, causal inferences cannot be established and residual confounding may persist despite multivariable adjustment; additionally, treatment heterogeneity, including concomitant corticosteroid use, may complicate interpretation of early imaging changes. Furthermore, exclusion of patients with isolated proctitis and the exploratory nature of the omics analyses may limit generalisability and require external validation. Trial Registration: Clinicaltrials.gov. EU CT number: 2026‐527929‐35‐00

Background/Objectives: Postoperative endoscopic recurrence is common after intestinal resection for Crohn’s disease (CD), making surveillance essential. We performed a systematic review and meta-analysis evaluating the diagnostic performance of intestinal ultrasonography (IUS) for postoperative endoscopic recurrence and the prognostic association of IUS findings with surgical outcomes in the overall CD population. Methods: MEDLINE (PubMed) and Embase were searched from inception through 1 July 2026, for prospective studies evaluating postoperative IUS in CD. Diagnostic accuracy was analyzed using random-effects bivariate meta-analysis to estimate pooled sensitivity, specificity, likelihood ratios, summary receiver operating characteristic (SROC) curves, and diagnostic odds ratios (DORs). Results: Twenty-six prospective studies were included, comprising 797 patients evaluated for postoperative endoscopic recurrence and 1060 patients evaluated for associations between IUS findings and subsequent intestinal surgery. A bowel-wall thickness (BWT) threshold of >3.0 mm demonstrated high diagnostic accuracy for detecting any postoperative endoscopic recurrence (Rutgeerts ≥ i1), with pooled sensitivity of 85%, specificity of 83%, DOR of 30.8, and SROC AUC of 0.91, positive likelihood ratio of 5.3, and negative likelihood ratio of 0.19. For postoperative endoscopic recurrence (Rutgeerts ≥ i2), pooled sensitivity and specificity were lower at 79% and 67%, respectively (DOR 8.3; SROC AUC 0.76). A BWT threshold of >5.0 mm identified severe endoscopic recurrence (Rutgeerts i3–i4) with sensitivity of 79% and specificity of 81%, while a threshold of ≥7.0 mm was associated with increased risk of intestinal resections in the overall CD population. Conclusions: IUS demonstrated high diagnostic performance for postoperative endoscopic recurrence of CD with balanced sensitivity and specificity, and favourable likelihood ratios, although performance varied according to the definition and severity of recurrence. Evidence regarding diagnostic accuracy for modified Rutgeerts scores remains limited. Overall, these findings support IUS as a complementary modality to ileocolonoscopy, enabling repeated postoperative monitoring and risk stratification for endoscopic recurrence and surgery.

Background and aims: Extraintestinal manifestations (EIMs) and immune-mediated inflammatory diseases (IMIDs) are common in inflammatory bowel diseases (IBD) and contribute substantially to morbidity. The aim was to evaluate the real-world effectiveness of JAK inhibitors on EIMs/IMIDs. Methods: This multicenter retrospective study included adults with ulcerative colitis (UC) or Crohn’s disease (CD) and one or more EIM/IMID initiating a JAK inhibitor (tofacitinib, upadacitinib, or filgotinib). Baseline was defined as treatment initiation; EIM/IMID and IBD activity were assessed at fixed timepoints using physician global assessment. Response rates are reported as observed, with patients discontinuing for worsening of the manifestation counted as non-responders. Logistic and Cox regression analyses identified factors associated with response and treatment discontinuation. Results: A total of 246 patients were included; 67% had two or more prior advanced therapies. Peripheral spondyloarthritis (SpA) (48%) and axial SpA (43%) were the most prevalent EIMs/IMIDs. Peripheral SpA response rates were 82% post-induction and 74% at month 12; axial SpA response rates were 71% and 59%, respectively. Psoriasis response was observed in 65% post-induction and in 50% at month 12, and hidradenitis suppurativa response in 91% and 78%, respectively. Steroid-free clinical IBD remission was 58% at month 12, and was independently associated with peripheral SpA response (adjusted odds ratio [aOR] 4.2, 95% CI 1.2-14.7). Treatment was discontinued in 31%; factors associated with discontinuation were filgotinib use (adjusted hazard ratio [aHR] 3.0, 95% CI 1.4-6.2) and co-existing axial and peripheral SpA (aHR 2.8, 95% CI 1.5-5.1). Conclusions: JAK inhibitors were associated with favorable physician-assessed outcomes for EIMs/IMIDs in treatment-experienced IBD patients. Co-existing axial and peripheral SpA was associated with treatment discontinuation, suggesting a more complex phenotype.

Background and Aims: Evaluating whether international endoscopic diagnostic guideline recommendations regarding ulcerative colitis are followed in routine clinical practice, and assessing the clinical value of performing a follow‐up ileocolonoscopy in patients diagnosed based on a sigmoidoscopy. Methods: This observational cohort study included all newly diagnosed adult patients with ulcerative colitisdiagnosed between May 1, 2021, and April 30, 2023, from The Copenhagen Inflammatory Bowel Disease Inception Cohort. The study included both patients with the initial endoscopic procedure done at a hospital or a private practice and three guideline‐adherent work‐up criteria were defined. Results: In total, 300 patients fulfilled inclusion criteria. Initial ileocolonoscopy with biopsies was performed in 190 patients, and among 101 patients with an initial sigmoidoscopy (including eight presenting with acute severe ulcerative colitis), 34 patients had a follow‐up ileocolonoscopy performed within 15 months. In total, 147 patients (49%) fulfilled the guideline‐adherent work‐up criteria. No significant differences were found when comparing, CRP, and fecal calprotectin, among other parameters, between patients who did and did not have a follow‐up ileocolonoscopy performed after the initial sigmoidoscopy. Conclusion: Half of the patients fulfilled the guideline‐adherent work‐up criteria. Nonadherence to the defined guideline criteria was mainly the absence of a follow‐up ileocolonoscopy within 15 months. Guideline adherence differed considerably between hospitals and private practitioners underscoring the need for improved diagnostic standardization. No significant differences were found between patients with and without follow‐up ileocolonoscopy after initial sigmoidoscopy.

Background: Biological treatments have substantially improved management of inflammatory bowel disease, but their profound immunosuppressive effects necessitate infection screening before initiation. Current guidelines recommend chest X-ray (CXR) alongside Mycobacterium tuberculosis testing. While this approach is widely accepted, the necessity of routine CXR in patients without tuberculosis (TB) risk factors has recently been questioned in low-incidence regions. Methods: We report a rare case of a patient with ulcerative colitis undergoing routine preinfliximab CXR revealing an apical right-lung infiltrate, that was not suspected based on clinical assessment and negative interferon-gamma release assays testing. In addition, we summarize the existing literature on invasive aspergillosis associated with tumor necrosis factor alpha inhibitors. Results: The patient had minimal clinical symptoms of pulmonary infection and remained afebrile with consistently normal C-reactive protein levels. Nevertheless, routine pretreatment CXR demonstrated an apical right-lung infiltrate, leading to cancelation of planned infliximab initiation. Subsequent analyses of bronchoalveolar fluid and sputum identified two strains of Aspergillus fumigatus . Despite prolonged antifungal therapy, the patient ultimately required a right-lung lobectomy. A comprehensive literature review identified three fatal cases of invasive aspergillosis following tumor necrosis factor alpha inhibitors, underscoring the clinical importance of detecting serious pulmonary infections prior to treatment initiation. Conclusions: Our case is, to our knowledge, the first report in inflammatory bowel disease to illustrate that CXR may uncover potentially life-threatening infections beyond TB in patients with limited clinical and biochemical signs of infection, supporting its continued role in prebiologic treatment workflows even in low-TB prevalence settings.

Background: Inhaled saline may improve mucus transport in respiratory diseases, for example, cystic fibrosis. This randomised, placebo‐controlled, crossover study examined the effect of inhaled dry NaCl on mucociliary clearance in patients with chronic obstructive pulmonary disease (COPD). Methods: Twenty‐five patients with GOLD stage I‐III COPD (72% with excess mucus) were tested on two separate days after inhalation from a dry powder inhaler containing either 40 mg dry NaCl or placebo (empty). Pulmonary mucociliary clearance was assessed using inhalation of a radioactive ^99m Tc‐labelled nanocolloid tracer and gamma camera imaging. Clearance was measured for 2 h post‐intervention. Co‐primary outcomes were clearance after 1 and 2 h. Results: The study was terminated early due to COVID‐19 after enrolling 25 of 35 planned patients. No significant differences were observed in mucociliary clearance between NaCl and placebo after 1 h (11.3% ± 9.0% vs. 11.4% ± 7.0%, p = 0.97) or 2 h (15.3% ± 9.8% vs.16.1% ± 8.7%, p = 0.55). Normalised clearance based on initial radioaerosol deposition also showed no difference. Conclusions: Inhalation of 40 mg dry NaCl was well tolerated without acute adverse effects in COPD patients. However, early termination left the study underpowered, increasing the risk of type II error. Non‐significant findings should not be interpreted as evidence of no effect. Larger, adequately powered trials are needed to clarify the impact of dry NaCl inhalation on mucociliary clearance in COPD.

Background/Objectives: Intestinal ultrasound (IUS) is increasingly used to monitor ulcerative colitis (UC), but its predictive value remains unclear. This systematic review evaluated the ability of IUS parameters and scores to predict short- and long-term treatment response, remission, and adverse outcomes in hospitalized and outpatient UC populations. Methods: A systematic review was conducted according to Cochrane and PRISMA guidelines. MEDLINE and Embase were searched for prospective studies assessing IUS as a predictor of clinical or endoscopic response, remission, relapse, or adverse outcomes in adult UC. Two reviewers independently performed screening, data extraction, and QUADAS-2 assessment. Results: Eighteen prospective studies were included: eleven outpatient studies and seven involving hospitalized patients treated with intravenous corticosteroids (IVCS). In hospitalized patients, bowel wall thickness (BWT) was the most consistent predictor of treatment failure, rescue therapy, colectomy, and clinical response. Baseline BWT showed variable performance, but once IVCS was initiated, early BWT change within 48–72 h was the strongest marker of disease trajectory. Non-responders had higher BWT and smaller reductions. A BWT ≥ 4 mm, absolute reduction ≤ 1 mm, or relative reduction ≤ 20% at 48 h reliably identified patients needing rescue therapy (area under the curve (AUC) values of 0.77 (95% confidence interval (CI) 0.71–0.74), 0.71 (95% CI 0.56–0.86), and 0.74 (95% CI 0.60–0.88)). Colectomy risk was similarly predicted: BWT < 3 mm at 48 h was associated with no colectomies, whereas BWT ≥ 4 mm or persistently elevated BWT at day 6 markedly increased risk (Odds ratio (OR) 9.5-fold (95% CI 1.4–64.0) and OR 8.3 (95% CI 1.7–40.0), respectively). Other sonographic features (loss of haustration, increased vascularity) added supplementary but less consistent value. In outpatients, BWT also demonstrated the strongest predictive accuracy. BWT ≤ 3.6 mm at 2 weeks and 3.5 mm or minimal reduction (<20% or <1 mm) indicated a low likelihood of long-term remission. Composite vascularity-based indices, particularly the Milan Ultrasound Criteria (MUC), strengthened prediction: MUC ≤ 4.3 or ≥2-point reduction at 12 weeks predicted long-term remission (AUROC 0.88 (95% CI 0.750–0.952) and 0.82 (95% CI 0.68–0.91), respectively), while MUC ≥ 7.7 indicated high risk of treatment failure or colectomy (AUROC 0.77 (95% CI: 0.73–0.82)). Conclusions: Across clinical settings, BWT consistently emerged as the strongest IUS predictor of UC treatment outcomes. Early BWT change within 48–72 h in hospitalized patients and absolute BWT values at 2–6 weeks in outpatients showed high predictive accuracy for response, remission, and colectomy. Composite indices incorporating vascularity further improved prediction. These findings support the incorporation of IUS into early treatment-response algorithms and underscore the need for standardized cut-offs and multicenter validation.

The gut-skin axis (GSA) embodies a complex, bidirectional interaction between the gastrointestinal (GI) system and skin, driven by immune modulation, systemic inflammation, and gut microbiota dynamics. Disruptions in gut homeostasis, including dysbiosis and increased intestinal permeability, are increasingly recognized as contributing factors to dermatological conditions such as acne, psoriasis, and atopic dermatitis. For gastroenterologists, appreciating this interplay is essential, as diseases and their treatments frequently present with cutaneous manifestations, offering diagnostic and therapeutic insights. This review explores the underlying mechanisms of the GSA, focusing on the microbiome and its metabolites as key regulators of inflammation and immunity. It underscores the clinical importance of microbiome-targeted therapies, such as probiotics, prebiotics, and dietary modifications, in addressing both GI and dermatological disorders. Furthermore, the review examines the influence of GI conditions, including inflammatory bowel disease and celiac disease on skin health. This article seeks to equip gastroenterologists with practical insights for identifying, diagnosing, and managing skin conditions associated with GI health. The article also highlights the current limitations in knowledge regarding the GSA. The GSA represents a promising avenue for therapeutic advancements, encouraging interdisciplinary collaboration between gastroenterology and dermatology to optimize patient care.