Treatment-based risk stratification of infections in inflammatory bowel disease: A comparison between anti-tumor necrosis factor-α and nonbiological exposure in real-world setting.

BACKGROUND AND AIM: Infective issues about anti-tumor necrosis factor (TNF)-α agents in inflammatory bowel disease (IBD) remain controversial, especially when compared with nonbiological treatments. This study aimed to evaluate the incidence and prevalence of several infections in anti-TNF-α-exposed patients compared with nonbiological treatments. METHODS: All naïve IBD subjects treated with anti-TNF-α and matched nonbiologic-exposed patients were included. RESULTS: Among 3453 patients in the database, 288 anti-TNF-α-exposed subjects and 288 nonbiologic-exposed IBD controls met inclusion criteria. Fifty-eight infections (20.1%) occurred during anti-TNF-α treatment versus 23 (8%) in the matched group (odds ratio [OR] 2.9, P < 0.001) (incidence 5.72 vs 0.96/100 patient-years, incidence ratio [IR] 6, P < 0.001). IR was higher for anti-TNF-α versus mesalamine/sulfasalazine (IR 40.8, P < 0.001), similar to azathioprine/6-mercaptopurine/methotrexate (IR 0.78, P = 0.32) and lower than corticosteroids (IR 0.05, P < 0.001). The incidence rate of serious infections was 1.3 in the anti-TNF-α-exposed versus 0.38/100 patient-years in nonexposed subjects (IR 3.44, P = 0.002), without significant difference between anti-TNF-α and azathioprine/6-mercaptopurine/methotrexate (1.3 vs 3.03/100 patient-years, IR 0.43, P = 0.1). Predictors of infections in anti-TNF-α-exposed patients were concomitant use of systemic steroids (OR 1.9, P = 0.02) or azathioprine (OR 2.6, P = 0.01) and a body mass index < 18.5 at time of infection (OR 2.2, P = 0.01). CONCLUSIONS: The risk of developing infections during anti-TNF-α therapy remains high, although not dissimilar to that found for other immunosuppressants, while concomitant immunosuppression and malnutrition appear the most important causes of infection.

Insights into disability and psycho-social care of patients with inflammatory bowel disease.

In recent years, the concept of disability has increasingly garnered attention as a crucial long-term target of inflammatory bowel disease (IBD) management. The treatment paradigm has changed dramatically from full control of the disease (clinical and endoscopic remission) toward physical and emotional well-being with the goal of preventing disability and normalizing quality of life. However, in certain cases, despite achieving good disease control, patients may still experience symptoms associated with disability, and reduced emotional wellness. These symptoms can significantly impact various biopsychosocial factors, including interpersonal relationships, educational or work-related activities, body image, and sexual functioning. Nevertheless, they often remain overlooked in the context of IBD care. In this narrative review, we aim to shed light on the burden of certain disability-related symptoms such as bowel urgency, sexual dysfunction, impaired fertility and fatigue, emphasizing the importance of acknowledging and validating them in a clinical setting. There is a demanding need for comprehensive care for IBD patients, with IBD clinicians being mindful of the psychosocial challenges faced by their patients. Providing timely and appropriate management of these challenges alongside IBD treatment is key to achieving holistic remission and enhancing the overall quality of life while reducing disability.

"Per ELISA": Time to adopt anti-transglutaminase/deamidated gliadin peptide diagnostic combination in coeliac disease of adults?

BACKGROUND: Anti-endomysial antibodies (EMA) and anti-tissue transglutaminases (a-tTg) play a pivotal role in coeliac disease (CD) diagnosis. Deamidated anti-gliadin peptides (DGP) were added to the CD diagnostic workup. AIMS: We aimed to compare the diagnostic accuracies of ELISA-based (a-tTg/DGP) and immunofluorescence-ELISA-based strategies (EMA/a-tTg) for CD diagnosis. METHODS: From November 2020 to November 2022, we undertook an observational prospective study including consecutive adult patients with suspected CD. All subjects were tested for EMA, a-tTg and DGP IgA. An ROC curve was plotted to establish the best specificity cut-off of a-tTg and DGP levels, which would predict the presence of Marsh≥2 and Marsh=3. The diagnostic accuracies of a-tTg/DG and EMA/a-tTg were compared. RESULTS: The study included 275 CD patients. Histology showed Marsh=1 in 9.9%, Marsh=2 in 4.5%, and Marsh=3 in 85.6.%. The best cut-off value of a-tTg for predicting Marsh≥2 was 42 U/mL, while the best cut-off for predicting atrophy was 68.4 U/mL. The best cut-off value of DGP for predicting Marsh≥2 was 56 U/mL, while the best cut-off for predicting atrophy was 78 U/mL. A-tTg/EMA showed 97% sensitivity and 100% specificity, whereas a-tTg/DGP showed 94% sensitivity and 100% specificity. CONCLUSION: A-tTg/DGP is accurate for CD diagnosis and could reduce costs and operator-dependency of EMA. DGP, together with a-tTg, could replace EMA in CD diagnosis.

Effectiveness and safety of newly introduced endoscopic submucosal dissection in a Western center: a real-life study.

OBJECTIVES: Endoscopic submucosal dissection (ESD) is a minimally invasive technique for the resection of superficial gastrointestinal lesions, providing high rates of 'en bloc' and R0 resection. East-West differences in ESD quality indicators have been reported. This study aims to assess feasibility, effectiveness, and safety of ESD for the treatment of superficial gastrointestinal (GI) lesions in a Western cohort. METHODS: Consecutive patients undergoing ESD at one Italian endoscopic referral center from September 2018 to March 2020 were included in this prospective study. Primary outcomes were technical success, R0 resection rate, curative resection rate, and adverse events (AEs). RESULTS: In total 111 patients (111 lesions) undergoing ESD were included. Anatomic site of the lesions was rectum in 56.8%, colon in 13.5%, stomach in 24.3%, and esophagus in 5.4% of cases, respectively. For upper GI procedures, technical success was 100%, and R0 and curative resection rates were 84.8% and 78.8%, respectively. For colorectal procedures, technical success was 98.7%, R0 and curative resection rates were 88.5% and 84.6%, respectively. Major AEs were reported in 12 cases (10.8%). CONCLUSION: The introduction of ESD in a Tertiary Center is feasible, effective, and safe, and should be taken into consideration for the treatment of superficial GI lesions requiring 'en bloc' resection.

Effectiveness of Partial Enteral Nutrition as Add-On to Biologics in Patients With Refractory and Difficult-to-Treat Crohn's Disease: A Pilot Study.

Background: Partial enteral nutrition (PEN) is a well-established treatment for children with Crohn's disease (CD). However, its efficacy in adults with CD remains uncertain. We aimed to assess the effectiveness of PEN as an add-on to escalated biological therapy in adults with CD who have lost response to biologics. Methods: We conducted a retrospective observational study including patients who had lost response to biologics and received PEN in combination with escalated treatment, compared to those treated only with escalated therapy. The primary endpoint was steroid-free clinical remission (CR) at 24 weeks. Secondary endpoints included transmural healing (TH) and response (TR) rates along with selected clinical outcomes. Results: Forty-two patients were screened; 12 (28.6%) were excluded for complicated disease and 30 (71.4%) were included in the final analysis. Fourteen (46.7%) patients completed PEN treatment at 8 weeks, while 16 patients (53.3%) discontinued treatment due to intolerance and continued with escalation of biologic (BT group). At 24 weeks, 9 patients (64.3%) in the PEN group achieved CR, compared to 4 patients (25%) in the BT group (P = .03). The TR rate was 64.9% in the PEN group and 25% in the BT group (P = .03). Patients receiving PEN exhibited an increase in albumin levels compared to those in the BT group (Δ = 0.5; P = .02). A higher rate of therapy changes (68.7%) was observed in the BT group compared to 14.2% in the PEN group (P = .004). Prior failure to 2 lines of biological therapy was associated with adherence to PEN (OR = 1.583; CI = 1.06-2.36; P = .01). Conclusions: In patients who had lost response to biologics, PEN in combination with escalated biologics was associated with CR and TR and improved nutritional status. Hence, the addition of PEN should be considered for patients with difficult-to-treat CD.

Time to grow up: readiness associated with improved clinical outcomes in pediatric inflammatory bowel disease patients undergoing transition.

Background: The transition from pediatric to adult healthcare in individuals with inflammatory bowel disease (IBD) poses significant challenges mainly due to the high burden of IBD during adolescence, a critical period of psychosocial development. So far, there are few longitudinal data linking transition readiness to long-term disease outcomes. Objective: We aimed to assess patients' readiness to transition and its impact on clinical outcomes, quality of life, and adherence to therapy. Design: An observational, prospective study was conducted in a tertiary adult and pediatric center, including adolescents aged ⩾17 years with a diagnosis of IBD, who underwent a 'structured transition' program including two joint adult-pediatric visits. Methods: Transition readiness skills were assessed with the Transition Readiness Assessment Questionnaire (TRAQ). All patients completed the TRAQ at the time of recruitment, which occurred during the initial joint adult-pediatric visit, to determine those deemed ready for transition versus those not ready. The Morisky Medication Adherence Scale and the 36-Item Short Form Health Survey Questionnaire (SF-36) were also completed at baseline and after 12 months. Clinical outcomes were collected at the 12-month follow-up. Results: In all, 80 patients were enrolled who had transitioned through a structured transition clinic and completed 12 months of follow-up. In total, 54 patients were ready for the transition, with a mean TRAQ = 3.2 ± 0.5. The number of clinical relapses and hospitalizations at 12 months was lower in ready compared to not-ready patients (p = 0.004 and p = 0.04, respectively). SF-36 did not differ between ready and not-ready patients and pre- and post-transition clinics (p > 0.05). Based on the receiver operating characteristic curve, a TRAQ cutoff ⩾3.16 could predict medication adherence with a sensibility of 77%, a specificity of 82%, and an AUC of 0.81 (0.71-0.91; p < 0.001). Conclusion: Patients ready for transition had better outcomes at 12 months compared to those who were not ready. Therefore, readiness assessment tools should be integrated into transition management to ensure that interventions are targeted, patient-centered, and responsive to individuals' changing needs.

Transition readiness associated with improved clinical outcomes The transition for individuals with inflammatory bowel disease (IBD) is a dynamic and complex process that must be planned and cannot simply be performed once the patient is 18 years old. Since it does not depend solely on the patient's age but also on developmental readiness, it requires preparation and education starting from early adolescence. In the current study, a 'joint-visit' including both pediatric and adult providers yields positive clinical outcomes over 12 months. Patients ready for transition reported fewer relapses, hospitalizations, and improved therapy adherence compared to those not ready. Readiness assessment tools should be integrated into transition clinics to facilitate targeted interventions for IBD patients based on the changing needs of individuals.

Hocus Pocus: the Role of Hand-held Ultrasonography in Predicting Disease Extension and Endoscopic Activity in Ulcerative Colitis.

BACKGROUND: Ulcerative colitis [UC] assessment still requires ileocolonoscopy [IC]. Intestinal ultrasound [IUS] has emerged as a non-invasive assessment tool, and the Milan Ultrasound Criteria [MUC] score has been validated to estimate and grade UC disease activity. Recently, hand-held IUS [HHIUS] has been used in several clinical settings, but data about its use in UC are limited. We aimed to evaluate the diagnostic accuracy of HHIUS compared with conventional IUS in detecting UC extension and activity. PATIENTS AND METHODS: From November 2021 to September 2022, we prospectively enrolled UC patients afferent to our third-level IBD Unit for IC evaluation. Patients underwent IC, HHIUS, and IUS. Ultrasound activity was defined by MUC >6.2, and endoscopic activity was defined by a Mayo endoscopic score [MES] >1. Cohen's k test was applied to test the concordance between IUS-MUC and HHIUS-MUC after MUC dichotomisation [MUC >6.2, yes/no]. RESULTS: In all, 86 patients with UC were enrolled. No significant difference was recorded between IUS and HHIUS at the per-segment extension [p = N.S.], and both procedures were comparable in terms of results of bowel wall thickness [BWT] and bowel wall stratification [BWS] assessment [p = N.S.]. IUS and HHIUS displayed excellent agreement when the MUC score system was applied [k = 0.86, p <0.01]. CONCLUSION: Hand-held intestinal ultrasound and IUS are comparable in UC extension definition and MUC evaluation. HHIUS could be reliable for detecting disease activity and estimating its extension, providing close monitoring. It also represents a non-invasive, easily practicable investigation, allowing immediate medical decisions with significant time and cost advantages.

Rates of Endoscopic Recurrence In Postoperative Crohn's Disease Based on Anastomotic Techniques: A Systematic Review And Meta-Analysis.

BACKGROUND: Patients with Crohn's disease (CD) after ileocolic resection may develop an endoscopic postoperative recurrence (ePOR) that reaches 40% to 70% of incidence within 6 months. Recently, there has been growing interest in the potential effect of anastomotic configurations on ePOR. Kono-S anastomosis has been proposed for reducing the risk of clinical and ePOR. Most studies have assessed the association of ileocolonic anastomosis and ePOR individually, while there is currently limited data simultaneously comparing several types of anastomosis. Therefore, we performed a systematic review and meta-analysis to assess the impact of different ileocolonic anastomosis on ePOR in CD. METHODS: We searched PubMed and Embase from inception to January 2023 for eligible studies reporting the types of anastomoses and, based on these, the rate of endoscopic recurrence at ≥6 months. Studies were grouped by conventional anastomosis, including side-to-side, end-to-end, and end-to-side vs Kono-S, and comparisons were made between these groups. Pooled incidence rates of ePOR were computed using random-effect modelling. RESULTS: Seventeen studies, with 2087 patients who underwent ileocolic resection for CD were included. Among these patients, 369 (17,7%) Kono-S anastomoses were performed, while 1690 (81,0%) were conventional ileocolic anastomosis. Endoscopic postoperative recurrence at ≥6 months showed a pooled incidence of 37.2% (95% CI, 27.7-47.2) with significant heterogeneity among the studies (P < .0001). In detail, patients receiving a Kono-S anastomosis had a pooled incidence of ePOR of 24.7% (95% CI, 6.8%-49.4%), while patients receiving a conventional anastomosis had an ePOR of 42.6% (95% CI, 32.2%-53.4%). CONCLUSIONS: Kono-S ileocolic anastomosis was more likely to decrease the risk of ePOR at ≥6 months compared with conventional anastomosis. Our findings highlight the need to implement the use of Kono-S anastomosis, particularly for difficult to treat patients. However, results from larger randomized controlled trials are needed to confirm these data.

This meta-analysis provides estimates of endoscopic postoperative recurrence based on different types of anastomosis. The results reveal a trend towards the superiority of Kono-S over conventional anastomosis, including side-to-side, endo-to-end and end-to-side, for decreasing the risk of endoscopic postoperative recurrence.

The Impact of Intestinal Ultrasound on the Management of Inflammatory Bowel Disease: From Established Facts Toward New Horizons.

Intestinal ultrasound (IUS) plays a crucial role as a non-invasive and accurate tool to diagnose and assess inflammatory bowel disease (IBD). The rationale for using IUS in Crohn's disease (CD), a transmural disease, is widely acknowledged. While the use of IUS in ulcerative colitis (UC), a mucosal disease, is often underestimated, but, recently, it is increasingly expanding. In the context of a treat-to-target approach, the role of IUS is shifting toward a monitoring tool for predicting response to therapy. Hence, adjusting therapeutic strategies based on IUS response could reduce the burden related to endoscopy and speed the decision process with the ultimate goal to alter the natural course of IBD. Assessment of bowel wall thickness (BWT) is the most reliable IUS measure. However, the development of validated and reproducible sonographic scores to measure disease activity and the identification of parameters of therapeutic response remain relevant issues to implement the daily adoption of IUS in clinical practice. Accordingly, this review focuses on the current literature investigating the impact of IUS on CD with emphasis on the concept of transmural healing (TH) and the main related advantages. We further explore new insights on the role of IUS in UC and its clinical implications.

Impact of Sarcopenia on Clinical Outcomes in a Cohort of Caucasian Active Crohn's Disease Patients Undergoing Multidetector CT-Enterography.

(1) Background: Sarcopenia has a high incidence in Crohn's disease (CD) with considerable heterogeneity among ethnicities and variable impact on clinical outcomes. Aim: to assess the impact of sarcopenia on clinical outcomes in a cohort of Caucasian patients with active CD undergoing CT-enterography (CTE) for clinical assessment. We further investigated the prevalence of sarcopenia and its predictors. (2) Methods: Caucasian CD patients with moderate−severe clinical activity, who underwent CTE in an emergency setting, were retrospectively recruited. The skeletal muscle index (SMI) at the third lumbar vertebra was used to detect sarcopenia in the early stages. Clinical malnutrition was defined according to global clinical nutrition criteria. Clinical outcomes included the rate of surgery and infections within one year. (3) Results: A total of 63 CD patients (34 M; aged 44 ± 17 years) were recruited, and 48 patients (68.3%) were sarcopenic. Malnutrition occurred in 28 patients (44.4%) with a significant correlation between body mass index (BMI) and sarcopenia (r = 0.5, p < 0.001). The overall rate of surgery was 33%, without a significant difference between sarcopenic and non-sarcopenic (p = 0.41). The rate of infection in patients with sarcopenia was significantly higher than in non-sarcopenic (42%vs15%, p = 0.03). BMI (OR 0.73,95%, CI 0.57−0.93) and extraintestinal manifestations (EIM) (OR 19.2 95%, CI 1.05−349.1) were predictive of sarcopenia (p < 0.05). (4) Conclusions: Sarcopenia was associated with an increased rate of infections, and it was observed in 68.3% of the Caucasian cohort with active CD.

Exclusive Enteral Nutrition in Adult Crohn's Disease: an Overview of Clinical Practice and Perceived Barriers.

Recently, the role of nutrition in the management of Crohn's disease (CD) is of increasing interest and the exploration of novel nutritional interventions to improve long-term management of the disease is challenging. So far, the majority of the studies on the role of exclusive enteral nutrition (EEN) in CD are conducted in the pediatric population and have highlighted the efficacy of EEN for achieving mucosal healing. This implicates that a similar approach would be beneficial in adult patients. However, the evidence for EEN in adults is heterogeneous, with meta-analyses reporting it as inferior to steroids while growing data demonstrate improvement in complicated CD. Currently, EEN is less used in adult patients with IBD. Indeed, the lack of palatability of enteral formula leads to difficulties in acceptance and compliance. The search for more tolerable and still effective diets has become an intense area of research aiming to explore the potential role of diet to control inflammation in patients with CD. Thus, this narrative review provides the state-of-the-art on the use of EEN treatment in CD and highlights the perceived barriers to its implementation in adult CD patients.