Background Few data are currently available about SB5 in inflammatory bowel diseases (IBD). The aim of this study was to assess the effectiveness and safety of SB5 in a cohort of patients with IBD in stable remission switched from the adalimumab (ADA) originator and in a cohort of patients with IBD naïve to ADA. Methods We prospectively enrolled patients with IBD who started ADA treatment with SB5 (naïve cohort) and those who underwent a nonmedical switch from the ADA originator to SB5 (switching cohort). Clinical remission and safety were assessed at baseline and at 3, 6, and 12 months. In addition, in a small cohort of patients who were switched, we assessed the ADA serum trough levels and antidrug antibodies at baseline, 3, and 6 months. Results In the naïve cohort, the overall remission rate at 12 months was 60.42%, whereas in the switching cohort it was 89.02%. Fifty-three (36.3%) patients experienced an adverse event, and injection site pain was the most common; it was significantly more frequent in the switching cohort (P = 0.001). No differences were found in terms of ADA serum trough levels at baseline, 3, and 6 months after switching. No patient developed antidrug antibodies after the switch. Conclusions We found that SB5 seemed effective and safe in IBD, both in the naïve cohort and in the switching cohort. Further studies are needed to confirm these data in terms of mucosal healing.

BackgroundTrichorhinophalangeal syndrome (TRPS) is a rare autosomal dominant disorder caused by defects involving the TRPS1 gene. It exhibits distinctive craniofacial, ectodermal and skeletal abnormalities, such as sparse hair, bulbous nasal tip and short deformed fingers, with extremely variable expressivity.Case presentationWe report the case of a 17 months old girl, who presented growth retardation and dysmorphic features. Postnatal growth was always below − 2 Standard Deviation for both weight and length and physical examination revealed relative macrocephaly, sparse hair, bulbous nasal tip, thin upper lip, protruding ears, prominent forehead, small jaw, and short hands and feet. Patient’s mother shared the same facial features, and presented sparse hair and small hands. The maternal grandfather and two uncles presented short stature, bulbous nasal tip, thin hair, and premature alopecia. Molecular analysis of TRPS1 gene showed a heterozygous c.2086C > T;(p.Arg696Ter) mutation both in the patient and her mother, confirming the diagnosis of TRPS, type I.ConclusionsClinical phenotype of TRPS can be subtle and the syndrome often remains undiagnosed. A comprehensive clinical examination and an exhaustive family history are crucial to reach the correct diagnosis, which is essential to perform adequate follow-up and timely therapeutic procedures.

Background The aim of the present study was to investigate outcomes of anti-TNF-alpha (ATA) withdrawal in selected pediatric patients with inflammatory bowel disease who achieved clinical remission and mucosal and histological healing (MH and HH). Methods A retrospective analysis was performed on children and adolescents affected by Crohn disease (CD) and ulcerative colitis (UC) who were followed up at 2 tertiary referral centers from 2008 through 2018. The main outcome measure was clinical relapse rates after ATA withdrawal. Results One hundred seventy patients received scheduled ATA treatment; 78 patients with CD and 56 patients with UC underwent endoscopic reassessment. We found that MH was achieved by 32 patients with CD (41%) and 30 patients with UC (53.6%); 26 patients with CD (33.3%) and 22 patients with UC (39.3%) achieved HH. The ATA treatment was suspended in 45 patients, 24 affected by CD and 21 by UC, who all achieved concurrently complete MH (Simplified Endoscopic Score for CD, 0; Mayo score, 0, respectively) and HH. All the patients who suspended ATA shifted to an immunomodulatory agent or mesalazine. In contrast, 17 patients, 8 with CD and 9 with UC, continued ATA because of growth needs, the persistence of slight endoscopic lesions, and/or microscopic inflammation. Thirteen out of 24 patients with CD who suspended ATA experienced disease relapse after a median follow-up time of 29 months, whereas no recurrence was observed among the 9 patients with CD who continued treatment (P = 0.05). Among the patients with UC, there were no significant differences in relapse-free survival among those who discontinued ATA and those who did not suspend treatment (P = 0.718). Conclusions Despite the application of rigid selection criteria, ATA cessation remains inadvisable in CD. In contrast, in UC, the concurrent achievement of MH and HH may represent promising selection criteria to identify patients in whom treatment withdrawal is feasible.

Background and objective: Acute severe colitis (ASC) is a potentially life-threatening event. Optimal timing for second-line treatment in children is mainly based on the clinical score Pediatric Ulcerative Colitis Activity Index. The aim of our study was to evaluate the potential role of bowel ultrasound scan (BUS) in predicting the need of second-line therapy in ASC. Methods: Patients younger than 18 years admitted to a single tertiary referral center with ASC were included. We retrospectively reviewed medical records collecting clinical and BUS data. Colonic wall thickness (CWT), loss of colonic wall stratification (CWS), presence of hyperechoic lymph nodes, and colonic wall flow evaluated at power Doppler were assessed at BUS performed within the third day of hospitalization. Results: Sixty-nine ASC episodes from 52 different patients were identified. CWT showed significantly higher values in patients who required second-line therapy (5.14 vs 3.69 mm; P < 0.001). Loss of CWS was present in 17 of 36 (47.2%) of steroid-resistant ASC versus only 1 of 33 of those responding to intravenous corticosteroids (P < 0.001, sensitivity = 47%, specificity = 97%). Using a receiver operating characteristic curve, a cut-off of 3.4 mm was individuated for CWT to predict steroid treatment failure, showing a sensitivity of 92% and a specificity of 52%. The multivariable binary logistic regression analysis identified thickened colonic wall (CWT >3.4 mm) and loss of CWS as independent predictors of steroid resistance. Conclusions: BUS is a noninvasive, easily accessible, and cost-effective resource that may identify at an early stage first-line therapy failure in pediatric ASC.

Objectives: Mucosal healing (MH) and histological healing (HH) have been recently proposed as a novel treatment target for inflammatory bowel disease (IBD). The aim of the present study was to evaluate real-life achievement of such outcomes in a cohort of pediatric patients with IBD treated with anti-TNF-alpha (ATA) agents. Methods: A retrospective analysis was performed on patients affected by IBD who received ATA and were followed up at two referral centers. Incidence and cumulative rates for MH and HH for each group were calculated. Results: Of 170 (105 Crohn's disease [CD] and 65 ulcerative colitis [UC]) patients, 78 with CD and 56 with UC underwent endoscopic re-assessment during the study period. MH was achieved by 32 CD (41%) and 30 UC (53.6%) patients; 26 CD (33.3%) and 22 UC (39.3%) patients achieved HH. MH incidence rate was 19.1/1000 and 47/1000 person-months, whereas HH incidence rate was 15.5/1000 and 34.7/1000 person-months for CD and UC, respectively. Remission at the end of induction was associated with higher MH and HH rates (HR: 2.43, P ¼ 0.049 and HR: 2.94, P ¼ 0.046, respectively) in CD. In UC, adalimumab was associated with lower MH and HH rates (HR: 0.16, P ¼ 0.004 and HR: 0.07, P ¼ 0.003). Conclusions: We reported a real-life experience arising from a large cohort of pediatric IBD who received ATA scheduled treatment. Less than half of patients with CD and only a little >50% of UC patients achieved MH. Microscopical inflammation was observed in 18.8% CD and 26.7% UC patients who achieved MH. Overall, MH and HH rates appear lower compared to previously published data.

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Background Ulcerative colitis tend to present with a more extensive phenotype and a more aggressive behavior in pediatric populations when compared to adult ones. Treatment targets are shifting from symptom alleviation to more objective outcomes, such as the healing of the mucosa and the complete resolution of microscopic inflammation. However, data regarding real-life attainment of such outcomes and their prognostic implications are lacking. Methods We performed a retrospective analysis on pediatric patients affected by UC who were followed up for at least, 12 month at a tertiary referral center. We included only patients who underwent endoscopic reassessment during clinical remission. Results Eighty-four patients were included. At diagnosis, patients were divided with regard to the extent of disease as assessed by the Paris classification as follows:, 45 (53.6%) showed pancolitis E4, 2 (2.4%) left colitis E3, 22 (26.2%) proctosigmoiditis E2, and, 15 (17.8%) proctitis E1. Globally, 14 (16.7%) patients presented with an acute severe colitis (ASC) attack at diagnosis. The median age at diagnosis was, 13 years and, 7 months (IQR=94 months). Patients were followed for a median time of, 18 months (IQR:, 22 months). The second endoscopy was performed after a median time of, 27 months (IQR=32). At the second endoscopic re-evaluation, 64 (76.2%) patients out of the total had regression of disease; whereas, 20 (23.8%) patients out of the total had progression of disease. Twenty (23.8%) patients had a Mayo score of, 1, whereas, 36 (42.8%) patients had a Mayo score of, 0. Complete histological healing was achieved by, 17 (20.2%) patients. When observing recurrence-free survival, patients who achieved partial and complete MH showed a significantly higher recurrence-free survival (p&lt;0.001 and p&lt;0.001, respectively). Lastly, when considering only patients who achieved at least partial MH, the subgroup with complete HH showed lower recurrence rates compared to those with persistent microscopic inflammation (p=0.049) Conclusion We reported the long-term outcomes of a selected group of pediatric patients with ulcerative colitis. Achievement of mucosal and histological healing appeared to protect against disease recurrence, with patients who resolved completely microscopic inflammation showing longer relapse-free survival rates.