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  • 1
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2022
    In:  Journal of Crohn's and Colitis Vol. 16, No. Supplement_1 ( 2022-01-21), p. i385-i385
    In: Journal of Crohn's and Colitis, Oxford University Press (OUP), Vol. 16, No. Supplement_1 ( 2022-01-21), p. i385-i385
    Abstract: Multiple clinical studies in children with Crohn’s disease (CD) have demonstrated the high efficacy of nutritional therapy with exclusive enteral nutrition (EEN) to induce remission and even to promote mucosal healing. However, EEN as inductive treatment may be not tolerated or inefficient and we are well aware of the paramount importance of a well conducted induction treatment for paediatric CD with the goal of an individualized induction treatment to improve the prognosis and the quality of life of inflammatory bowel disease (IBD) children. Methods A retrospective multicentre study including newly diagnosed children with CD treated with EEN as induction therapy was designed. The primary aim of the study was to study predictive factors of non- adherence to treatment. The secondary endpoint were predictive factors of clinical non-remission at the end of induction treatment. Those data together were analysed with the ultimate goal of trying to define an individualized induction treatment for children with CD. Results 376 CD children from, 14 IBD paediatric referral centres were enrolled in the study. The rate of EEN adherence was, 89 %. Colonic involvement and FC & gt;, 600 μg/g at diagnosis were found associated with a reduced EEN adherence in univariate and multivariate analysis. The remission rate of those who completed induction treatment was, 67%. A multivariate analysis showed that factor determining lower remission rate were age & gt;, 15 years and PCDAI & gt;, 50. With those results we were able to create a decisional algorithm which is provided in figure 1. Conclusion EEN administered for, 8 weeks is effective for inducing clinical remission. The rate of adherence is high but there is a group of patients (colonic involvement + hight FC) which are at risk of non-adherence and thus may be candidate for alternative dietary induction regimens. Moreover, older patients with moderate to severe active disease (PCDAI & gt;40), are at higher risk of failing clinical remission achievement after EEN and may benefit from an early anti-TNF alpha treatment. Personalized treatment strategies should be proposed weighing the benefits and risks based on each patient’s disease location, phenotype and disease activity with the overall aim of obtaining rapid control of inflammation to reduce long-term bowel damage.
    Type of Medium: Online Resource
    ISSN: 1873-9946 , 1876-4479
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 2
    In: Journal of Crohn's and Colitis, Oxford University Press (OUP), Vol. 17, No. Supplement_1 ( 2023-01-30), p. i662-i664
    Abstract: Current data on dual biologic or small molecules therapy in children are limited. The aim of the study was to evaluate the effectiveness and safety of dual therapy in paediatric patients with IBD. Methods This was a retrospective multicenter study from 14 centers affiliated with the IBD interest and Porto groups of ESPGHAN. We included children with IBD who were treated with combination of biologic agents or biologic and small molecule, with at least 3 months of follow-up under this therapy. Demographic, clinical, laboratory, endoscopic and imaging data were collected. Adverse events were recorded. All analyses were done in the intention-to-treat population. Children that discontinued therapy were considered treatment failures and were imputed for non-response, while missing data was imputed according to the last observation carried forward method. Results Sixty-two children [35 Crohn’s disease (CD), 27 ulcerative colitis (UC)], with a median age of 15.5 (IQR 13.1-16.8) years and disease duration of 3.8 (IQR 2.5-6.1) years were included. All children failed previous biologics and 47 (76%) failed at least two biologic agents. The dual therapy included anti-TNF agent and vedolizumab in 30 children (48%), anti-TNF and ustekinumab in 21 children (34%), vedolizumab and ustekinumab in 8 children (13%), and tofacitinib and other biologics in 3 children (5%). Clinical remission was observed in 21 (35%), 30 (50%) and 38 (63%) children at 3, 6 and 12 months, respectively. Of 27 children who were treated with corticosteroids at baseline, 20 (74.1%) were weaned within 3 months after the initiation of dual therapy. At 12 months of follow up, normalization of C-reactive protein and decrease in fecal calprotectin to & lt; 250 mcg/g were achieved in 75% and 64%, respectively. Endoscopic and transmural healing were observed in 2/23 (9%) and 5/16 (31%) children, respectively. Male sex and diagnosis of UC were associated with higher likelihood of clinical remission (p=0.017 and p=0.020, respectively). Adverse events were reported in 29 (47%) children. While most adverse event were mild, 8 were regarded as serious and 6 (10%) led to discontinuation of dual therapy. The serious adverse events included infusion reaction to infliximab, fatigue and headache following vedolizumab infusion, severe skin eruptions (3 patients), cellulitis and skin abscess, elevated liver enzymes and deep vein thrombosis. Conclusion Dual biologic or small molecules therapy may be effective in children with otherwise refractory IBD. The risk of serious adverse events should be considered before recommending dual therapy.
    Type of Medium: Online Resource
    ISSN: 1873-9946 , 1876-4479
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2389631-0
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  • 3
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2022
    In:  Journal of Crohn's and Colitis Vol. 16, No. Supplement_1 ( 2022-01-21), p. i110-i111
    In: Journal of Crohn's and Colitis, Oxford University Press (OUP), Vol. 16, No. Supplement_1 ( 2022-01-21), p. i110-i111
    Abstract: Ulcerative proctitis (UP), defined as a colonic location limited to the rectum, is a poorly investigated condition in children, usually considered as a minor form of Ulcerative Colitis (UC). The aim of the present study was to compare the disease course of paediatric patients affected by UP at diagnosis with the other UC locations. Methods This multicentre retrospective observational study has been carried out starting from the data prospectively registered in the IBD Registry of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP). Seventeen IBD referral centres adhering to the registry were included in the study. Patients age 0 to 18 years, who were diagnosed with UC according to the Porto criteria starting from January 1, 2009, to May 1st, 2021 were identified. Only children with a minimum follow-up of 12 months were included in the study. Once enrolled, children were subsequently divided in two groups based on Paris classification: group 1 (E1) and group 2 (E2, E3 and E4). Results Eight-hundred-eighty-five children were finally included in the study (median age at diagnosis: 11.2 years, range: 0–18 years; M/F: 434/451), of whom 176 (19.8%) belonging to group 1 and 709 (80.1%) to group 2. The median age at diagnosis was significantly higher in group 1 when compared to group 2 [11.9 (0–18) versus 11 (0–18) years, respectively; (p & lt;0.001)]. At diagnosis, the induction therapy was significantly different with 68 (39.5%) patients of group 1 undergoing steroid therapy versus 505 (71.2%) of group 2 (p & lt;0.001) and 79 (41.9%) of group 1 practising only mesalamine respect to 186 (26.2%) of group 2 (p & lt;0.001). A higher number of children from group 2 started immunosuppressive or biologic therapy as maintenance therapy at diagnosis [Group 1: 11 (6.2%) versus 173 (24.4%), respectively; (p & lt;0.001)]. The median follow-up of our cohort was 4.5 years (range 1–13 years). At the last follow-up, 67/176 (38%) children with UP showed an extension of their disease location without significant difference when compared to group 2 [265 (37.5%); p=0.9] , while 81 (45%) children from Group 1 were under immunosuppressive or biologic therapy versus 566 (79.8%) from group 2 (p & lt;0.001). Five children (3%) of Group 1 underwent colectomy during the follow up versus 45 (6.9%) of Group 2 (p=0.06). Conclusion UP is a frequent location of paediatric onset UC and the risk of endoscopic extension of proctitis is similar to the more extensive forms. A considerable number of patients with UP required immunosuppressive or biologic therapy during the follow-up and no significant difference was observed in terms of surgery. Overall, UP cannot be considered as a minor form of UC.
    Type of Medium: Online Resource
    ISSN: 1873-9946 , 1876-4479
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2389631-0
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  • 4
    In: Journal of Crohn's and Colitis, Oxford University Press (OUP), Vol. 16, No. Supplement_1 ( 2022-01-21), p. i112-i113
    Abstract: Very early-onset inflammatory bowel disease (VEOIBD) is diagnosed before the age of 6 years while infantile IBD occurs before the age of 2 years. We aimed to assess disease characteristics and long-term outcomes in these populations. Methods We conducted a retrospective longitudinal cohort study in 21 pediatric centers worldwide. Patients diagnosed with VEOIBD between the years 2008–2018 with at least 2 years of follow-up were included. Results The cohort included 243 patients (52% males), with median follow-up of 5.8 (IQR 3.2–8.4) years. Median age at diagnosis was 3.3 (IQR 1.8–4.5) years, with 69 (28%) diagnosed before the age of 2 years. Disease was classified as Crohn’s disease (CD), ulcerative colitis (UC) and IBD-unclassified (IBDU) in 30%, 59% and 11%, respectively. In patients with UC or IBDU, 75% presented with pancolitis. In patients with CD, 62% presented with isolated colonic disease and 32% with ileo-colonic disease, while 19% had perianal involvement. Genetic testing was performed in 96 (40%) patients [40 (58%) & lt;2 years, 56 (32%) 2–6 years, p=0.001], with monogenic diagnosis identified in 23% (33% and 16%, respectively, p=0.08). The most common findings were mutations in IL10-receptor (5 cases, 23%). Stricturing or penetrating disease was observed in 9 cases (4%). First induction therapies were corticosteroids, 5-aminosalicylic acid (5ASA) and nutritional therapy in 53%, 30% and 11%, respectively. Corticosteroids were more common as first induction in infantile vs. non-infantile IBD (64% vs. 49% respectively, p=0.003). Maintenance therapies included deep immune-suppression (mainly biologics and corticosteroids) in 51%, immunomodulators in 27%, and non-immunosuppressive agents (5-ASA, nutritional therapy and antibiotics) in 22% of patients, with no significant differences between age groups. Compared to patients diagnosed after 2 years of age, patients with infantile IBD presented with higher rates of IBDU, lower levels of hemoglobin and albumin and higher levels of CRP, lower weight (but not height) z-scores, had lower rates of response to first induction therapy and shorter time to hospitalization during follow-up (p & lt;0.05 for all). Colectomy was performed in 11% and diversion surgery in 4% of the cohort, with no significant differences between age groups. No malignancies and nor deaths were observed. At end of follow-up, 85% of patients were in corticosteroid free clinical remission. Conclusion Patients with VEOIBD, including infantile IBD, have fair long-term outcome with low rates of complications and surgical interventions. Nevertheless, patients with infantile IBD demonstrated more severe clinical features at presentation and a lower response to induction therapy.
    Type of Medium: Online Resource
    ISSN: 1873-9946 , 1876-4479
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2389631-0
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  • 5
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2022
    In:  Journal of Crohn's and Colitis Vol. 16, No. Supplement_1 ( 2022-01-21), p. i407-i408
    In: Journal of Crohn's and Colitis, Oxford University Press (OUP), Vol. 16, No. Supplement_1 ( 2022-01-21), p. i407-i408
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 1873-9946 , 1876-4479
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 6
    In: Blood, American Society of Hematology, Vol. 78, No. 10 ( 1991-11-15), p. 2740-2746
    Abstract: A novel 5.3-kb deletion of the alpha-globin gene cluster was observed in a family from Naples, Southern Italy. It removes the 5′ end of the alpha 2-globin gene, causing an alpha (+)-thalassemia defect. Because of the presence of the residual 3′ end of the alpha 2-globin gene, we indicated this new haplotype with the symbol (alpha)alpha 5.3. The 5′ breakpoint, the first to be reported in the intergene region of the psi alpha 2- and psi alpha 1-globin genes, is located 822 bp upstream of the cap site of the psi alpha 1-gene and about 150 bp upstream of a 300- nt Alu family member. The 3′ breakpoint is located in the IVS-1 nt 58 of the alpha 2-globin gene. The 5.3-kb deleted fragment shows particular characteristics: it contains four Alu sequences having long regions 80% complementary and the 5′-GGCC-3′ short repeat at both ends. The sequences spanning across the breakpoints on the same strand and containing this repeat on their 3′ and 5′ ends, respectively, are 17 of 25 base complementary. These particular features led us to assume the formation of a multistem-loop due to the intrastrand interaction between the complementary regions as intermediate to the deletion. The unusual localization of the 5′ breakpoint suggests that even the intergene region of the psi alpha 2- and psi alpha 1-globin genes may function as a deletion target.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 1991
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 7
    In: Blood, American Society of Hematology, Vol. 78, No. 10 ( 1991-11-15), p. 2740-2746
    Abstract: A novel 5.3-kb deletion of the alpha-globin gene cluster was observed in a family from Naples, Southern Italy. It removes the 5′ end of the alpha 2-globin gene, causing an alpha (+)-thalassemia defect. Because of the presence of the residual 3′ end of the alpha 2-globin gene, we indicated this new haplotype with the symbol (alpha)alpha 5.3. The 5′ breakpoint, the first to be reported in the intergene region of the psi alpha 2- and psi alpha 1-globin genes, is located 822 bp upstream of the cap site of the psi alpha 1-gene and about 150 bp upstream of a 300- nt Alu family member. The 3′ breakpoint is located in the IVS-1 nt 58 of the alpha 2-globin gene. The 5.3-kb deleted fragment shows particular characteristics: it contains four Alu sequences having long regions 80% complementary and the 5′-GGCC-3′ short repeat at both ends. The sequences spanning across the breakpoints on the same strand and containing this repeat on their 3′ and 5′ ends, respectively, are 17 of 25 base complementary. These particular features led us to assume the formation of a multistem-loop due to the intrastrand interaction between the complementary regions as intermediate to the deletion. The unusual localization of the 5′ breakpoint suggests that even the intergene region of the psi alpha 2- and psi alpha 1-globin genes may function as a deletion target.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 1991
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 8
    In: Journal of Crohn's and Colitis, Oxford University Press (OUP), Vol. 16, No. Supplement_1 ( 2022-01-21), p. i435-i435
    Abstract: Ustekinumab (UST) is an effective therapy for induction and maintenance of remission in Crohn’s disease (CD). Intensification of UST maintenance dosage has shown effectiveness in some adult patients, but no similar data are available in children. The aim of the study was to evaluate the effectiveness and safety of dose escalation of UST in paediatric CD. Methods This was a retrospective multicenter study from 25 centers affiliated to the IBD Interest and Porto groups of ESPGHAN. We included children with CD who initiated UST at a standard dosing and subsequently underwent dose escalation to intervals shorter than 8 weeks, or re-induction due to active disease. Demographic, clinical, laboratory, endoscopic and imaging data were collected at escalation and during a 12 months follow-up. Clinical remission was defined as weighted Paediatric Crohn’s Disease Activity Index (wPCDAI) & lt;12.5 and clinical response as a decline in & gt;17.5 points. Adverse events were explicitly recorded. Results Sixty-nine children, with a median age of 15.8 (IQR 13.8–16.9) years and disease duration of 4.3 (2.9–6.3) years were included. Sixty-eight (98.6%) and 59 (86.8%) children were biologic and immunomodulators experienced, respectively. UST dose was escalated after a median of 6 (3.6–12) months of therapy. Clinical response and remission were observed in 46 (67%) and 29 (42%) children at 3 months, respectively. The strongest predictor of clinical remission was lower wPCDAI at escalation (p=0.001). The median serum levels of C-reactive protein decreased from 14 (3–28.03) to 5 (1.1–20.5) mg/L at 3 months (p=0.012), and fecal calprotectin from 1110 (499–2300) to 248 (118–1159) mcg/g at 12 months (p=0.05). Endoscopic and transmural healing were achieved in 3/19 (16%) and 2/15 (13%) patients, respectively, of those with available tests. Overall, 13 patients (19%) discontinued therapy due to active disease, at a median of 3 (3–4.5) months. No serious adverse events were reported. Conclusion Two-thirds of children with active CD achieved response following dose escalation of UST.
    Type of Medium: Online Resource
    ISSN: 1873-9946 , 1876-4479
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 9
    Online Resource
    Online Resource
    Wiley ; 2010
    In:  ChemInform Vol. 25, No. 8 ( 2010-08-19), p. no-no
    In: ChemInform, Wiley, Vol. 25, No. 8 ( 2010-08-19), p. no-no
    Type of Medium: Online Resource
    ISSN: 0931-7597
    Language: English
    Publisher: Wiley
    Publication Date: 2010
    detail.hit.zdb_id: 2110203-X
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  • 10
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2023
    In:  Journal of Crohn's and Colitis Vol. 17, No. Supplement_1 ( 2023-01-30), p. i810-i812
    In: Journal of Crohn's and Colitis, Oxford University Press (OUP), Vol. 17, No. Supplement_1 ( 2023-01-30), p. i810-i812
    Abstract: We aimed at appraising real-life efficacy of Crohn’s Disease Exclusion Diet (CDED) coupled with partial enteral nutrition (PEN) in inducing clinical and biochemical remission at disease onset and in patients with loss of response to biologics in a tertiary-level center. We also aimed at identifying early responders to this dietary regimen. Methods We gathered clinical, anthropometric and laboratory data of patients aged less then 18 years of age with a diagnosis of CD, who were consecutively treated with CDED coupled with PEN as main treatment for the induction of remission or in the setting of loss of response to other therapies. We collected data of patients who received CDED plus PEN from April 2019 to June 2022 at diagnosis, at the beginning of the dietary treatment, and at the phase 1. Patients who interrupted diet during follow-up were considered as treatment failures on an intent to treat basis. We compared groups using chi-square, Fisher’s exact test, Mann-Whitney U or related-samples Wilcoxon signed rank tests or McNemar’s test as appropriate. Results 47 patients were retrospectively identified. Table 1. summarizes clinical and biochemical characteristics at diagnosis and at CDED with PEN initiation. 24 (51.1%) patients started CDED as induction therapy at disease onset, whereas 23 (48.9%) of them received CDED with PEN as add-on therapy. 32/47 (68%) patients achieved clinical remission (wPCDAI & lt; 12.5) at the end of phase 1, 16/24 patients (66.7%) who started CDED as induction therapy and 16/23 (69.5%) of those who started CDED as add-on, with no statistically significant difference among the two groups (p=1.00). Laboratory parameters significantly improved in both groups (Figure 1.). There were no statistically significant differences in clinical remission rates between patients with mild-to-moderate and severe disease at the end of phase 1 (25/35 vs 7/12, p=0.481). At disease onset, 14 patients added a concomitant treatment (11 patients added anti-TNF alpha, 3 patients added IMM and one patient added anti-TNF alpha + IMM) after a median time of 4 weeks (IQR: 3-5 weeks). 28 patients had clinical data gathered at week 3. Patients who achieved clinical response at week 3 (a change in wPCDAI & gt; 12.5) were more likely to be in clinical remission at the end of phase 1 (17/20 vs 1/8, p & lt;0.01), both in patients who started CDED at disease onset and in the add-on setting. Conclusion CDED with PEN confirmed its efficacy in a real-life setting, both as induction regimen and as add-on therapy, also in patients with clinically severe disease. Early clinical response predicts clinical remission at the end of phase 1, possibly allowing identification of dietary responsive disease. Table 1. Figure 1.
    Type of Medium: Online Resource
    ISSN: 1873-9946 , 1876-4479
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2389631-0
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