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Background Ulcerative proctitis (UP) is an uncommon presentation in paediatric patients with ulcerative colitis, accounting for Methods A retrospective cohort study involving 37 sites affiliated with the IBD Interest group of ESPGHAN. Data were collected at different timepoints from patients diagnosed with UP aged Results Two hundred and fifty patients with UP were included, with a median age at diagnosis of 14.5 (IQR 12.3-15.9) years, and a median follow-up of 2.7 (IQR 1.7-3.9) years. The most common presenting symptoms were bloody stools (94%), abdominal pain (59%) and diarrhea (53%). At diagnosis, the median pediatric ulcerative colitis activity index (PUCAI) score was 25 (IQR 20-35), and only 3 patients (1.3%) presented with ASC. Most children had normal inflammatory markers and albumin levels. the median fecal calprotectin level was 720 mcg/g (IQR 310-1800), while 16 patients (9.9%) had a calprotectin level Conclusion Disease burden is significant in paediatric patients that present with UP, with high rates of proximal disease extension and requirement for treatment escalation.

Background 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 < 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.

Background We previously reported the effectiveness of vedolizumab (VDZ) to induce remission in children with CD and UC enrolled in the prospective,multicenter VEDOKIDS study.In this extended analysis,we aimed to explore the effectiveness and safety of VDZ to maintain remission through week 30 Methods Children with CD or UC commenced on VDZ at any stage of the disease were followed at baseline and 2, 6, 14 and 30 weeks thereafter.Explicit demographic,clinical and safety data were prospectively recorded.The primary outcome was steroid-and EEN-free clinical remission (SFR) at 30 weeks,analyzed under the ITT principle with non-response imputation.Response was defined as change of ≥ 20 points in PUCAI or >20 points in wPCDAI and clinical remission as PUCAI Results A total of 142 children were enrolled (65 [46%] CD,77 [54%] UC;Table).At the end of the induction period,the rates of response were 75% in UC vs 64% in CD (p=0.2),of remission 52% vs 38% (p=0.1),and of SFR 47% vs 32% (p=0.08),respectively.At week 30,SFR rates were 47% in UC and 34% in CD (p=0.1);outcomes were also numerically higher in UC,but without statistical significance(Figure) Response to induction therapy predicted week 30 remission.Of the responders,19 (59%) children with CD and 31 (60%) with UC achieved SFR at week 30,while the corresponding figures for those not achieving response were 3 (12%; p=0.004) in CD and 5 (29%; p=0.03) in UC.Similarly,in multivariable model,response to induction treatment was highly associated with SFR at week 30,in both CD (OR 11.2 [95%CI 2.3-73]) and UC (OR 4.8 [95%CI 1.4-19]).Of the 22 patients who were responders but not remitters at week 14,four eventually achieved SFR at week 30 (1/10 [10%] in CD and 3/12 [25%] in UC) By week 30,159 AE's were reported by 72 children including one case of Hodgkin's lymphoma (VDZ was resumed after completing the chemotherapy);the patient was never exposed to thiopurines.No cases of progressive multifocal leukoencephalopathy or deaths were reported.Thirty-six AEs in 23 (16%) children were classified as possibly related to VDZ,11 of which (31%) were moderate and the others mild.Four children (1.4%) discontinued treatment due to AEs (one due to infusion reaction,one leukocytoclastic vasculitis,one azotemia and one due to fever and malaise Conclusion In this prospective multicenter study,VDZ was effective for maintaining remission in children with CD, and more so in UC.Contraty to common notions,children with CD not achieving complete remission by week 14 had a very low likelihood of entering remission thereafter.Safety profile was generally good except for one lymphoma case with questionable relation to VDZ

Background Vedolizumab (VDZ) is commonly used as an off-label therapy in children with ulcerative colitis (UC) but no predictive factors of response are available. Vedolizumab binds α4β7 integrin and blocks the migration of T-lymphocytes and other cells, including eosinophils, which are involved in the UC inflammatory process. The aim of our study was to explore the predictive value of pre-therapy mucosal eosinophil count on the response to vedolizumab induction therapy in a paediatric population with UC Methods This is a retrospective, monocentric study, including children with UC treated with VDZ in the Paediatric Gastroenterology Unit of Policlinico Umberto I Hospital – Sapienza University of Rome. Histopathological data were analyzed for eosinophil counts in high power fields (hpf) in the cecum, transverse colon, sigma, and rectum prior to VDZ treatment. Clinical remission and response were evaluated at week 14 based on the PUCAI score. Results Twenty-five UC patients treated with VDZ were enrolled. All patients had failed previous anti-TNF therapy. Median baseline eosinophil count was 21 eo/hpf (5-60) in the cecum, 20 eo/hpf (6-68) in transverse colon, 44 eo/hpf (12-77) in sigma and 31 eo/hpf (9-67) in rectum. Baseline median eosinophil mucosal count in sigma was significantly higher in patients in remission (51[30-82]/ vs. 19[8.5–46] eosinophils/hpf, P23 eosinophils/hpf, with a sensitivity of 85.7% and specificity of 66.7% (Youden’s index 0.83) with an area under the curve (AUC) of 0.778 Conclusion Mucosal eosinophil abundance in sigma may predict remission to vedolizumab induction in paediatric UC. More studies are warranted to confirm these preliminary results and further investigate the role of mucosal eosinophils as a marker of therapeutic response and in the pathogenesis of UC

Background High-risk (HR) Crohn’s Disease (CD) is associated with high surgical and progression rates. Therefore, recent ESPGHAN guidelines (GL) suggest starting an early anti-TNFα treatment to modify the natural history of the disease. The aim of our study was to evaluate the surgical rate in a population of HR-CD paediatric patients treated with up-front anti-TNFα agents and long-standing biologic therapy Methods This is a retrospective, observational, single-center study conducted at the Paediatric Gastroenterology, Hepatology, and Endoscopy Unit at Policlinico Umberto I Hospital – Sapienza University of Rome. We collected data from all patients diagnosed with CD under 18 years, with a minimum follow-up of 12 months. between June 2008 to July 2022. Patients were then stratified at the diagnosis into HR and LR, based on ESPGHAN GL criteria. Demographic, clinical, laboratory, endoscopic, and imaging data were collected at 6, 12, 24, 36, 48, and 60 months Results 130 patients were enrolled, 76 HR (58%) and 54 LR (42%) [median age 12.5 (IQR) yrs, female 45 (35%), medium follow-up 54±24 months]. The HR group included 39 patients (51%) with panenteric disease, 15 (20%) with a structuring behavior (B2), 3 (4%) with structuring/penetrating disease (B2-B3), and 26 (34%) with perianal involvement (p). Early anti-TNFα agents were started in 80% of patients 0.05]. Perianal disease resulted positively associated with surgical risk (p 0.002, OR 5.62 CI 1.84-17.15) while small bowel imaging at the diagnosis was a protective factor for surgery (p 0.017, OR 0.23 CI 0.07-0.77). No significant difference was found in the interval free from surgery between HR and LR, although HR children mainly needed surgery in the first 12 months after the diagnosis. Conclusion Our data suggest that paediatric patients with HR-CD treated with early anti-TNF agents and long-standing biologic therapy have a similar disease course and surgical risk to those with LR disease. At a 5-year follow-up, one-third of patients needed surgery, mainly in the first year after the diagnosis

Background Limited data are available on the use of Vedolizumab (VDZ) in paediatric Crohn’s Disease (CD) and Ulcerative Colitis (UC). We evaluated the effectiveness and safety of VDZ to induce remission at week 14 in the prospective, multicenter VEDOKIDS study. Methods We enrolled children (age 0–18 years) with CD or UC commenced on VDZ with a standardized dosing of 177mg/BSA up to 300mg at 0, 2, 6 and q8 weeks thereafter. Non-responders had their dose escalated to q4wks at the discretion of the local physician. Explicit demographic, clinical and safety data were prospectively recorded via REDcap. Clinical remission was defined as steroid- and EEN-free remission (i.e. wPCDAI Results 128 children were enrolled, 60 (47%) with CD, and 68 (53%) with UC (58 (45%) males, mean age 13.8±3.6, 93 (73%) failed previous anti-TNF, median disease duration 2.3 years (IQR 0.9–4.7)). Using the ITT principle, clinical and complete remission rates for CD at week 14 were 30% and 20%, respectively, and for UC 50% and 38%, respectively (Fig 1). Clinical remission rates of those receiving VDZ as first line biologics versus second line were 57% and 34%, respectively (p=0.019; Fig 2); the corresponding complete remission rates were 49% and 23% (p=0.004). In the UC group, disease activity at baseline measured by the PUCAI predicted clinical remission at week 14 (OR=0.95, 95%CI 0.93–0.98; median baseline PUCAI 15 (IQR 0–30) in those achieving remission and 45 (20–55) in those who did not; p=0.002). ESR (OR=0.94, 95%CI 0.89–0.98; p=0.009) and a trend towards extensive disease (L3 vs. L1 and L2; OR 0.14, 95%CI 0.18–1.036, p=0.054) predicted clinical remission in CD. During the 14 weeks, 113 adverse events (AE) were recorded in 58 children: 28 AEs were possibly related to VDZ, all of which were mild-moderate and only 3 (11%) led to discontinuation of VDZ (leukocytoclastic vasculitis, myalgia and dyspnea). There were 18 serious AEs, only one was graded as possibly related to VDZ (headache). There were 18 non-serious cases (19%) of upper respiratory infections (pharyngitis, tonsilitis, parotitis, and otitis media) and one Campylobacter jejuni which was graded as serious. Conclusion In this prospective multicenter study, VDZ was safe and effective for inducing remission in a refractory cohort of paediatric IBD, more so in UC. Disease severity and extent at baseline may predict clinical response.

Background 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%) 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 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.

Background 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 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.

Background Scarce data have investigated the association between pediatric Inflammatory bowel disease (IBD) and Eosinophilic esophagitis (EoE). We, therefore, aimed to describe the epidemiology and a possible peculiar phenotype and natural history of such association. Methods Case-control study based on the Italian Society for Pediatric Gastroenterology (SIGENP) national registry. All children with a concomitant diagnosis of IBD and EoE were included. Overall prevalence and incidence in 2 periods, 2009–2015 and 2016–2021, were calculated. Cases were matched with IBD only and EoE only patients in a 1:3 ratio. Phenotype and outcomes (courses of steroids, risk of complications, surgery, treatment escalation, and hospitalization) were compared between groups. Results Eleven patient (age 11,27 ± 2,83, Male 91%) with EoE-IBD out of 3090 patients with IBD only were identified, resulting in a prevalence of 0,35% and an incidence of 0,18% for the period 2009–2015 and 0,45% for the period 2016–2021. Treatment escalation rates were significantly higher in patients with IBD compared to EoE-IBD at 12 and 24-month follow-up (0 vs 30%, p = 0.04 and 9% Vs 45,5%, p = 0.03, respectively). Patients with IBD only were at a significantly higher risk of hospitalization than both EoE-IBD and EoE only patients (Log Rank p < 0.001). We found no significant differences in major outcomes related to the EoE course in EoE-IBD patients compared to EoE patients. Conclusion Overall, the incidence and prevalence of EoE in children with IBD are low, although the incidence seems to be rising in the six years. Having an EoE appears to be associated with a milder IBD disease course while having an IBD doesn’t seem to affect the natural history of EoE. More data are needed to better define the phenotype of such condition.

Background Telemedicine is one of the major changes that clinicians have encountered over the past decade; in particular during the COVID-19 pandemic, televisits were rapidly implemented to guarantee patients’ assistance, with the intention of Health Care Providers (HCPs) to continue to use them beyond the pandemic. The aim of our national survey was to evaluate the current usage of telemedicine for IBD patients from their perspective, investigating patients’ impressions about telemedicine and factors affecting them through a Machine Learning (ML) analysis. Methods In March 2021, the Italian IBD patients’ association (AMICI Onlus) distributed to their members - through its mailing list and on social media platforms - an anonymous online questionnaire investigating the use of telemedicine. Socio-demographic and IBD characteristics were collected; the usage, patients’ satisfaction and trust of telemedicine were assessed through Likert scales. ML tools - Decision Trees (DT) and Random Forest (RF) - were applied to identify the determinants of patient’s perceptions about telemedicine; the produced RF ranking displays two indicators: %IncMSE and IncNodePurity. Results Nine hundred and seventy-eight IBD patients (women 58.9%) from every Italian region completed the questionnaire. Among the respondents, 87 (8.9%) personally had a telemedicine experience; 153 reported that their Centre performed a telemedicine service during the COVID-19 pandemic (24.2% televisits, 39.2% e-mails, 24.8% phone-calls, 3.9 % dedicated website, 7.9% others). Overall, 707 (72.3%) would trust a telemedicine service, 760 (77.7%) would like to have it also with another HCP (e.g., nutritionist, psychologist) and 778/961 (81%) would like to use telemedicine in the future (17 did not answer to this specific question); 792 (81%) stated they thought useful to have the possibility to use telemedicine and 847 (86.6%) would like their Centre to offer them this facility. Considering this last question as the output at the DT, the variable which have been found to influence the most this patients’ willingness is patient’s perception of the usefulness of telemedicine in treating their disease, since it represented the root of the tree explaining the results. The RF rankings confirmed that this variable influenced the most patients’ perception with the highest levels of %IncMSE and IncNodePurity(Figure 1). Conclusion The practice of telemedicine in the management of IBD patients has not been very relevant throughout Italy so far (less than 10%), but more than four every five respondents would like to use telemedicine. Machine learning analysis shows that the perceived usefulness of telemedicine service is the key point for patients who would like it was a part of usual clinical practice.

Background 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)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.

Background 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 >, 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 >, 15 years and PCDAI >, 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>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.

Patients with ulcerative colitis often receive thiopurines as immunomodulators (IMs) to maintain remission and avoid corticosteroids. If unresponsive or intolerant to these agents, patients are treated with methotrexate, an antimetabolite never assessed in paediatric ulcerative colitis.To describe the experience with methotrexate in children with ulcerative colitis.Thirty-two patients (median age 13.9 years) received methotrexate. Pediatric Ulcerative Colitis Activity Index (PUCAI) and use of corticosteroids were the main outcomes evaluated at baseline and at 3, 6 and 12 months.Indications to methotrexate were azathioprine unresponsiveness in 18 patients, azathioprine intolerance/toxicity in 10 and spondyloarthropathy in four. Response or remission was achieved in 72%, 63% and 50% of patients at 3, 6 and 12 months respectively. Mean PUCAI were 49.5 ± 23.3 at baseline and 32.9 ± 21.9, 29.5 ± 21.8 and 29.4 ± 19.9 at 3, 6 and 12 months respectively (P: 0.03). At the beginning of methotrexate, 16 patients (50%) received corticosteroids that were discontinued in 13 of them (81%) by 6 months. At the end of the study, 11 patients (33%) needed short courses of corticosteroids for disease relapse.Methotrexate may be useful in treating children with ulcerative colitis, although large, controlled trials are warranted to define better its effectiveness.

Inflammatory bowel diseases (IBD) are often associated with extraintestinal manifestations (EIMs), which occur in approximately one third of patients. There is only few published data on the occurrence of these manifestations in children and adolescents, so most of the data are taken by studies in adult patients. The organs most commonly affected are joints, skin, eyes and biliary tract, although nearly every organ may be involved. Some of the EIMs are clearly related to intestinal disease activity (i.e., erythema nodosum, peripheral arthritis, orofacial lesions), whereas others occur independently (i.e., pyoderma gangrenosum, anterior uveitis/iritis, ankylosing spondylitis, primary sclerosing cholangitis). Many extraintestinal disorders may be direct inflammatory and metabolic complications of the intestinal inflammation (i.e., osteoporosis, growth retardation, nephrolithiasis, ureteral obstruction, thromboembolic disease). In this review we provide an overview on the prevalence and clinical aspects of the more commonly reported EIMs of Crohn's disease and ulcerative colitis in pediatric patients, focusing on specific issues of children affected by IBD (growth failure and metabolic osteopathy).

Purpose: To determine the significant correlations between retinal sensitivity measured by fundus-related microperimetry and the visual acuity and the foveal thickness measured by optical coherence tomography (OCT) in eyes with Diabetic Macular Edema (DME) during diurnal variations of blood glucose levels. Methods: 30 eyes with macular edema of 40 consecutive patients with type1 diabete and 20 eyes of 20 normal subjects were included in our study. Best corrected visual acuity (ETDRS charts), macular thickness, macular sensitivity, and blood glucose concentration were quantified in all patients twice a day (10 am, 5 pm). Optical coherence tomography (Stratus OCT, Zeiss) was used to quantify macular thickness; macular sensitivity and retinal fixation were evaluated with fundus related microperimeter (MP1,Nidek). Results: The mean sensitivities in examinated area were significantly lower in patients with DME than in normal subjects (P