Objective: To validate a core set of outcome measures for the evaluation of response to treatment in patients with juvenile dermatomyositis (DM).Methods: In 2001, a preliminary consensus‐derived core set for evaluating response to therapy in juvenile DM was established. In the present study, the core set was validated through an evidence‐based, large‐scale data collection that led to the enrollment of 294 patients from 36 countries. Consecutive patients with active disease were assessed at baseline and after 6 months. The validation procedures included assessment of feasibility, responsiveness, discriminant and construct ability, concordance in the evaluation of response to therapy between physicians and parents, redundancy, internal consistency, and ability to predict a therapeutic response.Results: The following clinical measures were found to be feasible, and to have good construct validity, discriminative ability, and internal consistency; furthermore, they were not redundant, proved responsive to clinically important changes in disease activity, and were associated strongly with treatment outcome and thus were included in the final core set: 1) physician's global assessment of disease activity, 2) muscle strength, 3) global disease activity measure, 4) parent's global assessment of patient's well‐being, 5) functional ability, and 6) health‐related quality of life.Conclusion: The members of the Paediatric Rheumatology International Trials Organisation, with the endorsement of the American College of Rheumatology and the European League Against Rheumatism, propose a core set of criteria for the evaluation of response to therapy that is scientifically and clinically relevant and statistically validated. The core set will help standardize the conduct and reporting of clinical trials and assist practitioners in deciding whether a child with juvenile DM has responded adequately to therapy.

Currently, there are between 300,000 and 500,000 childhood cancer survivors (CCSs) in Europe. A significant proportion is at high risk, and at least 60% of them develop adverse health-related outcomes that can appear several years after treatment completion. Many survivors are unaware of their personal risk, and there seems to be a general lack of information among healthcare providers about pathophysiology and natural history of treatment-related complications. This can generate incorrect or delayed diagnosis and treatments. The Survivorship Passport (SurPass) consists of electronic documents, which summarise the clinical history of the childhood or adolescent cancer survivor. It was developed by paediatric oncologists of the PanCare and SIOPE networks and IT experts of Cineca, together with parents, patients, and survivors' organisations within the European Union-funded European Network for Cancer research in Children and Adolescents. It consists of a template of a web-based, simply written document, translatable in all European languages, to be given to each CCS. The SurPass provides a summary of each survivor's clinical history, with detailed information about the original cancer and of treatments received, together with personalised follow-up and screening recommendations based on guidelines published by the International Guidelines Harmonization Group and PanCareSurFup. The SurPass data schema contains a maximum of 168 variables and uses internationally approved nomenclature, except for radiotherapy fields, where a new classification was defined by radiotherapy experts. The survivor-specific screening recommendations are mainly based on treatment received and are automatically suggested, thanks to built-in algorithms. These may be adapted and further individualised by the treating physician in case of special disease and survivor circumstances. The SurPass was tested at the Istituto Giannina Gaslini, Italy, and received positive feedback. It is now being integrated at the institutional, regional and national level. The SurPass is potentially an essential tool for improved and more harmonised follow-up of CCS. It also has the potential to be a useful tool for empowering CCSs to be responsible for their own well-being and preventing adverse events whenever possible. With sufficient commitment on the European level, this solution should increase the capacity to respond more effectively to the needs of European CCS.

Purpose: We aimed to test the hypothesis that medulloblastoma (MB) variants show a different age distribution and clinical behavior reflecting their specific biology, and that MB occurring at very young age is associated with cancer predisposition syndromes such as Gorlin syndrome (GS). Experimental Design: We investigated the frequency, age distribution, location, response to treatment, outcome, and association with familial cancer predisposition syndromes in a series of 82 cases of MB in patients ages <14 years diagnosed at the Giannina Gaslini Children's Hospital, Genoa, between 1987 and 2004. Results: Desmoplastic MB and MB with extensive nodularity (MBEN), were present in 22 of 82 cases (27%) and were more frequent in children ages ≤3 years (13 of 25; 52%). In this age group, MBEN was significantly more frequent than desmoplastic MB and classic MB (P < 0.001) and had a good prognosis. MBEN was associated with GS in 5 of 12 cases. Overall, 8 cases occurred in the context of familial tumor predisposition syndromes (5 GS, 1 each NF1, Li-Fraumeni, and Fragile X) and 7 of these patients were ages ≤3 years at diagnosis. Desmoplastic histology and a more intensive treatment represented independent favorable prognostic factors in multivariate analysis (P = 0.003 and P = 0.0139, respectively). Metastasis was a predictor of bad outcome (P = 0.0001). Conclusions: Our data indicate that biologically different MB entities warrant risk-adapted treatment and that MBEN is strongly associated with GS. Patients, ages ≤3 years, with MB and their families should be investigated for tumor predisposition syndromes such as GS.

Central diabetes insipidus (CDI) is considered idiopathic in 20% to 50% of affected subjects. The purpose of this study was to determine whether a systematic diagnostic workup could achieve better etiologic diagnosis in children and adolescents presenting with polyuria and polydipsia. This is a prospective study conducted at a tertiary referral center. Patients underwent clinical and endocrine evaluations every 6 months and neuroimaging every 6 months for 2 years and yearly for 3 years. Endocrine function and neuroimaging were also reassessed after adult height achievement. A total of 85 consecutive patients with CDI were enrolled at a median age of 7.5 years; those with idiopathic CDI were stratified based on pituitary stalk thickness. To establish the etiology of CDI, we determined the time lag between its onset and the specific diagnosis, the long-term impact on pituitary function, and the overall long-term outcomes. Of the subjects, 24 (28.2%) received an etiologic diagnosis at presentation and 11 (13%) within 2.5 years (n = 7 germinomas and n = 4 Langerhans cell histiocytosis), 7 (8.2%) were lost to follow-up, and 43 (50.6%) were considered to have idiopathic disease and were followed until the median age of 17.3 years. Neuroimaging identified 40 of 43 patients with self-limited inflammatory/autoimmune pituitary stalk thickness within the first 6 months, the severity of which was significantly correlated to pituitary dysfunction. The probability of >10-year-survival without an anterior pituitary defect was related to the severity of pituitary stalk thickness, and 53% showed permanent anterior pituitary defects. Three patients developed Langerhans cell histiocytosis and 1 developed Hodgkin lymphoma after a median of 9 and 13 years, respectively. A diagnostic etiology was achieved in 96% of patients with CDI. Risk stratification based on the degree of pituitary stalk thickness is of prognostic value for long-term outcomes including permanent pituitary dysfunction. New guidance is provided for the management of these patients.

The availability of methotrexate and the introduction of multiple biological agents have revolutionized the treatment of juvenile idiopathic arthritis (JIA). Several international and national drug registries have been implemented to accurately monitor the long-term safety/efficacy of these agents. This report aims to present the combined data coming from Pharmachild/PRINTO registry and the national registries from Germany (BiKeR) and Sweden. Descriptive statistics was used for demographic, clinical data, drug exposure, adverse events (AEs) and events of special interest (ESIs). For the Swedish register, AE data were not available. Data from a total of 15,284 patients were reported: 8274 (54%) from the Pharmachild registry and 3990 (26%) and 3020 (20%) from the German and the Swedish registries, respectively. Pharmachild children showed a younger age (median of 5.4 versus 7.6 years) at JIA onset and shorter disease duration at last available visit (5.3 versus 6.1–6.8) when compared with the other registries. The most frequent JIA category was the rheumatoid factor–negative polyarthritis (range of 24.6–29.9%). Methotrexate (61–84%) and etanercept (24%–61.8%) were the most frequently used synthetic and biologic disease-modifying anti-rheumatic drugs (DMARDs), respectively. There was a wide variability in glucocorticoid use (16.7–42.1%). Serious AEs were present in 572 (6.9%) patients in Pharmachild versus 297 (7.4%) in BiKeR. Infection and infestations were the most frequent AEs (29.4–30.1%) followed by gastrointestinal disorders (11.5–19.6%). The most frequent ESIs were infections (75.3–89%). This article is the first attempt to present a very large sample of data on JIA patients from different national and international registries and represents the first proposal for data merging as the most powerful tool for future analysis of safety and effectiveness of immunosuppressive therapies in JIA. The Pharmachild registry is registered at ClinicalTrials.gov ( NCT01399281 ) and at the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) ( http://www.encepp.eu/encepp/viewResource.htm?id=19362 ). The BiKeR registry is registered at ENCePP ( http://www.encepp.eu/encepp/viewResource.htm?id=20591 ).

To compare the long-term disease state, in terms of activity and damage, of children with juvenile idiopathic arthritis (JIA) who had their disease onset in methotrexate (MTX) or biologic eras. Patients were included in MTX or biologic era cohort depending on whether their disease presentation occurred before or after January 2000. All patients had disease duration ≥ 5 years and underwent a prospective cross-sectional assessment, which included measurement of disease activity and damage. Inactive disease (ID) and low disease activity (LDA) states were defined according to Wallace, JADAS10, and cJADAS10 criteria. Articular and extraarticular damage was assessed with the Juvenile Arthritis Damage Index (JADI). MTX and biologic era cohorts included 239 and 269 patients, respectively. Patients were divided in the “functional phenotypes” of oligoarthritis and polyarthritis. At cross-sectional visit, patients in the biologic era cohort with either oligoarthritis or polyarthritis had consistently higher frequencies of ID and LDA by all criteria. The measurement of disease damage at cross-sectional visit revealed that the frequency of impairment of > 1 JADI-Articular items was higher in MTX than in biologic era cohort (17.6% versus 11% in oligoarthritis and 52.6% versus 21.8% in polyarthritis). Likewise, frequency of involvement of > 1 JADI-Extraarticular items was higher in the MTX than in the biologic era cohort (26.5% versus 16.2% in oligoarthritis and 31.4% versus 13.5% in polyarthritis). Our study provides evidence of the remarkable outcome improvement obtained with the recent therapeutic advance in JIA.