Summary Background Comparative assessment of treatment results in paediatric hepatoblastoma trials has been hampered by small patient numbers and the use of multiple disparate staging systems by the four major trial groups. To address this challenge, we formed a global coalition, the Children’s Hepatic tumors International Collaboration (CHIC), with the aim of creating a common approach to staging and risk stratification in this rare cancer. Methods The CHIC steering committee—consisting of leadership from the four major cooperative trial groups (the International Childhood Liver Tumours Strategy Group, Children’s Oncology Group, the German Society for Paediatric Oncology and Haematology, and the Japanese Study Group for Paediatric Liver Tumours)—created a shared international database that includes comprehensive data from 1605 children treated in eight multicentre hepatoblastoma trials over 25 years. Diagnostic factors found to be most prognostic on initial analysis were PRETreatment EXTent of disease (PRETEXT) group; age younger than 3 years, 3–7 years, and 8 years or older; α fetoprotein (AFP) concentration of 100 ng/mL or lower and 101–1000 ng/mL; and the PRETEXT annotation factors metastatic disease (M), macrovascular involvement of all hepatic veins (V) or portal bifurcation (P), contiguous extrahepatic tumour (E), multifocal tumour (F), and spontaneous rupture (R). We defined five clinically relevant backbone groups on the basis of established prognostic factors: PRETEXT I/II, PRETEXT III, PRETEXT IV, metastatic disease, and AFP concentration of 100 ng/mL or lower at diagnosis. We then carried the additional factors into a hierarchical backwards elimination multivariable analysis and used the results to create a new international staging system. Findings Within each backbone group, we identified constellations of factors that were most predictive of outcome in that group. The robustness of candidate models was then interrogated using the bootstrapping procedure. Using the clinically established PRETEXT groups I, II, III, and IV as our stems, we created risk stratification trees based on 5 year event-free survival and clinical applicability. We defined and adopted four risk groups: very low, low, intermediate, and high. Interpretation We have created a unified global approach to risk stratification in children with hepatoblastoma on the basis of rigorous statistical interrogation of what is, to the best of our knowledge, the largest dataset ever assembled for this rare paediatric tumour. This achievement provides the structural framework for further collaboration and prospective international cooperative study, such as the Paediatric Hepatic International Tumour Trial (PHITT). Funding European Network for Cancer Research in Children and Adolescents, funded through the Framework Program 7 of the European Commission (grant number 261474); Children’s Oncology Group CureSearch grant contributed by the Hepatoblastoma Foundation; Practical Research for Innovative Cancer Control and Project Promoting Cli...

Introduction Contemporary state-of-the-art management of cancer is increasingly defined by individualized treatment strategies. For very rare tumors, like hepatoblastoma, the development of biologic markers, and the identification of reliable prognostic risk factors for tailoring treatment, remains very challenging. The Children's Hepatic tumors International Collaboration (CHIC) is a novel international response to this challenge. Methods Four multicenter trial groups in the world, who have performed prospective controlled studies of hepatoblastoma over the past two decades (COG; SIOPEL; GPOH; and JPLT), joined forces to form the CHIC consortium. With the support of the data management group CINECA, CHIC developed a centralized online platform where data from eight completed hepatoblastoma trials were merged to form a database of 1605 hepatoblastoma cases treated between 1988 and 2008. The resulting dataset is described and the relationships between selected patient and tumor characteristics, and risk for adverse disease outcome (event-free survival; EFS) are examined. Results Significantly increased risk for EFS-event was noted for advanced PRETEXT group, macrovascular venous or portal involvement, contiguous extrahepatic disease, primary tumor multifocality and tumor rupture at enrollment. Higher age (≥8 years), low AFP (<100 ng/ml) and metastatic disease were associated with the worst outcome. Conclusion We have identified novel prognostic factors for hepatoblastoma, as well as confirmed established factors, that will be used to develop a future common global risk stratification system. The mechanics of developing the globally accessible web-based portal, building and refining the database, and performing this first statistical analysis has laid the foundation for future collaborative efforts. This is an important step for refining of the risk based grouping and approach to future treatment stratification, thus we think our collaboration offers a template for others to follow in the study of rare tumors and diseases.

Conclusion:In patients with a hemodialysis access graft and an asymptomatic central venous stenosis (CVS) of Ͼ50%, treatment of the CVS results in more rapid stenosis progression compared with a nontreatment approach.Summary: The authors evaluated the natural history of Ͼ50% asymptomatic CVSs in hemodialysis patients. Outcome of serial treatment of CVS with percutaneous catheter-based techniques (PTA) was also evaluated. All patients in this study required maintenance procedures for their dialysis access.Between 1998 and 2004, 35 patients (19 men, 16 women), with a mean age of 58.7 years, were found to have asymptomatic CVS of Ͼ50%. CVS was measured by using venograms obtained before and after PTA. Patients with arm swelling, multiple CVSs, or indwelling catheters, were excluded. CVS progression was calculated by comparing degrees of stenoses with serial venographic examinations.The mean severity of CVSs before intervention was 71% (range, 50% to 100%), with 62% of lesions having associated collateral vessels. Twenty eight percent of CVSs were not treated. The mean degree of stenosis in the untreated group was 72% (range, 30% to 100%). Mean progression of stenosis in the untreated group was -0.8% point per day. No untreated CVS progressed to symptoms, stent placement, or developed additional CVS.PTA was used to treat 62 CVS lesions (72%). The mean degree of stenosis in the treated group was 74% (range, 50% to 100%) before and 40% (range, 0% to 75%) after treatment. In the treated group, mean progression of CVS was 0.21% per day after treatment. Six of the 62 treated CVS lesions were monitored, with symptomatic escalation of the CVS as manifested by arm swelling, need for stent placement, or development of additional CVS lesions.Comment: Treatment of an asymptomatic CVS in a dialysis patient is not a good thing. One is reminded of the old adage that it is wise to avoid poking a skunk. A major weakness of this study is that the patients were undergoing maintenance procedures for their dialysis access. We do not know if the CVS contributed to the need for the dialysis access maintenance. It would be interesting to know if there was a higher rate of repeat procedures for maintenance of dialysis access in patients with treated vs untreated CVS.

Aim of the study was to estimate the prevalence and incidence of rheumatoid arthritis (RA) from an administrative cohort consisting of 2,268,514 males and 2,446,769 females, aged ≥ 18 years, from 32 Italian Health Districts. The diagnosis of RA was certified by a qualified specialist and confirmed by ≥3 prescriptions of "specific drugs" (corticosteroids, DMARDs or "biological" agents) during 2011. Patients on "specific drugs" qualified as "active RA"; those who never had more than 4 prescriptions in the past were classified as "unlikely RA," and those previously on chronic treatment but who discontinued therapy for >1 year were classified as "remission RA." The patients with a diagnosis of RA were 22,801 (0.48 %) with a prevalence of "active RA," "remission RA" and "confirmed RA" (Active + Remission RA) of 0.32, 0.09 and 0.41 % (95 % CI 0.38-0.44), respectively. The classification criteria tested in a fifth of the study population by direct analysis yielded >90 % accuracy and precision. The yearly incidence of "active RA" per 100,000 subjects was 48 (95 % CI 40-57) and 20 (95 % CI 10-30) for women and men, respectively. The peak for both prevalence and incidence was around the eighth decade of life. The female/male ratios for both prevalence and incidence were ca. 2.6 before the fifth decade of life, but approached unity in the ninth decade of life. The overall prevalence and incidence of RA in a large sample of the Italian population is only marginally lower than that reported from a similar administrative database of Sweden. With advancing age, the female/male ratio declines to about one.

Even though the prevalence of psychotropic drug prescriptions in Italian children is lower than that reported in other countries (e.g. United States, Canada, Netherlands, UK), the increase in antidepressant prescriptions raises some concerns. Data concerning safety and efficacy of these antidepressants in pediatrics are still limited and further studies are needed to guarantee evidence based therapeutic approaches in children, adolescents and their families.