Strategic use of levofolinic acid for methotrexate-induced side effects in juvenile idiopathic arthritis: a prospective observational study

Objective: To evaluate the efficacy of levofolinic acid (LVF) administered 48 h before methotrexate (MTX) in reducing gastrointestinal side effects without interference with drug efficacy. Methods: A prospective observational study was performed including patients with Juvenile Idiopathic Arthritis (JIA) reporting significant gastrointestinal discomfort after MTX despite taking a dose of LVF 48 h after MTX. Patients with anticipatory symptoms were excluded. A LVF supplemental dose was added 48 h before MTX and patients were followed every 3–4 months. At each visit data on gastrointestinal symptoms, disease activity (JADAS, ESR, CRP values) and treatment changes were collected. Friedman test for repeated measures analyzed differences between these variables over time. Results: Twenty-one patients were recruited and followed for at least 12 months. All patients received MTX subcutaneously (mean 9.54 mg/m2) and LVF 48 h before and after MTX (mean 6.5 mg/dose), 7 received a biological agent too. Complete remission of gastrointestinal side effects was reported in 61.9% of study patients at first visit (T1) and increased over time (85.7%, 95.2%, 85.7% and 100% at T2, T3, T4, T5, respectively). MTX efficacy was maintained as showed by significant reduction of JADAS and CRP (p = 0.006 and 0.008) from T1 to T4 and it was withdrawn for remission in 7/21. Conclusions: LVF given 48 h before MTX significantly reduced gastrointestinal side effects and did not reduce drug’s efficacy. Our results suggest that this strategy may improve compliance and quality of life in patients with JIA and other rheumatic diseases treated with MTX

Mycophenolate mofetil for methotrexate-resistant juvenile localized scleroderma

Objectives: To investigate safety and efficacy of MMF in patients with severe or MTX-refractory juvenile localized scleroderma. Methods: Consecutive juvenile localized scleroderma patients undergoing systemic treatment were included in a retrospective longitudinal study. Patients treated with MMF because they were refractory or intolerant to MTX (MMF-group) were compared with responders to MTX (MTX-group). Disease activity was assessed by Localized Scleroderma Cutaneous Assessment Tool and thermography. Disease course was established on the number of relapses and treatment changes. Relapse-free survival was examined by Kaplan-Meier analysis. Results: MMF and MTX groups included 22 and 47 patients, respectively. No significant difference in demographics, follow-up duration and treatment before diagnosis was observed between groups. The most represented clinical subtypes in the MMF-group were pansclerotic morphea and mixed subtype (P = 0.008 and P = 0.029, respectively), and linear scleroderma of the face in the MTX-group (P = 0.048). MMF was started because of MTX resistance (18 patients), relapse during MTX tapering/withdrawal (3 patients) and anaphylaxis to MTX (1 patient). After mean 9.4 years of follow-up, 90.9% of patients on MMF and 100% of those on MTX had inactive disease. No significant difference in relapse-free survival between the groups was found (P = 0.066, log-rank test), although MMF likely induced more persistent remission. MMF was well tolerated and combination of MMF and MTX did not increase its efficacy. Conclusion: The present study adds strong evidence on the efficacy and tolerance of MMF in severe and/or MTX-refractory juvenile localized scleroderma. Further controlled studies are needed to prove its efficacy as first line treatment

Complementary and alternative medicine (CAM) in pediatric rheumatology: an European perspective

To analyse the use of complementary and alternative medicine (CAM) in children with rheumatic diseases, treated at a paediatric rheumatology centre in Italy

Prognostic role of euthyroid sick syndrome in MIS-C: results from a single-center observational study

Background: Euthyroid sick syndrome (ESS) is characterized by low serum levels of free triiodothyronine (fT3) with normal or low levels of thyroid stimulating hormone (TSH) and free thyroxine (fT4) and is reported in different acute clinical situations, such as sepsis, diabetic ketoacidosis and after cardiac surgery. Our aim was to evaluate the predicting role of ESS for disease severity in patients with Multisystem Inflammatory Syndrome in children (MIS-C). Methods: A single-centre observational study on consecutive patients with MIS-C. Before treatment clinical, and laboratory data were collected and, in a subset of patients, thyroid function tests were repeated 4 weeks later. Variables distribution was analyzed by Mann-Whitney U-test and correlations between different parameters were calculated by Spearman's Rho coefficient. Results: Forty-two patients were included and 36 (85.7%) presented ESS. fT3 values were significantly lower in patients requiring intensive care, a strong direct correlation was shown between fT3 and Hb, platelet count and ejection fraction values. A significant inverse correlation was retrieved between fT3 levels and C-reactive protein, brain natriuretic peptide, IL-2 soluble receptor and S-100 protein. Subjects with severe myocardial depression (EF < 45%) had lower fT3 values than subjects with higher EF. The thyroid function tests spontaneously normalized in all subjects who repeated measurement 4 weeks after admission. Conclusion: ESS is a frequent and transient condition in acute phase of MIS-C. A severe reduction of fT3 must be considered as important prognostic factor for severe disease course, with subsequent relevant clinical impact in the management of these patients

Monoarticular juvenile idiopathic arthritis as a distinct clinical entity A proof-of-concept study

Background: Currently, monoarticular Juvenile Idiopathic Arthritis (monoJIA) is included in the ILAR classification as oligoarticular subtype although various aspects, from clinical practice, suggest it as a separate entity. Objectives: To describe the clinical characteristics of persistent monoJIA. Methods: Patients with oligoJIA and with at least two years follow-up entered the study. Those with monoarticular onset and persistent monoarticular course were compared with those with oligoJIA. Variables considered were: sex, age at onset, presence of benign joint hypermobility (BJH), ANA, uveitis, therapy and outcome. Patients who had not undergone clinical follow-up for more than 12 months were contacted by structured telephone interview. Results: Of 347 patients with oligoJIA, 196 with monoarticular onset entered the study and 118 (60.2%), identified as persistent monoJIA, were compared with 229 oligoJIA. The mean follow-up was 11.4 years. The switch from monoarticular onset to oligoarticular course of 78 patients (38.8%) occurred by the first three years from onset. In comparison with oligoJIA, the most significant features of monoJIA were later age at onset (6.1 vs. 4.7 years), lower female prevalence (70.3 vs. 83.4%), higher frequency of BJH (61.9 vs. 46.3%), lower frequency of uveitis (14.4 vs. 34.1%) and ANA+ (68.6 vs. 89.5%) and better long-term outcome. Conclusions: MonoJIA, defined as persistent arthritis of unknown origin of a single joint for at least three years, seems to be a separate clinical entity from oligoJIA. This evidence may be taken into consideration for its possible inclusion into the new classification criteria for JIA and open new therapeutic perspectives

Iodine Extravasation Quantification on Dual-Energy CT of the Brain Performed after Mechanical Thrombectomy for Acute Ischemic Stroke Can Predict Hemorrhagic Complications

BACKGROUND AND PURPOSE: Intracerebral hemorrhage represents a potentially severe complication of revascularization of acute ischemic stroke. The aim of our study was to assess the capability of iodine extravasation quantification on dual-energy CT performed immediately after mechanical thrombectomy to predict hemorrhagic complications. MATERIALS AND METHODS: Because this was a retrospective study, the need for informed consent was waived. Eighty-five consecutive patients who underwent brain dual-energy CT immediately after mechanical thrombectomy for acute ischemic stroke between August 2013 and January 2017 were included. Two radiologists independently evaluated dual-energy CT images for the presence of parenchymal hyperdensity, iodine extravasation, and hemorrhage. Maximum iodine concentration was measured. Follow-up CT examinations performed until patient discharge were reviewed for intracerebral hemorrhage development. The correlation between dual-energy CT parameters and intracerebral hemorrhage development was analyzed by the Mann-Whitney U test and Fisher exact test. Receiver operating characteristic curves were generated for continuous variables. RESULTS: Thirteen of 85 patients (15.3%) developed hemorrhage. On postoperative dual-energy CT, parenchymal hyperdensities and iodine extravasation were present in 100% of the patients who developed intracerebral hemorrhage and in 56.3% of the patients who did not ( P = .002 for both). Signs of bleeding were present in 35.7% of the patients who developed intracerebral hemorrhage and in none of the patients who did not ( P P CONCLUSIONS: The presence of parenchymal hyperdensity with a maximum iodine concentration of >1.35 mg/mL may identify patients developing intracerebral hemorrhage with 100% sensitivity and 67.6% specificity

The state of interprofessional collaboration in Northern Italy: a mixed methods study.

Abstract Health care systems are facing continual reorganizations in response to scientific and technological innovations as well as financial constraints. Simultaneously the rising prevalence of chronic diseases call for a kind of health care organization in which interprofessional collaboration (IPC) functions on a high level. This article describes a research project that aims to generate an empirical account of the current state of IPC in the South Tyrolean Health Trust, located in a bilingual region in northern Italy. The study will employ a sequential mixed methods' design. A survey will be followed by individual and focus group interviews. An innovative aspect of the study is that it will include participants from six different health professions (dieticians, nurses, occupational therapists, physicians, physiotherapists, and speech therapists). Qualitative data analysis will draw on the negotiated order/structural ordering approach and on the social world/arena perspective. The results are expected to generate specific recommendations to improve IPC in the South Tyrolean Health Trust and inform further research