Opportunistic infections in immunosuppressed patients with juvenile idiopathic arthritis: analysis by the Pharmachild Safety Adjudication Committee

Background To derive a list of opportunistic infections (OI) through the analysis of the juvenile idiopathic arthritis (JIA) patients in the Pharmachild registry by an independent Safety Adjudication Committee (SAC). Methods The SAC (3 pediatric rheumatologists and 2 pediatric infectious disease specialists) elaborated and approved by consensus a provisional list of OI for use in JIA. Through a 5 step-procedure, all the severe and serious infections, classified as per MedDRA dictionary and retrieved in the Pharmachild registry, were evaluated by the SAC by answering six questions and adjudicated with the agreement of 3/5 specialists. A final evidence-based list of OI resulted by matching the adjudicated infections with the provisional list of OI. Results A total of 772 infectious events in 572 eligible patients, of which 335 serious/severe/very severe non-OI and 437 OI (any intensity/severity), according to the provisional list, were retrieved. Six hundred eighty-two of 772 (88.3%) were adjudicated as infections, of them 603/682 (88.4%) as common and 119/682 (17.4%) as OI by the SAC. Matching these 119 opportunistic events with the provisional list, 106 were confirmed by the SAC as OI, and among them infections by herpes viruses were the most frequent (68%), followed by tuberculosis (27.4%). The remaining events were divided in the groups of non-OI and possible/patient and/or pathogen-related OI. Conclusions We found a significant number of OI in JIA patients on immunosuppressive therapy. The proposed list of OI, created by consensus and validated in the Pharmachild cohort, could facilitate comparison among future pharmacovigilance studies

Glycosylation of immunoglobulin G is regulated by a large network of genes pleiotropic with inflammatory diseases

Effector functions of immunoglobulin G (IgG) are regulated by the composition of a glycan moiety, thus affecting activity of the immune system. Aberrant glycosylation of IgG has been observed in many diseases, but little is understood about the underlying mechanisms. We performed a genome-wide association study of IgG N-glycosylation (N = 8090) and, using a data-driven network approach, suggested how associated loci form a functional network. We confirmed in vitro that knockdown of IKZF1 decreases the expression of fucosyltransferase FUT8, resulting in increased levels of fucosylated glycans, and suggest that RUNX1 and RUNX3, together with SMARCB1, regulate expression of glycosyltransferase MGAT3. We also show that variants affecting the expression of genes involved in the regulation of glycoenzymes colocalize with variants affecting risk for inflammatory diseases. This study provides new evidence that variation in key transcription factors coupled with regulatory variation in glycogenes modifies IgG glycosylation and has influence on inflammatory diseases.Molecular Epidemiolog

American College of Rheumatology Provisional Criteria for Clinically Relevant Improvement in Children and Adolescents With Childhood-Onset Systemic Lupus Erythematosus

10.1002/acr.23834ARTHRITIS CARE & RESEARCH715579-59

Investigating the cut points of CCQ, CAT and MMRC according to gold 2013 with SGRQ as standard

Rationale In the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2013 strategy document, assessment of symptoms is advised to be performed by the Clinical COPD Questionnaire (CCQ), COPD Assessment Test (CAT), or modified Medical Research Council (mMRC). Cut points of resp. CCQ≥1, CAT≥10 and mMRC≥2 indicate highly symptomatic patients (groups B and D). Recently a cut point of ≥25 of the St. George Respiratory Questionnaire (SGRQ) has been suggested as gold standard.1 The current study investigates the criterion validity of CCQ, CAT and mMRC using the advised cut point of SGRQ based on sensitivity and specificity analysis. Methods Two datasets were used: A) 238 patients participated in a 3-week Pulmonary Rehabilitation (PR) program (63% male, 51%FEV1pred., 40 mean packyears, 57 mean age, 40/39/21% GOLD stage II/III/IV) and B) 90 patients from primary care2, 90% male, 56%FEV pred., 1 16/47/30/6% GOLD I/II/III/IV. Primary outcome is the correspondence between recommended cut point of the SGRQ, CCQ, CAT and mMRC expressed in sensitivity and specificity using receiver operating characteristic (ROC) curves. Taking into account the possibility of unsatisfactory sensitivity and specificity, scatterplots with regression lines were used to visually explore alternative cut points, which were consecutively evaluated using ROC curves. Results Mean total CCQ, CAT, SGRQ scores and median mMRC: dataset A: resp. 2.9, 20.2, 50.1, and 2, and dataset B: 1.6, 14.1, 36.3, and 2. The table shows ROC analysis results using the suggested SGRQ cut point of 25. Visual inspection of the scatterplots revealed that SGRQ=20 might serve as more corresponding cut point, with ROC results in the table. This was confirmed by regression analysis. Conclusions In these two samples the suggested cut point for the SGRQ (≥25) does not seem to correspond well to the established cut points of both the CCQ and CAT, resulting in low specificity levels, the correspondence with mMRC seems satisfactory for the rehabilitation sample. A SGRQ threshold of ≥20 shows good sensitivity and specificity for CCQ and CAT, as well as improved specificity for the mMRC. This value corresponds better to established cut points for CCQ, CAT and mMRC in both patient groups. (Table Presented)

INSAID Variant Classification and Eurofever Criteria Guide Optimal Treatment Strategy in Patients with TRAPS: Data from the Eurofever Registry

Background: TNF receptor–associated periodic syndrome (TRAPS) is a rare autoinflammatory disease caused by dominant mutation of the TNF super family receptor 1A (TNFRSF1A) gene. Data regarding long-term treatment outcomes are lacking. Objective: To assess correlations of genotype-phenotypes in patients with TRAPS, as defined by the International Study Group for Systemic Autoinflammatory Diseases (INSAID) classification and Eurofever criteria, with treatment responses. Methods: Data from 226 patients with variants of the TNFRSF1A gene and enrolled in the Eurofever registry were classified according to the INSAID classification in groups A (pathogenic or likely pathogenic variants), B (variants of uncertain significance or not classified variants), and C (benign or likely benign variants) and screened for Eurofever criteria. Results: In group A (127 of 226 patients, 56%), all fulfilled Eurofever criteria and 20 of 127 patients (16%) developed AA amyloidosis. In group B (78 of 226 patients, 35%), 40 of 78 patients (51%) did not fulfill Eurofever criteria, displaying a lower incidence of abdominal pain (P 85% complete response). No patients on anti-IL-1 treatments developed AA amyloidosis, and 7 women with a history of failure to conceive had successful pregnancies. Conclusion: Anti-IL-1 drugs are the best maintenance treatment in patients with TRAPS. The diagnosis of TRAPS should be considered very carefully in patients of group B not fulfilling Eurofever criteria and group C, and colchicine may be preferable as the first maintenance treatment

INSAID Variant Classification and Eurofever Criteria Guide Optimal Treatment Strategy in Patients with TRAPS: Data from the Eurofever Registry

Background: TNF receptor\u2013associated periodic syndrome (TRAPS) is a rare autoinflammatory disease caused by dominant mutation of the TNF super family receptor 1A (TNFRSF1A) gene. Data regarding long-term treatment outcomes are lacking. Objective: To assess correlations of genotype-phenotypes in patients with TRAPS, as defined by the International Study Group for Systemic Autoinflammatory Diseases (INSAID) classification and Eurofever criteria, with treatment responses. Methods: Data from 226 patients with variants of the TNFRSF1A gene and enrolled in the Eurofever registry were classified according to the INSAID classification in groups A (pathogenic or likely pathogenic variants), B (variants of uncertain significance or not classified variants), and C (benign or likely benign variants) and screened for Eurofever criteria. Results: In group A (127 of 226 patients, 56%), all fulfilled Eurofever criteria and 20 of 127 patients (16%) developed AA amyloidosis. In group B (78 of 226 patients, 35%), 40 of 78 patients (51%) did not fulfill Eurofever criteria, displaying a lower incidence of abdominal pain (P <.02) and higher efficacy rate of on-demand nonsteroidal anti-inflammatory drugs (P <.02) and colchicine (P <.001). Group C (21 of 226 patients, 9%) presented a milder disease (P <.02) and none fulfilled Eurofever criteria. Anti-IL-1 drugs were the most frequently used in patients fulfilling Eurofever criteria, with the highest efficacy rate (>85% complete response). No patients on anti-IL-1 treatments developed AA amyloidosis, and 7 women with a history of failure to conceive had successful pregnancies. Conclusion: Anti-IL-1 drugs are the best maintenance treatment in patients with TRAPS. The diagnosis of TRAPS should be considered very carefully in patients of group B not fulfilling Eurofever criteria and group C, and colchicine may be preferable as the first maintenance treatment

Clubes recreativos: identidades e conflitos entre os trabalhadores paulistanos (1900-1920)

http://dx.doi.org/10.5007/1984-9222.2011v3n5p233Este artigo analisa alguns dos clubes recreativos fundados e freqüentados pelos trabalhadores da cidade de São Paulo no início do século XX. Além do lazer, os referidos clubes ofereciam acesso à cultura letrada, à informação e auxílios para os associados. Dessa maneira, são espaços privilegiados para a análise do processo de formação da classe trabalhadora da cidade