Serum cytokines and their predictive value in pulmonary involvement of systemic sclerosis.

OBJECTIVE: To identify serum cytokines which predict mortality and/or disease progression in patients with systemic sclerosis, especially with pulmonary involvement. METHODS: Serum cytokines (IL-6, IL-7, IL-8, IL-10, CCL2, CCL4, TGF-ß, TNF-α) were measured in 125 SSc patients, who were recruited and observed in our outpatient clinic. Of these, 60 had pulmonary involvement, classified as either interstitial lung disease (ILD, 43 patients), pulmonary arterial hypertension (PAH, 7 patients) or pulmonary hypertension and ILD (PH-ILD, 10 patients). The association of serum cytokines with clinical features was analysed and their correlation with BAL cytokines measured in a subset of SSc patients with ILD. RESULTS: Serum cytokines were detected at different levels: high (TGF-ß, median 287.5 pg/ml; CCL2, median 89.7 pg/ml; CCL4, median 104.2 pg/ml), low (IL-6, median 3.2 pg/ml; IL-7 median 2.3 pg/ml; IL-8, median 5.2 pg/ml; TNF-α, median 0 pg/ml but with a bimodal distribution) and very low (IL-10, median 0.4 pg/ml). IL-6 and IL-7 were predictive for death in a Cox regression analysis in all SSc patients as well as in all patients with pulmonary involvement; IL-6 was predictive for mortality in SSc-ILD patients. In a multivariate analysis, cytokine levels could also predict a change in lung function, e.g. IL-7 was a predictor for a decline of diffusion capacity (DLCO) by 20 or 30% in ILD patients. In a subset of ILD patients, serum cytokines were compared to BAL cytokines, but revealed only few correlations. CONCLUSION: In conclusion, the analysis of serum cytokines implicates a role as biomarkers, distinct from BAL.

Escalation Therapy of Steroid Refractory Multiple Sclerosis Relapse with Tryptophan Immunoadsorption - Observational Multicenter Study with 147 Patients.

BACKGROUND: A marked proportion of multiple sclerosis (MS) relapses is followed by incomplete recovery. Our aim was to considerably increase the evidence of the clinical use of immunoadsorption (IA) as escalation therapy for patients with MS relapse. METHODS: A retrospective multicenter study was performed in MS patients with steroid refractory relapse who were treated with tryptophan IA. The main outcome parameter was change of acute relapse-related disability assessed by Expanded Disability Status Scale (EDSS) and visual acuity (VA) measurements for patients with optic neuritis (ON). IA treatments were performed using single-use tryptophan adsorbers. RESULTS: Data of 147 MS patients and 786 single IA treatments were analyzed. Treatment with IA was commenced in mean 32 ± 35 days after the onset of relapse. One hundred and five out of 147 patients (71.4%) improved functionally after mean 5.4 IA treatments within 7-10 days. EDSS improved from median 5 (interquartile range, IQR 3.5) to 4 (IQR 2.5) (p < 0.001). In patients with ON (n = 32), VA improved after the IA series in 84% of cases from median 0.2 (IQR 0.6) to 0.6 (IQR 0.66) (p < 0.001). In 98.9% of IA treatments, no clinically relevant side effect was reported. CONCLUSION: Tryptophan IA was found to be effective and well tolerated as escalation therapy for MS relapse.

Quality of life in childhood immune thrombocytopenia: international validation of the kids' ITP tools.

BACKGROUND: The Kids ITP Tools (KIT) is a disease-specific measure of health-related quality of life for children with immune thrombocytopenia (ITP). To facilitate use in international trials it has been cross-culturally adapted for France, Germany, the United Kingdom and Uruguay. This study assessed the validity and reliability of the translated KIT in comparison to generic quality of life measures. METHODS: Children 2-18 years of age with ITP and their parents were recruited in France, Germany, the United Kingdom and Uruguay. Participants completed the KIT, PedsQL and KINDL. We examined the Pearson's correlation between these measures for our pooled sample and estimated the reliability over a 2-week time period. Findings were further explored by country. RESULTS: A total of 127 families (81 children self-reported) participated. Mean child-reported scores were: KIT 74.3 (SD = 15.3), PedsQL 81.3 (SD = 13.0), and KINDL 70.5 (SD = 14.3). Corresponding mean parent proxy-reported scores were: 70.6 (SD = 18.1), 75.7 (SD = 16.8) and 72.3 (SD = 12.7), respectively. Correlation between KIT and the generic measures was consistent with our a priori hypothesis (PedsQL r = 0.54, KINDL r = 0.48, both P < 0.0001). Child KIT scores for newly diagnosed ITP patients were significantly lower than for chronic ITP patients (67.3 vs. 77.3; P = 0.005). There was a significant correlation (P < 0.001) between the child and parent proxy KIT scores (ICC = 0.52). Child KIT test-retest reliability was acceptable at 0.71. CONCLUSIONS: The cross-culturally translated KIT is valid and reliable with acceptable correlation to the PedsQL and KINDL. There is a significant difference in child self-reported KIT scores between newly diagnosed and chronic ITP.

Measuring disease-specific quality of life in rare populations: a practical approach to cross-cultural translation.

BACKGROUND: Disease-specific quality of life (QoL) measures have enhanced the capacity of outcome measures to evaluate subtle changes and differences between groups. However, when the specific disease is rare, the cohort of patients is small and international collaboration is often necessary to accomplish meaningful research. As many of the QoL measures have been developed in North American English, they require translation to ensure their usefulness in a multi-cultural and/or international society. Published guidelines provide formal methods to achieve cross-culturally comparable versions of a QoL tool. However, these guidelines describe a rigorous process that is not always feasible, particularly in rare disease groups. The objective of this manuscript is to describe the process that was developed to achieve accurate cross-cultural translations of a disease-specific QoL measure, to overcome the challenges of a small sample size, i.e. children with a rare disorder. PROCEDURE: A measurement study was conducted in the United Kingdom (UK), France, Germany and Uruguay, during which the validated measure was translated into the languages of the respective countries. RESULTS: This is a report of a modified, child-centric, cross-cultural translation and adaptation process in which culturally appropriate and methodologically valid translations of a disease-specific QoL measure, the Kids' ITP Tools (KIT), were performed in children with immune thrombocytopenic purpura (ITP). The KIT was translated from North American English into UK English, French, German, and Spanish. CONCLUSION: This study was a successful international collaboration. The modified process through which culturally appropriate and methodologically valid translations of QoL measures may be achieved in a pediatric population with a relatively rare disorder is reported.