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OBJECTIVES: Cryopyrin-Associated Periodic Syndromes (CAPS) encompasses a spectrum of Interleukin-1 (IL-1) driven systemic diseases with dramatic individual and societal burden. The study aimed to identify parameters and instruments to refine real-life Treat-to-Target (T2T) strategies and control CAPS disease activity. METHODS: A single-centre, longitudinal study of consecutive children and adults diagnosed with CAPS and treated with anti-IL-1 therapy was performed. Demographics, clinical phenotype and NLRP3 gene variants in addition to serial inflammatory markers and Physician and Patient/Parent Global Assessments (PGA/PPGA) were captured. Effectiveness of anti-IL-1 T2T strategies and factors associated with therapy escalation were determined. RESULTS: A total of 54 CAPS patients with 759 follow-up visits were included; 31/54 (57%) were children; the median follow-up was 108 months (12-620). The moderate CAPS phenotype was present in 89%; overall 59% had pathogenic/likely pathogenic NLRP3 variants. Therapy adjustments were documented in 50/759 visits including 35 therapy escalations and 15 reductions; 74% of the therapy escalation visits were for children. At time of visit, 63% showed moderate, 37% severe clinical disease activity. Inflammatory markers remained largely normal. Significant improvement was observed in both PGA/PPGA throughout the study (p< 0.01). At the last follow-up, 96% of patients achieved remission. CONCLUSION: Guidance for refining real-life T2T strategies in CAPS cohorts can be drawn from serial assessments of PGA and PPGA reliably reflecting changes in disease activity. Individual parameters including age and NLRP3 gene variants are important predictors, while the sensitivity of inflammatory markers is limited due to the confounding anti-IL-1 therapy.
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Background: Effective control of disease activity in Interleukin-1 autoinflammatory diseases (IL-1 AID) is crucial to prevent damage. The aim was to longitudinally analyze the impact of protocolized disease activity-based treatment adjustments in a real-life cohort. Methods: A single-center study of consecutive children with IL-1 AID followed between January 2016 and December 2019 was performed. Demographics, phenotypes, genotypes, inflammatory markers, physician (PGA), and patient/parent (PPGA) global assessment were captured. Disease activity and treatment changes were assessed. The impact of distinct parameters on disease activity trajectories was analyzed. Results: A total of 56 children were included, median follow-up was 2.1 years reflecting 361 visits. Familial Mediterranean Fever was the most common IL-1 AID. At the first visit, 68% of the patients had moderate/severe disease activity. Disease activity-based treatment adjustments were required in 28/56 children (50%). At last follow-up, 79% had a well-controlled disease. Both PGA and PPGA decreased significantly over time (p < 0.001; p < 0.017, respectively), however, both differed statistically at last visit (p < 0.001). Only PGA showed a significant estimated mean decrease across all IL-1 AID over time. Conclusions: Disease activity-based treatment adjustments can effectively refine treat-to-target strategies, enable personalized precision health approaches, and improve outcomes in children with IL-1 AID.
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INTRODUCTION: Several scoring systems have been developed to predict postoperative mortality and complications in patients undergoing cardiac surgery. However, these computer-based calculations are time- and cost-intensive. A simple but highly predictive test for postoperative risk would be of clinical benefit with respect to increasingly scarce hospital resources. We therefore assessed the predictive power of fibroblast growth factor 23 (FGF23) measurement compared with an established scoring system. METHODS: We conducted a prospective interdisciplinary observational study at the Saarland University Medical Centre that included 859 patients undergoing elective cardiac surgery between January 2010 and March 2011 with a median follow-up after discharge of 822 days. We compared a single preoperative measurement of FGF23 as a prognostic tool with the 18 parameters comprising EuroSCORE II with respect to postoperative mortality, acute kidney injury, non-occlusive mesenteric ischemia, clinical course and long-term outcome. RESULTS: Preoperative FGF23 levels were highly predictive of postoperative outcome and complications. The predictive value of FGF23 for mortality in the receiver operating characteristic curve was greater than the EuroSCORE II (area under the curve: 0.800 versus 0.725). Moreover, preoperative FGF23 independently predicted postoperative acute kidney injury and non-occlusive mesenteric ischemia comparably to the EuroSCORE II. Finally, FGF23 was found to be an independent predictor of clinical course parameters, including duration of surgery, ventilation time and length of stay. CONCLUSIONS: In patients undergoing elective cardiac surgery, a simple preoperative FGF23 measurement is a powerful indicator of surgical mortality, postoperative complications and long-term outcome. Its utility compares to the widely used EuroSCORE II.
