Frequent, quantitative bone planar scintigraphy for determination of bone anabolism in growing mice.

BACKGROUND: To provide insight into bone turnover, quantitative measurements of bone remodeling are required. Radionuclide studies are widely used in clinical care, but have been rarely used in the exploration of the bone in preclinical studies. We describe a bone planar scintigraphy method for frequent assessment of bone activity in mice across the growing period. Since repeated venous radiotracer injections are hardly feasible in mice, we investigated the subcutaneous route. METHODS: Repeated 99mTc-hydroxymethylene diphosphonate (HMDP) tracer bone planar scintigraphy studies of the knee region and µCT to measure femur growth rate were performed in eight mice between week 6 and week 27 of life, i.e., during their growth period. Three independent investigators assessed the regions of interest (ROI). An index was calculated based on the counts in knees ROI (normalized by pixels and seconds), corrected for the activity administered, the decay between administration and imaging, and individual weights. RESULTS: A total of 93 scintigraphy studies and 85 µCT were performed. Repeated subcutaneous tracer injections were well tolerated and allowed for adequate radionuclide studies. Mean scintigraphic indexes in the knees ROI decreased from 87.4 ± 2.6 × 10-6 counts s-1 pixel-1 MBq-1 g-1 at week 6 to 15.0 ± 3.3 × 10-6 counts s-1 pixel-1 MBq-1 g-1 at week 27. The time constant of the fitted exponential decay was equal to 23.5 days. As control mean femur length assessed by µCT increased from 12.2 ± 0.8 mm at week 6 to 15.8 ± 0.2 mm at week 22. The time constant of the fitted Gompertz law was equal to 26.7 days. A correlation index of -0.97 was found between femur growth and decrease of bone tracer activity count between week 6 and 24. CONCLUSION: This methodological study demonstrates the potential of repeated bone planar scintigraphy in growing mice, with subcutaneous route for tracer administration, for quantitative assessment of bone remodeling.

Safety of biological agents in paediatric rheumatic diseases: A real-life multicenter retrospective study using the JIRcohorte database.

OBJECTIVE: To analyse and report the incidence of side effects of biological agents in paediatric patients with inflammatory diseases using of real-life follow-up cohort. METHODS: In this international, observational, retrospective, multicentre study of children treated by biological agents and followed in the Juvenile Inflammatory Rheumatism (JIR) cohort (JIRcohorte) network, a Kaplan-Meier method was used to estimate the occurrence of adverse events. A Cox model was constructed to identify independent predictors of adverse events. RESULTS: Overall 813 patients totalling 3439 patients-year (PY) of biological agents were included. The main diagnosis was juvenile idiopathic arthritis (84%). A total of 222 patients (27.3%) had 419 adverse events, representing an incidence rate of 12.2 per 100 PY 95% CI [11.0; 13.4]. The overall incidence rate of serious adverse events was 3.9 per 100 PY 95% CI [3.2; 4.6]. Tocilizumab and infliximab were significantly associated with adverse events and canakinumab with serious adverse events. Univariate and multivariable analysis of adverse events and serious adverse events indicated that patients under biological agents with concomitant immunosuppressive drugs (excluding methotrexate) suffered from more of these events. CONCLUSION: This study suggests an overall an acceptable safety of biologic agents in children with inflammatory rheumatic diseases treated with biological agents. However, the concomitant prescription of immunosuppressive drugs with biological agents represents a substantial risk of adverse events.

[Peritoneal equilibration test: Conventional versus adapted. Preliminary study]. / Tests d'équilibration péritonéaux : conventionnel versus adapté. Étude de faisabilité.

Conventional automated peritoneal dialysis (APD) is prescribed as a repetition of cycles with the same dwell time and the same fill volume. Water and sodium balance remains a common problem among patients on peritoneal dialysis. More recently, adapted automated peritoneal dialysis was described, as a combination of short dwells with a low volume, in order to enhance ultrafiltration, followed by long dwells with a large fill volume to favor solute removal. We performed a preliminary crossover study on 4 patients. The total amount of dialysate was the same, i.e. 2L/m2 as well as the total duration of the test, i.e. 150 minutes. The conventional test was made with two identical cycles, each cycle had a fill volume of 1L/m2 and a duration of 75 minutes, while the adapted test was performed with one short cycle, i.e. 30 minutes with a low fill volume, i.e. 0.6L/m2, followed by a long cycle, i.e. 120 minutes, with a large fill volume, i.e. 1.4L/m2. Sodium extraction was improved by 29.3mmol/m2 (169%) in the adapted test in comparison to the conventional test. Ultrafiltration was enhanced by 159mL/m2 (128%) in the adapted test compared to the conventional one. Glucose absorption was decreased by 35% in the adapted test in comparison to the conventional test and osmotic conductance was also improved. In conclusion, adapted dialysis may allow for a better volume and sodium balance, since we observed an improvement in sodium extraction and ultrafiltration. This pre-study authorizes an improvement of the European Pediatric Study's protocol on Adapted APD, already started and which will continue in the next months.