Bech, Jesper Nørgaard

Abstract Rationale Diffuse alveolar hemorrhage (DAH) is a life-threatening manifestation of antineutrophil cytoplasmic antibody–associated vasculitis (AAV). The PEXIVAS (Plasma Exchange and Glucocorticoids in Severe Antineutrophil Cytoplasmic Antibody–Associated Vasculitis) (NCT00987389) trial was the largest in AAV and the first to enroll participants with DAH requiring mechanical ventilation. Objectives Evaluate characteristics, treatment effects, and outcomes for patients with AAV with and without DAH. Methods PEXIVAS randomized 704 participants to plasma exchange (PLEX) or no-PLEX and reduced or standard-dose glucocorticoids (GC). DAH status was defined at enrollment as no-DAH, nonsevere, or severe (room air oxygen saturation of ≤ 85% as measured by pulse oximetry, or use of mechanical ventilation). Measurements and Main Results At enrollment, 191 (27.1%) participants had DAH (61 severe, including 29 ventilated) and were younger, more frequently relapsing, PR3 (proteinase 3)-ANCA positive, and had lower serum creatinine but were more frequently dialyzed than participants without DAH (n = 513; 72.9%). Among those with DAH, 8/95 (8.4%) receiving PLEX died within 1 year versus 15/96 (15.6%) with no-PLEX (hazard ratio, 0.52; confidence interval [CI], 0.21–1.24), whereas 13/96 (13.5%) receiving reduced GC died versus 10/95 (10.5%) with standard GC (hazard ratio, 1.33; CI, 0.57–3.13). When ventilated, ventilator-free days were similar with PLEX versus no-PLEX (medians, 25; interquartile range [IQR], 22–26 vs. 22–27) and fewer with reduced GC (median, 23; IQR, 20–25) versus standard GC (median, 26; IQR, 25–28). Treatment effects on mortality did not vary by presence or severity of DAH. Overall, 23/191 (12.0%) with DAH died within 1 year versus 34/513 (6.6%) without DAH. End-stage kidney disease and serious infections did not differ by DAH status or treatments. Conclusions Patients with AAV and DAH differ from those without DAH in multiple ways. Further data are required to confirm or refute a benefit of PLEX or GC dosing on mortality. Original clinical trial registered with www.clinicaltrials.gov (NCT00987389).

Abstract BackgroundMethods for assessing bone metabolism which can replace the gold standard bone biopsy are sorely needed in the clinical setting in patients with chronic kidney disease - mineral and bone disorder (CKD-MBD). The aim of the present study was implementation, validation and comparison of non-invasive dynamic and static whole-body (WB) [18F]NaF PET/CT scan methods to replace invasive bone biopsy, used for quantitative analysis of bone clearance in CKD-MBD patients.MethodsSeventeen patients with CKD-MBD underwent a 60-minute dynamic scan followed by a 30-minute static WB scan. Tracer kinetics in four thoracic vertebrae were analyzed using non-linear regression with the Hawkins model and two different Patlak-analysis methods using image-derived arterial input functions obtained from the left myocardial ventricle and the thoracic aorta. For future use in WB PET/CT scans, we validated the use of a semi-population input function. The resulting kinetic parameters (Ki, K1, k2, k3, k4, V0) were compared between the different methods of analysis using the various derived input functions.ResultsDynamic kinetic results from both standard and single-point Patlak analyses correlate well with non-linear regression analysis, but Ki results using Patlak analysis are generally lower for all tested input functions compared to regression analysis. Single-point Patlak analysis on WB scans correlates well with standard Patlak analysis on dynamic scans but show 13-21% higher Ki-values. ConclusionsOur results show good correlation between dynamic and static analysis of skeletal plasma clearance but different Ki-values depending on the analysis method and choice of input function used. Thus, WB [18F]NaF PET/CT scans can be applied in future studies, but the results should not be compared uncritically with results obtained using non-linear regression analysis.