Morphology parameters for intracranial aneurysm rupture risk assessment

OBJECTIVE—The aim of this study is to identify image-based morphological parameters that correlate with human intracranial aneurysm (IA) rupture. METHODS—For 45 patients with terminal or sidewall saccular IAs (25 unruptured, 20 ruptured), three-dimensional geometries were evaluated for a range of morphological parameters. In addition to five previously studied parameters (aspect ratio, aneurysm size, ellipticity index, nonsphericity index, and undulation index), we defined three novel parameters incorporating the parent vessel geometry (vessel angle, aneurysm [inclination] angle, and [aneurysm-to-vessel] size ratio) and explored their correlation with aneurysm rupture. Parameters were analyzed with a two-tailed independent Student's t test for significance; significant parameters (P < 0.05) were further examined by multivariate logistic regression analysis. Additionally, receiver operating characteristic analyses were performed on each parameter. RESULTS—Statistically significant differences were found between mean values in ruptured and unruptured groups for size ratio, undulation index, nonsphericity index, ellipticity index, aneurysm angle, and aspect ratio. Logistic regression analysis further revealed that size ratio (odds ratio, 1.41; 95% confidence interval, 1.03−1.92) and undulation index (odds ratio, 1.51; 95% confidence interval, 1.08−2.11) had the strongest independent correlation with ruptured IA. From the receiver operating characteristic analysis, size ratio and aneurysm angle had the highest area under the curve values of 0.83 and 0.85, respectively. CONCLUSION—Size ratio and aneurysm angle are promising new morphological metrics for IA rupture risk assessment. Because these parameters account for vessel geometry, they may bridge the gap between morphological studies and more qualitative location-based studies

Safety, pharmacokinetics, and pharmacodynamics of epratuzumab in Japanese patients with moderate-to-severe systemic lupus erythematosus: Results from a phase 1/2 randomized study

<div><p></p><p><i>Objectives</i>: This 12-week, randomized, double-blind, placebo-controlled, multicenter phase 1/2 study (NCT01449071) assessed the safety, pharmacokinetics, and pharmacodynamics of epratuzumab in Japanese patients with moderate-to-severe systemic lupus erythematosus despite standard of care.</p><p><i>Methods</i>: Twenty patients were randomized 1:1:1:1:1 to placebo or one of four epratuzumab dose regimens (100 mg every other week [Q2W], 400 mg Q2W, 600 mg every week [QW], or 1200 mg Q2W) administered during an initial 4-week dosing period. Adverse events (AEs), pharmacokinetics and pharmacodynamics were assessed.</p><p><i>Results</i>: Nineteen of 20 patients completed the study. All placebo patients and 13 of 16 epratuzumab patients reported ≥1 AE, 2 of 16 epratuzumab patients reported a serious AE. <i>C</i>_max and AUC_τ increased proportionally with dose after first and last infusion, <i>t</i>_1/2 was similar across groups (∼13 days). Epratuzumab treatment was associated with decreased CD22 mean fluorescence intensity in total B cells (CD19⁺CD22⁺) and unswitched memory B cells (CD19⁺IgD⁺CD27⁺). Small-to-moderate decreases were observed in total B cell (CD20⁺) count.</p><p><i>Conclusions</i>: Epratuzumab was well-tolerated, with no new safety signals identified. The pharmacokinetics appeared linear after first and last infusions. Treatment with epratuzumab was associated with CD22 downregulation and with small-to-moderate decreases in total B cell count.</p></div