Molecular Patterns of Extreme and Persistent Cholesterol Efflux Capacity.

Objective: Cholesterol efflux capacity (CEC), the ability of extracellular acceptors to pick-up cholesterol from macrophages, is a clinically relevant cardiovascular biomarker. CEC is inversely associated with incident atherosclerotic cardiovascular disease events. However, CEC is only modestly associated with HDL-C (high-density lipoprotein cholesterol) levels, which may explain the failure of HDL-C raising therapies to improve atherosclerotic cardiovascular disease outcomes. Determinants of variation in CEC are not well understood. Thus, we sought to establish whether extreme high and low CEC is a robust persistent phenotype and to characterize associations with cholesterol, protein, and phospholipids across the particle size distribution. Approach and Results: CEC was previously measured in 2924 participants enrolled in the Dallas Heart Study, a multi-ethnic population-based study from 2000 to 2002. We prospectively recruited those who were below the 10th and above 90th percentile of CEC. Our study revealed that extreme low and high CEC are persistent, robust phenotypes after 15 years of follow-up. Using size exclusion chromatography, CEC to fractionated plasma depleted of apolipoprotein B (fraction-specific CEC) demonstrated significant differences in CEC patterns between persistent high and low efflux groups. Fraction-specific CEC was correlated with fraction-specific total phospholipid but not apolipoprotein A-I, cholesterol, or total protein. These correlations varied across the size distribution and differed among persistent high versus low efflux groups. Conclusions: Extreme high and low CEC are persistent and robust phenotypes. CEC patterns in fractionated plasma reveal marked variation across the size distribution. Future studies are warranted to determine specific molecular species linked to CEC in a size-specific manner.

Effects of Technical Errors on the Outcomes of Operatively Managed Femoral Neck Fractures in Adults Less than 50 Years of Age.

OBJECTIVE: To evaluate the effect of technical errors (TEs) on the outcomes after repair of femoral neck fractures in young adults. DESIGN: Multicenter retrospective clinical study. SETTING: 26 North American Level 1 Trauma Centers. PATIENTS: Skeletally mature patients younger than 50 years of age with 492 femoral neck fractures treated between 2005 and 2017. INTERVENTION: Operative repair of femoral neck fracture. MAIN OUTCOME MEASUREMENTS: The association between TE (malreduction and deviation from optimal technique) and treatment failure (fixation failure, nonunion, malunion, osteonecrosis, malunion, and revision surgery) were examined using logistic regression analysis. RESULTS: Overall, a TE was observed in 50% (n = 245/492) of operatively managed femoral neck fractures in young patients. Two or more TEs were observed in 10% of displaced fractures. Treatment failure in displaced fractures occurred in 27% of cases without a TE, 56% of cases with 1 TE, and 86% of cases with 2 or more TEs. TEs were encountered less frequently in treatment of nondisplaced fractures compared with displaced fractures (39% vs. 53%, P < 0.001). Although TE(s) in nondisplaced fractures increased the risk of treatment failure and/or major reconstructive surgery (22% vs. 9%, P < 0.001), they were less frequently associated with treatment failure when compared with displaced fractures with a TE (22% vs. 69% P < 0.001). CONCLUSIONS: TEs were found in half of all femoral neck fractures in young adults undergoing operative repair. Both the occurrence and number of TEs were associated with an increased risk for failure of treatment. Preoperative planning for thoughtful and well-executed reduction and fixation techniques should lead to improved outcomes for young patients with femoral neck fractures. This study should also highlight the need for educational forums to address this subject. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.