Citations

Introduction: Risk of lobar and non-lobar intracerebral hemorrhage (ICH) varies among blacks, whites and Hispanics. We sought to determine whether these differences could be due to variability in the effects of Apolipoprotein E (APOE) epsilon (ε) alleles, the most potent genetic risk factor for ICH. Methods: Primary ICH cases and controls were collected from US and European sites contributing to the International Stroke Genetic Consortium (ISGC). We meta-analyzed the effects of APOE allele status on ICH risk applying a two-stage clustering approach based on race/ethnicity and the contributing study. Models were adjusted for age, sex, history of hypertension, hypercholesterolemia, warfarin, statin and antiplatelet use, smoking and alcohol use. A propensity score analysis was used to model the influence of APOE against the burden of hypertension across races/ethnicities. Results: 13,124 subjects (54.5% male, median age 66 years) were included. In whites, APOE ε2 (odds ratio (OR)=1.85, 95% confidence interval (CI)=1.27-2.69, p<0.001) and APOE ε4 (OR=1.94, 95% CI=1.58-2.38, p<0.001) were independently associated with lobar ICH risk, however within self-identified Hispanics and blacks, no associations were found (Figure). After propensity score-matching for hypertension burden, APOE ε4 was associated with lobar ICH risk among whites (OR=1.12, 95% CI=1.08-1.17) and Hispanics (OR=1.07, 95% CI=1.01-1.15, p=0.01), but not blacks (OR=1.02 95% CI=0.98-1.07, p=0.251). APOE ε2 and ε4 did not show an effect on non-lobar ICH risk in any race/ethnicity. Conclusion: APOE ε4 and ε2 alleles affect lobar ICH risk variably by race and ethnicity. Associations are confirmed in whites but can be shown in Hispanics only when the excess burden of hypertension is propensity score-matched. Further studies are needed to explore interactions between APOE alleles and environmental exposures that vary by race and ethnicity in representative populations at risk for ICH.

Level of Evidence : 5 Technical Efficacy : Stage 5 J. Magn. Reson. Imaging 2019.

The measurement of peak oxygen uptake (VO2peak) is an important metric for evaluating cardiac transplantation (HTx) eligibility. However, it is unclear which factors (e.g., recipient demographics, clinical parameters, cardiac rehabilitation (CR) participation) influence VO2peak following HTx. Consecutive HTx patients with cardiopulmonary exercise testing (CPET) between 2007–2016 were included. VO2peak was measured from CPET standard protocol. Regression analyses determined predictors of the highest post-HTx VO2peak (i.e., quartile 4: VO2peak > 20.1 mL/kg/min). One hundred-forty HTx patients (women: n = 41 (29%), age: 52 ± 12 years, body mass index (BMI): 27 ± 5 kg/m2) were included. History of diabetes (Odds Ratio (OR): 0.17, 95% Confidence Interval (CI): 0.04–0.77, p = 0.021), history of dyslipidemia (OR: 0.42, 95% CI: 0.19–0.93, p = 0.032), BMI (OR: 0.90, 95% CI: 0.82–0.99, p = 0.022), hemoglobin (OR: 1.29, 95% CI: 1.04–1.61, p = 0.020), white blood cell count (OR: 0.81, 95% CI: 0.66–0.98, p = 0.033), CR exercise sessions (OR: 1.10, 95% CI: 1.04–1.15, p < 0.001), and pre-HTx VO2peak (OR: 1.17, 95% CI: 1.07–1.29, p = 0.001) were significant predictors. Multivariate analysis showed CR exercise sessions (OR: 1.10, 95% CI: 1.03–1.16, p = 0.002), and pre-HTx VO2peak (OR: 1.16, 95% CI: 1.04–1.30, p = 0.007) were independently predictive of higher post-HTx VO2peak. Pre-HTx VO2peak and CR exercise sessions are predictive of a greater VO2peak following HTx. These data highlight the importance of CR exercise session attendance and pre-HTx fitness in predicting VO2peak post-HTx.

Abstract Cavernous malformations (CM) of the anterior midbrain are best reached through an orbitozygomatic (OZ) approach with removal of the orbital rim and wide Sylvian fissure dissection. Our surgical video demonstrates this approach to resect a ruptured CM in a 36-yr-old woman who presented with headaches, left face and left arm paresthesias/weakness, and right-sided partial oculomotor nerve (CN III) palsy. Initial magnetic resonance imaging (MRI) showed a midbrain CM, and the patient was managed conservatively. However, 1 wk later, she presented again with worsened left arm and leg weakness and complete CN III palsy. Seven Tesla MRI demonstrated a larger hematoma, and the CM with new mass effect and upper pons extension. The patient underwent a right modified OZ craniotomy and Sylvian fissure split under guidance of intraoperative neuronavigation and with neuromonitoring. The carotid-oculomotor triangle and the Liliequist membrane were dissected to access the midbrain, and CN III was identified and followed posteriorly to the midbrain. Confirmed with neuronavigation, a longitudinal incision of the midbrain was performed, and the CM was encountered. The hematoma and CM were debulked and removed in a piece-meal fashion, leaving hemosiderin-stained brain intact to prevent unnecessary additional damage to the midbrain. Postoperative MRI confirmed gross-total resection, and the patient's weakness recovered substantially. In this video, we demonstrate that the brainstem is no longer forbidden surgical territory, and show how the use of neuronavigation for surgical planning, positioning, and approach, in addition to the understanding of safe entry zones and meticulous microsurgical technique have made safe and effective surgery on the brainstem possible.

Background: Proteomic approaches allow measurement of thousands of proteins in a single specimen, which can accelerate biomarker discovery. However, applying these technologies to massive biobanks is not currently feasible because of the practical barriers and costs of implementing such assays at scale. To overcome these challenges, we used a “virtual proteomic” approach, linking genetically predicted protein levels to clinical diagnoses in >40 000 individuals. Methods: We used genome-wide association data from the Framingham Heart Study (n=759) to construct genetic predictors for 1129 plasma protein levels. We validated the genetic predictors for 268 proteins and used them to compute predicted protein levels in 41 288 genotyped individuals in the Electronic Medical Records and Genomics (eMERGE) cohort. We tested associations for each predicted protein with 1128 clinical phenotypes. Lead associations were validated with directly measured protein levels and either low-density lipoprotein cholesterol or subclinical atherosclerosis in the MDCS (Malmö Diet and Cancer Study; n=651). Results: In the virtual proteomic analysis in eMERGE, 55 proteins were associated with 89 distinct diagnoses at a false discovery rate q<0.1. Among these, 13 associations involved lipid (n=7) or atherosclerosis (n=6) phenotypes. We tested each association for validation in MDCS using directly measured protein levels. At Bonferroni-adjusted significance thresholds, levels of apolipoprotein E isoforms were associated with hyperlipidemia, and circulating C-type lectin domain family 1 member B and platelet-derived growth factor receptor-β predicted subclinical atherosclerosis. Odds ratios for carotid atherosclerosis were 1.31 (95% CI, 1.08–1.58; P =0.006) per 1-SD increment in C-type lectin domain family 1 member B and 0.79 (0.66–0.94; P =0.008) per 1-SD increment in platelet-derived growth factor receptor-β. Conclusions: We demonstrate a biomarker discovery paradigm to identify candidate biomarkers of cardiovascular and other diseases.