Purpose:To evaluate the relationship between pulse wave velocity (PWV) from the aortic arch and subsequent cerebral microvascular disease independent of other baseline cardiovascular risk factors among the participants in the multiethnic Dallas Heart Study. Materials and Methods:Each subject gave written consent to participate in this HIPAA-compliant, institutional review board-approved prospective study. Aortic arch PWV was measured with phase-contrast magnetic resonance (MR) imaging in a population sample (n = 1270) drawn from the probabilitybased Dallas Heart Study. Seven years later, the volume of white matter hyperintensities (WMHs) was determined from brain MR images. Linear regression was conducted with aortic arch PWV, 15 other cardiovascular risk factors, and age, sex, and ethnicity included as predictors of WMH. The authors implemented a smoothly clipped absolute deviation-penalized variable selection method to evaluate an optimal predictive risk factor model. Results:Aortic arch PWV helped predict WMH volume independent of the other demographic and cardiovascular risk factors (regression coefficient: 0.29; standard error: 0.06; 95% confidence interval: 0.17, 0.42; P , .0001). The optimal predictor variables of subsequent WMH volume adjusted for sex and ethnicity included aortic arch PWV, age, systolic blood pressure, hypertension treatment, and congestive heart failure. The authors estimated that a 1% increase in aortic arch PWV (in meters per second) is related to a 0.3% increase in subsequent WMH volume (in milliliters) when all other variables in the model are held constant. Conclusion:Aortic arch PWV measured with phase-contrast MR imaging is a highly significant independent predictor of subsequent WMH volume, with a higher standardized effect than any other cardiovascular risk factor assessed except for age. In an optimal predictive model of subsequent WMH burden, aortic arch PWV provides a distinct contribution along with systolic blood pressure, hypertension treatment, congestive heart failure, and age.
The effects of hormonal contraceptives on structural features of the hypothalamus and pituitary are incompletely understood. One prior study reported microstructural changes in the hypothalamus with oral contraceptive pill (OCP) use. However, effects on hypothalamic volume have not been reported. One prior study reported volumetric changes in the pituitary. However, this study was limited by including participants evaluated for neurological symptoms. We sought to determine if OCP use is associated with alteration of hypothalamic or pituitary volume. High-resolution 3T MRI was performed for a prospective cohort of 50 healthy women from 2016 to 2018, which comprised 21 OCP users (age, 19–29) and 29 naturally cycling women (age, 18–36). Participants were excluded if they were pregnant or had significant medical conditions including neurological, psychiatric, and endocrine disorders. After confirming reliability of the image analysis techniques, 5 raters independently performed manual segmentation of the hypothalamus and semi-automated intensity threshold-based segmentation of the pituitary using ITK-SNAP. Total intracranial volume was estimated using FreeSurfer. A general linear model tested the association of OCP use with hypothalamic and pituitary volumes. Hypothalamic (B = -81.2 ± 24.9, p = 0.002) and pituitary (B = -81.2 ± 38.7, p = 0.04) volumes in OCP users were smaller than in naturally cycling women. These findings may be related to interference with known trophic effects of sex hormones and suggest a structural correlate of central OCP effects.
MYC/BCL2 protein co-expression (i.e., double expressor) has been shown to be a negative predictor of outcome in diffuse large B-cell lymphoma (DLBCL). We aimed to establish the incidence of double expressor status in patients with de novo DLBCL and identify the predictive value of this biomarker on treatment response through systematic review and meta-analysis. PubMed and Embase were searched for studies published through December 2019 that reported proportions of double expressor DLBCL. The pooled proportions of MYC and BCL2 expression, both alone and in combination, were computed using the inverse variance method for calculating weights and by the DerSimonian–Laird method. The pooled odds ratios (ORs) of complete remission (CR) rate were calculated, and meta-regression analysis was conducted to explore heterogeneity. Forty-one studies (7054 patients) were included. The pooled incidence of double expressor status in DLBCL was 23% (95% confidence interval [CI], 20–26%), with an adjusted estimate of 31% (95% CI, 27–36%). Neither MYC/BCL2 protein cutoff values, race, mean, or median age of included patients, or overall study quality was a significant factor of heterogeneity (p ≥ 0.20). Cases without double expressor status demonstrated a higher probability of CR to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone treatment (OR, 2.69; 95% CI, 1.55–4.67). Our results reaffirm the predictive power of this important biomarker.
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