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Abstract Background Diabetes (DM) is associated with increased risk of macro/microvascular disease and cognitive decline. Inflammation and vascular calcification may be contributing factors. Bromodomain and extraterminal (BET) proteins coordinate gene transcription and modify the transcriptional response to hyperglycemia, and inflammation. Apabetalone competitively and selectively inhibits binding between BET proteins and acetyl-lysine marks on histone tails: normalizing transcriptional profiles to physiological levels; reducing in vitro alkaline phosphatase (ALP) transcription and in vivo plasma ALP in a dose-dependent manner. Phase 2 trials with apabetalone show improved renal function in the chronic kidney disease (CKD) subgroups. Furthermore, treatment showed a 55% reduction in CVD events with more pronounced benefit among patients with DM, low HDL-cholesterol (HDL-C) and high sensitivity C-reactive protein (hsCRP). Methods The double-blind, placebo controlled phase 3 BETonMACE trial is testing the hypothesis that apabetalone 100 mg b.i.d., added to standard care, reduces major adverse cardiovascular events (MACE: CV death, non-fatal myocardial infarction or stroke) in patients with DM, acute coronary syndrome (ACS) within the preceding 7–90 days, low HDL-C (30 mL/min/1.7m2. The trial will continue until at least 250 MACE, providing 80% power to detect a 30% reduction. Secondary endpoints include changes in eGFR in patients with baseline eGFR 30 to

Background and purposeDTI, magnetization transfer, T2*-weighted imaging, and cross-sectional area can quantify aspects of spinal cord microstructure. However, clinical adoption remains elusive due to complex acquisitions, cumbersome analysis, limited reliability, and wide ranges of normal values. We propose a simple multiparametric protocol with automated analysis and report normative data, analysis of confounding variables, and reliability.Materials and methodsForty healthy subjects underwent T2WI, DTI, magnetization transfer, and T2*WI at 3T in

Background and purposeT2*-weighted imaging provides sharp contrast between spinal cord GM and WM, allowing their segmentation and cross-sectional area measurement. Injured WM demonstrates T2*WI hyperintensity but requires normalization for quantitative use. We introduce T2*WI WM/GM signal-intensity ratio and compare it against cross-sectional area, the DTI metric fractional anisotropy, and magnetization transfer ratio in degenerative cervical myelopathy.Materials and methodsFifty-eight patients with degenerative cervical myelopathy and 40 healthy subjects underwent 3T MR imaging, covering C1-C7. Metrics were automatically extracted at maximally compressed and uncompressed rostral/caudal levels. Normalized metrics were compared with t tests, area under the curve, and logistic regression. Relationships with clinical measures were analyzed by using Pearson correlation and multiple linear regression.ResultsThe maximally compressed level cross-sectional area demonstrated superior differences (P = 1 × 10-13), diagnostic accuracy (area under the curve = 0.890), and univariate correlation with the modified Japanese Orthopedic Association score (0.66). T2*WI WM/GM showed strong differences (rostral: P = 8 × 10-7; maximally compressed level: P = 1 × 10-11; caudal: P = 1 × 10-4), correlations (modified Japanese Orthopedic Association score; rostral: -0.52; maximally compressed level: -0.59; caudal: -0.36), and diagnostic accuracy (rostral: 0.775; maximally compressed level: 0.860; caudal: 0.721), outperforming fractional anisotropy and magnetization transfer ratio in most comparisons and cross-sectional area at rostral/caudal levels. Rostral T2*WI WM/GM showed the strongest correlations with focal motor (-0.45) and sensory (-0.49) deficits and was the strongest independent predictor of the modified Japanese Orthopedic Association score (P = .01) and diagnosis (P = .02) in multivariate models (R2 = 0.59, P = 8 × 10-13; area under the curve = 0.954, respectively).ConclusionsT2*WI WM/GM shows promise as a novel biomarker of WM injury. It detects damage in compressed and uncompressed regions and contributes substantially to multivariate models for diagnosis and correlation with impairment. Our multiparametric approach overcomes limitations of individual measures, having the potential to improve diagnostics, monitor progression, and predict outcomes.