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It remains unclear whether aggressive low-density lipoprotein cholesterol (LDL-C) management (<1.8 mmol/L) can slow the process of vein graft stenosis. This study aimed to explore the impact of baseline LDL-C levels on vein graft patency in patients on ticagrelor with or without aspirin 1 year after coronary artery bypass grafting (CABG). This was a post hoc analysis of the DACAB (Different Antiplatelet Therapy Strategy After Coronary Artery Bypass Graft Surgery) trial (NCT02201771), a randomized controlled trial (ticagrelor + aspirin or ticagrelor vs aspirin) of patients undergoing CABG in China. The study subjects were stratified as LDL-low (baseline LDL-C <1.8 mmol/L, 148 patients with 430 vein grafts) versus LDL-high (baseline LDL-C ≥1.8 mmol/L, 352 patients with 1030 vein grafts). The primary outcome was the 1-year vein graft patency (Fitzgibbon grade A) assessed by coronary computed tomographic angiography or coronary angiography. Baseline/1-year LDL-C were 1.4/1.6 and 2.6/2.4 mmol/L in the LDL-low and LDL-high subgroups, respectively. Regardless of antiplatelet regimen, no significant inter-subgroup difference was observed for 1-year graft patency (LDL-low: 83.8% [359/430 grafts]; LDL-high: 82.3% [848/1030 grafts]; adjusted OR for non-patency [OR adj ], 0.96; 95% confidence interval [CI], 0.62-1.50, P =.857). For both subgroups, the 1-year graft patency rates were greater with ticagrelor + aspirin versus aspirin (LDL-low: OR adj , 0.41; 95% CI, 0.17-0.97; LDL-high: OR adj , 0.38; 95% CI, 0.20-0.71; inter P =.679). In general, baseline LDL-C is not associated with 1-year vein graft patency after CABG. Regardless of the baseline LDL-C levels, ticagrelor + aspirin was superior to aspirin alone in maintaining vein graft patency. The primary factor causing early vein graft disease might not be atherosclerosis but thrombosis. [Display omitted] [ABSTRACT FROM AUTHOR]

Chronic stress is associated with impairment of synapse plasticity in hippocampus and cognitive dysfunction in rodent and human. Notably, corticosterone (CORT) is believed to take responsibility for dendritic atrophy and reduction of spine number induced by chronic stress in hippocampus. But little is known about the molecular mechanisms underlying CORT induced abnormal synapse plasticity and cognitive dysfunction. Drebrin is an F-actin binding protein that modulates memory formation and maintenance by controlling the genesis and morphology of dendritic spines. In addition, miRNAs have been reported to participate in the negative regulation of protein-coding genes. In this study, five miRNAs capable of targeting Drebrin were selected by searching miRNA databases. One of these miRNAs, miR-19b-3p, was found to be upregulated in the hippocampal neurons of mice with chronic restraint stress (CRS). Luciferase reporter assay and Fluorescence in situ hybridization (FISH) were employed to identify the interaction between miR-19b-3p and Drebrin. In addition, silencing miR-19b-3p expression in vivo using an antagomir or in vitro using an inhibitor increased Drebrin expression, ameliorated the abnormal dendritic structure and upregulated the spine density in hippocampal CA1 pyramidal neurons of CRS mice and primary hippocampal neurons cultured under CORT stimulation, respectively. Electrophysiological analysis revealed that inhibition of miR-19b-3p rescued the limited synaptic transmission and synaptic plasticity in hippocampal neurons. Moreover, blocking miR-19b-3p drastically protected against cognitive deficits in CRS mice. These in vivo and in vitro findings indicate that the upregulation of miR-19b-3p exacerbates CRS-induced abnormal synaptic plasticity and cognitive impairment by targeting Drebrin. • CRS stimulation was able to up-regulate miR-19b-3p and down-regulate Drebrin in hippocampal neurons. • CORT mediated miR-19b-3p/Drebrin axis under CRS stimulation. • Inhibition of miR-19b-3p rescued abnormal synaptic plasticity and cognitive deficits by targeting Drebrin in CRS mice. [ABSTRACT FROM AUTHOR]

BMT CTN 1401 is an academically led randomized study of a personalized cancer vaccine in which the combination of DC/MM fusion vaccine and lenalidomide maintenance after autoHCT is compared with maintenance alone as upfront treatment of MM (NCT#02728102). Assessment of the percentage of patients achieving CR and therapy-induced changes in MM-specific immunity are the primary clinical and immunologic endpoints, respectively. The protocol represents a transformative open source approach to cell therapy in MM and required collection of tumor cells prior to treatment initiation and vaccine production at day 60 after autoHCT. The process featured a multi-step approach of procedural standardization, training, and centralized verification of manufactured product/release criteria. Here we present initial analysis of accrual and vaccine manufacturing. Enrollment of 203 patients completed within 26 months with 140 patients randomized. Drop-out rate from enrollment to randomization was 31% (expected 30%). Sixty-eight patients were randomized to the DC/MM fusion vaccine arm, with 63 having products successfully manufactured and approved for release at 14 manufacturing sites. Vaccine products for 5 patients were not approved for release for the following reasons: final TC/DC viability did not meet release criteria (n = 3), product failed to meet sterility release criteria (n = 1), and disease progression prior to manufacture (n = 1). Among 63 participants who received vaccine, mean DC viability and CD86 expression was 79.3% (Standard Deviation = 11.3) and 80.6% (SD = 12.9), respectively. Mean viability and percent cells co-expressing DC and tumor antigens was 78.6% (SD = 13.0) and 47.9% (SD = 11.4), respectively. The process devised for BMT CTN 1401 led to rapid patient accrual and successful point-of-care DC/MM fusion vaccine generation. Feasibility of serial sample collection and performance of immunologic correlates were demonstrated. This multi-center collaboration highlights the development of a personalized tumor vaccine platform that serves as a model for future immunotherapy trials in MM. [ABSTRACT FROM AUTHOR]