Gilbertrowe5690

BACKGROUND The aim of this study was to assess the association of high-sensitivity cardiac troponin (hs-cTnT) and other cardiac, kidney, hyperglycemia, and inflammatory biomarkers with peripheral neuropathy (PN) in a community-based population. METHODS We conducted a cross-sectional analysis of 3056 black and white participants in the Atherosclerosis Risk in Communities (ARIC) study who underwent standardized monofilament PN testing and had measures of cardiac function (hs-cTnT, N-terminal pro-B-type natriuretic peptide [NT-proBNP], and growth differentiation factor 15 [GDF15]), kidney function (serum creatinine, cystatin C, β-2 microglobulin, urine albumin-to-creatinine ratio), hyperglycemia (fasting glucose, hemoglobin A1c [Hb A1c], fructosamine, glycated albumin, 1,5-anhydroglucitol), and inflammation (C-reactive protein) assessed at visit 6 (2016-2017; age 71-94 years). We used logistic regression to assess the associations of these biomarkers (modeled in diabetes-specific tertiles) with PN in older adult Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email journals.permissions@oup.com.AIMS Elevated lipoprotein(a) [Lp(a)] is strongly associated with an increased cardiovascular disease (CVD) risk. We previously reported that pro-inflammatory activation of circulating monocytes is a potential mechanism by which Lp(a) mediates CVD. Since potent Lp(a)-lowering therapies are emerging, it is of interest whether patients with elevated Lp(a) experience beneficial anti-inflammatory effects following large reductions in Lp(a). METHODS AND RESULTS Using transcriptome analysis, we show that circulating monocytes of healthy individuals with elevated Lp(a), as well as CVD patients with increased Lp(a) levels, both have a pro-inflammatory gene expression profile. The effect of Lp(a)-lowering on gene expression and function of monocytes was addressed in two local sub-studies, including 14 CVD patients with elevated Lp(a) who received apolipoprotein(a) [apo(a)] antisense (AKCEA-APO(a)-LRx) (NCT03070782), as well as 18 patients with elevated Lp(a) who received proprotein convertase subtilisin/kexin type 9 antibody (PCSK9ab) treatment (NCT02729025). AKCEA-APO(a)-LRx lowered Lp(a) by 47% and reduced the pro-inflammatory gene expression in monocytes of CVD patients with elevated Lp(a), which coincided with a functional reduction in transendothelial migration capacity of monocytes ex vivo (-17%, P  less then  0.001). In contrast, PCSK9ab treatment lowered Lp(a) by 16% and did not alter transcriptome nor functional properties of monocytes, despite an additional reduction of 65% in low-density lipoprotein cholesterol (LDL-C). CONCLUSION Potent Lp(a)-lowering following AKCEA-APO(a)-LRx, but not modest Lp(a)-lowering combined with LDL-C reduction following PCSK9ab treatment, reduced the pro-inflammatory state of circulating monocytes in patients with elevated Lp(a). These ex vivo data support a beneficial effect of large Lp(a) reductions in patients with elevated Lp(a). © The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.Intravenous third-line anaesthetic agents are typically titrated in refractory status epilepticus to achieve either seizure suppression or burst suppression on continuous EEG. However, the optimum treatment paradigm is unknown and little data exist to guide the withdrawal of anaesthetics in refractory status epilepticus. Premature withdrawal of anaesthetics risks the recurrence of seizures, whereas the prolonged use of anaesthetics increases the risk of treatment-associated adverse effects. This study sought to measure the accuracy of features of EEG activity during anaesthetic weaning in refractory status epilepticus as predictors of successful weaning from intravenous anaesthetics. We prespecified a successful anaesthetic wean as the discontinuation of intravenous anaesthesia without developing recurrent status epilepticus, and a wean failure as either recurrent status epilepticus or the resumption of anaesthesia for the purpose of treating an EEG pattern concerning for incipient status epilepticus. We evalh an area under the curve of 83.3%. Distinct signatures in the spatial networks of functional connectivity emerge during successful anaesthetic liberation in status epilepticus; these findings are absent in patients with anaesthetic wean failure. Identifying features that emerge during successful anaesthetic weaning may allow faster and more successful anaesthetic liberation after refractory status epilepticus. © The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email journals.permissions@oup.com.Transapical mitral valve repair with NeoChord implantation is effective and safe to replace ruptured chordae due to degenerative disease. TAS-102 Redo transapical neochordae implantation has never been reported in the literature. We present a case report of a 53-year-old man who underwent a reoperative neochord implantation for recurrent severe mitral regurgitation, resulting from degenerative disease progression with a new native chordal rupture. We report the midterm durability of reoperative Neochord repair. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.BACKGROUND Recent advances in the study and clinical applications of circulating tumor DNA (ctDNA) are limited by practical considerations of sample collection. Whole-genome sequencing (WGS) is increasingly used for analysis of ctDNA, identifying copy-number alterations and fragmentation patterns. We hypothesized that low-depth/shallow WGS (sWGS) data may be generated from minute amounts of cell-free DNA, and that fragment-size selection may remove contaminating genomic DNA from small blood volumes. Dried blood spots have practical advantages for sample collection, may facilitate serial sampling, and could support novel study designs in humans and animal models. METHODS We developed a protocol for the isolation and analysis of cell-free DNA from dried blood spots using filter paper cards and bead-based size selection. DNA extracted and size-selected from dried spots was analyzed using sWGS and polymerase chain reaction (PCR). RESULTS Analyzing a 50 μL dried blood spot from frozen whole blood of a patient with melanoma, we identified ctDNA based on the presence of tumor-specific somatic copy-number alterations, and found a fragment-size profile similar to that observed in plasma DNA.