BACKGROUND:We report the development of a novel high-sensitivity cardiac troponin T (hs-cTnT) assay, a modification of the Roche fourth-generation cTnT assay, and validation of the analytical performance of this assay.

BACKGROUND:We sought to determine the diagnostic performance of the new high-sensitivity cardiac troponin T (hs-cTnT) assay for early detection of non-STsegment myocardial infarction (NSTEMI) in patients with acute coronary syndrome.

Methylation at 5-cytosine (5-mC) is a fundamental epigenetic DNA modification associated recently with cardiac disease. In contrast, the role of 5-hydroxymethylcytosine (5-hmC)—5-mC's oxidation product—in cardiac biology and disease is unknown. Here we assess the hydroxymethylome in embryonic, neonatal, adult and hypertrophic mouse cardiomyocytes, showing that dynamic modulation of hydroxymethylated DNA is associated with specific transcriptional networks during heart development and failure. DNA hydroxymethylation marks the body of highly expressed genes as well as distal regulatory regions with enhanced activity. Moreover, pathological hypertrophy is characterized by a shift towards a neonatal 5-hmC distribution pattern. We also show that the ten-eleven translocation 2 (TET2) enzyme regulates the expression of key cardiac genes, such as Myh7, through 5-hmC deposition on the gene body and at enhancers. Thus, we provide a genome-wide analysis of 5-hmC in the cardiomyocyte and suggest a role for this epigenetic modification in heart development and disease.

BackgroundIn eligible patients with acute ischaemic stroke, rapid revascularisation is crucial for good outcome. At our treatment centre, we had achieved and sustained a median door-to-needle time of under 30 min. We hypothesised that further improvement could be achieved through implementing a revised treatment protocol and in situ simulation-based team training sessions. This report describes a quality improvement project aiming to reduce door-to-needle times in stroke thrombolysis.MethodsAll members of the acute stroke treatment team were surveyed to tailor the interventions to local conditions. Through a review of responses and available literature, the improvement team suggested changes to streamline the protocol and designed in situ simulation-based team training sessions. Implementation of interventions started in February 2017. We completed 14 simulation sessions from February to June 2017 and an additional 12 sessions from November 2017 to March 2018. Applying Kirkpatrick’s four-level training evaluation model, participant reactions, clinical behaviour and patient outcomes were measured. Statistical process control charts were used to demonstrate changes in treatment times and patient outcomes.ResultsA total of 650 consecutive patients, including a 3-year baseline, treated with intravenous thrombolysis were assessed. Median door to needle times were significantly reduced from 27 to 13 min and remained consistent after 13 months. Risk-adjusted cumulative sum charts indicate a reduced proportion of patients deceased or bedridden after 90 days. There was no significant change in balancing measures (stroke mimics, fatal intracranial haemorrhage and prehospital times).ConclusionsImplementing a revised treatment protocol in combination with in situ simulation-based team training sessions for stroke thrombolysis was followed by a considerable reduction in door-to-needle times and improved patient outcomes. Additional work is needed to assess sustainability and generalisability of the interventions.

All single-point cTnTs, except on admission, give a good estimation of infarct size and perform as well as peak cTnT or AUC cTnT. Infarct estimation by single-point measurements, particularly cTnTD4, may gain clinical acceptance because the measurement is easy and inexpensive.

Background: Inhibition of platelet aggregation by clopidogrel may be insufficient in up to 30% of users. These nonresponders carry an increased risk of cardiovascular events. We reported here a simple assay to study clopidogrel responsiveness. Methods: Electrical impedance aggregometry was performed in diluted whole blood in the presence of 5 and 20 mol/L ADP. Some samples were incubated with 0.1 mmol/L methyl-S-adenosine monophosphate (Me-SAMP), a P2Y 12 receptor blocker, to maximize inhibition of aggregation before aggregometry. To validate the assay, we analyzed 6-min impedance in 21 healthy probands and 244 patients with coronary artery disease (CAD). Results: At 5 mol/L ADP, the imprecision of the assay was 11%. Mean (SD) impedance of the healthy cohort was 12.2 (2.2) ⍀. The mean ؊ 3 SD was used to define the cutoff for clopidogrel responsiveness: responders and nonresponders exhibited a 6-min impedance <5 ⍀ and >5 ⍀, respectively. Samples from nonresponders were incubated with MeSAMP and analyzed again to distinguish pharmacokinetic and pharmacodynamic types of resistance. Sixteen percent of CAD patients were classified as nonresponders (38 and 2 cases of pharmacokinetic and pharmacodynamic resistance, respectively). Female sex was strongly associated with clopidogrel resistance (P ‫؍‬ 0.0002, Fisher exact test). A higher clopidogrel loading dose (P ‫؍‬ 0.0353, MannWhitney U-test) was given to responders (median, 450

BACKGROUND:Using a new precommercial high-sensitivity cardiac troponin T (hsTnT) assay, we evaluated whether hsTnT increases after reversible myocardial ischemia.

DCIS presented overlapping groups of morphology and distribution of calcification by grade, but fine pleomorphic and fine linear and fine linear branching calcifications with grouped and segmental distributions were associated with high grade DCIS. Seeking for further knowledge that allows separation of non-high grade from high grade DCIS has to continue to improve the quality of mammographic screening.