Synthesis of the Alleged Structures of Fortisterol and Herbarulide and Structural Revision of Herbarulide.

The alleged structures of 5,6-epoxy-5,6-secosteroids fortisterol and herbarulide differ only in the stereoconfiguration of C24. Applying insights into the hypothetical biosynthesis of this class of natural products, we devised a short synthetic access (four and eight steps, respectively) starting from commercial ergosterol and featuring an alkoxy radical rearrangement. The comparison of nuclear magnetic resonance spectroscopic data revealed herbarulide having the proposed structure of fortisterol, whereas synthesis of another two diastereomers could not conclusively prove the true structure of fortisterol.

Cardiomyocyte injury induced by hemodynamic cardiac stress: Differential release of cardiac biomarkers.

Objective: We explored whether hemodynamic cardiac stress leads to a differential release of cardiomyocyte injury biomarkers, used in the diagnosis of acute myocardial infarction (AMI).

Methods: In an observational international multicenter study, we enrolled 831 unselected patients presenting with symptoms suggestive of AMI to the emergency department. The final diagnosis was adjudicated by two independent cardiologists.

Direct comparison of high-sensitivity-cardiac troponin I vs. T for the early diagnosis of acute myocardial infarction.

Aim: It is unknown whether cardiac troponin (cTn) I or cTnT is the preferred biomarker in the early diagnosis of acute myocardial infarction without ST segment elevation (NSTEMI).

Methods And Results: In a prospective multicentre study, we measured cTnI and cTnT using clinically available high-sensitivity assays (hs-cTnI Abbott and hs-cTnT Roche) and compared their diagnostic and prognostic accuracies in consecutive patients presenting to the emergency department with acute chest pain. The final diagnosis was adjudicated by two independent cardiologists using all information pertaining to the individual patient.

Sex-specific chest pain characteristics in the early diagnosis of acute myocardial infarction.

Importance: Whether sex-specific chest pain characteristics (CPCs) would allow physicians in the emergency department to differentiate women with acute myocardial infarction (AMI) from women with other causes of acute chest pain more accurately remains unknown. OBJECTIVE To improve the management of suspected AMI in women by exploring sex-specific CPCs.

Design, Setting, And Participants: From April 21, 2006, through August 12, 2012, we enrolled 2475 consecutive patients (796 women and 1679 men) presenting with acute chest pain to 9 emergency departments in a prospective multicenter study.

Heart failure therapy-induced early ST2 changes may offer long-term therapy guidance.

Background: Biomarkers may help to monitor and tailor treatment in patients with acute heart failure (AHF).

Methods And Results: Levels of ST2, a novel biomarker integrating hypervolemic cardiac strain and proinflammatory signals, were measured at presentation to the emergency department (ED) and after 48 hours in 207 patients with AHF. Patients were stratified according to their early ST2 response (responders: ST2 decrease ≥25%; nonresponders: ST2 decrease <25%) and beta-blocker, renin-angiotensin-aldosterone system (RAAS) blockade, or diuretic treatment status at hospital discharge.

Serial changes in high-sensitivity cardiac troponin I in the early diagnosis of acute myocardial infarction.

Background: Current guidelines require a change (rise and/or fall) in levels of cardiac troponin (cTn) for the diagnosis of acute myocardial infarction (AMI). It is unknown whether absolute or relative changes provide higher accuracy when using high-sensitivity cTnI assays.

Methods: In a prospective international multicentre study, we assessed the diagnostic accuracy of early absolute and relative changes in cTnI measured with two novel pre-commercial high-sensitivity assays (Siemens and Beckman Coulter) in 943 unselected patients presenting to the ED with suspected AMI.

Rapid rule out of acute myocardial infarction using undetectable levels of high-sensitivity cardiac troponin.

Background: We examined whether undetectable levels of high-sensitivity cardiac Troponin (hs-cTn) can be used to rule out acute myocardial infarction (AMI) with a single blood draw at presentation to the emergency department (ED).

Methods And Results: In a prospective multicenter study we used 4 different hs-cTn assays (hs-cTnT Roche, and hs-cTnI Siemens, hs-cTnI Beckman Coulter and hs-cTnI Abbott) in consecutive patients presenting with acute chest pain. The final diagnosis of AMI was adjudicated by two independent cardiologists using all available data including serial hs-cTnT levels.

Early diagnosis of myocardial infarction using absolute and relative changes in cardiac troponin concentrations.

Background: Absolute changes in high-sensitivity cardiac troponin T (hs-cTnT) seem to have higher diagnostic accuracy in the early diagnosis of acute myocardial infarction compared with relative changes. It is unknown whether the same applies to high-sensitivity cardiac troponin I (hs-cTnI) assays and whether the combination of absolute and relative change might further increase accuracy.

Methods: In a prospective, international multicenter study, high-sensitivity cardiac troponin (hs-cTn) was measured with 3 novel assays (hs-cTnT, Roche Diagnostics Corp, Indianapolis, Ind; hs-cTnI, Beckman Coulter Inc, Brea, Calif; hs-cTnI, Siemens, Munich, Germany) in a blinded fashion at presentation and after 1 and 2 hours in a blinded fashion in 830 unselected patients with suspected acute myocardial infarction.

Risk stratification in patients with acute chest pain using three high-sensitivity cardiac troponin assays.

Aims: Several high-sensitivity cardiac troponin (hs-cTn) assays have recently been developed. It is unknown which hs-cTn provides the most accurate prognostic information and to what extent early changes in hs-cTn predict mortality.

Methods And Results: In a prospective, international multicentre study, cTn was simultaneously measured with three novel [high-sensitivity cardiac Troponin T (hs-cTnT), Roche Diagnostics; hs-cTnI, Beckman-Coulter; hs-cTnI, Siemens] and a conventional assay (cTnT, Roche Diagnostics) in a blinded fashion in 1117 unselected patients with acute chest pain.

Comparison of the performances of cardiac troponins, including sensitive assays, and copeptin in the diagnostic of acute myocardial infarction and long-term prognosis between women and men.

Background: Concerns have been raised about possible gender disparities in cardiac investigations and/or outcome. This study sought to examine and compare the diagnostic and prognostic performance of selected cardiac biomarkers in women versus men.

Methods: In a prospective, multicenter cohort of patients with acute chest pain cardiac troponin T (cTnT) (fourth-generation Roche assay), high-sensitivity cTnT (hs-cTnT), and copeptin were measured at presentation.

Normal presenting levels of high-sensitivity troponin and myocardial infarction.

Objective: To analyse whether levels of high-sensitivity cardiac troponin (hs-cTn) below their respective 99th percentile can be used as a single parameter to rule out acute myocardial infarction (AMI) at presentation.

Design: Prospective, multicentre study.

Main Outcome Measures: We measured hs-cTn using four different methods (hs-cTnT Roche, hs-cTnI Siemens, hs-cTnI Beckman Coulter and hs-cTnI Abbott) in consecutive patients presenting to the emergency department with acute chest pain.

Validation of high-sensitivity troponin I in a 2-hour diagnostic strategy to assess 30-day outcomes in emergency department patients with possible acute coronary syndrome.

Objectives: The study objective was to validate a new high-sensitivity troponin I (hs-TnI) assay in a clinical protocol for assessing patients who present to the emergency department with chest pain.

Background: Protocols using sensitive troponin assays can accelerate the rule out of acute myocardial infarction in patients with low-risk (suspected) acute coronary syndrome (ACS).

Methods: This study evaluated 2 prospective cohorts of patients in the emergency department with ACS in an accelerated diagnostic pathway integrating 0- and 2-h hs-TnI results, Thrombolysis In Myocardial Infarction (TIMI) risk scores, and electrocardiography.

Heart-type fatty acid-binding protein in the early diagnosis of acute myocardial infarction.

Objective: To investigate the diagnostic and prognostic role of heart-type fatty acid-binding protein (hFABP) compared with copeptin and in addition to high-sensitivity cardiac troponin T (hs-cTnT) in patients with chest pain suspected of acute myocardial infarction (AMI).

Design: Diagnostic and prognostic performances of hFABP, copeptin and hs-cTnT were evaluated and compared. The final diagnosis was adjudicated by two independent cardiologists.

Uric acid for diagnosis and risk stratification in suspected myocardial infarction.

Background: Hypoxia precedes cardiomyocyte necrosis in acute myocardial infarction (AMI). We therefore hypothesized that uric acid - as a marker of oxidative stress and hypoxia - might be useful in the early diagnosis and risk stratification of patients with suspected AMI.

Materials And Methods: In this prospective observational study, uric acid was measured at presentation in 892 consecutive patients presenting to the emergency department with suspected AMI.