Androgen deprivation decreases prostate specific antigen in the absence of tumor: implications for interpretation of PSA results

Background: Prostate-specific antigen (PSA) is used as an outcome measure for relapsed disease in prostate cancer. Nonetheless, there are considerable concerns about its indiscriminate use as a surrogate endpoint for cell growth or survival. We hypothesized that treatment with a luteinizing hormone releasing hormone (LHRH) analog would decrease PSA levels even in the absence of malignant disease. Methods: We determined testosterone and PSA levels in 30 healthy volunteers after a single intramuscular injection of a LHRH depot formulation. Testosterone and PSA levels were quantified by radioimmunoassay and electrochemi-luminescence immunoassay, respectively. Results: After an initial flare-up during the first 3 days testosterone decreased reaching castration levels in 18 of the 30 young men (60%). After the nadir on day 28, testosterone levels increased to normal again. Changes in PSA paralleled those of testosterone. Castration reduced PSA levels by 29% (95% CI 19%-39%) compared to baseline (p<0.0001). Conclusions: LHRH superagonists decrease PSA levels by testosterone deprivation. Conferring these findings to tumor patients, decreases in PSA after treatment with LHRH analogs might not only reflect disease regression but also a direct testosterone mediated effect on PSA. Thus, PSA levels should be cautiously interpreted when patients receive hormonal therap

Performance of a Qualitative Point-of-Care Strip Test to Detect DOAC Exposure at the Emergency Department:A Cohort-Type Cross-Sectional Diagnostic Accuracy Study

An accurate point-of-care test for detecting effective anticoagulation by direct oral anticoagulants (DOACs) in emergencies is an unmet need. We investigated the accuracy of a urinary qualitative strip test (DOAC Dipstick) to detect relevant DOAC exposure in patients who presented to an emergency department. In this prospective single-center cohort-type cross-sectional study, adults on DOAC treatment were enrolled. We assessed clinical sensitivity and specificity of DOAC Dipstick factor Xa and thrombin inhibitor pads to detect DOAC plasma levels ≥30 ng/mL using urine samples as the testing matrix. Liquid chromatography coupled with tandem-mass spectrometry was used as the reference standard method for plasma and urine measurement of DOAC concentrations. Of 293 patients enrolled, 265 patients were included in the analysis, of whom 92 were treated with rivaroxaban, 65 with apixaban, 77 with edoxaban, and 31 with dabigatran. The clinical sensitivity and specificity of the dipstick on urine samples to detect ≥30 ng/mL dabigatran plasma levels were 100% (95% confidence interval [CI]: 87–100%) and 98% (95% CI: 95–99%), respectively. The sensitivity and specificity of the dipstick to detect ≥30 ng/mL factor Xa inhibitor plasma levels were 97% (95% CI: 94–99%) and 69% (95% CI: 56–79%), respectively. The DOAC Dipstick sensitively identified effective thrombin and factor Xa inhibition in a real-world cohort of patients presenting at an emergency department. Therefore, the dipstick might provide a valuable test to detect relevant DOAC exposure in emergencies, although further studies will be needed to confirm these findings

Effects of prasugrel on platelet inhibition during systemic endotoxaemia: a randomized controlled trial

A B S T R A C T P2Y 12 receptor antagonists have become a mainstay for the treatment of CVD (cardiovascular diseases). However, they have rarely been evaluated under pathophysiological conditions apart from arterial diseases. We hypothesized interactions between prasugrel and enhanced vWF (von Willebrand Factor) release in a model of systemic inflammation, and compared the pharmacodynamic effects of prasugrel against placebo on agonist-induced platelet aggregation and shear-induced platelet plug formation. A total of 20 healthy male volunteers were enrolled in a double-blind placebo-controlled two-way crossover trial. Each volunteer received either placebo or a 60 mg loading dose of prasugrel 2 h before endotoxin or placebo infusion. Platelet inhibition was measured with MEA (multiple electrode aggregometry), the PFA-100 system and the VASP (vasodilator-stimulated phosphoprotein) phosphorylation assay. Prasugrel blunted various platelet aggregation pathways, including those induced by ADP (− 81 %), AA (arachidonic acid) (− 60 %), ristocetin (− 75 %; P &lt; 0.001 for all) and, to a lesser degree, collagen or TRAP (thrombinreceptor-activating peptide). Prasugrel decreased shear-induced platelet plug formation, but vWF release during endotoxaemia partly antagonized the inhibitory effect of prasugrel as measured with the PFA-100 system. Endotoxaemia acutely decreased ristocetin and TRAP-induced platelet aggregation, and enhanced ristocetin-induced aggregation after 24 h. Strong in vivo blockade of P2Y 12 inhibits a broad spectrum of platelet aggregation pathways. However, vWF release may reduce prasugrel&apos;s effects under high-shear conditions

Heart / Cardiac biomarkers predict mortality in emergency patients presenting with atrial fibrillation

Objectives: To assess the predictive value of N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitive troponin T (hs-TnT) serum levels for mid-term mortality in patients presenting with symptomatic atrial fibrillation (AF) to an emergency department. Methods: Non-interventional cohort/follow-up study, including consecutive patients presenting to a tertiary care university emergency department due to symptomatic AF between 2012 and 2016. Multivariable Cox proportional hazard regression models were used to estimate the mortality rates and hazards per 100 patient-years (pry) for NT-proBNP and hs-TnT serum levels in quintiles. Results: 2574 episodes of 1754 patients (age 68 (IQR 5875) years, female gender 1199 (44%), CHADS-VASc 3 (IQR 14)) were recorded. Following the exclusion of incomplete datasets, 1780 episodes were available for analysis. 162 patients deceased during the mid-term follow-up (median 23 (IQR 438) months); the mortality rate was 4.72/100 pry. Hazard for death increased with every quintile of NT-proBNP by 1.53 (HR; 95%CI 1.27 to 1.83; p<0.001) and by 1.31 (HR; 95%CI 1.10 to 1.55; p=0.002) with every quintile of hs-TnT in multivariate Cox-regression analysis. No interaction between NT-proBNP and hs-TnT levels could be observed. Conclusion: Elevated NT-proBNP and hs-TnT levels are independently associated with increased mid-term mortality in patients presenting to an emergency department due to symptomatic AF.(VLID)489869

High Platelet Reactivity after Transition from Cangrelor to Ticagrelor in Hypothermic Cardiac Arrest Survivors with ST-Segment Elevation Myocardial Infarction

Transition from cangrelor to oral P2Y12 inhibitors after PCI carries the risk of platelet function recovery and acute stent thrombosis. Whether the recommended transition regimen is appropriate for hypothermic cardiac arrest survivors is unknown. We assessed the rate of high platelet reactivity (HPR) after transition from cangrelor to ticagrelor in hypothermic cardiac arrest survivors. Adult survivors of out-of-hospital cardiac arrest with ST-segment elevation myocardial infarction (STEMI), who were treated for hypothermia (33 &deg;C &plusmn; 1) and received intravenous cangrelor during PCI and subsequent oral loading with 180mg ticagrelor were enrolled in this prospective observational cohort study. Platelet function was assessed using whole blood aggregometry. HPR was defined as AUC &gt; 46U. The primary endpoint was the rate of HPR (%) at predefined time points during the first 24 h after cangrelor cessation. Poisson regression was used to estimate the relationship between the overlap time of cangrelor and ticagrelor co-administration and the number of subsequent HPR episodes, expressed as incidence rate ratio (IRR) with 95% confidence interval (95%CI). Between December 2017 and October 2019 16 patients (81% male, 58 years) were enrolled. On average, ticagrelor was administered 39 min (IQR 5&ndash;50) before the end of cangrelor infusion. The rate of HPR was highest 90 min after cangrelor cessation and was present in 44% (7/16) of patients. The number of HPR episodes increased significantly with decreasing overlap time of cangrelor and ticagrelor co-administration (IRR 1.03, 95%CI 1.01&ndash;1.05; p = 0.005). In this selected cohort of hypothermic cardiac arrest survivors who received cangrelor during PCI, ticagrelor loading within the recommended time frame before cangrelor cessation resulted in a substantial amount of patients with HPR

Standardized contrast-enhanced ultrasound (CEUS) in clinical acute and emergency medicine and critical care (CEUS Acute) Consensus statement of DGIIN, DIVI, DGINA, DGAI, DGK, oGUM, SGUM and DEGUM

The present document describes the possible applications of contrast-enhanced ultrasound (CEUS) in emergency examinations. Guidelines on contrast medium ultrasound in acute and emergency care and intensive care medicine have not yet been published. Evidence-based CEUS guidelines were first provided by the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) and the World Federation for Ultrasound in Medicine and Biology (WFUMB). The presented recommendations describe the possible applications and protocols of CEUS in acute care