Point-of-Care Ultrasonography in Patients With Acute Dyspnea: An Evidence Report for a Clinical Practice Guideline by the American College of Physicians.

BACKGROUND: Dyspnea is a common and often debilitating symptom with a complex diagnostic work-up. PURPOSE: To evaluate the benefits, harms, and diagnostic test accuracy of point-of-care ultrasonography (POCUS) in patients with acute dyspnea. (PROSPERO: CRD42019126419). DATA SOURCES: Searches of multiple electronic databases without language limitations (January 2004 to August 2020) and reference lists of pertinent articles and reviews. STUDY SELECTION: Five randomized controlled trials (RCTs) and 44 prospective cohort-type studies in patients with acute dyspnea evaluated POCUS as a diagnostic tool to determine the underlying cause of dyspnea. Two investigators independently screened the literature for inclusion. DATA EXTRACTION: Data abstraction by a single investigator was confirmed by a second investigator; 2 investigators independently rated risk of bias and determined certainty of evidence. DATA SYNTHESIS: Point-of-care ultrasonography, when added to a standard diagnostic pathway, led to statistically significantly more correct diagnoses in patients with dyspnea than the standard diagnostic pathway alone. In-hospital mortality and length of hospital stay did not differ significantly between patients who did or did not receive POCUS in addition to standard diagnostic tests. Finally, POCUS consistently improved the sensitivities of standard diagnostic pathways to detect congestive heart failure, pneumonia, pulmonary embolism, pleural effusion, or pneumothorax; specificities increased in most but not all studies. LIMITATIONS: Most studies assessed diagnostic test accuracy, which has limited utility for clinical decision making. Studies rarely reported on the proportion of indeterminate sonography results, and no evidence is available on adverse health outcomes of false-positive or false-negative POCUS results. CONCLUSION: Point-of-care ultrasonography can improve the correctness of diagnosis in patients with acute dyspnea. PRIMARY FUNDING SOURCE: American College of Physicians.

Can simvastatin reduce COPD exacerbations? A randomised double-blind controlled study.

BACKGROUND: Several studies have shown that statins have beneficial effects in COPD regarding lung function decline, rates and severity of exacerbation, hospitalisation and need for mechanical ventilation. METHODS: We performed a randomised double-blind placebo-controlled single-centre trial of simvastatin at a daily dose of 40 mg versus placebo in patients with Global Initiative for Chronic Obstructive Lung Disease criteria grades 2-4 at a tertiary care pulmonology department in Austria. Scheduled treatment duration was 12 months and the main outcome parameter was time to first exacerbation. RESULTS: Overall, 209 patients were enrolled. In the 105 patients taking simvastatin, time to first exacerbation was significantly longer compared to the 104 patients taking placebo: median 341 versus 140 days (log-rank test p<0.001). Hazard ratio for risk of first exacerbation for the simvastatin group was 0.51 (95% CI 0.34-0.75; p=0.001). Rate of exacerbations was significantly lower with simvastatin: 103 (41%) versus 147 (59%) (p=0.003). The annualised exacerbation rate was 1.45 events per patient-year in the simvastatin group and 1.9 events per patient-year in the placebo group (incidence rate ratio 0.77, 95% CI 0.60-0.99). We found no effect on quality of life, lung function, 6-min walk test and high-sensitivity C-reactive protein. More patients dropped out in the simvastatin group compared to the placebo group (39 versus 29). CONCLUSION: In our single-centre RCT, simvastatin at a dose of 40 mg daily significantly prolonged time to first COPD exacerbation and reduced exacerbation rate.

Mid-regional pro-atrial natriuretic peptide independently predicts short-term mortality in COVID-19.

BACKGROUND: Mid-regional pro-atrial natriuretic peptide (MR-proANP) is a strong prognostic marker in several inflammatory, respiratory and cardiovascular conditions, but has not been studied in COVID-19 yet. METHODS: This prospective, observational study of patients with COVID-19 infection was conducted from 6 June to 26 November 2020 in different wards of a tertiary hospital. MR-proANP, N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitive cardiac troponin I levels on admission were collected and tested for their association with disease severity and 28-day mortality. RESULTS: A total of 213 eligible patients with COVID-19 were included in the final analyses of whom 13.2% (n = 28) died within 28 days. Median levels of MR-proANP at admission were significantly higher in nonsurvivors (307 pmol/L IQR, [161 - 532] vs 75 pmol/L [IQR, 43 - 153], P < .001) compared to survivors and increased with disease severity and level of hypoxaemia. The area under the ROC curve for MR-proANP predicting 28-day mortality was 0.832 (95% CI 0.753 - 0.912, P < .001). An optimal cut-off point of 160 pmol/L yielded a sensitivity of 82.1% and a specificity of 76.2%. MR-proANP was a significant predictor of 28-day mortality independent of clinical confounders, comorbidities and established prognostic markers of COVID-19 (HR 2.77, 95% CI 1.21 - 6.37; P = .016), while NT-proBNP failed to independently predict 28-day mortality and had a numerically lower AUC compared to MR-proANP. CONCLUSION: Higher levels of MR-proANP at admission are associated with disease severity of COVID-19 and act as a powerful and independent prognostic marker of 28-day mortality.

Increased Fibrinolysis as a Specific Marker of Poor Outcome After Cardiac Arrest.

OBJECTIVES: Recent data suggest that early increased fibrinolysis may be associated with unfavorable prognosis in cardiac arrest. The current study aimed to assess whether there is an optimal fibrinolysis cutoff value as determined by thrombelastometry at hospital admission to predict poor outcome in a cohort of adult patients with out-of-hospital cardiac arrest. DESIGN: Prospective observational cohort study. SETTING: Emergency department of a 2.100-bed tertiary care facility in Vienna, Austria, Europe. PATIENTS: Patients with out-of-hospital cardiac arrest of presumed cardiac origin, subjected to targeted temperature management, who had achieved return of spontaneous circulation at admission were analyzed. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fibrinolysis was assessed by thrombelastometry at the bedside immediately after hospital admission and is given as maximum lysis (%). The outcome measure was the optimal cutoff for maximum lysis at hospital admission to predict poor outcome (a composite of Cerebral Performance Category 3-5 or death) at day 30, assessed by receiver operating characteristic curve analysis. Seventy-eight patients (61% male, median 59 yr) were included in the study from March 2014 to March 2017. Forty-two patients (54%) had a poor 30-day outcome including 23 nonsurvivors (30%). The maximum lysis cutoff at admission predicting poor 30-day outcome with 100% specificity (95% CI, 90-100%) was greater than or equal to 20%. Tissue-type plasminogen activator antigen levels were likewise elevated in patients with poor neurologic outcome or death 52 ng/mL (interquartile range, 26-79 ng/mL) versus 29 ng/mL (interquartile range, 17-49 ng/mL; p = 0.036). CONCLUSIONS: Increased fibrinolysis at admission assessed by thrombelastometry specifically predicts poor outcome in cardiac arrest with presumed cardiac etiology.

Vernakalant is superior to ibutilide for achieving sinus rhythm in patients with recent-onset atrial fibrillation: a randomized controlled trial at the emergency department.

Aims: Ibutilide is a rapid-acting antiarrhythmic drug with worldwide use for conversion of recent-onset atrial fibrillation. Vernakalant, approved in the EU in 2010, is likewise used intravenously, with proven efficacy and safety compared with placebo and amiodarone in randomized clinical trials. The aim of our study was to compare the time to conversion and the conversion rate within 90 min in patients with recent-onset atrial fibrillation treated with vernakalant or ibutilide. Methods and Results: A randomized controlled trial registered at clinicaltrials.gov (NCT01447862) was performed in 100 patients with recent-onset atrial fibrillation treated at the emergency department of a tertiary care hospital. Patients received up to two short infusions of vernakalant (n = 49; 3 mg/kg followed by 2 mg/kg if necessary) or ibutilide (n = 51; 1 mg followed by another 1 mg if necessary) according to the manufacturer's instructions. Clinical and laboratory variables, adverse events, conversion rates, and time to conversion were recorded. Time to conversion of AF to sinus rhythm was significantly shorter in the vernakalant group compared with the ibutilide group (median time: 10 vs. 26 min, P = 0.01), and likewise the conversion success within 90 min was significantly higher in the vernakalant group (69 vs. 43%, log-rank P = 0.002). No serious adverse events occurred. Conclusion: Vernakalant was superior to ibutilide in converting recent-onset atrial fibrillation to sinus rhythm in the emergency department setting.

Potent irreversible P2Y12 inhibition does not reduce LPS-induced coagulation activation in a randomized, double-blind, placebo-controlled trial.

Platelets play an important role in the activation of coagulation. P2Y12 receptor inhibition may be beneficial in inflammatory states. Prasugrel, a potent irreversible inhibitor of P2Y12 receptor-induced platelet activation may reduce activation of coagulation in a human LPS (lipopolysaccharide) model. A double-blind, randomized, crossover trial with a minimum washout period of 6 weeks was performed. Sixteen subjects were randomly assigned to a treatment group that received prasugrel or placebo 2 h before infusion of a bolus of LPS (2 ng/kg of body weight), whereas four subjects were assigned to a control group receiving prasugrel or placebo without LPS. hcDNA (histone-complexed DNA), coagulation and platelet-specific parameters were measured by enzyme immunoassay. Leucocyte aggregate formation was analysed by flow cytometry, and thromboelastometry was performed. LPS infusion markedly activated coagulation. However, prasugrel did not reduce changes in prothrombin fragments 1 and 2 (F1+2), thrombin-antithrombin complexes, microparticle-associated tissue factor, CD40 ligand, P-selectin, platelet-leucocyte aggregation, hcDNA levels or the coagulation profile measured by thromboelastometry. hcDNA plasma levels increased approximately 6-fold after LPS infusion in both treatment groups, but not in the control groups. Potent irreversible P2Y12 inhibition by prasugrel does not affect LPS-induced coagulation activation. The 6-fold increased hcDNA plasma levels after infusion of LPS indicates the formation of neutrophil extracellular traps during sterile inflammation.

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 therapy.

Association of Interleukin-32 and Interleukin-34 with Cardiovascular Disease and Short-Term Mortality in COVID-19.

BACKGROUND: Excess cardiovascular (CV) morbidity and mortality has been observed in patients with COVID-19. Both interleukin-32 (IL-32) and interleukin-34 (IL-34) have been hypothesized to contribute to CV involvement in COVID-19. METHODS: This prospective, observational study of patients with laboratory-confirmed COVID-19 infection was conducted from 6 June to 22 December 2020 in a tertiary care hospital in Vienna, Austria. IL-32 and IL-34 levels on admission were collected and tested for their association with CV disease and short-term mortality in patients with COVID-19. CV disease was defined by the presence of coronary artery disease, heart failure, stroke or atrial fibrillation and patients were stratified by CV disease burden. RESULTS: A total of 245 eligible patients with COVID-19 were included, of whom 37 (15.1%) reached the primary endpoint of 28-day mortality. Of the total sample, 161 had no CV disease (65.7%), 69 had one or two CV diseases (28.2%) and 15 patients had ≥three CV diseases (6.1%). Median levels of IL-32 and IL-34 at admission were comparable across the three groups of CV disease burden. IL-32 and IL-34 failed to predict mortality upon both univariable and multivariable Cox regression analysis. The two CV disease groups, however, had a significantly higher risk of mortality within 28 days (one or two CV diseases: crude HR 4.085 (95% CI, 1.913-8.725), p < 0.001 and ≥three CV diseases: crude HR 13.173 (95% CI, 5.425-31.985), p < 0.001). This association persisted for those with ≥three CV diseases after adjustment for age, gender and CV risk factors (adjusted HR 3.942 (95% CI, 1.288-12.068), p = 0.016). CONCLUSION: In our study population of hospitalized patients with COVID-19, IL-32 and IL-34 did not show any associations with CV disease or 28-day mortality in the context of COVID-19. Patients with multiple CV diseases, however, had a significantly increased risk of short-term mortality.

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

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<0.001 for all) and, to a lesser degree, collagen or TRAP (thrombin-receptor-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's effects under high-shear conditions.

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.

[Standardized contrast-enhanced ultrasound (CEUS) in clinical acute and emergency medicine and critical care (CEUS Acute) : Consensus statement of DGIIN, DIVI, DGINA, DGAI, DGK, ÖGUM, SGUM and DEGUM]. / Standardisierte Kontrastmittelsonographie (CEUS) in der klinischen Akut- und Notfallmedizin sowie Intensivmedizin (CEUS Akut) : Konsensuspapier der DGIIN, DIVI, DGINA, DGAI, DGK, ÖGUM, SGUM und 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.

Association of Intravenous Potassium and Magnesium Administration With Spontaneous Conversion of Atrial Fibrillation and Atrial Flutter in the Emergency Department.

Importance: Whether the simultaneous intravenous administration of potassium and magnesium is associated with the probability of spontaneous conversion to sinus rhythm (SCV) in the acute treatment of atrial fibrillation (AF) and atrial flutter (AFL) is unknown. Objective: To assess potassium and magnesium administration and SCV probability in AF and AFL in the emergency department. Design, Setting, and Participants: A registry-based cohort study was conducted in the Department of Emergency Medicine of the Medical University of Vienna, Austria. All consecutive patients with AF or AFL were screened between February 6, 2009, and February 16, 2020. Interventions: Intravenous administration of potassium, 24 mEq, and magnesium, 145.8 mg. Main Outcomes and Measures: The primary outcome was the probability of SCV during the patient's stay in the emergency department. Multivariable cluster-adjusted logistic regression was used to estimate the association between potassium and magnesium administration and the probability of SCV. Results: A total of 2546 episodes of nonpermanent AF (median patient age, 68 [IQR, 58-75] years, 1411 [55.4%] men) and 573 episodes of nonpermanent AFL (median patient age, 68 [IQR, 58-75] years; 332 [57.9%] men) were observed. In AF episodes, intravenous potassium and magnesium administration vs no administration was associated with increased odds of SCV (19.2% vs 10.4%; odds ratio [OR], 1.98; 95% CI, 1.53-2.57). In AFL episodes, in contrast, no association was noted for the probability of SCV with potassium and magnesium vs no administration (13.0% vs 12.5%; OR, 1.05; 95% CI, 0.65-1.69). Conclusions and Relevance: The findings of this registry-based cohort study on intravenous administration of potassium and magnesium suggest an increased probability of SCV in nonpermanent AF, but not AFL, during a patients' stay in the emergency department.

Improvement of outcome prediction of hospitalized patients with COVID-19 by a dual marker strategy using high-sensitive cardiac troponin I and copeptin.

BACKGROUND: COVID-19 has been associated with a high prevalence of myocardial injury and increased cardiovascular morbidity. Copeptin, a marker of vasopressin release, has been previously established as a risk marker in both infectious and cardiovascular disease. METHODS: This prospective, observational study of patients with laboratory-confirmed COVID-19 infection was conducted from June 6th to November 26th, 2020 in a tertiary care hospital. Copeptin and high-sensitive cardiac troponin I (hs-cTnI) levels on admission were collected and tested for their association with the primary composite endpoint of ICU admission or 28-day mortality. RESULTS: A total of 213 eligible patients with COVID-19 were included of whom 55 (25.8%) reached the primary endpoint. Median levels of copeptin and hs-cTnI at admission were significantly higher in patients with an adverse outcome (Copeptin 29.6 pmol/L, [IQR, 16.2-77.8] vs 17.2 pmol/L [IQR, 7.4-41.0] and hs-cTnI 22.8 ng/L [IQR, 11.5-97.5] vs 10.2 ng/L [5.5-23.1], P < 0.001 respectively). ROC analysis demonstrated an optimal cut-off of 19.3 pmol/L for copeptin and 16.8 ng/L for hs-cTnI and an increase of either biomarker was significantly associated with the primary endpoint. The combination of raised hs-cTnI and copeptin yielded a superior prognostic value to individual measurement of biomarkers and was a strong prognostic marker upon multivariable logistic regression analysis (OR 4.274 [95% CI, 1.995-9.154], P < 0.001). Addition of copeptin and hs-cTnI to established risk models improved C-statistics and net reclassification indices. CONCLUSION: The combination of raised copeptin and hs-cTnI upon admission is an independent predictor of ICU admission or 28-day mortality in hospitalized patients with COVID-19.

Red Cell Distribution Width Upon Hospital Admission Predicts Short-Term Mortality in Hospitalized Patients With COVID-19: A Single-Center Experience.

Background: Coronavirus disease (COVID-19) was first described at the end of 2019 in China and has since spread across the globe. Red cell distribution width (RDW) is a potent prognostic marker in several medical conditions and has recently been suggested to be of prognostic value in COVID-19. Methods: This retrospective, observational study of consecutive patients with COVID-19 was conducted from March 12, 2020 to December 4, 2020 in the Wilhelminenhospital, Vienna, Austria. RDWlevels on admission were collected and tested for their predictive value of 28-day mortality. Results: A total of 423 eligible patients with COVID-19 were included in the final analyses and 15.4% died within 28 days (n = 65). Median levels of RDWwere significantly higher in non-survivors compared to survivors [14.6% (IQR, 13.7-16.3) vs. 13.4% (IQR, 12.7- 14.4), P < 0.001]. Increased RDW was a significant predictor of 28-day mortality [crude odds ratio (OR) 1.717, 95% confidence interval (CI) 1.462-2.017; P = < 0.001], independent of clinical confounders, comorbidities and established prognostic markers of COVID-19 (adjusted OR of the final model 1.368, 95% CI 1.126-1.662; P = 0.002). This association remained consistent upon sub-group analysis. Our study data also demonstrate that RDW levels upon admission for COVID-19 were similar to previously recorded, non-COVID-19 associated RDW levels [14.2% (IQR, 13.3-15.7) vs. 14.0% [IQR, 13.2-15.1]; P = 0.187]. Conclusions: In this population, RDWwas a significant, independent prognostic marker of short-term mortality in patients with COVID-19.

Predicting spontaneous conversion to sinus rhythm in symptomatic atrial fibrillation: The ReSinus score.

BACKGROUND: The optimal management of patients presenting to the Emergency Department with hemodynamically stable symptomatic atrial fibrillation remains unclear. We aimed to develop and validate an easy-to-use score to predict the individual probability of spontaneous conversion to sinus rhythm in these patients METHODS: This retrospective cohort study analyzed 2426 cases of first-detected or recurrent hemodynamically stable non-permanent symptomatic atrial fibrillation documented between January 2011 and January 2019 in an Austrian academic Emergency Department atrial fibrillation registry. Multivariable analysis was used to develop and validate a prediction score for spontaneous conversion to sinus rhythm during Emergency Department visit. Clinical usefulness of the score was assessed using decision curve analysis RESULTS: 1420 cases were included in the derivation cohort (68years, 57-76; 43% female), 1006 cases were included in the validation cohort (69years, 58-76; 47% female). Six variables independently predicted spontaneous conversion. These included: duration of atrial fibrillation symptoms (<24hours), lack of prior cardioversion history, heart rate at admission (>125bpm), potassium replacement at K+ level ≤3.9mmol/l, NT-proBNP (<1300pg/ml) and lactate dehydrogenase level (<200U/l). A risk score weight was assigned to each variable allowing classification into low (0-2), medium (3-5) and moderate (6-8) probability of spontaneous conversion. The final score showed good calibration (p=0.44 and 0.40) and discrimination in both cohorts (c-indices: 0.74 and 0.67) and clinical net benefit CONCLUSION: The ReSinus score, which predicts spontaneous conversion to sinus rhythm, was developed and validated in a large cohort of patients with hemodynamically stable non-permanent symptomatic atrial fibrillation and showed good calibration, discrimination and usefulness REGISTRATION: NCT03272620.

Platelet hyperfunction is decreased by additional aspirin loading in patients presenting with myocardial infarction on daily aspirin therapy.

OBJECTIVE: Currently 162-325 mg aspirin is recommended for the treatment of acute coronary syndrome. We tested the effect of an additional loading dose of 250 mg aspirin at the onset of acute coronary syndrome in patients who were already on chronic therapy with 100 mg aspirin. DESIGN: This was a prospective trial in patients presenting with symptoms suggestive of acute coronary syndrome that included a randomized, double-blind, placebo-controlled trial subgroup. SETTING: An emergency department in a tertiary care center. PATIENTS: Consecutive patients with symptoms suggestive of acute coronary syndrome were enrolled, including a cohort already on chronic aspirin therapy. INTERVENTIONS: Patients received an intravenous infusion of 250 mg aspirin. MEASUREMENTS AND MAIN RESULTS: Platelet function was measured with a platelet function analyzer in 234 patients before and after aspirin infusion. Aspirin infusion prolonged collagen epinephrine closure times in almost all patients. Aspirin infusion further lowered thromboxane B(2) levels in patients with acute coronary syndrome who were on chronic aspirin therapy before admission. Concomitantly, collagen epinephrine closure times increased by 22% from 223 secs (95% confidence interval, 192-255 secs) before to 273 secs (95% confidence interval, 252-294 secs) after aspirin infusion (p < .01). Eleven patients with ST-elevation myocardial infarction on daily aspirin therapy (53%) displayed platelet hyperfunction (collagen epinephrine closure times <193 secs). Additional aspirin infusion further decreased platelet function in these patients with ST-elevation myocardial infarction (30% prolongation of collagen epinephrine closure times; p < .01), and only two patients with ST-elevation myocardial infarction still displayed platelet hyperfunction (p = .02). CONCLUSION: Aspirin loading in the emergency room further reduced thromboxane B(2) levels and further inhibited platelet function in many patients with acute coronary syndrome already on 100 mg aspirin.

Single dose granulocyte colony-stimulating factor markedly enhances shear-dependent platelet function in humans.

Granulocyte colony-stimulating factor (G-CSF) has been associated with the induction of a hypercoagulable state in patients as well as peripheral blood stem donors. Interestingly, sparse data exist on the kinetics of platelet and coagulation activation in response to G-CSF and it is unknown if G-CSF augments shear-dependent platelet function. These two issues are addressed in the current trial. Thirty-six healthy volunteers were enrolled into this study. All subjects received a single-dose of 5 microg/kg filgrastim intravenously. The effects of recombinant G-CSF on platelet and coagulation function were assessed by the platelet function analyzer PFA-100 (collagen/epinephrine (CEPI-CT), collagen/ADP (CADP-CT) closure times), von Willebrand factor activity (vWF : RiCO) ELISA, tissue factor (TF)-mRNA expression on circulating leukocytes and rotation thrombelastography (ROTEM). G-CSF time-dependently enhanced shear dependent platelet function measured by the PFA-100: CEPI-CT declined by 48% and CADP-CT by 31% with nadir values after 24 h (p < 0.001 as compared to baseline) and returned to near-baseline values after 72 hours. In accordance, VWF : RiCO increased by 59% after 24 h (p < 0.001) and returned to baseline 48 h later. TF-mRNA peaked after 4 hours (>6 fold increase p < 0.001) and reached near-baseline values after 24 hours. Nadir closure times were seen after 24 hours (-15%; p < 0.001). Single-dose administration of 5 microg/kg G-CSF significantly enhances shear-dependent platelet function and strongly induces leukocyte TF-mRNA, which translates into shortened clotting times ex vivo.

Hyperkalemia: A persisting risk. A case report and update on current management.

We report a case of hemodynamic instability due to bradycardia on the basis of severe hyperkalemia. Diabetic ketoacidosis and acute kidney injury together with polypharmacy triggered the acute onset. Potentially life-threatening hyperkalemia is often induced by drug interactions. ECG features may be crucial for diagnosis, and treatment depends on setting and resources.

The Impact of the COVID-19 Pandemic on Incidences of Atrial Fibrillation and Electrical Cardioversion at a Tertiary Care Emergency Department: An Inter- and Intra-year Analysis.

Background: National authorities have introduced measures as lockdowns against spreading of COVID-19 and documented incidences of multiple non-COVID-19 diseases have dropped. Yet, data on workload dynamics concerning atrial fibrillation and electrical cardioversion whilst a national lockdown are scarce and may assist in future planning. Methods: Documented cases of atrial fibrillation and respective electrical cardioversion episodes at the Emergency Department of the Medical University of Vienna, Austria, from 01/01/2020 to 31/05/2020 were assessed. As reference groups, those incidences were calculated for the years 2017, 2018, and 2019. Inter- and intra-year analyses were conducted through Chi-square test and Poisson regression. Results: A total of 2,310 atrial fibrillation-, and 511 electrical cardioversion episodes were included. We found no significant incidence differences in inter-year analyses of the time periods from January to May, or of the weeks pre- and post the national lockdown due to the COVID-19 pandemic. However, the intra-year analysis of the year 2020 showed a trend toward decreased atrial fibrillation incidences (rate-ratio 0.982, CI 0.964-1.001, p = 0.060), and significantly increased electrical cardioversion incidences in the post-lockdown period (rate ratio 1.051, CI 1.008-10.96, p = 0.020). Conclusion: The decreased atrial fibrillation incidences are in line with international data. However, an increased demand of electrical cardioversions during the lockdown period was observed. A higher threshold to seek medical attention may produce a selected group with potentially more severe clinical courses. In addition, lifestyle modifications during isolation and a higher stress level may promote atrial fibrillation episodes to be refractory to other therapeutic approaches than electrical cardioversion.