Emergency Department Utilization Following Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Center Retrospective Longitudinal Analysis of 557 Patients.

Allogeneic hematopoietic stem cell transplantation (HSCT) recipients are at risk of various complications during post-transplantation follow-up. Some patients may refer to an emergency department (ED) for medical attention, but data on ED visits by HSCT recipients are lacking. In the present study, we aimed to assess ED utilization in HSCT recipients and associated risk factors during post-transplantation follow-up, identify subgroups of HSCT recipients presenting to the ED, analyze outcomes and prognostic factors for hospitalization and 30-day mortality after ED visits, and assess mortality hazard following an ED presentation. The study involved a retrospective single-center longitudinal analysis including 557 consecutive recipients of allogeneic HSCT at the Medical University of Vienna, Austria, between January 2010 and January 2020. Descriptive statistics, event estimates accounting for censored data with competing risks, latent class analysis, and multivariate regression models were used for data analysis. Out of 557 patients (median age at HSCT, 49 years [interquartile range (IQR), 39 to 58 years]; 233 females and 324 males), 137 (25%) presented to our center's ED at least once during post-HSCT follow-up (median individual follow-up, 2.66 years; IQR, .72 to 5.59 years). Cumulative incidence estimates of a first ED visit in the overall cohort were 19% at 2 years post-HSCT, 25% at 5 years post-HSCT, and 28% at 10 years post-HSCT. These estimates were increased to 34%, 41%, and 43%, respectively, in patients residing in Vienna. Chronic graft-versus-host disease (GVHD) was the sole risk factor showing a statistically significant association with ED presentation in multivariate analysis (hazard ratio [HR], 2.34; 95% confidence interval [CI], 1.63 to 3.35). Patients presented to the ED with various and often multiple symptoms. We identified 3 latent patient groups in the ED, characterized mainly by the time from HSCT, chronic GVHD, and documented pulmonary infection. Hospitalization was required in 132 of all 216 analyzed ED visits (61%); in-hospital mortality and 30-day mortality rates were 13% and 7%, respectively. Active acute GVHD, systemic steroids, documented infection, pulmonary infiltrates, and oxygen supplementation were statistically significant predictors of hospitalization; shorter time from HSCT, pulmonary infiltrates, and hemodynamic instability were independent risk factors for 30-day mortality. ED presentation during the last 30 days increased the mortality hazard in the overall cohort (HR, 4.56; 95% CI, 2.68 to 7.76) after adjustment for relevant confounders. One-quarter of the patients visited the ED for medical attention at least once during post-HSCT follow-up. Depending on the presence of identified risk factors, a significant proportion of patients may require hospitalization and be at risk for adverse outcomes. Screening for these risk factors and specialist consultation should be part of managing most HSCT recipients presenting to the ED.

Micellar Curcumin: Pharmacokinetics and Effects on Inflammation Markers and PCSK-9 Concentrations in Healthy Subjects in a Double-Blind, Randomized, Active-Controlled, Crossover Trial.

SCOPE: Preclinical models have demonstrated the anti-inflammatory and lipid-lowering effects of curcumin. Innovative formulations have been developed to overcome the poor bioavailability of native curcumin. The study hypothesizes that the bioavailability of micellar curcumin is superior to native curcumin and investigates the potential anti-inflammatory and proprotein convertase subtilisin/kexin type 9 (PCSK9) concentration lowering effects. METHODS AND RESULTS: In this double-blind, randomized, crossover trial, 15 healthy volunteers receive micellar or native curcumin (105 mg day-1 ) for 7 days with a ≥7 days washout period. Curcumin and metabolite concentrations are quantified by high-performance liquid chromatography with fluorescence detection (HPLC-FD), and pharmacokinetics are calculated. To analyze anti-inflammatory effects, blood samples (baseline, 2 h, 7 days) are stimulated with 50 ng mL-1 lipopolysaccharides (LPS). Interleukin (IL)-6, tumor-necrosis factor (TNF-α), and PCSK9 concentrations are quantified. Micellar curcumin demonstrates improved bioavailability (≈39-fold higher maximum concentrations, ≈14-fold higher area-under-the-time-concentration curve, p < 0.001) but does not reduce pro-inflammatory cytokines in the chosen model. Subjects receiving micellar curcumin have significantly lower PCSK9 concentrations (≈10% reduction) after 7 days compared to baseline (p = 0.038). CONCLUSION: Micellar curcumin demonstrates an improved oral bioavailability but does not show anti-inflammatory effects in this model. Potential effects on PCSK9 concentrations warrant further investigation.

The difference between arterial pCO2 and etCO2 after cardiac arrest - Outcome predictor or marker of unfavorable resuscitation circumstances?

INTRODUCTION: In former studies, the arterio-alveolar carbon dioxide gradient (ΔCO2) predicted in-hospital mortality after initially survived cardiac arrest. As early outcome predictors are urgently needed, we evaluated ΔCO2 as predictor for good neurological outcome in our cohort. METHODS: We retrospectively analyzed all patients ≥18 years of age after non-traumatic in- and out of hospital cardiac arrest in the year 2018 from our resuscitation database. Patients without advanced airway management, incomplete datasets or without return of spontaneous circulation were excluded. The first arterial pCO2 after admission and the etCO2 in mmHg at the time of blood sampling were recorded from patient's charts. We then calculated ΔCO2 (pCO2 - etCO2). For baseline analyses, ΔCO2 was dichotomized into a low and high group with separation at the median. Good neurological outcome on day 30, expressed as Cerebral Performance Category 1-2, defined our primary endpoint. Survival to 30 days was used as secondary endpoint. RESULTS: Out of 302 screened patients, 128 remained eligible for analyses. ΔCO2 was lower in 30-day survivors with good neurological outcome (12.2 mmHg vs. 18.8 mmHg, p = 0.009) and in 30-day survivors (12.5 mmHg vs. 20.0 mmHg, p = 0.001). In patients with high ΔCO2, a cardiac etiology of arrest was found less often. They had a higher body mass index, longer duration of resuscitation, higher amounts of epinephrine, lower pO2 levels but both higher pCO2 and blood lactate levels, resulting in lower blood pH and HCO3- levels at admission. In a crude binary logistic regression analysis, ΔCO2 was associated with 30-day neurological outcome (OR = 1.041 per mmHg of ΔCO2, 95% CI 1.008-1.074, p = 0.014). This association persisted after the adjustment for age, sex, witnessed arrest and shockable first rhythm. However, after addition of the duration of resuscitation or the cumulative epinephrine dosage to the model, ΔCO2 lost its association. CONCLUSION: ΔCO2 at admission after a successfully resuscitated cardiac arrest is associated with 30 days survival with good neurological outcome. However, a higher ΔCO2 may rather be a surrogate for unfavorable resuscitation circumstances than an independent outcome predictor.

Multi-phasic life-threatening anaphylaxis refractory to epinephrine managed by extracorporeal membrane oxygenation (ECMO): A case report.

We present a case of a 52-year-old patient suffering from multi-phasic life-threatening anaphylaxis refractory to epinephrine treatment. Extracorporeal membrane oxygenation (ECMO) therapy was initiated as the ultima ratio to stabilize the patient hemodynamically during episodic severe bronchospasm. ECMO treatment was successfully weaned after 4 days. Mastocytosis was diagnosed as the underlying condition. Although epinephrine is recommended as a first-line treatment for anaphylaxis, this impressive case provides clear evidence of its limited therapeutic success and emphasizes the need for causal therapies.

Disseminated Intravascular Coagulation Score Predicts Mortality in Patients with Liver Disease and Low Fibrinogen Level.

BACKGROUND: Alongside its original diagnostic intention, the International Society on Thrombosis and Haemostasis' (ISTH) disseminated intravascular coagulation (DIC) score predicts mortality in various patient groups. OBJECTIVES: We investigated whether coagulopathy quantified by the DIC score can predict 30-day mortality in patients with liver disease and low fibrinogen levels. METHODS: We retrospectively analyzed all patients admitted to the Vienna General Hospital between 2003 and 2014 with a fibrinogen level of <150 mg/dL, a history of liver disease, and ≥2 pathological DIC parameters. We used a Cox regression and receiver operating characteristic analysis to assess the predictive value of the ISTH DIC score in its original (DIC-2001) and revised form (DIC-2018). RESULTS: A total of 1,333 patients were screened, and 388 of these patients (38% female, median age: 58 years, interquartile range: 48-66 years) were analyzed. The DIC-2001 (hazard ratio [HR]: 2.08, 95% confidence interval [CI]: 1.78-2.59, p < 0.001) and DIC-2018 (HR: 1.73, 95% CI: 1.51-2.05, p < 0.001) predicted 30-day mortality. The results remained robust in several sensitivity analyses. CONCLUSION: The ISTH DIC-2001 and DIC-2018 scores predicted 30-day mortality in patients with liver disease and low fibrinogen levels. The DIC score deserves further investigation in this population as it likely reflects different dimensions of the underlying disease.

Advanced pharmacodynamics of cangrelor in healthy volunteers: a dose-finding, open-label, pilot trial.

BACKGROUND: High on-treatment platelet reactivity (HTPR) remains a major problem in the acute management of ST-elevation myocardial infarction (STEMI), leading to higher rates of stent thrombosis and mortality. We aimed to investigate a novel, prehospital treatment strategy using cangrelor and tested its pharmacodynamic effects in a model using healthy volunteers. METHODS: We conducted a dose-finding, open-label, pilot trial including 12 healthy volunteers and tested three ascending bolus infusions of cangrelor (5 mg, 10 mg and 20 mg) and a bolus infusion followed by a continuous infusion via an intravenous (IV) flow regulator. Platelet function was assessed using multiple electrode aggregometry (MEA), vasodilator-stimulated phosphoprotein phosphorylation assay (VASP-P) and the platelet function analyzer. In an ex vivo experiment, epinephrine was used to counteract the antiplatelet effect of cangrelor. RESULTS: All cangrelor bolus infusions resulted in immediate and pronounced platelet inhibition. Bolus infusions of cangrelor 20 mg resulted in sufficient platelet inhibition assessed by MEA for 20 min in 90% of subjects. Infusion of cangrelor via the IV flow regulator resulted in sufficient platelet inhibition throughout the course of administration. Ex vivo epinephrine, in concentrations of 200 and 500 ng/mL was able to partially reverse the antiplatelet effect of cangrelor in a dose-dependent manner. CONCLUSIONS: Weight-adapted bolus infusions followed by a continuous infusion of cangrelor via IV flow regulator result in immediate and pronounced platelet inhibition in healthy subjects. Cangrelor given as weight-adapted bolus infusion followed by a continuous infusion using an IV flow regulator may be a viable treatment approach for effective and well controllable prehospital platelet inhibition. TRIAL REGISTRATION: EC (Medical University of Vienna) 1835/2019 and EudraCT 2019-002792-34 .

The association of early diarrhea after successful resuscitation following out-of-hospital cardiac arrest with neurological outcome: A retrospective observational study.

ABSTRACT: Gastrointestinal ischemia with reperfusion tissue injury contributes to post-cardiac arrest syndrome. We hypothesized that diarrhea is a symptom of intestinal ischemia/reperfusion injury and investigated whether the occurrence of early diarrhea (≤12 hours) after successful cardiopulmonary resuscitation is associated with an unfavorable neurological outcome.We analyzed data from the Vienna Clinical Cardiac Arrest Registry. Inclusion criteria comprised ≥18 years of age, a witnessed, non-traumatic out-of-hospital cardiac arrest, return of spontaneous circulation (ROSC), initial shockable rhythm, and ST-segment elevation in electrocardiogram after ROSC with consecutive coronary angiography. Patients with diarrhea caused by other factors (e.g., infections, antibiotic treatment, or chronic diseases) were excluded. The primary endpoint was neurological function between patients with or without "early diarrhea" (≤12 hours after ROSC) according to cerebral performance categories.We included 156 patients between 2005 and 2012. The rate of unfavorable neurologic outcome was higher in patients with early diarrhea (67% vs 37%). In univariate analysis, the crude odds ratio for unfavorable neurologic outcome was 3.42 (95% confidence interval, 1.11-10.56, P = .03) for early diarrhea. After multivariate adjustment for traditional prognostication markers the odds ratio of early diarrhea was 5.90 (95% confidence interval, 1.28-27.06, P = .02).In conclusion, early diarrhea within 12 hours after successful cardiopulmonary resuscitation was associated with an unfavorable neurological outcome.

Initial Blood pH, Lactate and Base Deficit Add No Value to Peri-Arrest Factors in Prognostication of Neurological Outcome After Out-of-Hospital Cardiac Arrest.

Background: In cardiac arrest survivors, metabolic parameters [pH value, lactate concentration, and base deficit (BD)] are routinely added to peri-arrest factors (including age, sex, bystander cardiopulmonary resuscitation, shockable first rhythm, resuscitation duration, adrenaline dose) to enhance early outcome prediction. However, the additional value of this strategy remains unclear. Methods: We used our resuscitation database to screen all patients ≥18 years who had suffered in- or out-of-hospital cardiac arrest (IHCA, OHCA) between January 1st, 2005 and May 1st, 2019. Patients with incomplete data, without return of spontaneous circulation or treatment with sodium bicarbonate were excluded. To analyse the added value of metabolic parameters to prognosticate neurological function, we built three models using logistic regression. These models included: (1) Peri-arrest factors only, (2) peri-arrest factors plus metabolic parameters and (3) metabolic parameters only. Receiver operating characteristics curves regarding 30-day good neurological function (Cerebral Performance Category 1-2) were analysed. Results: A total of 2,317 patients (OHCA: n = 1842) were included. In patients with OHCA, model 1 and 2 had comparable predictive value. Model 3 was inferior compared to model 1. In IHCA patients, model 2 performed best, whereas both metabolic (model 3) and peri-arrest factors (model 1) demonstrated similar power. PH, lactate and BD had interchangeable areas under the curve in both IHCA and OHCA. Conclusion: Although metabolic parameters may play a role in IHCA, no additional value in the prediction of good neurological outcome could be found in patients with OHCA. This highlights the importance of accurate anamnesis especially in patients with OHCA.

Change of Hemoglobin Levels in the Early Post-cardiac Arrest Phase Is Associated With Outcome.

Background: The post-cardiac arrest (CA) phase is characterized by high fluid requirements, endothelial activation and increased vascular permeability. Erythrocytes are large cells and may not leave circulation despite massive capillary leak. We hypothesized that dynamic changes in hemoglobin concentrations may reflect the degree of vascular permeability and may be associated with neurologic function after CA. Methods: We included patients ≥18 years, who suffered a non-traumatic CA between 2013 and 2018 from the prospective Vienna Clinical Cardiac Arrest Registry. Patients without return of spontaneous circulation (ROSC), with extracorporeal life support, with any form of bleeding, undergoing surgery, receiving transfusions, without targeted temperature management or with incomplete datasets for multivariable analysis were excluded. The primary outcome was neurologic function at day 30 assessed by the Cerebral Performance Category scale. Differences of hemoglobin concentrations at admission and 12 h after ROSC were calculated and associations with neurologic function were investigated by uni- and multivariable logistic regression. Results: Two hundred and seventy-five patients were eligible for analysis of which 143 (52%) had poor neurologic function. For every g/dl increase in hemoglobin from admission to 12 h the odds of poor neurologic function increased by 26% (crude OR 1.26, 1.07-1.49, p = 0.006). The effect remained unchanged after adjustment for fluid balance and traditional prognostication markers (adjusted OR 1.27, 1.05-1.54, p = 0.014). Conclusion: Increasing hemoglobin levels in spite of a positive fluid balance may serve as a surrogate parameter of vascular permeability and are associated with poor neurologic function in the early post-cardiac arrest period.

Admission C-reactive protein concentrations are associated with unfavourable neurological outcome after out-of-hospital cardiac arrest.

Whether admission C-reactive protein (aCRP) concentrations are associated with neurological outcome after out-of-hospital cardiac arrest (OHCA) is controversial. Based on established kinetics of CRP, we hypothesized that aCRP may reflect the pre-arrest state of health and investigated associations with neurological outcome. Prospectively collected data from the Vienna Clinical Cardiac Arrest Registry of the Department of Emergency Medicine were analysed. Adults (≥ 18 years) who suffered a non-traumatic OHCA between January 2013 and December 2018, without return of spontaneous circulation or extracorporeal cardiopulmonary resuscitation therapy were eligible. The primary endpoint was a composite of unfavourable neurologic function or death (defined as Cerebral Performance Category 3-5) at 30 days. Associations of CRP levels drawn within 30 min of hospital admission were assessed using binary logistic regression. ACRP concentrations were overall low in our population (n = 832), but higher in the unfavourable outcome group [median: 0.44 (quartiles 0.15-1.44) mg/dL vs. 0.26 (0.11-0.62) mg/dL, p < 0.001]. The crude odds ratio for higher aCRP concentrations was 1.19 (95% CI 1.10-1.28, p < 0.001, per mg/dL) to have unfavourable neurological outcome. After multivariate adjustment for traditional prognostication markers the odds ratio of higher aCRP concentrations was 1.13 (95% CI 1.04-1.22, p = 0.002). Sensitivity of aCRP was low, but specificity for unfavourable neurological outcome was 90% for the cut-off at 1.5 mg/dL and 97.5% for 5 mg/dL CRP. In conclusion, high aCRP levels are associated with unfavourable neurological outcome at day 30 after OHCA.

Prolonged Activated Partial Thromboplastin Time after Successful Resuscitation from Cardiac Arrest is Associated with Unfavorable Neurologic Outcome.

Coagulation abnormalities after successful resuscitation from cardiac arrest may be associated with unfavorable neurologic outcome. We investigated a potential association of activated partial thromboplastin time (aPTT) with neurologic outcome in adult cardiac arrest survivors. Therefore, we included all adults ≥18 years of age who suffered a nontraumatic cardiac arrest and had achieved return of spontaneous circulation between January 2013 and December 2018. Patients receiving anticoagulants or thrombolytic therapy and those subjected to extracorporeal membrane oxygenation support were excluded. Routine blood sampling was performed on admission as soon as a vascular access was available. The primary outcome was 30-day neurologic function, assessed by the Cerebral Performance Category scale (3-5 = unfavorable neurologic function). Multivariable regression was used to assess associations between normal (≤41 seconds) and prolonged (>41 seconds) aPTT on admission (exposure) and the primary outcome. Results are given as odds ratio (OR) with 95% confidence intervals (95% CIs). Out of 1,591 cardiac arrest patients treated between 2013 and 2018, 360 patients (32% female; median age: 60 years [interquartile range: 48-70]) were eligible for analysis. A total of 263 patients (73%) had unfavorable neurologic function at day 30. aPTT prolongation >41 seconds was associated with a 190% increase in crude OR of unfavorable neurologic function (crude OR: 2.89; 95% CI: 1.78-4.68, p < 0.001) and with more than double the odds after adjustment for traditional risk factors (adjusted OR: 2.01; 95% CI: 1.13-3.60, p = 0.018). In conclusion, aPTT prolongation on admission is associated with unfavorable neurologic outcome after successful resuscitation from cardiac arrest.

Can we predict the severe course of COVID-19 - a systematic review and meta-analysis of indicators of clinical outcome?

Background: COVID-19 has been reported in over 40million people globally with variable clinical outcomes. In this systematic review and meta-analysis, we assessed demographic, laboratory and clinical indicators as predictors for severe courses of COVID-19. Methods: We systematically searched multiple databases (PubMed, Web of Science Core Collection, MedRvix and bioRvix) for publications from December 2019 to May 31st 2020. Random-effects meta-analyses were used to calculate pooled odds ratios and differences of medians between (1) patients admitted to ICU versus non-ICU patients and (2) patients who died versus those who survived. We adapted an existing Cochrane risk-of-bias assessment tool for outcome studies. Results: Of 6,702 unique citations, we included 88 articles with 69,762 patients. There was concern for bias across all articles included. Age was strongly associated with mortality with a difference of medians (DoM) of 13.15 years (95% confidence interval (CI) 11.37 to 14.94) between those who died and those who survived. We found a clinically relevant difference between non-survivors and survivors for C-reactive protein (CRP; DoM 69.10, CI 50.43 to 87.77), lactate dehydrogenase (LDH; DoM 189.49, CI 155.00 to 223.98), cardiac troponin I (cTnI; DoM 21.88, CI 9.78 to 33.99) and D-Dimer (DoM 1.29mg/L, CI 0.9 - 1.69). Furthermore, cerebrovascular disease was the co-morbidity most strongly associated with mortality (Odds Ratio 3.45, CI 2.42 to 4.91) and ICU admission (Odds Ratio 5.88, CI 2.35 to 14.73). Discussion: This comprehensive meta-analysis found age, cerebrovascular disease, CRP, LDH and cTnI to be the most important risk-factors in predicting severe COVID-19 outcomes and will inform decision analytical tools to support clinical decision-making.