[Cancer patients in the emergency department]. / Krebspatienten in der Notaufnahme.

A growing number of patients are living with cancer or have a history of cancer leading to increasing adverse effects of treatment or disease necessitating emergency department (ED) consultation. Long-term cancer survivors are at higher risk of comorbidities causing a substantial increase in health care resource utilization. The most frequent reasons for cancer-related ED visits are dyspnea, fever, pain, gastrointestinal or neurological symptoms leading to high hospital and intensive care unit admission rates. Acute respiratory failure in cancer patients necessitates timely diagnostic testing, whereby computed tomography is superior to chest X­ray. Delay in intensive care unit (ICU) admission or mechanical ventilation increases mortality. Febrile neutropenia is an emergency with urgent need for antibiotic treatment. Treatment of neutropenic and nonneutropenic patients with sepsis does not differ. Cardiovascular disease is now the second leading cause of long-term morbidity and mortality among cancer survivors. Immunotherapy can lead to substantial and in some patients life-threatening complications that may not easily be recognized in the ED. Cancer-specific emergencies such as leukostasis, tumorlysis or hypercalcemia rarely present to ED and require interdisciplinary care. The constantly growing cancer population is likely to increase ED utilization. Knowledge about cancer treatment and disease-associated complications is crucial for emergency physicians. Palliative care education should secure appropriate end-of-life care avoiding futile interventions.

Opportunities for Participation in Randomized Controlled Trials for Patients with Multiple Myeloma: Trial Access Depends on Restrictive Eligibility Criteria and Patient Expectations.

Randomized controlled trials (RCT) are the driver of therapeutic innovations. However, it has been frequently shown that less than 5% of adult cancer patients enroll in clinical trials, although 70% of patients are considered as being willing to participate. Barriers to trial participation have been extensively studied. Although there is evidence that trial participation correlates with improved survival and reduced mortality, the rate of participation has not changed substantially. We provide retrospective data from a single-center analysis of 411 patients with multiple myeloma (MM) who were treated at the University Hospital Duesseldorf in Germany between January 2014 and December 2016. Each patient was analyzed for the real-world possibility of participating in a clinical study, based on the inclusion and exclusion (I/E) criteria and the recruiting period of open studies. The overall rate of study participation was 19%. A total of 53% of NDMM patients were eligible for first-line studies (GMMG-HD6, LenaMain). Of these, 80% consented to enrolment (42% of all). In contrast, only 38% of the RRMM population was eligible (GMMG-Relapse, Castor, Tourmaline, Admyre). Of these, only 22% (7% of all) consented. This was confirmed by virtual analysis, showing that only 29% of all RRMM patients would have been eligible for six internationally recruiting trials leading to later drug approval. The majority of cases were rendered ineligible by only one I/E criterion. The most common criteria were study-specific (prior therapies or refractory disease to a specific drug), kidney disease, and previous malignancy, followed by internal, neurologic, and infectious disease. In summary, this single-center analysis showed that I/E criteria permit study participation for most NNDM patients, with a dramatic decrease in the RRMM population. This is aggravated by the fact that the willingness for study participation also significantly declines in RRMM. Thus, addressing patient expectations and priorities seems to be the most promising approach to increasing patient enrollment in clinical trials.

18F-FDG-PET/CT in relapsed multiple myeloma: Are prognostic thresholds different from first-line therapy?

PURPOSE: While 18F-FDG PET/CT yields valuable prognostic information for patients in first-line therapy of multiple myeloma (MM), its prognostic relevance in relapse is not established. Available studies of relapsed MM describe prognostic thresholds for frequently used PET/CT parameters that are significantly higher than those identified in the first-line setting. The purpose of this study was to evaluate the prognostic role of PET/CT in relapsed MM, based on parameters used in the first-line setting. METHODS: Our retrospective study included 36 patients with MM who had received autologous or allogeneic stem cell transplantation, suffered at least one relapse, and underwent FDG-PET/CT at relapse. Number of focal bone lesions (FL), maximal standardised uptake value (SUVmax), and presence of PET-positive extramedullary lesions (EMD) were analysed. RESULTS: For the number of FLs, the prognostic value was demonstrated with a cut-off of > 3 (median OS 3.8 months vs. not reached, p = 0.003). Median OS of patients with SUVmax ≤ 4 was not reached, while it was 3.9 months in patients with SUVmax > 4 (p = 0.014). Presence of EMD was a significant prognostic parameter too, with median OS of 3.6 months versus not reached (p = 0.004). The above-mentioned parameters showed prognostic significance for PFS as well. Combination of higher ISS stage and PET/CT parameters identified patients with particularly short OS (3.7 months vs. not reached, p < 0.001) and PFS (3.6 vs. 11.7 months p < 0.001). CONCLUSION: The PET/CT parameters SUVmax > 4, nFL > 3, and presence of EMD identify patients with poor prognosis not only in the first-line setting but also in relapsed MM.

Case Report: Convalescent Plasma Achieves SARS-CoV-2 Viral Clearance in a Patient With Persistently High Viral Replication Over 8 Weeks Due to Severe Combined Immunodeficiency (SCID) and Graft Failure.

We describe the unique disease course and cure of SARS-CoV-2 infection in a patient with SCID and graft failure. In absence of a humoral immune response, viral clearance was only achieved after transfusion of convalescent plasma. This observation underscores the necessity of the humoral immune response for SARS-CoV-2 clearance.

Plasma sphingosine-1-phosphate concentrations are associated with systolic heart failure in patients with ischemic heart disease.

OBJECTIVE: Sphingosine-1-Phosphate (S1P) is a bioactive sphingolipid with important functions in immunity, inflammation and cardiovascular biology. S1P is associated with prevalence and severity of coronary artery disease and myocardial infarction. However, its relevance in ischemic cardiomyopathy is unknown. We aimed to investigate associations of plasma S1P and other sphingolipids with the extent of heart failure in patients with ischemic heart disease. METHODS AND RESULTS: 74 patients with ischemic heart disease were investigated in this observational study. Plasma concentrations of S1P, C16 ceramide and sphingomyelin (SM) were measured using liquid chromatography/tandem mass-spectrometry and associated with objective (echocardiography) and subjective (dyspnea) signs of heart failure. Plasma S1P and SM but not C16 ceramide concentrations were negatively associated with left ventricular ejection fraction (LVEF) and dyspnea (ranked by New York Heart Association; LVEF: S1P standardized coefficient beta: -0.25; 95%CI: -273 to -13nM, p=0.03; SM beta: -0.24; 95%CI: -16,310 to -413nM, p=0.04; NYHA: S1P beta: -0.3; 95%CI: -174 to -26nM, p=0.009; SM beta: -0.46; 95%CI: -13,462 to -5013nM, p<0.001). ROC analysis revealed that S1P and SM predicted impaired LVEF with optimal cut-off levels below 843nM and 77µM, respectively. CONCLUSION: S1P is associated with the impairment of LVEF and dyspnea. Considering the major effects of S1P on cardiac and vascular functions in experimental models, we put forward the hypothesis that S1P is causally involved in the pathophysiology of heart failure. Interfering pharmacologically with S1P receptors may have an impact on ischemic cardiomyopathy.

Thromboxane Formation Assay to Identify High On-Treatment Platelet Reactivity to Aspirin.

Platelet inhibition by aspirin is indispensable in the secondary prevention of cardiovascular events. Nevertheless, impaired aspirin antiplatelet effects (high on-treatment platelet reactivity [HTPR]) are frequent. This is associated with an enhanced risk of cardiovascular events. The current gold standard to evaluate platelet hyper-reactivity despite aspirin intake is the light-transmittance aggregometry (LTA). However, pharmacologically, the most specific test is the measurement of arachidonic acid (AA)-induced thromboxane (TX) B2 formation. Currently, the optimal cut-off to define HTPR to aspirin by inhibition of TX formation is not known. Therefore, in this pilot study, we aimed to calculate a TX formation cut-off value to detect HTPR defined by the current gold standard LTA. We measured platelet function in 2,507 samples. AA-induced TX formation by ELISA and AA-induced LTA were used to measure aspirin antiplatelet effects. TX formation correlated nonlinearly with the maximum of aggregation in the AA-induced LTA (Spearman's rho R = 0.7396; 95% CI 0.7208-0.7573, p < 0.0001). Receiver operating characteristic analysis and Youden's J statistics revealed 209.8 ng/mL as the optimal cut-off value to detect HTPR to aspirin with the TX ELISA (area under the curve: 0.92, p < 0.0001, sensitivity of 82.7%, specificity of 90.3%). In summary, TX formation ELISA is reliable in detecting HTPR to aspirin. The calculated cut-off level needs to be tested in trials with clinical end points.

Analgesic medication with dipyrone in patients with coronary artery disease: Relation to MACCE.

BACKGROUND: The non-opioid analgesic dipyrone can trigger life-threatening blood formation disorders. However, it is frequently used, as many patients with coronary artery disease (CAD) rely on non-opioid analgesics to relieve pain. In this study, we investigated the incidence of death, myocardial infarction (MI) or stroke in CAD patients with aspirin and dipyrone comedication as compared to aspirin-alone. METHODS: We conducted an observational pilot study in 72 CAD patients with aspirin ± dipyrone comedication in the department of cardiology of the University Hospital Düsseldorf. The primary end point was a composite of death, myocardial infarction (MI) or stroke. The secondary end points were the components of the primary end point. The median follow-up period was 3.2years. RESULTS: The primary end point occurred 67% of patients in the aspirin+dipyrone group as compared to 31% in the aspirin-alone group (odds ratio [OR] 4.5, 95% confidence interval [CI] 1.7 to 12.3; P=0.0028;). All-cause mortality was significantly higher in the aspirin+dipyrone group (44%) than the aspirin-alone group (22%; OR 2.8, 95% CI 1.01 to 7.8; P=0.049). Ischemic events (MI and stroke) were more frequent in the aspirin+dipyrone group as compared to the aspirin alone group as well (OR 4, 95% CI 1.1 to 14; P=0.03). CONCLUSION: In this hypothesis generating pilot analysis, dipyrone medication in aspirin treated coronary artery disease patients is associated with an increased cumulative incidence of death, MI or stroke as well as all-cause mortality and ischemic events. These data have to be confirmed in larger registries and trials. CLINICAL TRIAL REGISTRATION: http://clinicaltrials.gov/ct2/show/NCT01402804; Identifier: NCT01402804; Date of registration: July 25, 2011.

SeQuent Please vs. Pantera Lux drug coated balloon angioplasty in real life: Results from the Düsseldorf DCB registry.

BACKGROUND: In-stent restenosis (ISR) is still a major concern in interventional cardiology. Drug coated balloon (DCB) angioplasty has been shown to be a promising option in treatment of ISR. However heterogeneity of different DCBs in suppression of neointimal growth has been described in a porcine model of coronary ISR. Therefore, in this registry analysis, we compared two frequently used paclitaxel eluting DCBs, the SeQuent Please and the Pantera Lux DCB. METHODS: 571 patients were treated with DCB angioplasty at the Heinrich-Heine University Düsseldorf between 2009 and 2012. Follow-up was conducted during ambulatory care at our department. Major adverse cardiac events (death, myocardial infarction [MI] and target lesion revascularization) were registered during hospitalization and follow-up. RESULTS: Patient characteristics, prior diseases, clinical presentation, ejection fraction, procedural success and lost-for-follow-up did not differ between patients treated with the SeQuent Please and. The Pantera Lux DCB. MACE during hospital course were similar as well (Pantera Lux: 6 patients [1.6%] vs. SeQuent®Please: 3 patients [1.5%], relative risk 1.06, 95% confidence interval 0.3-4.2, P=0.93). Event free survival was significantly longer in patients treated with the Pantera Lux DCB as compared to SeQuent Please DCB (Hazard ratio: 0.65, 95% confidence interval 0.43-0.98; P value of log-rank test: 0.0405). CONCLUSION: MACE free survival was longer in Pantera Lux DCB treated patients as compared to SeQuent Please treated patients. This finding has to be confirmed in future clinical trials.