Biomarkers Improve Diagnostics of Sepsis in Adult Patients With Suspected Organ Dysfunction Based on the Quick Sepsis-Related Organ Failure Assessment (qSOFA) Score in the Emergency Department.

OBJECTIVES: Consensus regarding biomarkers for detection of infection-related organ dysfunction in the emergency department is lacking. We aimed to identify and validate biomarkers that could improve risk prediction for overt or incipient organ dysfunction when added to quick Sepsis-related Organ Failure Assessment (qSOFA) as a screening tool. DESIGN: In a large prospective multicenter cohort of adult patients presenting to the emergency department with a qSOFA score greater than or equal to 1, admission plasma levels of C-reactive protein, procalcitonin, adrenomedullin (either bioavailable adrenomedullin or midregional fragment of proadrenomedullin), proenkephalin, and dipeptidyl peptidase 3 were assessed. Least absolute shrinkage and selection operator regression was applied to assess the impact of these biomarkers alone or in combination to detect the primary endpoint of prediction of sepsis within 96 hours of admission. SETTING: Three tertiary emergency departments at German University Hospitals (Jena University Hospital and two sites of the Charité University Hospital, Berlin). PATIENTS: One thousand four hundred seventy-seven adult patients presenting with suspected organ dysfunction based on qSOFA score greater than or equal to 1. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The cohort was of moderate severity with 81% presenting with qSOFA = 1; 29.2% of these patients developed sepsis. Procalcitonin outperformed all other biomarkers regarding the primary endpoint (area under the curve for receiver operating characteristic [AUC-ROC], 0.86 [0.79-0.93]). Adding other biomarkers failed to further improve the AUC-ROC for the primary endpoint; however, they improved the model regarding several secondary endpoints, such as mortality, need for vasopressors, or dialysis. Addition of procalcitonin with a cutoff level of 0.25 ng/mL improved net (re)classification by 35.2% compared with qSOFA alone, with positive and negative predictive values of 60.7% and 88.7%, respectively. CONCLUSIONS: Biomarkers of infection and organ dysfunction, most notably procalcitonin, substantially improve early prediction of sepsis with added value to qSOFA alone as a simple screening tool on emergency department admission.

Examining the impact of a symptom assessment application on patient-physician interaction among self-referred walk-in patients in the emergency department (AKUSYM): study protocol for a multi-center, randomized controlled, parallel-group superiority trial.

BACKGROUND: Due to the increasing use of online health information, symptom checkers have been developed to provide an individualized assessment of health complaints and provide potential diagnoses and an urgency estimation. It is assumed that they support patient empowerment and have a positive impact on patient-physician interaction and satisfaction with care. Particularly in the emergency department (ED), symptom checkers could be integrated to bridge waiting times in the ED, and patients as well as physicians could take advantage of potential positive effects. Our study therefore aims to assess the impact of symptom assessment application (SAA) usage compared to no SAA usage on the patient-physician interaction in self-referred walk-in patients in the ED population. METHODS: In this multi-center, 1:1 randomized, controlled, parallel-group superiority trial, 440 self-referred adult walk-in patients with a non-urgent triage category will be recruited in three EDs in Berlin. Eligible participants in the intervention group will use a SAA directly after initial triage. The control group receives standard care without using a SAA. The primary endpoint is patients' satisfaction with the patient-physician interaction assessed by the Patient Satisfaction Questionnaire. DISCUSSION: The results of this trial could influence the implementation of SAA into acute care to improve the satisfaction with the patient-physician interaction. TRIAL REGISTRATION: German Clinical Trials Registry DRKS00028598 . Registered on 25.03.2022.

Critical appraisal of the 2020 ESC guideline recommendations on diagnosis and risk assessment in patients with suspected non-ST-segment elevation acute coronary syndrome.

Multiple new recommendations have been introduced in the 2020 ESC guidelines for the management of acute coronary syndromes with a focus on diagnosis, prognosis, and management of patients presenting without persistent ST-segment elevation. Most recommendations are supported by high-quality scientific evidence. The guidelines provide solutions to overcome obstacles presumed to complicate a convenient interpretation of troponin results such as age-, or sex-specific cutoffs, and to give practical advice to overcome delays of laboratory reporting. However, in some areas, scientific support is less well documented or even missing, and other areas are covered rather by expert opinion or subjective recommendations. We aim to provide a critical appraisal on several recommendations, mainly related to the diagnostic and prognostic assessment, highlighting the discrepancies between Guideline recommendations and the existing scientific evidence.

Assessment of celiac artery compression using color-coded duplex sonography.

BACKGROUND: Median arcuate ligament syndrome (MALS) is a rare condition due to compression of the celiac artery (CA) by an anatomically abnormal median arcuate ligament. With ultrasonography (US) as first-line diagnostic modality in patients with unclear abdominal pain, there is limited data on its diagnostic performance in MALS. OBJECTIVE: To investigate the value of CA peak systolic velocity (PSV) in the workup of patients with suspected MALS. METHODS: Patients with diagnosis of MALS between 2009 and 2019 were referred by Department of Visceral Surgery after clinical and gastroenterological workup. Diagnosis was confirmed by surgery or further cross-sectional imaging. B-mode US findings and PSV in the CA during various respiratory states were compared between patients with a final MALS diagnosis and patients not meeting the diagnostic criteria. RESULTS: Patients with proven MALS (n = 10) had higher median CA PSV during normal inspiratory breath-hold (239 [IQR, 159-327] vs. 138 [IQR, 116-152] cm/s; p < #x003C;< #x200A;0.001), and expiratory breath-hold (287 [IQR, 191-412] vs. 133 [IQR, 115-194] cm/s; p < #x003C;< #x200A;0.001) compared to patients without MALS (n = 26). CA PSV in both inspiratory breath-hold (AUC 0.88, 95% CI 0.77-1.00) and expiratory breath-hold (AUC 0.89, 95% CI 0.78-1.00) was of diagnostic value for confirming MALS. The best diagnostic performance (100% sensitivity, 80% specificity) was found for the combination of CA PSVexpiration + 2.4 · PSVinspiration > 550 cm/s . CONCLUSIONS: Since results on optimal cutoff values are inconsistent, a combination of CA PSVs during breathing maneuvers may help to diagnose or rule out MALS.

[Discussion paper for a hospital financing reform in Germany from the perspective of intensive care medicine]. / Diskussionspapier für eine Reform der Krankenhausfinanzierung in Deutschland aus der Perspektive der Intensivmedizin.

In Germany, there are currently many voices calling for a reform of hospital planning and reimbursement to correct some aberrations of the last decades and to enable the system to cope with future challenges. Some recent political decisions to change the structures of emergency medical services as well as the introduction of mandatory nurse-to-patient ratios and the exclusion of the cost for nursing from the case-based hospital reimbursement represent first steps of a reform, which also affects intensive care and emergency medicine. In this discussion paper a group of intensivists, emergency physicians, medical controllers, and representatives of nurses suggest more far-reaching changes, which can be summarized in 5 points: (1) General hospitals with intensive care units (ICU) and emergency departments (ED) which are part of the emergency medical system should be considered as an element of public service and be planned accordingly. (2) The planning of the intensive care infrastructure should be based on the three levels of emergency medical services to identify hospitals that are system relevant and to define appropriate criteria for structure and quality measures. (3) Hospital reimbursement should consist of a base amount (covering costs for hospital staff, infrastructure plus investments) and case-based fees (covering material costs). (4) To determine the requirements for nurses, physicians, and other medical staff, adequate tools for ICU and ED should be applied. (5) For these purposes as well as for quality management and optimal medical care, hospitals should be provided with a substantially improved IT-infrastructure.

Cost analysis of early discharge using combined copeptin/cardiac troponin testing versus serial cardiac troponin testing in patients with suspected acute coronary syndrome.

BACKGROUND: Symptoms indicating acute coronary syndrome are commonly seen in emergency rooms, but only 10% of patients are actually diagnosed with acute myocardial infarction (AMI). The Guidelines for the diagnosis of patients with suspected AMI include either multiple testing of cardiac troponin (cTN) or a single combined test of cTN and copeptin, which facilitates earlier diagnosis or exclusion of AMI. The aim of the present analysis was to investigate the impact of combined copeptin/cTN testing on health care resource consumption and related costs both during and after initial hospital treatment. METHODS AND RESULTS: The analysis was based on the BIC-8 trial and financial data of participating study sites. A cost analysis was carried out primarily from the hospital perspective and secondarily from the perspective of German statutory health insurers. The underlying assumptions of the investigation were tested for robustness in additional sensitivity analyses. In total, the data of 713 patients (n = 359 combined copeptin/cTN testing, n = 354 serial cTN testing) were evaluated. From a hospital perspective, the combined copeptin/cTN testing showed a reduced number of medical procedures and a lower frequency of inpatient admissions. The average staff time was significantly reduced by a mean of 49 minutes (95% confidence interval (CI) 46 to 53) per patient, accompanied by a significant mean reduction of 131 minutes (95%CI 104 to 158) in the time patients stayed in the emergency room. The initial hospital treatment was less cost-intensive. Over the entire study period, no significant cost differences were observed between the groups for health insurance. CONCLUSION: The combined copeptin/cTN testing has the potential to save costs and staff time in acute care and for the entire hospital stay. The primary explanations for these findings are early identification and ruling out patients without AMI along with the associated reduced need for acute medical treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT01498731.

Drug-eluting stents in clinical routine: a 1-year follow-up analysis based on German health insurance administrative data from 2008 to 2014.

OBJECTIVES: To describe the use of drug-eluting stents (DESs) in the largest population of statutory health insurance members in Germany, including newly developed bio-resorbable vascular scaffolds (BVSs), and to evaluate 1-year complication rates of DES as compared with bare metal stents (BMSs) in this cohort. DESIGN: Routine data analysis of statutory health insurance claims data from the years 2008 to 2014. SETTING: The German healthcare insurance Allgemeine Ortskrankenkasse covers approximately 30% of the German population and is the largest nationwide provider of statutory healthcare insurance in Germany. PARTICIPANTS AND INTERVENTIONS: We included all patients with a claims record for a percutaneous coronary intervention (PCI) with either DES or BMS and additionally, from 2013, BVS. Patients with acute myocardial infarction (AMI) were excluded. MAIN OUTCOME MEASURE: major adverse cerebrovascular and cardiovascular event (MACCE, defined as mortality, AMI, stroke and transient ischaemic attack), bypass surgery, PCI and coronary angiography) at 1 year after the intervention. RESULTS: A total of 243 581 PCI cases were included (DES excluding BVS: 143 765; BVS: 1440; BMS: 98 376). The 1-year MACCE rate was 7.42% in the DES subgroup excluding BVS and 11.29% in the BMS subgroup. The adjusted OR for MACCE was 0.72 (95% CI 0.70 to 0.75) in patients with DES excluding BVS as compared with patients with BMS. In the BVS group, the proportion of 1-year MACCE was 5.0%. CONCLUSION: The analyses demonstrate a lower MACCE rate for PCI with DES. BVSs are used in clinical routine in selected cases and seem to provide a high degree of safety, but data are still sparse.

Qualitative process analysis and modelling of emergency care workflow and interface management: identification of critical process steps.

OBJECTIVES: Over the past few years, the number of patients attending emergency services has increased steadily. As a result, emergency departments (EDs) worldwide face frequent crowding, with the risk of reduced treatment quality and impaired patient outcome, patient and staff dissatisfaction and inefficient use of ED resources. A qualitative process analysis and process modelling was used as a method to detect critical process steps in the ED with respect to time and efficiency. METHODS: The analysis was carried out by independent external process experts. Over a period of 1 week, the complete treatment process of 25 patients was recorded. The monitoring of overall activities, decision points, causalities and interfaces was based on the treatment of 100 additional patients and on interviews with nurses and physicians. The project was closed with the identification of the three most critical process steps and modelling of the standard emergency care process in an event-process chain (EPC). RESULTS: The most time-crucial steps detected by the analysis were the process of developing a tentative diagnosis, including consultation and advice seeking by inexperienced physicians, the interface to imaging diagnostics and the search of hospital beds for inpatients. The results were visualized by standardized modelling of an event-process chain (EPC). CONCLUSION: The process analysis helped to identify inefficient process steps in the ED. Modelling with EPC is a useful tool to visualize and to understand the complexity of the emergency medical care and to identify key performance indicators for effective quality management.

N-terminal pro brain natriuretic peptide in the management of patients in the medical emergency department (PROMPT): correlation with disease severity, utilization of hospital resources, and prognosis in a large, prospective, randomized multicentre trial.

AIMS: N-terminal pro brain natriuretic peptide (NT-proBNP) is a potent marker of heart failure and other cardiac diseases. The value of NT-proBNP testing in the medical emergency department (ED) was assessed in patients >65 years old. METHODS AND RESULTS: This large, prospective, randomized, controlled, multicentre trial was conducted in six medical EDs. Data for evaluation of the primary endpoint of hospitalization were available for 1086 patients. Median NT-proBNP was 582 pg/mL. A total of 16% of patients presented with NT-proBNP <150 pg/mL (low), 55% with NT-proBNP between 150 and 1800 pg/mL (intermediate), and 29% with NT-proBNP >1800 pg/mL (high). NT-proBNP was positively correlated with hospital admission [ odds ratio (OR) for high vs. low 2.9, P < 0.0001], length of stay (8.5 days vs. 3.5 days for high vs. low, P < 0.01), in-hospital death (3.9% vs. 0% for high vs. low, P < 0.01), 6 months re-hospitalization (OR for high vs. low 5.1, P < 0.0001), and 6 months death or re-hospitalization (OR for high vs. low 5.7, P < 0.0001). Knowledge of NT-proBNP had no significant effect on the primary endpoint hospital admission and the secondary endpoints intermediate/intensive care unit (IMC/ICU) admission, length of stay, re-hospitalization and death, or re-hospitalization in the total cohort. However, patients with high open NT-proBNP (>1800 pg/mL) were more likely to be admitted to the hospital (P < 0.05) and IMC/ICU (P < 0.05), whereas patients with low open NT-proBNP (<150 pg/mL) were less likely to be admitted (P < 0.05) compared with patients with blinded NT-proBNP. CONCLUSION: Although NT-proBNP does not affect overall hospitalization, it is associated with better stratification of patient care and is strongly correlated with subsequent utilization of hospital resources and prognosis.

Choline in acute coronary syndrome: an emerging biomarker with implications for the integrated assessment of plaque vulnerability.

Whole-blood choline, plasma choline and serum choline are emerging biomarkers in acute coronary syndrome related to coronary plaque instability with platelet thrombus formation and ischemia. Whole-blood choline is an early predictor for cardiac events, which adds to troponins, natriuretic peptides and inflammatory markers. Serum choline is highly predictive for myocardial infarction and discriminates high- from low-risk subgroups in troponin-positive patients. Choline is a candidate marker to aid decision making in the emergency room in the upcoming era of sensitive troponin tests and the growing need to differentiate between ischemic and nonischemic etiologies of troponin elevations. The integrated approach of in vitro choline measurement in combination with advanced techniques of in vivo choline imaging represents a novel future strategy for detecting vulnerable plaques. This paper provides an up-to-date review of choline in acute coronary syndrome including key aspects of pathophysiology, analytical methods, clinical studies and implications for the integrated assessment of plaque vulnerability.

Development of an optimized multimarker strategy for early risk assessment of patients with acute coronary syndromes.

BACKGROUND: A multitude of biomarkers have been suggested for early risk-assessment in patients admitted to the emergency department with suspected acute coronary syndromes. We used logistic regression synergistically with classification and regression tree (CART) analysis to define a multimarker strategy and the cut-off values and sequencing needed to optimize risk stratification in a low to moderate risk population of the emergency department. METHODS: 432 unselected patients (59.7+/-14.5 y, 60.4% male) admitted to the emergency department (ED) with acute coronary syndromes (ACS) were enrolled. Cardiac troponin I (cTnI), N-terminal pro-B-Type natriuretic peptide (NT-proBNP), high sensitivity C-reactive protein (hsCRP), placental growth factor (PlGF), lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) and D-dimers were measured by immunoassay and whole blood choline (WBCHO) and plasma choline (PLCHO) were measured using LC/MS from baseline samples. Logistic regression and CART analysis were used to define the importance of the various biomarkers tested and to define their hierarchy with respect to the prediction of major adverse cardiac events (MACE; cardiac death, non-fatal MI, unstable angina, CHF requiring admission, urgent PCI and CABG) over the 42-day follow-up period. RESULTS: A combination of NT-proBNP, WBCHO and Lp-PLA2 with cutoffs identified by CART-analysis was optimal for risk-stratification and superior to all other possible combinations of markers. Increased concentrations of both NT-proBNP (>1400 ng/l) and WBCHO (>21 micromol/l) identified patients with very high risk (RR=2.4, 39% primary endpoint) while low concentrations of NT-proBNP (< or = 1400 ng/l), WBCHO (< or = 17 micromol/l) and LP-PLA2 (< or = 210 microg/l) indicated very low risk (0% primary endpoint). WBCHO > 17 micromol/l additionally identified a subgroup with intermediate risk (RR=3.0, 13.5% primary endpoint) in patients with NT-proBNP concentrations < or = 1400 ng/l. Troponin when increased was highly prognostic but was not often positive in this early cohort. CONCLUSIONS: A multimarker strategy defined synergistically by logistic regression and by classification and regression tree (CART) analysis can stratify patients into risk groups ranging from very low risk (0% MACE) to very high risk (39.5% MACE) based on admission values.