Nonspecific stress biomarkers for mortality prediction in older emergency department patients presenting with falls: a prospective multicenter observational study.

BACKGROUND: Older patients presenting to the emergency department (ED) after falling are increasingly prevalent. Falls are associated with functional decline and death. Biomarkers predicting short-term mortality might facilitate decisions regarding resource allocation and disposition. D-dimer levels are used to rule out thromboembolic disease, while copeptin and adrenomedullin (MR-proADM) may be used as measures of the patient`s stress level. These nonspecific biomarkers were selected as potential predictors for mortality. METHODS: Prospective, international, multicenter, cross-sectional observation was performed in two tertiary and two regional hospitals in Germany and Switzerland. Patients aged 65 years or older presenting to the ED after a fall were enrolled. Demographic data, Activities of Daily Living (ADL), and D-dimers were collected upon presentation. Copeptin and MR-proADM levels were determined from frozen samples. Primary outcome was 30-day mortality; and secondary outcomes were mortality at 90, 180, and 365 days. RESULTS: Five hundred and seventy-two patients were included. Median age was 83 [IQR 78, 89] years, 236 (67.7%) were female. Mortality overall was 3.1% (30 d), 5.4% (90 d), 7.5% (180 d), and 13.8% (365 d), respectively. Non-survivors were older, had a lower ADL index and higher levels of all three biomarkers. Elevated levels of MR-proADM and D-dimer were associated with higher risk of mortality. MR-proADM and D-dimer showed high sensitivity and low negative likelihood ratio regarding short-term mortality, whereas copeptin did not. CONCLUSION: D-dimer and MR-proADM levels might be useful as prognostic markers in older patients presenting to the ED after a fall, by identifying patients at low risk of short-term mortality. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02244983.

Blood calprotectin as a biomarker for infection and sepsis - the prospective CASCADE trial.

BACKGROUND: Early in the host-response to infection, neutrophils release calprotectin, triggering several immune signalling cascades. In acute infection management, identifying infected patients and stratifying these by risk of deterioration into sepsis, are crucial tasks. Recruiting a heterogenous population of patients with suspected infections from the emergency department, early in the care-path, the CASCADE trial aimed to evaluate the accuracy of blood calprotectin for detecting bacterial infections, estimating disease severity, and predicting clinical deterioration. METHODS: In a prospective, observational trial from February 2021 to August 2022, 395 patients (n = 194 clinically suspected infection; n = 201 controls) were enrolled. Blood samples were collected at enrolment. The accuracy of calprotectin to identify bacterial infections, and to predict and identify sepsis and mortality was analysed. These endpoints were determined by a panel of experts. RESULTS: The Area Under the Receiver Operating Characteristic (AUROC) of calprotectin for detecting bacterial infections was 0.90. For sepsis within 72 h, calprotectin's AUROC was 0.83. For 30-day mortality it was 0.78. In patients with diabetes, calprotectin had an AUROC of 0.94 for identifying bacterial infection. CONCLUSIONS: Calprotectin showed notable accuracy for all endpoints. Using calprotectin in the emergency department could improve diagnosis and management of severe infections, in combination with current biomarkers. CLINICAL TRIAL REGISTRATION NUMBER: DRKS00020521.

Advance directives in the emergency department-a systematic review of the status quo.

BACKGROUND: Providing individualised healthcare in line with patient wishes is a particular challenge for emergency healthcare professionals. Documentation of patient wishes (DPW), e.g. as advance directives, can guide clinicians in making end-of-life decisions that respect the patient's wishes and autonomy. However, patient centered decisions are hindered by limited availability of DPWs in emergency settings. OBJECTIVE: This systematic review aims to congregate present data on recorded rates for DPW existence and availability in the emergency department (ED) as well as contributing factors for these rates. METHODS: We searched MEDLINE, Google Scholar, Embase and Web of Science databases in September 2023. Publications providing primary quantitative data on DPW in the ED were assessed. Publications referring only to a subset of ED patients (other than geriatric) and investigating DPW issued after admission were excluded. RESULTS: A total of 22 studies from 1996 to 2021 were included in the analysis. Most were from the US (n = 12), followed by Australia (n = 4), Canada (n = 2), South Korea, Germany, the United Kingdom and Switzerland (n = 1 each). In the general adult population presenting to the ED, 19.9-27.8% of patients reported having some form of DPW, but only in 6.8% or less it was available on presentation. In the geriatric population, DPW rates (2.6-79%) as well as their availability (1.1-48.8%) varied widely. The following variables were identified as positive predictors of having DPW, among others: higher age, poorer overall health, as well as sociodemographic factors, such as female gender, having children, being in a relationship, higher level of education or a recent previous presentation to hospital. CONCLUSIONS: Existence and availability of a recorded DPW among ED patients was low in general and even in geriatric populations mostly well below 50%. While we were able to gather data on prevalence and predictors, this was limited by heterogeneous data. We believe further research is needed to explore the quality of DPW and measures to increase both rates of existence and availability of DPW in the ED.

Diagnostic and prognostic value of cardiac troponins in emergency department patients presenting after a fall: A prospective, multicenter study.

BACKGROUND: Emergency department (ED) presentations after a ground-level fall (GLF) are common. Falls were suggested to be another possible presenting feature of a myocardial infarction (MI), as unrecognized MIs are common in older adults. Elevated high-sensitivity cardiac troponin (hs-cTn) concentrations could help determine the etiology of a GLF in ED. We investigated the prevalence of both MI and elevated high-sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI), as well as the diagnostic accuracy of hs-cTnT and hs-cTnI regarding MI, and their prognostic value in older ED patients presenting after a GLF. METHODS: This was a prospective, international, multicenter, cohort study with a follow-up of up to 1 year. Patients aged 65 years or older presenting to the ED after a GLF were prospectively enrolled. Two outcome assessors independently reviewed all discharge records to ascertain final gold standard diagnoses. Hs-cTnT and hs-cTnI levels were determined from thawed samples for every patient. RESULTS: In total, 558 patients were included. Median (IQR) age was 83 (77-89) years, and 67.7% were female. Elevated hs-cTnT levels were found in 384 (68.8%) patients, and elevated hs-cTnI levels in 86 (15.4%) patients. Three patients (0.5%) were ascertained the gold standard diagnosis MI. Within 30 days, 18 (3.2%) patients had died. Nonsurvivors had higher hs-cTnT and hs-cTnI levels compared with survivors (hs-cTnT 40 [23-85] ng/L in nonsurvivors and 20 [13-33] ng/L in survivors; hs-cTnI 25 [14-54] ng/L in nonsurvivors and 8 [4-16] ng/L in survivors; p < 0.001 for both). CONCLUSIONS: A majority of patients (n = 364, 68.8%) presenting to the ED after a fall had elevated hs-cTnT levels and 86 (15.4%) elevated hs-cTnI levels. However, the incidence of MI in these patients was low (n = 3, 0.5%). Our data do not support the opinion that falls may be a common presenting feature of MI. We discourage routine troponin testing in this population. However, hs-cTnT and hs-cTnI were both found to have prognostic properties for mortality prediction up to 1 year.

Deficits in blood culture collection in the emergency department if sepsis is suspected: results of a retrospective cohort study.

PURPOSE: Blood cultures (BCs) are key for pathogen detection in septic patients. We investigated the extent to which sampling was performed and what factors were associated with the absence of general or inadequate BC sampling. METHODS: We conducted a retrospective cohort study of hospitalized patients with sepsis admitted to one of three EDs in 2018. Primary outcome was the extent of general BC collection of at least 1 set. Secondary outcome was the extent of adequate BC sampling, defined as ≥ 2 sets before antibiotic therapy (AT). Multivariable logistic regression analysis was performed to identify factors associated with deficits in both outcomes. RESULTS: 1143 patients were analyzed. BCs were collected from 946 patients. Single BCs were taken from 520 patients, ≥ 2 sets from 426 patients. Overall, ≥ 2 BCs were taken from 349 patients before AT. BC sampling before AT occurred significantly more frequently when ≥ 2 BC sets were taken rather than a single one (81.9%, versus 68.4%, p < 0.001) and this also led to the highest pathogen detection rate in our cohort (65.6%). A body temperature of ≥ 38 °C was the a supporting factor for general and adequate BC collection in all three EDs. Retrospective analysis of 533 patients showed that the qSOFA score had no influence on general or adequate BC collection. CONCLUSION: Data on everyday clinical practice in the pre-analytical phase of microbiological diagnostics shows considerable deficits and indicates the need for more implementation of best practice. The variations identified in BC sampling between EDs should be further investigated.

Sepsis incidence, suspicion, prediction and mortality in emergency medical services: a cohort study related to the current international sepsis guideline.

PURPOSE: Sepsis suspicion by Emergency Medical Services (EMS) is associated with improved patient outcomes. This study assessed sepsis incidence and recognition by EMS and analyzed which of the screening tools recommended by the Surviving Sepsis Campaign best facilitates sepsis prediction. METHODS: Retrospective cohort study of claims data from health insurances (n = 221,429 EMS cases), and paramedics' and emergency physicians' EMS documentation (n = 110,419); analyzed outcomes were: sepsis incidence and case fatality compared to stroke and myocardial infarction, the extent of documentation for screening-relevant variables and sepsis suspicion, tools' intersections for screening positive in identical EMS cases and their predictive ability for an inpatient sepsis diagnosis. RESULTS: Incidence of sepsis (1.6%) was similar to myocardial infarction (2.6%) and stroke (2.7%); however, 30-day case fatality rate was almost threefold higher (31.7% vs. 13.4%; 11.8%). Complete vital sign documentation was achieved in 8.2% of all cases. Paramedics never, emergency physicians rarely (0.1%) documented a sepsis suspicion, respectively septic shock. NEWS2 had the highest sensitivity (73.1%; Specificity:81.6%) compared to qSOFA (23.1%; Sp:96.6%), SIRS (28.2%; Sp:94.3%) and MEWS (48.7%; Sp:88.1%). Depending on the tool, 3.7% to 19.4% of all cases screened positive; only 0.8% in all tools simultaneously. CONCLUSION: Incidence and mortality underline the need for better sepsis awareness, documentation of vital signs and use of screening tools. Guidelines may omit MEWS and SIRS as recommendations for prehospital providers since they were inferior in all accuracy measures. Though no tool performed ideally, NEWS2 qualifies as the best tool to predict the highest proportion of septic patients and to rule out cases that are likely non-septic.

German Porphyria Registry (PoReGer)-Background and Setup.

Porphyrias, as most rare diseases, are characterized by complexity and scarcity of knowledge. A national registry in one of the largest European populations that prospectively collects longitudinal clinical and laboratory data are an important and effective tool to close this gap. The German Porphyria Registry (PoReGer) was founded by four centers with longstanding expertise in the field of porphyrias and rare diseases (Charité-Universitätsmedizin Berlin, Porphyria Center Saxony Chemnitz, University Medical Center Hamburg-Eppendorf, University Medical Center Göttingen) and the German reference laboratory for porphyria, and is supported by the largest German porphyria patient organization. A specified data matrix for three subgroups (acute, chronic blistering cutaneous, acute non-blistering cutaneous) includes data on demographics, specific porphyria-related symptoms, clinical course, general medical history, necessary follow-up assessments (including laboratory and imaging results), symptomatic and disease-modifying therapies, and side-effects. Additionally, the registry includes patient-reported outcome measures on quality of life, depression, and fatigue. PoReGer aims to broaden and deepen the understanding on all porphyria-related subjects. We expect these data to significantly improve the management and care of porphyria patients. Additionally, the data can be used for educational purposes to increase awareness, for the planning of healthcare services, and for machine learning algorithms for early detection of porphyrias.

Detect Acute Porphyrias in Emergency Departments (DePorED) - a pilot study.

BACKGROUND: Acute porphyrias (APs) are a group of rare metabolic diseases related to a disturbed heme biosynthesis. Symptoms may first occur as life threatening attacks, comprising abdominal pain and/or variable neuro-psychiatric symptoms, thus leading to presentation in emergency departments (ED) first. Due to the low prevalence, diagnosis of AP is often missed, even after readmission to the ED. Therefore, strategies are needed to consider APs in ED patients with unexplained abdominal pain, especially since early and adequate treatment will avoid an unfavorable clinical course. Aim of this prospective study was to investigate the prevalence of APs in ED patients and thus, addressing feasibility of screening for rare diseases, such as APs in the real life setting. METHODS: From September 2019 to March 2021, patients presenting to the ED of three German tertiary care hospitals with moderate to severe prolonged abdominal pain (Visual Analog Scale, VAS > 4 out of 10 points) not otherwise explained were screened and prospectively enrolled. In addition to standard of care (SOC) diagnostics a blood and urine sample for plasma fluorescence scan and biochemical porphyrin analysis were sent to a certified German porphyria laboratory. RESULTS: Overall, of 653 screened patients, 68 patients (36 females; mean age 36 years) were included for biochemical porphyrin analysis. No patient with AP was detected. The most frequent discharge diagnoses included "abdominal and digestive symptoms" (n = 22, 32%), "gastrooesophageal diseases" (n = 18, 27%), "infectious bowel disease" (n = 6, 9%) and "biliopancreatic diseases" (n = 6, 9%). Although not primarily addressed, we observed an increase in knowledge of the ED staffs at all study sites regarding our screening algorithm and thus, awareness for APs. CONCLUSIONS: To the best of our knowledge, we performed the first prospective screening project for APs in the ED. Although we detected no patient with AP in this study, we demonstrated the feasibility of a multicenter screening process for APs by building up a well-working infrastructure comprising laboratory testing as well as data management. This enables the set-up of a larger scale revised follow-up study with a central focus on structured education, thus, possibly acting as blueprint for other rare diseases.

A program for volunteers accompanying older patients with cognitive dysfunction to improve the quality of emergency department care: A pilot study.

Admission to an emergency department (ED) is challenging for older patients with cognitive dysfunction (PWCD). Targeted patient-oriented approaches to improve the care for PWCD are needed. The aim of this pilot study was to design and evaluate a program for volunteers to support PWCD in the ED. Volunteers (N = 9) first received a training and during the following six months (N = 90 shifts), they accompanied PWCD (N = 112) during their stay. Results showed that the training increased volunteers' knowledge and expertise, but not shift-related self-efficacy. The most frequent strategies applied were conversations, holding hands and touching, and providing food and drinks. After six months, volunteers reported a great sense of meaningfulness and felt that they were highly appreciated by the patients. ED nurses' sceptical attitudes towards the program decreased. The program is beneficial for PWCD, appears to be meaningful for volunteers and is appreciated by ED nurses.

Medical and cardio-vascular emergency department visits during the COVID-19 pandemic in 2020: is there a collateral damage? A retrospective routine data analysis.

BACKGROUND: In this retrospective routine data analysis, we investigate the number of emergency department (ED) consultations during the COVID-19 pandemic of 2020 in Germany compared to the previous year with a special focus on numbers of myocardial infarction and acute heart failure. METHODS: Aggregated case numbers for the two consecutive years 2019 and 2020 were obtained from 24 university hospitals and 9 non-university hospitals in Germany and assessed by age, gender, triage scores, disposition, care level and by ICD-10 codes including the tracer diagnoses myocardial infarction (I21) and heart failure (I50). RESULTS: A total of 2,216,627 ED consultations were analyzed, of which 1,178,470 occurred in 2019 and 1,038,157 in 2020. The median deviation in case numbers between 2019 and 2020 was - 14% [CI (- 11)-(- 16)]. After a marked drop in all cases in the first COVID-19 wave in spring 2020, case numbers normalized during the summer. Thereafter starting in calendar week 39 case numbers constantly declined until the end of the year 2020. The decline in case numbers predominantly concerned younger [- 16%; CI (- 13)-(- 19)], less urgent [- 18%; CI (- 12)-(- 22)] and non-admitted cases [- 17%; CI (- 13)-(- 20)] in particular during the second wave. During the entire observation period admissions for chest pain [- 13%; CI (- 21)-2], myocardial infarction [- 2%; CI (- 9)-11] and heart failure [- 2%; CI (- 10)-6] were less affected and remained comparable to the previous year. CONCLUSIONS: ED visits were noticeably reduced during both SARS-CoV-2 pandemic waves in Germany but cardiovascular diagnoses were less affected and no refractory increase was noted. However, long-term effects cannot be ruled out and need to be analysed in future studies.

Antimicrobial resistance control in the emergency department: a need for concrete improvement.

BACKGROUND: Rational use of antibiotics (AB) and infection prevention and control (IPC) are key measures for reducing antimicrobial resistance (AMR) in healthcare. Nonetheless, transferring evidence into clinical practice in emergency medicine has proven difficult. The extent to which structural requirements for implementing AMR control exist in German emergency departments (ED) was determined in a survey. METHODS: Aspects of antimicrobial stewardship (AMS) and IPC implementation were surveyed within the German Association for Emergency Medicine (Deutsche Gesellschaft interdisziplinäre Notfall- und Akutmedizin e.V, DGINA) in 2018. Data were collected using an anonymous online questionnaire on ED characteristics, ED-based-link personnel for IPC and AMS, education and training, process monitoring and specific requirements for AMS and IPC as availability of AMR data and alcohol-based hand rub (AHR) consumption data. Data were analysed descriptively. RESULTS: 66 EDs with in median [interquartile range (IQR)] of 30,900 [23,000; 40,000] patient visits participated in the survey. EDs' healthcare worker (HCW) received regular training on hand hygiene (HH) in 67% and on AMS in 20% of EDs. Surveillance of AHR consumption was performed by 73% EDs, surveillance of AB consumption by 64%. Regular audits on HH were performed in 39%. Training and audit activities, showed no significant variations according to EDs' organizational characteristics. HCWs received immediate feedback of HH performance in 29%, in 23% a regular structured feedback of HH was provided. ED-based physicians with (1) specific IPC responsibilities and training were available in 61%, with (2) AMS training and responsibility in 15%. 83% had ED based IPC link nurses with precise ICP responsibilities in place. Essentially resistance data existed at the hospital level (74%) rather than at ED- or regional level (15% and 14% respectively). CONCLUSIONS: Management of AMR varies in German EDs, especially in accordance to hospital size and level of emergency care. IPC seems to receive more attention than AMS. Our data indicate the need for more implementation of regular IPC and AMS training in connection with monitoring and feedback in German EDs.

Influence of appropriate emergency department utilization and verbal communication on physicians' (dis)satisfaction with doctor-patient interactions with special consideration of migrational backgrounds.

In recent years, utilization of emergency departments (EDs) has increased continuously, both in Germany and internationally. Inappropriate use of EDs is believed to be partly responsible for this trend. The topic of doctor-patient interaction (DPI) has received little attention in research. However, successful DPI is not only important for adherence and treatment success, but also for the satisfaction of medical staff. This non-interventionl cross-sectional study attempts to identify factors influencing physicians' satisfaction with DPIs, with a particular focus on the appropriate utilization of EDs and verbal communication. We carried out tripartite data collection in three EDs of major referral hospitals in Berlin between July 2017 and July 2018. Migration experience, communication and language problems, level of education, and a large gap between physicians' and patients' perceived urgency regarding the utilization of EDs influence the quality of the doctor-patient relationships and interactions.

Prospective validation of a transcriptomic severity classifier among patients with suspected acute infection and sepsis in the emergency department.

BACKGROUND AND IMPORTANCE: mRNA-based host response signatures have been reported to improve sepsis diagnostics. Meanwhile, prognostic markers for the rapid and accurate prediction of severity in patients with suspected acute infections and sepsis remain an unmet need. IMX-SEV-2 is a 29-host-mRNA classifier designed to predict disease severity in patients with acute infection or sepsis. OBJECTIVE: Validation of the host-mRNA infection severity classifier IMX-SEV-2. DESIGN, SETTINGS AND PARTICIPANTS: Prospective, observational, convenience cohort of emergency department (ED) patients with suspected acute infections. OUTCOME MEASURES AND ANALYSIS: Whole blood RNA tubes were analyzed using independently trained and validated composite target genes (IMX-SEV-2). IMX-SEV-2-generated risk scores for severity were compared to the patient outcomes in-hospital mortality and 72-h multiorgan failure. MAIN RESULTS: Of the 312 eligible patients, 22 (7.1%) died in hospital and 58 (18.6%) experienced multiorgan failure within 72 h of presentation. For predicting in-hospital mortality, IMX-SEV-2 had a significantly higher area under the receiver operating characteristic (AUROC) of 0.84 [95% confidence intervals (CI), 0.76-0.93] compared to 0.76 (0.64-0.87) for lactate, 0.68 (0.57-0.79) for quick Sequential Organ Failure Assessment (qSOFA) and 0.75 (0.65-0.85) for National Early Warning Score 2 (NEWS2), ( P = 0.015, 0.001 and 0.013, respectively). For identifying and predicting 72-h multiorgan failure, the AUROC of IMX-SEV-2 was 0.76 (0.68-0.83), not significantly different from lactate (0.73, 0.65-0.81), qSOFA (0.77, 0.70-0.83) or NEWS2 (0.81, 0.75-0.86). CONCLUSION: The IMX-SEV-2 classifier showed a superior prediction of in-hospital mortality compared to biomarkers and clinical scores among ED patients with suspected infections. No improvement for predicting multiorgan failure was found compared to established scores or biomarkers. Identifying patients with a high risk of mortality or multiorgan failure may improve patient outcomes, resource utilization and guide therapy decision-making.

[Use of emergency rooms by so-called multiple users: results of a prospective study with special consideration of the migration status]. / Inanspruchnahme von Notaufnahmen durch sog. Mehrfachnutzer/-innen: Ergebnisse einer prospektiven Studie unter besonderer Berücksichtigung des Migrationsstatus.

Objectives: Can we identify predictive factors for the group of so-called multiple users (MU; 4 and more uses of an emergency department [ED] in the past 12 months)? Are people with a migration background more likely to be classified in the MU group? Methodology: Included were consecutive patients who visited three EDs in Berlin from July 2017 to July 2018. Using a questionnaire, diseases, reasons for visiting the ED and socioeconomic factors were recorded. Comparisons between migrants (1st generation), their descendants (2nd generation) and nonmigrants were assessed using logistic regression. Results: A total of 2339 patients were included in the evaluation (repeat rate 56%), of which 901 had a migration background. Young women (<30 years), chronically ill, pregnant women, patients with severe complaints and people with (self-assessed) moderate and poor health quality as well as those without medical referral had a greater chance of multiple use of ED. Conclusion: MU burden the already increasing patient volume of ED. However, they represent a heterogeneous group of patients, among whom people with a migration background are not common. Further research is warranted to better understand the factors that lead to frequent use and to develop effective strategies to address the complex health needs of MUs.

Plasma Proteome Fingerprints Reveal Distinctiveness and Clinical Outcome of SARS-CoV-2 Infection.

BACKGROUND: We evaluated how plasma proteomic signatures in patients with suspected COVID-19 can unravel the pathophysiology, and determine kinetics and clinical outcome of the infection. METHODS: Plasma samples from patients presenting to the emergency department (ED) with symptoms of COVID-19 were stratified into: (1) patients with suspected COVID-19 that was not confirmed (n = 44); (2) non-hospitalized patients with confirmed COVID-19 (n = 44); (3) hospitalized patients with confirmed COVID-19 (n = 53) with variable outcome; and (4) patients presenting to the ED with minor diseases unrelated to SARS-CoV-2 infection (n = 20). Besides standard of care diagnostics, 177 circulating proteins related to inflammation and cardiovascular disease were analyzed using proximity extension assay (PEA, Olink) technology. RESULTS: Comparative proteome analysis revealed 14 distinct proteins as highly associated with SARS-CoV-2 infection and 12 proteins with subsequent hospitalization (p < 0.001). ADM, IL-6, MCP-3, TRAIL-R2, and PD-L1 were each predictive for death (AUROC curve 0.80-0.87). The consistent increase of these markers, from hospital admission to intensive care and fatality, supported the concept that these proteins are of major clinical relevance. CONCLUSIONS: We identified distinct plasma proteins linked to the presence and course of COVID-19. These plasma proteomic findings may translate to a protein fingerprint, helping to assist clinical management decisions.

Alpha-single chains of collagen type VI inhibit the fibrogenic effects of triple helical collagen VI in hepatic stellate cells.

The interaction of extracellular matrix (ECM) components with hepatic stellate cells (HSCs) is thought to perpetuate fibrosis by stimulating signaling pathways that drive HSC activation, survival and proliferation. Consequently, disrupting the interaction between ECM and HSCs is considered a therapeutical avenue although respective targets and underlying mechanisms remain to be established. Here we have interrogated the interaction between type VI collagen (CVI) and HSCs based on the observation that CVI is 10-fold upregulated during fibrosis, closely associates with HSCs in vivo and promotes cell proliferation and cell survival in cancer cell lines. We exposed primary rat HSCs and a rat hepatic stellate cell line (CFSC) to soluble CVI and determined the rate of proliferation, apoptosis and fibrogenesis in the absence of any additional growth factors. We find that CVI in nanomolar concentrations prevents serum starvation-induced apoptosis. This potent anti-apoptotic effect is accompanied by induction of proliferation and acquisition of a pronounced pro-fibrogenic phenotype characterized by increased α-smooth muscle actin, TGF-ß, collagen type I and TIMP-1 expression and diminished proteolytic MMP-13 expression. The CVI-HSC interaction can be disrupted with the monomeric α2(VI) and α3(VI) chains and abrogates the activating CVI effects. Further, functional relevant α3(VI)-derived 30 amino acid peptides lead to near-complete inhibition of the CVI effect. In conclusion, CVI serves as a potent mitogen and activating factor for HSCs. The antagonistic effects of the CVI monomeric chains and peptides point to linear peptide sequences that prevent activation of CVI receptors which may allow a targeted antifibrotic therapy.

A Novel 29-Messenger RNA Host-Response Assay From Whole Blood Accurately Identifies Bacterial and Viral Infections in Patients Presenting to the Emergency Department With Suspected Infections: A Prospective Observational Study.

OBJECTIVES: The rapid diagnosis of acute infections and sepsis remains a serious challenge. As a result of limitations in current diagnostics, guidelines recommend early antimicrobials for suspected sepsis patients to improve outcomes at a cost to antimicrobial stewardship. We aimed to develop and prospectively validate a new, 29-messenger RNA blood-based host-response classifier Inflammatix Bacterial Viral Non-Infected version 2 (IMX-BVN-2) to determine the likelihood of bacterial and viral infections. DESIGN: Prospective observational study. SETTING: Emergency Department, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Germany. PATIENTS: Three hundred twelve adult patients presenting to the emergency department with suspected acute infections or sepsis with at least one vital sign change. INTERVENTIONS: None (observational study only). MEASUREMENTS AND MAIN RESULTS: Gene expression levels from extracted whole blood RNA was quantified on a NanoString nCounter SPRINT (NanoString Technologies, Seattle, WA). Two predicted probability scores for the presence of bacterial and viral infection were calculated using the IMX-BVN-2 neural network classifier, which was trained on an independent development set. The IMX-BVN-2 bacterial score showed an area under the receiver operating curve for adjudicated bacterial versus ruled out bacterial infection of 0.90 (95% CI, 0.85-0.95) compared with 0.89 (95% CI, 0.84-0.94) for procalcitonin with procalcitonin being used in the adjudication. The IMX-BVN-2 viral score area under the receiver operating curve for adjudicated versus ruled out viral infection was 0.83 (95% CI, 0.77-0.89). CONCLUSIONS: IMX-BVN-2 demonstrated accuracy for detecting both viral infections and bacterial infections. This shows the potential of host-response tests as a novel and practical approach for determining the causes of infections, which could improve patient outcomes while upholding antimicrobial stewardship.

CD169/SIGLEC1 is expressed on circulating monocytes in COVID-19 and expression levels are associated with disease severity.

Coronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Type I interferons are important in the defense of viral infections. Recently, neutralizing IgG auto-antibodies against type I interferons were found in patients with severe COVID-19 infection. Here, we analyzed expression of CD169/SIGLEC1, a well described downstream molecule in interferon signaling, and found increased monocytic CD169/SIGLEC1 expression levels in patients with mild, acute COVID-19, compared to patients with severe disease. We recommend further clinical studies to evaluate the value of CD169/SIGLEC1 expression in patients with COVID-19 with or without auto-antibodies against type I interferons.

Association of sex with the clinical course and outcome of internal emergency department patients: a secondary data analysis.

BACKGROUND AND IMPORTANCE: Differences between men and women visiting the emergency department (ED) with nonsurgical complaints have mostly been investigated in small, diagnosis-based subpopulations. OBJECTIVE: This study investigated sex-differences in an unselected cohort of nonsurgical ED patients. DESIGN: Secondary data of all patients attending two EDs of the Charité, Universitätsmedizin Berlin collected in the framework of their medical evaluation was reviewed. SETTINGS AND PARTICIPANTS: Within a 1-year-period all 34 333 adult internal patients presenting to one of the two EDs were included and analysed. OUTCOMES MEASURE AND ANALYSES: Sex-stratified descriptive analysis of the in-hospital course and outcome of the ED patients was performed as primary endpoint. Admission data, ED processes and diagnoses were analyzed as secondary endpoints. MAIN RESULTS: A total of 51.2% of all patients were women. Women were slightly younger (median 56 years vs. men 58 years; P < 0.001) and presented more frequently with abdominal pain and headache. Men rather showed chest pain and dyspnea. Accordingly, women had more gastroenterological diseases; men were more often diagnosed with cardiological and pneumological diseases. Women were less frequently admitted for inpatient treatment [35.3 vs. men 43.7%; difference 8.4 percentage points (95% confidence interval (CI), 7.3-9.4)] and intensive care treatment [5.8 vs. men 9.0%; difference 3.2 percentage points (95% CI, 2.7-3.8)]. Inpatient-mortality did not show significant sex differences [4.6 women vs. 4.8% men; difference 0.2 percentage points (95% CI, -0.6 to 0.8)]. CONCLUSIONS: There are significant differences in characteristics, symptoms, diagnoses and clinical course between men and women. Further investigations could identify causes and measures like sex-specific algorithms for ED-work processes.