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.

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.

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.

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.

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.

[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.

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.

SARS-CoV-2 antigen rapid immunoassay for diagnosis of COVID-19 in the emergency department.

BACKGROUND: In the emergency department (ED) setting, rapid testing for SARS-CoV-2 is likely associated with advantages to patients and healthcare workers, for example, enabling early but rationale use of limited isolation resources. Most recently, several SARS-CoV-2 rapid point-of-care antigen tests (AGTEST) became available. There is a growing need for data regarding their clinical utility and performance in the diagnosis of SARS-CoV-2 infection in the real life setting EDs. METHODS: We implemented AGTEST (here: Roche/SD Biosensor) in all four adult and the one paediatric EDs at Charité - Universitätsmedizin Berlin in our diagnostic testing strategy. Test indication was limited to symptomatic suspected COVID-19 patients. Detailed written instructions on who to test were distributed and testing personnel were trained in proper specimen collection and handling. In each suspected COVID-19 patient, two sequential deep oro-nasopharyngeal swabs were obtained for viral tests. The first swab was collected for nucleic acid testing through SARS-CoV-2 real-time reverse transcriptase (rt)-PCR diagnostic panel (PCRTEST) in the central laboratory. The second swab was collected to perform the AGTEST. Analysis of routine data was prospectively planned and data were retrieved from the medical records after the inclusion period in the adult or paediatric ED. Diagnostic performance was calculated using the PCRTEST as reference standard. False negative and false positive AGTEST results were analysed individually and compared with viral concentrations derived from the calibrated PCRTEST. RESULTS: We included n = 483 patients including n = 202 from the paediatric ED. N = 10 patients had to be excluded due to missing data and finally n = 473 patients were analysed. In the adult cohort, the sensitivity of the AGTEST was 75.3 (95%CI: 65.8/83.4)% and the specificity was 100 (95%CI: 98.4/100)% with a SARS-CoV-2 prevalence of 32.8%; the positive predictive value was 100 (95%CI: 95.7/100)% and the negative predictive value 89.2 (95%CI: 84.5/93.9)%. In the paediatric cohort, the sensitivity was 72.0 (95%CI: 53.3/86.7)%, the specificity was 99.4 (95%CI:97.3/99.9)% with a prevalence of 12.4%; the positive predictive value was 94.7 (95%CI: 78.3/99.7)% and the negative predictive value was 96.2 (95%CI:92.7/98.3)%. Thus, n = 22 adult and n = 7 paediatric patients showed false negative AGTEST results and only one false positive AGTEST occurred, in the paediatric cohort. Calculated viral concentrations from the rt-PCR lay between 3.16 and 9.51 log10 RNA copies/mL buffer. All false negative patients in the adult ED cohort, who had confirmed symptom onset at least seven days earlier had less than 5 × 105 RNA copies/mL buffer. CONCLUSIONS: We conclude that the use of AGTEST among symptomatic patients in the emergency setting is useful for the early identification of COVID-19, but patients who test negative require confirmation by PCRTEST and must stay isolated until this result becomes available. Adult patients with a false negative AGTEST and symptom onset at least one week earlier have typically a low SARS-CoV-2 RNA concentration and are likely no longer infectious.

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.

Non-contact monitoring of agitation and use of a sheltering device in patients with dementia in emergency departments: a feasibility study.

BACKGROUND: Agitation is common in geriatric patients with cognitive impairment, e.g. in persons with dementia (PWD), who are admitted to an emergency department (ED). It might be a first sign of upcoming delirium and is associated with a higher risk of an unfavorable clinical course. Hence, monitoring of vital signs and enhanced movement as indicators of upcoming agitation is essential in these patients during their stay in the ED. Since PWD rarely tolerate fixed monitoring devices, a novel developed non-contact monitoring system (NCMSys) might represent an appropriate alternative. Aim of this feasibility study was to test the validity of a NCMSys and of the tent-like "Charité Dome" (ChD), aimed to shelter PWD from the busy ED environment. Furthermore, effects of the ChD on wellbeing and agitation of PWD were investigated. METHODS: Both devices were attached to patient's bed. Tests on technical validity and safety issues of NCMSys and ChD were performed at the iDoc institute with six healthy volunteers. A feasibility study evaluating the reliability of the NCMSys with and without the ChD was performed in the real-life setting of an ED and on a geriatric-gerontopsychiatric ward. 19 patients were included, ten males and nine females; mean age: 77.4 (55-93) years of which 14 were PWD. PWD inclusion criteria were age ≥ 55 years, a dementia diagnosis and a written consent (by patients or by a custodian). Exclusion criteria were acute life-threatening situations and a missing consent. RESULTS: Measurements of heart rate, changes in movement and sound emissions by the NCMSys were valid, whereas patient movements affected respiratory rate measurements. The ChD did not impact patients' vital signs or movements in our study setting. However, 53% of the PWD (7/13) and most of the patients without dementia (4/5) benefited from its use regarding their agitation and overall wellbeing. CONCLUSIONS: The results of this feasibility study encourage a future controlled clinical trial in geriatric ED patients, including PWD, to further evaluate if our concept of non-contact measurement of vital signs and movement combined with the "Charité Dome" helps to prevent upcoming agitation in this vulnerable patient group in the ED. TRIAL REGISTRATION: ICTRP: "Charité-Dome-Study - DRKS00014737" (retrospectively registered).

K⁺-channel inhibition reduces portal perfusion pressure in fibrotic rats and fibrosis associated characteristics of hepatic stellate cells.

BACKGROUND & AIMS: In liver fibrosis, activated hepatic stellate cells (HSC) secrete excess extracellular matrix, thus, represent key targets for antifibrotic treatment strategies. Intermediate-conductance Ca(2) (+) -activated K(+) -channels (KCa3.1) are expressed in non-excitable tissues affecting proliferation, migration and vascular resistance rendering KCa3.1 potential targets in liver fibrosis. So far, no information about KCa3.1 expression and their role in HSC exists. Aim was to quantify the KCa3.1 expression in HSC depending on HSC activation and investigation of antifibrotic properties of the specific KCa3.1 inhibitor TRAM-34 in vitro and in vivo. METHODS: KCa3.1 expression and functionality were studied in TGF-ß1-activated HSC by quantitative real time PCR, western-blot and patch-clamp analysis respectively. Effects of TRAM-34 on HSC proliferation, cell cycle and fibrosis-related gene expression were assessed by [(3) H]-thymidine incorporation, FACS-analysis and RT-PCR respectively. In vivo, vascular resistance and KCa3.1 gene and protein expression were determined in bile duct ligated rats by in situ liver perfusion, Taqman PCR and immunohistochemistry respectively. RESULTS: Fibrotic tissues and TGF-ß1-activated HSC exhibited higher KCa3.1-expressions than normal tissue and untreated cells. KCa3.1 inhibition with TRAM-34 reduced HSC proliferation by induction of cell cycle arrest and reduced TGF-ß1-induced gene expression of collagen I, alpha-smooth muscle actin and TGF-ß1 itself. Furthermore, TRAM-34 blocked TGF-ß1-induced activation of TGF-ß signalling in HSC. In vivo, TRAM-34 reduced the thromboxane agonist-induced portal perfusion pressure. CONCLUSION: Inhibition of KCa3.1 with TRAM-34 downregulates fibrosis-associated gene expression in vitro, and reduces portal perfusion pressure in vivo. Thus, KCa3.1 may represent novel targets for the treatment of liver fibrosis.

Towards compression-sensitive magnetic resonance elastography of the liver: sensitivity of harmonic volumetric strain to portal hypertension.

PURPOSE: To assess induced oscillating volumetric strain as a biomarker for intrahepatic blood pressure abnormalities. MATERIALS AND METHODS: Harmonic vibrations of 25 and 50 Hz frequency were induced in the liver and measured by fast 3D vector field magnetic resonance elastography (MRE), followed by processing of the decomposed curl (shear) and divergence (compression) fields. After an initial study on an excised sheep liver, a group of 13 patients with hepatic hypertension were examined before and after implantation of a transjugular intrahepatic portosystemic shunt (TIPS). RESULTS: In the sheep liver specimen, volumetric strain decreased with excess portal pressure, whereas shear strain was not sensitive to portal pressure. In the patient cohort, volumetric strain was significantly higher after TIPS placement (P = 1.38·10(-5) ), while neither shear strain nor the shear modulus were affected. Normalized changes in volumetric strain were significantly correlated with the hepatic venous pressure gradient (R(2) = 0.7258, P = 6.95·10(-5) ) and portal venous pressure (R(2) = 0.5028, P = 0.0016). CONCLUSION: These results indicate for the first time the sensitivity of volumetric strain to symptomatically high values of tissue pressure and motivate further developments in compression-sensitive MRE and poroelastography towards image-based and noninvasive markers of tissue pressure.

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.

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.

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.

The inhibitor of Ca(2+)-dependent K+ channels TRAM-34 blocks growth of hepatocellular carcinoma cells via downregulation of estrogen receptor alpha mRNA and nuclear factor-kappaB.

Hepatocellular carcinoma (HCC) is the most common liver malignancy still demanding for novel therapeutic options. Since the ion channel inhibitor TRAM-34 (1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole) was shown to block growth in various cancer cells, we investigated anti-tumor effects of TRAM-34 in human HCC cell lines. We found that TRAM-34 reduced HCC cell proliferation without induction of apoptosis. This was due to a decreased mRNA expression of estrogen receptor alpha (ESR1) and a reduced activation of NF-kappaB, which both are implicated in the development of HCC. Therefore, TRAM-34 might represent a novel therapeutic target for the treatment of HCC.

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.