Publications by authors named "Martin Möckel"

158 Publications

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

Eur J Emerg Med 2021 Apr 5. Epub 2021 Apr 5.

Department for Pediatric Cardiology and Intensive Care, Medical Hospital of the University of Munich, Ludwig Maximilians University Munich, Munich Department of Emergency and Acute Medicine, Campus Mitte and Virchow, Charité - Universitätsmedizin Berlin, Berlin Thermo Fisher Scientific, Clinical Diagnostic, BRAHMS GmbH, Hennigsdorf Department of Emergency and Acute Medicine, Campus Benjamin Franklin, Berlin, Germany.

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.
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http://dx.doi.org/10.1097/MEJ.0000000000000793DOI Listing
April 2021

Point-of-care testing for influenza in a university emergency department: A prospective study.

Influenza Other Respir Viruses 2021 Apr 4. Epub 2021 Apr 4.

Emergency and Acute Medicine, Campus Virchow Klinikum and Campus Charité Mitte, Charité Universitätsmedizin Berlin, Berlin, Germany.

Background: Seasonal influenza is a burden for emergency departments (ED).

Objectives: The aim of this study was to investigate whether point-of-care (POC) PCR testing can be used to reduce staff sick days and improve diagnostic and therapeutic procedures.

Methods: Using a cross-over design, the cobas® Liat® Influenza A/B POC PCR test (Liat) was compared with standard clinical practice during the 2019/2020 influenza season. All adult patients (aged ≥ 18 years) with fever (≥38°C) and respiratory symptoms were included. Primary end points were the prevalence of influenza infections in the ED and staff sick days. Secondary end points were frequency of antiviral and antibacterial therapy, time between admission and test result or treatment initiation, patient disposition, ED length of stay (LOS), and for inpatients mortality and LOS. Nurses were interviewed about handling and integration of POC testing. The occurrence of SARS-CoV-2 infections coincided with the second half of the study.

Results: A total of 828 patients were enrolled in the study. All 375 patients of the intervention group were tested with Liat, and 103 patients of them (27.6%) tested positive. During the intervention period, staff sick days were reduced by 34.4% (P = .023). Significantly, more patients in the intervention group received antiviral therapy with neuraminidase inhibitors (7.2% vs 3.8%, P = .028) and tested patients received antibiotics more frequently (40.0% vs 31.6%, P = .033). Patients with POC test were transferred to external hospitals significantly more often (5.6% vs 1.3%, P = .01).

Conclusion: We conclude that POC testing for influenza is useful in the ED, especially if it is heavily frequented by patients with respiratory symptoms.
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http://dx.doi.org/10.1111/irv.12857DOI Listing
April 2021

Which parameters support disposition decision in suspected COVID-19 cases in the emergency department (ED): a German clinical cohort study.

BMJ Open 2021 03 31;11(3):e044853. Epub 2021 Mar 31.

Emergency and Acute Medicine, Campus Mitte and Virchow, Charite Universitatsmedizin Berlin, Berlin, Germany.

Objectives: One major goal of the emergency department (ED) is to decide, whether patients need to be hospitalised or can be sent home safely. We aim at providing criteria for these decisions without knowing the SARS-CoV-2 test result in suspected cases.

Setting: Tertiary emergency medicine.

Participants: All patients were treated at the ED of the Charité during the pandemic peak and underwent SARS-CoV-2 testing. Patients with positive test results were characterised in detail and underwent a 14-day-follow-up.

Primary And Secondary Outcome Measures: Logistic regression and classification and regression tree (CART) analyses were performed to identify predictors (primary endpoint), which confirm safe discharge. The clinical endpoint was all-cause mortality or need for mechanical ventilation during index stay or after readmission.

Results: The primary test population of suspected COVID-19 consisted of n=1255 cases, 45.2% were women (n=567). Of these, n=110 tested positive for SARS-CoV-2 (8.8%). The median age of SARS-CoV-2-positive cases was 45 years (IQR: 33-66 years), whereas the median age of the group tested negative for SARS-CoV-2 was 42 years (IQR: 30-60 years) (p=0.096). 43.6% were directly admitted to hospital care.CART analysis identified the variables oxygen saturation (<95%), dyspnoea and history of cardiovascular (CV) disease to distinguish between high and low-risk groups. If all three variables were negative, most patients were discharged from ED, and the incidence of the clinical endpoint was 0%. The validation cohort confirmed the safety of discharge using these variables and revealed an incidence of the clinical endpoint from 14.3% in patients with CV disease, 9.4% in patients with dyspnoea and 18.2% in patients with O satuaration below 95%.

Conclusions: Based on easily available variables like dyspnoea, oxygen saturation, history of CV disease, approximately 25% of patients subsequently confirmed with COVID-19 can be identified for safe discharge.

Trial Registration Number: DRKS00023117.
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http://dx.doi.org/10.1136/bmjopen-2020-044853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015792PMC
March 2021

Diverting less urgent utilizers of emergency medical services to primary care: is it feasible? Patient and morbidity characteristics from a cross-sectional multicenter study of self-referring respiratory emergency department consulters.

BMC Res Notes 2021 Mar 24;14(1):113. Epub 2021 Mar 24.

Institute of General Practice, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.

Objective: Diversion of less urgent emergency medical services (EMS) callers to alternative primary care (PC) is much debated. Using data from the EMACROSS survey of respiratory ED patients, we aimed to characterize self-referred EMS patients, compare these with non-EMS patients, and assess scope and acceptability of a potential redirection to alternative PC.

Results: Of n = 292 self-referred patients, n = 99 were transported by EMS. Compared to non-EMS patients, these were older, triaged more urgently and arrived out-of-hours more frequently. The share of chronically and severely ill patients was greater. Out-of-hours ED visit, presence of a chronic pulmonary condition as well as a hospital diagnosis of respiratory failure were identified as determinants of EMS utilization in a logistic model, while consultation for access and quality motives as well as migrant status decreased the probability. EMS-transported lower urgency outpatients visiting during regular physicians' hours were defined as potential PC cases and evaluated descriptively (n = 9). As a third was medically complex and potentially less suitable for PC, redirection potential could be estimated at only 6% of EMS cases. This would be reduced to 2% if considering patients' judgment concerning the appropriate setting. Overall, the scope for PC diversion of respiratory EMS patients seems limited.
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http://dx.doi.org/10.1186/s13104-021-05517-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992314PMC
March 2021

Cardiovascular biomarkers in patients with COVID-19.

Eur Heart J Acute Cardiovasc Care 2021 Feb 28. Epub 2021 Feb 28.

Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

The coronavirus disease 2019 (COVID-19) pandemic has increased awareness that severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2) may have profound effects on the cardiovascular system. COVID-19 often affects patients with pre-existing cardiac disease, and may trigger acute respiratory distress syndrome (ARDS), venous thromboembolism (VTE), acute myocardial infarction (AMI), and acute heart failure (AHF). However, as COVID-19 is primarily a respiratory infectious disease, there remain substantial uncertainty and controversy whether and how cardiovascular biomarkers should be used in patients with suspected COVID-19. To help clinicians understand the possible value as well as the most appropriate interpretation of cardiovascular biomarkers in COVID-19, it is important to highlight that recent findings regarding the prognostic role of cardiovascular biomarkers in patients hospitalized with COVID-19 are similar to those obtained in studies for pneumonia and ARDS in general. Cardiovascular biomarkers reflecting pathophysiological processes involved in COVID-19/pneumonia and its complications have a role evaluating disease severity, cardiac involvement, and risk of death in COVID-19 as well as in pneumonias caused by other pathogens. First, cardiomyocyte injury, as quantified by cardiac troponin concentrations, and haemodynamic cardiac stress, as quantified by natriuretic peptide concentrations, may occur in COVID-19 as in other pneumonias. The level of those biomarkers correlates with disease severity and mortality. Interpretation of cardiac troponin and natriuretic peptide concentrations as quantitative variables may aid in risk stratification in COVID-19/pneumonia and also will ensure that these biomarkers maintain high diagnostic accuracy for AMI and AHF. Second, activated coagulation as quantified by D-dimers seems more prominent in COVID-19 as in other pneumonias. Due to the central role of endothelitis and VTE in COVID-19, serial measurements of D-dimers may help physicians in the selection of patients for VTE imaging and the intensification of the level of anticoagulation from prophylactic to slightly higher or even therapeutic doses.
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http://dx.doi.org/10.1093/ehjacc/zuab009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989520PMC
February 2021

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

Clin Res Cardiol 2021 Feb 26. Epub 2021 Feb 26.

3rd Department of Internal Medicine, Cardiology and Intensive Care Medicine, Wilhelminenhospital, Vienna, Austria.

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.
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http://dx.doi.org/10.1007/s00392-021-01821-2DOI Listing
February 2021

Biomarkers of coagulation and fibrinolysis in acute myocardial infarction: a joint position paper of the Association for Acute CardioVascular Care and the European Society of Cardiology Working Group on Thrombosis.

Eur Heart J Acute Cardiovasc Care 2020 Nov 7. Epub 2020 Nov 7.

Department of Cardiology, Aarhus University Hospital, Palle Juul-Jensens Blvd. 161, 8200 Aarhus N, Denmark.

The formation of a thrombus in an epicardial artery may result in an acute myocardial infarction (AMI). Despite major advances in acute treatment using network approaches to allocate patients to timely reperfusion and optimal antithrombotic treatment, patients remain at high risk for thrombotic complications. Ongoing activation of the coagulation system as well as thrombin-mediated platelet activation may both play a crucial role in this context. Whether measurement of circulating biomarkers of coagulation and fibrinolysis could be useful for risk stratification in secondary prevention is currently not fully understood. In addition, measurement of such biomarkers could be helpful to identify thrombus formation as the leading mechanism for AMI. The introduction of biomarkers of myocardial injury such as high-sensitivity cardiac troponins made rule-out of AMI even more precise. However, elevated markers of myocardial injury cannot provide proof of a type 1 AMI, let alone thrombus formation. The combined measurement of markers of myocardial injury with biomarkers reflecting ongoing thrombus formation might be helpful for the fast and correct diagnosis of an atherothrombotic type 1 AMI. This position paper gives an overview of the current knowledge and possible role of biomarkers of coagulation and fibrinolysis for the diagnosis of AMI, risk stratification, and individualized treatment strategies in patients with AMI.
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http://dx.doi.org/10.1093/ehjacc/zuaa025DOI Listing
November 2020

Impact of the COVID-19 shutdown on orthopedic trauma numbers and patterns in an academic Level I Trauma Center in Berlin, Germany.

PLoS One 2021 16;16(2):e0246956. Epub 2021 Feb 16.

Center for Musculoskeletal Surgery, Charité -Universitätsmedizin Berlin, Berlin, Germany.

Background: The COVID-19 pandemic led to the implementation of drastic shutdown measures worldwide. While quarantine, self-isolation and shutdown laws helped to effectively contain and control the spread of SARS-CoV-2, the impact of COVID-19 shutdowns on trauma care in emergency departments (EDs) remains elusive.

Methods: All ED patient records from the 35-day COVID-19 shutdown (SHUTDOWN) period were retrospectively compared to a calendar-matched control period in 2019 (CTRL) as well as to a pre (PRE)- and post (POST)-shutdown period in an academic Level I Trauma Center in Berlin, Germany. Total patient and orthopedic trauma cases and contacts as well as trauma causes and injury patterns were evaluated during respective periods regarding absolute numbers, incidence rate ratios (IRRs) and risk ratios (RRs).

Findings: Daily total patient cases (SHUTDOWN vs. CTRL, 106.94 vs. 167.54) and orthopedic trauma cases (SHUTDOWN vs. CTRL, 30.91 vs. 52.06) decreased during the SHUTDOWN compared to the CTRL period with IRRs of 0.64 and 0.59. While absolute numbers decreased for most trauma causes during the SHUTDOWN period, we observed increased incidence proportions of household injuries and bicycle accidents with RRs of 1.31 and 1.68 respectively. An RR of 2.41 was observed for injuries due to domestic violence. We further recorded increased incidence proportions of acute and regular substance abuse during the SHUTDOWN period with RRs of 1.63 and 3.22, respectively.

Conclusions: While we observed a relevant decrease in total patient cases, relative proportions of specific trauma causes and injury patterns increased during the COVID-19 shutdown in Berlin, Germany. As government programs offered prompt financial aid during the pandemic to individuals and businesses, additional social support may be considered for vulnerable domestic environments.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246956PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886210PMC
February 2021

Ambiguities.

Authors:
Martin Möckel
October 2020

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

Biomarkers 2021 May 18;26(3):213-220. Epub 2021 Feb 18.

Department of Emergency and Acute Medicine, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Berlin, Germany.

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  = 483 patients including  = 202 from the paediatric ED.  = 10 patients had to be excluded due to missing data and finally  = 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,  = 22 adult and  = 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 × 10 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.
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http://dx.doi.org/10.1080/1354750X.2021.1876769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898296PMC
May 2021

The accuracy of initial diagnoses in coma: an observational study in 835 patients with non-traumatic disorder of consciousness.

Scand J Trauma Resusc Emerg Med 2021 Jan 12;29(1):15. Epub 2021 Jan 12.

Department of Neurology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany.

Background: Management of patients with coma of unknown etiology (CUE) is a major challenge in most emergency departments (EDs). CUE is associated with a high mortality and a wide variety of pathologies that require differential therapies. A suspected diagnosis issued by pre-hospital emergency care providers often drives the first approach to these patients. We aim to determine the accuracy and value of the initial diagnostic hypothesis in patients with CUE.

Methods: Consecutive ED patients presenting with CUE were prospectively enrolled. We obtained the suspected diagnoses or working hypotheses from standardized reports given by prehospital emergency care providers, both paramedics and emergency physicians. Suspected and final diagnoses were classified into I) acute primary brain lesions, II) primary brain pathologies without acute lesions and III) pathologies that affected the brain secondarily. We compared suspected and final diagnosis with percent agreement and Cohen's Kappa including sub-group analyses for paramedics and physicians. Furthermore, we tested the value of suspected and final diagnoses as predictors for mortality with binary logistic regression models.

Results: Overall, suspected and final diagnoses matched in 62% of 835 enrolled patients. Cohen's Kappa showed a value of κ = .415 (95% CI .361-.469, p < .005). There was no relevant difference in diagnostic accuracy between paramedics and physicians. Suspected diagnoses did not significantly interact with in-hospital mortality (e.g., suspected class I: OR .982, 95% CI .518-1.836) while final diagnoses interacted strongly (e.g., final class I: OR 5.425, 95% CI 3.409-8.633).

Conclusion: In cases of CUE, the suspected diagnosis is unreliable, regardless of different pre-hospital care providers' qualifications. It is not an appropriate decision-making tool as it neither sufficiently predicts the final diagnosis nor detects the especially critical comatose patient. To avoid the risk of mistriage and unnecessarily delayed therapy, we advocate for a standardized diagnostic work-up for all CUE patients that should be triggered by the emergency symptom alone and not by any suspected diagnosis.
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http://dx.doi.org/10.1186/s13049-020-00822-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805149PMC
January 2021

Ythdf is a N6-methyladenosine reader that modulates Fmr1 target mRNA selection and restricts axonal growth in Drosophila.

EMBO J 2021 Feb 11;40(4):e104975. Epub 2021 Jan 11.

Center for Integrative Genomics, Génopode Building, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.

N6-methyladenosine (m A) regulates a variety of physiological processes through modulation of RNA metabolism. This modification is particularly enriched in the nervous system of several species, and its dysregulation has been associated with neurodevelopmental defects and neural dysfunctions. In Drosophila, loss of m A alters fly behavior, albeit the underlying molecular mechanism and the role of m A during nervous system development have remained elusive. Here we find that impairment of the m A pathway leads to axonal overgrowth and misguidance at larval neuromuscular junctions as well as in the adult mushroom bodies. We identify Ythdf as the main m A reader in the nervous system, being required to limit axonal growth. Mechanistically, we show that the m A reader Ythdf directly interacts with Fmr1, the fly homolog of Fragile X mental retardation RNA binding protein (FMRP), to inhibit the translation of key transcripts involved in axonal growth regulation. Altogether, this study demonstrates that the m A pathway controls development of the nervous system and modulates Fmr1 target transcript selection.
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http://dx.doi.org/10.15252/embj.2020104975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883056PMC
February 2021

One fits all hs troponin or more personalized dual markers strategies in the primary diagnostic assessment of patients with suspected acute coronary syndrome?

Authors:
Martin Möckel

Biomarkers 2020 12 24;25(8):611-612. Epub 2020 Nov 24.

Department of Emergency and Acute Medicine, Campus Mitte and Virchow, Charite Universitatsmedizin Berlin, Berlin, Germany.

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http://dx.doi.org/10.1080/1354750X.2020.1841293DOI Listing
December 2020

Analysis of standards of quality for outcomes in acute heart failure patients directly discharged home from emergency departments and their relationship with the emergency department direct discharge rate.

J Cardiol 2021 Mar 12;77(3):245-253. Epub 2020 Oct 12.

Emergency Department, Hospital Clínico San Carlos, Madrid, Instituto de Investigación Sanitaria San Carlos (IdISSC), Universidad Complutense de Madrid, Spain.

Objective: Experts recommended that direct discharge without hospitalization (DDWH) for emergency departments (EDs) able to observe acute heart failure (AHF) patients should be >40%, and these discharged patients should fulfil the following outcome standards: 30-day all-cause mortality <2% (outcome A); 7-day ED revisit due to AHF < 10% (outcome B); and 30-day ED revisit/hospitalization due to AHF < 20% (outcome C). We investigated these outcomes in a nationwide cohort and their relationship with the ED DDWH percentage.

Methods: We analyzed the EAHFE registry (includes about 15% of Spanish EDs), calculated DDWH percentage of each ED, and A/B/C outcomes of DDWH patients, overall and in each individual ED. Relationship between ED DDWH and outcomes was assessed by linear and quadratic regression models, non-weighted and weighted by DDWH patients provided by each ED.

Results: Among 17,420 patients, 4488 had DDWH (25.8%, median ED stay = 0 days, IQR = 0-1). Only 12.9% EDs achieved DDWH > 40%. Considering DDWH patients altogether, outcomes A/C were above the recommended standards (4.3%/29.4%), while outcome B was nearly met (B = 10.1%). When analyzing individual EDs, 58.1% of them achieved the outcome B standard, while outcomes A/C standards were barely achieved (19.3%/9.7%). We observed clinically relevant linear/quadratic relationships between higher DDWH and worse outcomes B (weighted R = 0.184/0.322) and C (weighted R = 0.430/0.624), but not with outcome A (weighted R = 0.002/0.022).

Conclusions: The EDs of this nationwide cohort do not fulfil the standards for AHF patients with DDWH. High DDWH rates negatively impact ED revisit or hospitalization but not mortality. This may represent an opportunity for improvement in better selecting patients for early ED discharge and in ensuring early follow-up after ED discharge.
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http://dx.doi.org/10.1016/j.jjcc.2020.09.002DOI Listing
March 2021

Evaluation of outcome relevance of quality indicators in the emergency department (ENQuIRE): study protocol for a prospective multicentre cohort study.

BMJ Open 2020 09 17;10(9):e038776. Epub 2020 Sep 17.

Department of Trauma Surgery, Otto von Guericke University, Magdeburg, Germany.

Introduction: Quality of emergency department (ED) care affects patient outcomes substantially. Quality indicators (QIs) for ED care are a major challenge due to the heterogeneity of patient populations, health care structures and processes in Germany. Although a number of quality measures are already in use, there is a paucity of data on the importance of these QIs on medium-term and long-term outcomes. The evaluation of outcome relevance of quality indicators in the emergency department study (ENQuIRE) aims to identify and investigate the relevance of QIs in the ED on patient outcomes in a 12-month follow-up.

Methods And Analysis: The study is a prospective non-interventional multicentre cohort study conducted in 15 EDs throughout Germany. Included are all patients in 2019, who were ≥18 years of age, insured at the Techniker Krankenkasse (statutory health insurance (SHI)) and gave their written informed consent to the study.The primary objective of the study is to assess the effect of selected quality measures on patient outcome. The data collected for this purpose comprise medical records from the ED treatment, discharge (claims) data from hospitalised patients, a patient questionnaire to be answered 6-8 weeks after emergency admission, and outcome measures in a 12-month follow-up obtained as claims data from the SHI.Descriptive and analytical statistics will be applied to provide summaries about the characteristics of QIs and associations between quality measures and patient outcomes.

Ethics And Dissemination: Approval of the leading ethics committee at the Medical Faculty of the University of Magdeburg (reference number 163/18 from 19 November 2018) has been obtained and adapted by responsible local ethics committees.The findings of this work will be disseminated by publication of peer-reviewed manuscripts and presentations as conference contributions (abstracts, poster or oral presentations).Moreover, results will be discussed with clinical experts and medical associations before being proposed for implementation into the quality management of EDs.

Trial Registration Number: German Clinical Trials Registry (DRKS00015203); Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2020-038776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500312PMC
September 2020

Self-referred walk-in patients in the emergency department - who and why? Consultation determinants in a multicenter study of respiratory patients in Berlin, Germany.

BMC Health Serv Res 2020 Sep 10;20(1):848. Epub 2020 Sep 10.

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of General Practice, Charitéplatz 1, 10117, Berlin, Germany.

Background: Emergency department (ED) consultations are on the rise, and frequently consultations by non-urgent patients have been held accountable. Self-referred walk-in (SRW) consulters supposedly represent a predominantly less urgent patient population. The EMACROSS study aimed to explore consultation determinants and motives in SRW patients with respiratory symptoms.

Methods: Multicenter survey of adult ED patients with respiratory complaints in eight emergency departments in central Berlin, Germany. Secondary hospital records data including diagnoses was additionally assessed. Characteristics of SRW and non-SRW patients were compared. Determinants of SRW consultation were evaluated by binary logistic regression. Consultation motives were analyzed descriptively. As a supplemental approach, network analysis (lasso-regularized mixed graphical model) was performed to explore connections between consultation determinants, consultation features and motives.

Results: Between June 2017 and November 2018, n = 472 participants were included, the median age was 55 years (range 18-96), 53.2% of patients were male and n = 185 cases (39.2%) were SRW consulters. The SRW group showed lower proportions of potentially severe (pneumonia and respiratory failure, p < 0.001, χ test) and chronic pulmonary conditions. Determinants of SRW consultation identified by logistic regression were younger age (p < 0.001), tertiary education (p = 0.032), being a first-generation migrant (p = 0.002) or tourist (p = 0.008), having no regular primary care provider (p = 0.036) and no chronic pulmonary illness (p = 0.017). The area under the curve (AUC) for the model was 0.79. Personal distress and access problems in ambulatory care were stated most frequently as consultation motives in the SRW group; network analysis showed the scarcity of associations between demographic and medical SRW determinants and motives triggering the actual decision to consult.

Conclusions: As to "who" consults, this study identified demographic and medical predictors of SRW utilization. The said markers seem only remotely connected to "why" people decide for SRW visits. To alleviate ED crowding by addressing frequent SRW consultation motives, interventions focused on the ability for symptom self-assessment and at better-accessible alternative care seem sensible.

Trial Registration: German Clinical Trials Register ( DRKS00011930 ); date: 2017/04/25.
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http://dx.doi.org/10.1186/s12913-020-05689-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7481545PMC
September 2020

Medical Emergencies During the COVID-19 Pandemic.

Dtsch Arztebl Int 2020 08;117(33-34):545-552

Departments of Emergency and Acute Medicine, Campus Mitte and Virchow-Klinikum Charité-Universitätsmedizin Berlin

Background: In this study, we investigate the number of emergency room consultations during the COVID-19 pandemic of 2020 in Germany compared to figures from the previous year.

Methods: Case numbers from calendar weeks 1 through 22 of the two consecutive years 2019 and 2020 were obtained from 29 university hospitals and 7 non-university hospitals in Germany. Information was also obtained on the patients' age, sex, and urgency, along with the type of case (outpatient/inpatient), admitting ward, and a small number of tracer diagnoses (I21, myocardial infarction; J44, COPD; and I61, I63, I64, G45, stroke /TIA), as well as on the number of COVID-19 cases and of tests performed for SARS-CoV-2, as a measure of the number of cases in which COVID-19 was suspected or at least included in the differential diagnoses.

Results: A total of 1 022 007 emergency room consultations were analyzed, of which 546 940 took place in 2019 and 475 067 in 2020. The number of consultations with a positive test for the COVID-19 pathogen was 3122. The total number of emergency room consultations in the observation period was 13% lower in 2020 than in 2019, with a maximum drop by 38% coinciding with the highest number of COVID-19 cases (calendar week 14; 572 cases). After the initiation of interpersonal contact restrictions in 2020, there was a marked drop in COVID-19 case numbers, by a mean of -240 cases per week per emergency room (95% confidence interval [-284; -128]). There was a rise in case numbers thereafter, by a mean of 17 patients per week [14; 19], and the number of cases of myocardial infarction returned fully to the level seen in 2019.

Conclusion: In Germany, the COVID-19 pandemic led to a significant drop in medical emergencies of all kinds presenting to the nation's emergency departments. A recovery effect began to be seen as early as calendar week 15, but the levels seen in 2019 were not yet reached overall by calendar week 22; only the prevalence of myocardial infarction had renormalized by then. The reasons for this require further investigation.
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http://dx.doi.org/10.3238/arztebl.2020.0545DOI Listing
August 2020

Plasma Angiotensin Peptide Profiling and ACE (Angiotensin-Converting Enzyme)-2 Activity in COVID-19 Patients Treated With Pharmacological Blockers of the Renin-Angiotensin System.

Hypertension 2020 11 27;76(5):e34-e36. Epub 2020 Aug 27.

From the Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany (U.K., A.S., M.M., R.R., F.K.).

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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480797PMC
November 2020

What role does the GP play for emergency department utilizers? A qualitative exploration of respiratory patients' perspectives in Berlin, Germany.

BMC Fam Pract 2020 07 30;21(1):154. Epub 2020 Jul 30.

Institute of General Practice, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.

Background: While motives for emergency department (ED) self-referrals have been investigated in a number of studies, the relevance of general practitioner (GP) care for these patients has not been comprehensively evaluated. Respiratory symptoms constitute an important utilization trigger in both EDs and in primary care. In this qualitative study, we aimed to explore the role of GP care for patients visiting EDs as outpatients for respiratory complaints and the relevance of the relationship between patient and GP in the decision making process leading up to an ED visit.

Methods: Qualitative descriptive study. Semi-structured, face-to-face interviews with a sample of 17 respiratory ED patients in Berlin, Germany. Interviews were recorded and transcribed verbatim. Qualitative content analysis was performed. The study was embedded into the EMACROSS (Emergency and Acute Care for Respiratory Diseases beyond Sectoral Separation) cohort of ED patients with respiratory symptoms, which is part of EMANet (Emergency and Acute Medicine Network for Health Care Research).

Results: Three patterns of GP utilization could be differentiated: long-term regular consulters, sporadic consulters and patients without GP. In sporadic consulters and patients without GP, an ambivalent or even aversive view of GP care was prevalent, with lack of confidence in GPs' competence and a deficit in trust as seemingly relevant influencing factors. Regardless of utilization or relationship type, patients frequently made contact with a GP before visiting an ED.

Conclusions: With regard to respiratory symptoms, our qualitative data suggest a hypothesis of limited relevance of patients' primary care utilization pattern and GP-patient relationship for ED consultation decisions.
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http://dx.doi.org/10.1186/s12875-020-01222-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393893PMC
July 2020

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

Clin Hemorheol Microcirc 2020 ;76(3):413-423

Department of Radiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.

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.
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http://dx.doi.org/10.3233/CH-200903DOI Listing
February 2021

Sexually assaulted women: Results of a retrospective analysis of 850 women in Germany.

Eur J Obstet Gynecol Reprod Biol 2020 Jul 1;250:117-123. Epub 2020 May 1.

Clinic for Gynaecology, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Germany. Electronic address:

Objective: According to prevalence studies, at least 5-6 % of women in Europe experience rape in their lives. The initial treatment after a sexual assault can influence the individual healing process positively. In Germany, there are hardly any studies that investigate larger collection of cases of sexual assault treated in hospitals. However, knowledge about characteristics of cases of sexual assault is a prerequisite for the optimal processing of primary care.

Study Design: For this study, the retrospective collection of data on cases of suspected sexual assault of patients presented for treatment at the Charité was carried out. Standardized findings sheets as part of a rape kit used in all cases were evaluated. Overall, 850 cases from the period between 01.01.2011 and 30.06.2016 were analyzed. The statistical evaluation was descriptive.

Results: The median age of patient was 26 years (range 16-92). Penetration (vaginal/anal/oral) occurred in 75 % of cases. The suspect was unknown to 48,4 % of those affected, 26 % came from a circle of friends or acquaintances. 15,5 % were partners or expartners. 2/3 of the sexual assaults took place in private rooms, especially in the apartments of the victims. More than 2/3 of the women had drunk alcohol in temporal proximity to the crime. Extragenital injuries were present in 61,4 % of those affected and anogenital injuries in 25,4 %. Extragenital injuries were predominantly classified as mild (92,9 % in general physical examination and 62,4 % in eyes-nose-throat-examination). 42,1 % of the assaults took place on the weekend. 74,8 % of the patients presented themselves within 24 h of the suspected offence.

Conclusion: To our knowledge, this is the largest analysis of cases of sexually assaulted women treated at a hospital in Germany. The results point to important components of primary care, e.g. standardized injury recording and alcohol measurement, as these can serve as evidence in subsequent court proceedings. The structures of the first care of victims after sexual assault should consider that the majority of those affected present themselves at the weekend.
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http://dx.doi.org/10.1016/j.ejogrb.2020.04.059DOI Listing
July 2020

Application of the fourth universal definition of myocardial infarction in clinical practice.

Biomarkers 2020 Jun 14;25(4):322-330. Epub 2020 May 14.

Department of Medical Sciences, Uppsala University and Uppsala Clinical Research Center, Uppsala University, Sweden.

The Fourth Universal Definition of Myocardial Infarction (MI) has highlighted the different pathophysiological mechanisms that may lead to ischaemic and non-ischaemic myocardial injury and has emphasised that the diagnosis of myocardial infarction requires the presence of acute myocardial ischaemia in the setting of acute myocardial injury. This case based review intends to illustrate basic principles on how to apply this new, revised definition in clinical practice. The distinction between different types of MIs (type 1 or type 2) and the delineation of MI from acute non-ischaemic myocardial injury may be challenging in individual patients, which is illustrated by presenting and discussing real-life routine cases. Type 1 MI is a consequence of coronary plaque rupture or erosion with intracoronary thrombus formation that is usually apparent on coronary angiography. Plausible triggering mechanisms causing myocardial oxygen supply/demand mismatch must be identified for the diagnosis of type 2 MI and its treatment should focus initially on management of the underlying disease attributable to acute myocardial ischaemia.
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http://dx.doi.org/10.1080/1354750X.2020.1764108DOI Listing
June 2020

How emergency departments prepare for virus disease outbreaks like COVID-19.

Eur J Emerg Med 2020 06;27(3):161-162

Department of Infectious Diseases and Respiratory Medicine, Charité - Universitätsmedizin, Berlin, Germany.

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http://dx.doi.org/10.1097/MEJ.0000000000000703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202109PMC
June 2020

Improve Management of acute heart failure with ProcAlCiTonin in EUrope: results of the randomized clinical trial IMPACT EU Biomarkers in Cardiology (BIC) 18.

Eur J Heart Fail 2020 02 12;22(2):267-275. Epub 2019 Dec 12.

Abteilung Innere Medizin III Kardiologie, Angiologie und Pneumologie, Medizinische Universitätsklinik Heidelberg, Heidelberg, Germany.

Aim: To determine whether initiation of antibiotic therapy (ABX) by procalcitonin (PCT) within 8 h of admission in patients presenting to the emergency department with symptoms and signs of acute heart failure (AHF) and elevated natriuretic peptides would improve clinical outcomes.

Methods And Results: The study was a randomized multicentre clinical trial conducted at 16 sites in Europe. Patients were randomized to either a PCT-guided strategy or standard care. Patients with PCT-guided strategy (n = 370) had ABX initiated if PCT was > 0.2 μg/L. Patients with standard care (n = 372) had AHF care in accordance with published guidelines without PCT. The primary endpoint was 90-day all-cause mortality. Pre-specified secondary endpoints included 30-day all-cause mortality and readmission and rate of pneumonia. The Data Safety and Review Committee recommended stopping the study for futility when 762 of the planned 792 patients had been enrolled. A total of 742 patients could be analysed. Patients were elderly (median age: 77 years), 38% were women, and had typical signs and symptoms of AHF. All-cause mortality at 90 days was 10.3% in the PCT-guided group vs. 8.2% in standard care (P = 0.316). Thirty-day readmission was significantly higher in the PCT-guided group vs. standard care but the difference vanished until day 90. The rate of pneumonia was overall low (7.5%) and not different between groups.

Conclusions: In patients with AHF, a strategy of PCT-guided initiation of ABX was not more effective than a standard care strategy in improving clinical outcomes.
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http://dx.doi.org/10.1002/ejhf.1667DOI Listing
February 2020

[Discussion paper for a hospital financing reform in Germany from the perspective of intensive care medicine].

Med Klin Intensivmed Notfmed 2020 Feb;115(1):59-66

Geschäftsbereich Medizincontrolling, München Klinik, Thalkirchner Str. 48, 80337, München, Deutschland.

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.
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http://dx.doi.org/10.1007/s00063-019-00629-3DOI Listing
February 2020

Causes of brain dysfunction in acute coma: a cohort study of 1027 patients in the emergency department.

Scand J Trauma Resusc Emerg Med 2019 Nov 7;27(1):101. Epub 2019 Nov 7.

Department of Neurology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Augustenburger Platz 1, 13353, Berlin, Germany.

Background: Coma of unknown etiology (CUE) is a major challenge in emergency medicine. CUE is caused by a wide variety of pathologies that require immediate and targeted treatment. However, there is little empirical data guiding rational and efficient management of CUE. We present a detailed investigation on the causes of CUE in patients presenting to the ED of a university hospital.

Methods: One thousand twenty-seven consecutive ED patients with CUE were enrolled. Applying a retrospective observational study design, we analyzed all clinical, laboratory and imaging findings resulting from a standardized emergency work-up of each patient. Following a predefined protocol, we identified main and accessory coma-explaining pathologies and related these with (i.a.) GCS and in-hospital mortality.

Results: On admission, 854 of the 1027 patients presented with persistent CUE. Their main diagnoses were classified into acute primary brain lesions (39%), primary brain pathologies without acute lesions (25%) and pathologies that affected the brain secondarily (36%). In-hospital mortality associated with persistent CUE amounted to 25%. 33% of patients with persistent CUE presented with more than one coma-explaining pathology. In 173 of the 1027 patients, CUE had already resolved on admission. However, these patients showed a spectrum of main diagnoses similar to persistent CUE and a significant in-hospital mortality of 5%.

Conclusion: The data from our cohort show that the spectrum of conditions underlying CUE is broad and may include a surprisingly high number of coincidences of multiple coma-explaining pathologies. This finding has not been reported so far. Thus, significant pathologies may be masked by initial findings and only appear at the end of the diagnostic work-up. Furthermore, even transient CUE showed a significant mortality, thus rendering GCS cutoffs for selection of high- and low-risk patients questionable. Taken together, our data advocate for a standardized diagnostic work-up that should be triggered by the emergency symptom CUE and not by any suspected diagnosis. This standardized routine should always be completed - even when initial coma-explaining diagnoses may seem evident.
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http://dx.doi.org/10.1186/s13049-019-0669-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6836468PMC
November 2019

The RNA-binding ubiquitin ligase MKRN1 functions in ribosome-associated quality control of poly(A) translation.

Genome Biol 2019 10 22;20(1):216. Epub 2019 Oct 22.

Institute of Molecular Biology (IMB), Ackermannweg 4, 55128, Mainz, Germany.

Background: Cells have evolved quality control mechanisms to ensure protein homeostasis by detecting and degrading aberrant mRNAs and proteins. A common source of aberrant mRNAs is premature polyadenylation, which can result in non-functional protein products. Translating ribosomes that encounter poly(A) sequences are terminally stalled, followed by ribosome recycling and decay of the truncated nascent polypeptide via ribosome-associated quality control.

Results: Here, we demonstrate that the conserved RNA-binding E3 ubiquitin ligase Makorin Ring Finger Protein 1 (MKRN1) promotes ribosome stalling at poly(A) sequences during ribosome-associated quality control. We show that MKRN1 directly binds to the cytoplasmic poly(A)-binding protein (PABPC1) and associates with polysomes. MKRN1 is positioned upstream of poly(A) tails in mRNAs in a PABPC1-dependent manner. Ubiquitin remnant profiling and in vitro ubiquitylation assays uncover PABPC1 and ribosomal protein RPS10 as direct ubiquitylation substrates of MKRN1.

Conclusions: We propose that MKRN1 mediates the recognition of poly(A) tails to prevent the production of erroneous proteins from prematurely polyadenylated transcripts, thereby maintaining proteome integrity.
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http://dx.doi.org/10.1186/s13059-019-1814-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805484PMC
October 2019