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Reactive aldehydes are produced by normal cellular metabolism or after alcohol consumption, and they accumulate in human tissues if aldehyde clearance mechanisms are impaired. Their toxicity has been attributed to the damage they cause to genomic DNA and the subsequent inhibition of transcription and replication. However, whether interference with other cellular processes contributes to aldehyde toxicity has not been investigated. We demonstrate that formaldehyde induces RNA-protein crosslinks (RPCs) that stall the ribosome and inhibit translation in human cells. RPCs in the messenger RNA (mRNA) are recognized by the translating ribosomes, marked by atypical K6-linked ubiquitylation catalyzed by the RING-in-between-RING (RBR) E3 ligase RNF14, and subsequently resolved by the ubiquitin- and ATP-dependent unfoldase VCP. Our findings uncover an evolutionary conserved formaldehyde-induced stress response pathway that protects cells against RPC accumulation in the cytoplasm, and they suggest that RPCs contribute to the cellular and tissue toxicity of reactive aldehydes.
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RNA , Ubiquitina-Proteína Ligases , Humanos , RNA/metabolismo , Ubiquitinação , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Formaldeído/toxicidade , Aldeídos/toxicidade , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Splicing of pre-mRNAs critically contributes to gene regulation and proteome expansion in eukaryotes, but our understanding of the recognition and pairing of splice sites during spliceosome assembly lacks detail. Here, we identify the multidomain RNA-binding protein FUBP1 as a key splicing factor that binds to a hitherto unknown cis-regulatory motif. By collecting NMR, structural, and in vivo interaction data, we demonstrate that FUBP1 stabilizes U2AF2 and SF1, key components at the 3' splice site, through multivalent binding interfaces located within its disordered regions. Transcriptional profiling and kinetic modeling reveal that FUBP1 is required for efficient splicing of long introns, which is impaired in cancer patients harboring FUBP1 mutations. Notably, FUBP1 interacts with numerous U1 snRNP-associated proteins, suggesting a unique role for FUBP1 in splice site bridging for long introns. We propose a compelling model for 3' splice site recognition of long introns, which represent 80% of all human introns.
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Sítios de Splice de RNA , Splicing de RNA , Humanos , Sítios de Splice de RNA/genética , Íntrons/genética , Fatores de Processamento de RNA/genética , Fatores de Processamento de RNA/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Precursores de RNA/genética , Precursores de RNA/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismoRESUMO
The Anopheles mosquito is one of thousands of species in which sex differences play a central part in their biology, as only females need a blood meal to produce eggs. Sex differentiation is regulated by sex chromosomes, but their presence creates a dosage imbalance between males (XY) and females (XX). Dosage compensation (DC) can re-equilibrate the expression of sex chromosomal genes. However, because DC mechanisms have only been fully characterized in a few model organisms, key questions about its evolutionary diversity and functional necessity remain unresolved1. Here we report the discovery of a previously uncharacterized gene (sex chromosome activation (SOA)) as a master regulator of DC in the malaria mosquito Anopheles gambiae. Sex-specific alternative splicing prevents functional SOA protein expression in females. The male isoform encodes a DNA-binding protein that binds the promoters of active X chromosomal genes. Expressing male SOA is sufficient to induce DC in female cells. Male mosquitoes lacking SOA or female mosquitoes ectopically expressing the male isoform exhibit X chromosome misregulation, which is compatible with viability but causes developmental delay. Thus, our molecular analyses of a DC master regulator in a non-model organism elucidates the evolutionary steps that lead to the establishment of a chromosome-specific fine-tuning mechanism.
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Processamento Alternativo , Anopheles , Mecanismo Genético de Compensação de Dose , Proteínas de Insetos , Caracteres Sexuais , Diferenciação Sexual , Cromossomo X , Animais , Feminino , Masculino , Anopheles/genética , Anopheles/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Diferenciação Sexual/genética , Cromossomo X/genética , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismoRESUMO
Piwi-interacting RNAs (piRNAs) direct PIWI proteins to transposons to silence them, thereby preserving genome integrity and fertility. The piRNA population can be expanded in the ping-pong amplification loop. Within this process, piRNA-associated PIWI proteins (piRISC) enter a membraneless organelle called nuage to cleave their target RNA, which is stimulated by Gtsf proteins. The resulting cleavage product gets loaded into an empty PIWI protein to form a new piRISC complex. However, for piRNA amplification to occur, the new RNA substrates, Gtsf-piRISC, and empty PIWI proteins have to be in physical proximity. In this study, we show that in silkworm cells, the Gtsf1 homolog BmGtsf1L binds to piRNA-loaded BmAgo3 and localizes to granules positive for BmAgo3 and BmVreteno. Biochemical assays further revealed that conserved residues within the unstructured tail of BmGtsf1L directly interact with BmVreteno. Using a combination of AlphaFold modeling, atomistic molecular dynamics simulations, and in vitro assays, we identified a novel binding interface on the BmVreteno-eTudor domain, which is required for BmGtsf1L binding. Our study reveals that a single eTudor domain within BmVreteno provides two binding interfaces and thereby interconnects piRNA-loaded BmAgo3 and BmGtsf1L.
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Bombyx , Animais , Proteínas Argonautas/genética , Proteínas Argonautas/metabolismo , Bombyx/genética , Bombyx/metabolismo , RNA de Interação com Piwi , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Domínio TudorRESUMO
N6-methyladenosine (m6 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 m6 A alters fly behavior, albeit the underlying molecular mechanism and the role of m6 A during nervous system development have remained elusive. Here we find that impairment of the m6 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 m6 A reader in the nervous system, being required to limit axonal growth. Mechanistically, we show that the m6 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 m6 A pathway controls development of the nervous system and modulates Fmr1 target transcript selection.
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Adenosina/análogos & derivados , Axônios/fisiologia , Proteínas de Drosophila/metabolismo , Proteína do X Frágil da Deficiência Intelectual/metabolismo , Neurônios/citologia , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/metabolismo , Adenosina/metabolismo , Animais , Proteínas de Drosophila/genética , Drosophila melanogaster , Proteína do X Frágil da Deficiência Intelectual/genética , Neurônios/fisiologia , RNA Mensageiro/genética , Proteínas de Ligação a RNA/genéticaRESUMO
OBJECTIVES: Consensus regarding biomarkers for detection of infection-related organ dysfunction in the emergency department is lacking. We aimed to identify and validate biomarkers that could improve risk prediction for overt or incipient organ dysfunction when added to quick Sepsis-related Organ Failure Assessment (qSOFA) as a screening tool. DESIGN: In a large prospective multicenter cohort of adult patients presenting to the emergency department with a qSOFA score greater than or equal to 1, admission plasma levels of C-reactive protein, procalcitonin, adrenomedullin (either bioavailable adrenomedullin or midregional fragment of proadrenomedullin), proenkephalin, and dipeptidyl peptidase 3 were assessed. Least absolute shrinkage and selection operator regression was applied to assess the impact of these biomarkers alone or in combination to detect the primary endpoint of prediction of sepsis within 96 hours of admission. SETTING: Three tertiary emergency departments at German University Hospitals (Jena University Hospital and two sites of the Charité University Hospital, Berlin). PATIENTS: One thousand four hundred seventy-seven adult patients presenting with suspected organ dysfunction based on qSOFA score greater than or equal to 1. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The cohort was of moderate severity with 81% presenting with qSOFA = 1; 29.2% of these patients developed sepsis. Procalcitonin outperformed all other biomarkers regarding the primary endpoint (area under the curve for receiver operating characteristic [AUC-ROC], 0.86 [0.79-0.93]). Adding other biomarkers failed to further improve the AUC-ROC for the primary endpoint; however, they improved the model regarding several secondary endpoints, such as mortality, need for vasopressors, or dialysis. Addition of procalcitonin with a cutoff level of 0.25 ng/mL improved net (re)classification by 35.2% compared with qSOFA alone, with positive and negative predictive values of 60.7% and 88.7%, respectively. CONCLUSIONS: Biomarkers of infection and organ dysfunction, most notably procalcitonin, substantially improve early prediction of sepsis with added value to qSOFA alone as a simple screening tool on emergency department admission.
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Biomarcadores , Serviço Hospitalar de Emergência , Escores de Disfunção Orgânica , Pró-Calcitonina , Sepse , Humanos , Sepse/diagnóstico , Sepse/sangue , Biomarcadores/sangue , Masculino , Feminino , Estudos Prospectivos , Pessoa de Meia-Idade , Idoso , Pró-Calcitonina/sangue , Adrenomedulina/sangue , Insuficiência de Múltiplos Órgãos/diagnóstico , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/etiologia , Proteína C-Reativa/análise , Adulto , Encefalinas/sangue , Precursores de ProteínasRESUMO
OBJECTIVES: This study aimed to explore the role of CT in septic patients presenting to the emergency department (ED). MATERIALS AND METHODS: We performed a retrospective secondary analysis of 192 septic patients from a prospective observational study, i.e., the "LIFE POC" study. Sepsis was diagnosed in accordance with the Sepsis-3 definition. Clinical and radiological data were collected from the hospital administration and radiological systems. Information on mortality and morbidity was collected. Time-to-CT between CT scan and sepsis diagnosis (ttCTsd) was calculated. Diagnostic accuracy was assessed with the final sepsis source as reference standard. The reference standard was established through the treating team of the patient based on all available clinical, imaging, and microbiological data. RESULTS: Sixty-two of 192 patients underwent a CT examination for sepsis focus detection. The final septic source was identified by CT in 69.4% (n = 43). CT detected septic foci with 81.1% sensitivity (95% CI, 68.0-90.6%) and 55.6% specificity (95% CI, 21.2-86.3%). Patients with short versus long ttCTsd did not differ in terms of mortality (16.1%, n = 5 vs 9.7, n = 3; p = 0.449), length of hospital stay (median 16 d, IQR 9 d 12 h-23 d 18 h vs median 13 d, IQR 10 d 00 h-24 d 00 h; p = 0.863), or duration of intensive care (median 3d 12 h, IQR 2 d 6 h-7 d 18 h vs median 5d, IQR 2 d-11 d; p = 0.800). CONCLUSIONS: Our findings show a high sensitivity of CT in ED patients with sepsis, confirming its relevance in guiding treatment decisions. The low specificity suggests that a negative CT requires further ancillary diagnostic tests for focus detection. The timing of CT did not affect morbidity or mortality outcomes. CLINICAL RELEVANCE STATEMENT: In patients with sepsis who present to the ED, CT can be used to identify infectious foci on the basis of clinical suspicion, but should not be used as a rule-out test. Scientific evidence for the optimal timing of CT beyond clinical decision-making is currently missing, as potential mortality benefits are clouded by differences in clinical severity at the time of ED presentation. KEY POINTS: ⢠In patients with sepsis who present to the ED, CT for focus identification has a high sensitivity and can thereby be valuable for patient management. ⢠As the specificity is considerably lower, a thorough microbiological assessment is important in these cases. ⢠The timing of CT did not affect morbidity and mortality outcomes in this study, which might be due to variability in clinical severity at the time of ED presentation.
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The new guideline on acute coronary syndrome (ACS) of the European Society of Cardiology (ESC) replaces two separate guidelines on ST-elevation myocardial infarction (STEMI) and non-ST-elevation (NSTE) ACS. This change of paradigm reflects the experts view that the ACS is a continuum, starting with unstable angina and ending in cardiogenic shock or cardiac arrest due to severe myocardial ischemia. Secondary, partly non-atherosclerotic-caused myocardial infarctions ("type 2") are not integrated in this concept.With respect to acute care in the setting of emergency medicine and the chest pain unit structures, the following new aspects have to be taken into account:1. New procedural approach as "think A.C.S." meaning "abnormal ECG," "clinical context," and "stable patient"2. New recommendation regarding a holistic approach for frail patients3. Revised recommendations regarding imaging and timing of invasive strategy in suspected NSTE-ACS4. Revised recommendations for antiplatelet and anticoagulant therapy in STEMI5. Revised recommendations for cardiac arrest and out-of-hospital cardiac arrest6. Revised recommendations for in-hospital management (starting in the CPU/ED) and ACS comorbid conditionsIn summary, the changes are mostly gradual and are not based on extensive new evidence, but more on focused and healthcare process-related considerations.
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Síndrome Coronariana Aguda , Serviço Hospitalar de Emergência , Guias de Prática Clínica como Assunto , Síndrome Coronariana Aguda/terapia , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/complicações , Humanos , Europa (Continente) , Serviço Hospitalar de Emergência/normas , Cardiologia/normas , Serviços Médicos de Emergência/normasRESUMO
BACKGROUND: Emergency departments (ED) worldwide have to cope with rising patient numbers. Low-acuity consulters who could receive a more suitable treatment in primary care (PC) increase caseloads, and lack of PC attachment has been discussed as a determinant. This qualitative study explores factors that contribute to non-utilization of general practitioner (GP) care among patients with no current attachment to a GP. METHOD: Qualitative semi-structured telephone interviews were conducted with 32 low-acuity ED consulters with no self-reported attachment to a GP. Participants were recruited from three EDs in the city center of Berlin, Germany. Data were analyzed by qualitative content analysis. RESULTS: Interviewed patients reported heterogeneous factors contributing to their PC utilization behavior and underlying views and experiences. Participants most prominently voiced a rare need for medical services, a distinct mobility behavior, and a lack of knowledge about the role of a GP and health care options. Views about and experiences with GP care that contribute to non-utilization were predominantly related to little confidence in GP care, preference for directly consulting medical specialists, and negative experiences with GP care in the past. Contrasting their reported utilization behavior, many interviewees still recognized the advantages of GP care continuity. CONCLUSION: Understanding reasons of low-acuity ED patients for GP non-utilization can play an important role in the design and implementation of patient-centered care interventions for PC integration. Increasing GP utilization, continuity of care and health literacy might have positive effects on patient decision-making in acute situations and in turn decrease ED burden. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00023480; date: 2020/11/27.
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Serviço Hospitalar de Emergência , Clínicos Gerais , Atenção Primária à Saúde , Pesquisa Qualitativa , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Serviço Hospitalar de Emergência/estatística & dados numéricos , Adulto , Clínicos Gerais/psicologia , Entrevistas como Assunto , Idoso , Gravidade do Paciente , AlemanhaRESUMO
BACKGROUND: Utilization by low acuity patients contributes to emergency department (ED) crowding. Both knowledge deficits about adequate care levels and access barriers in primary care are important promoters of such presentations. Concurrently, not having a general practitioner (GP) increases the likelihood of low-acuity ED utilization. This pilot study thus investigated feasibility, acceptance, and potential effects of an ED-delivered intervention for low-acuity patients with no regular primary care provider, consisting of an educational leaflet on acute care options and an optional GP appointment scheduling service. METHODS: Low-acuity ED consulters not attached to a GP were given an information leaflet about alternative care offers for acute health problems and offered optional personal appointment scheduling at a local GP practice. Patients were surveyed on demographics, medical characteristics, health care utilization, valuation of the intervention, and reasons for not being attached to a GP and visiting the ED. A follow-up survey was conducted after twelve months. Trends in health and health care utilization were evaluated. RESULTS: Between December 2020 and April 2022, n = 160 patients were enrolled, n = 114 were followed up. The study population was characterized by young age (mean 30.6 years) and predominantly good general health. Besides good health, personal mobility was a central reason for not being attached to a GP, but general preference for specialists and bad experiences with primary care were also mentioned. Most frequently stated motives for the ED consultation were subjective distress and anxiety, a belief in the superiority of the hospital, and access problems in primary care. The interventional offers were favorably valued, 52.5% (n = 84) accepted the GP appointment scheduling service offer. At follow-up, GP utilization had significantly increased, while there were no significant changes regarding utilization of other providers, including ED. An additional practice survey showed a 63.0% take-up rate for the appointment service. CONCLUSIONS: With this pilot study, we were able to show that a personalized appointment scheduling service seems to be a promising approach to promote GP attachment and increase primary care utilization in patients without a regular GP in a highly urbanized setting. Further larger-scale studies are needed to investigate potential quantitative effects on ED visits. TRIAL REGISTRATION: German Clinical Trials Register (DRKS00023480); date 2020/11/27.
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Visitas ao Pronto Socorro , Serviço Hospitalar de Emergência , Atenção Primária à Saúde , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Agendamento de Consultas , Berlim , Visitas ao Pronto Socorro/organização & administração , Visitas ao Pronto Socorro/estatística & dados numéricos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Projetos Piloto , Inquéritos e QuestionáriosRESUMO
The turn-around-time (TAT) of diagnostic and screening measures such as testing for SARS-CoV-2 can affect a patient's length of stay (LOS) in the hospital as well as the emergency department (ED). This, in turn, can affect clinical outcomes. Therefore, a reliable and time-efficient SARS-CoV-2 testing strategy is necessary, especially in the ED. In this randomised controlled trial, n = 598 ED patients presenting to one of three university hospital EDs in Berlin, Germany, and needing hospitalisation were randomly assigned to two intervention groups and one control group. Accordingly, different SARS-CoV-2 testing strategies were implemented: rapid antigen and point-of-care (POC) reverse transcription polymerase chain reaction (rtPCR) testing with the Roche cobas® Liat® (LIAT) (group one n = 198), POC rtPCR testing with the LIAT (group two n = 197), and central laboratory rtPCR testing (group three, control group n = 203). The median LOS in the hospital as an inpatient across the groups was 7 days. Patients' LOS in the ED of more than seven hours did not differ significantly, and furthermore, no significant differences were observed regarding clinical outcomes such as intensive care unit stay or death. The rapid and POC test strategies had a significantly (p < 0.01) shorter median TAT (group one 00:48 h, group two 00:21 h) than the regular central laboratory rtPCR test (group three 06:26 h). However, fast SARS-CoV-2 testing strategies did not reduce ED or inpatient LOS significantly in less urgent ED admissions. Testing strategies should be adjusted to the current circumstances including crowding, SARS-CoV-2 incidences, and patient cohort. This trial is registered with DRKS00023117.
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BACKGROUND: This analysis addresses the characteristics of two emergency department (ED) patient populations defined by three model diseases (hip fractures, respiratory, and cardiac symptoms) making use of survey (primary) and routine (secondary) data from hospital information systems (HIS). Our aims were to identify potential systematic inconsistencies between both data samples and implications of their use for future ED-based health services research. METHODS: The research network EMANET prospectively collected primary data (n=1442) from 2017-2019 and routine data from 2016 (n=9329) of eight EDs in a major German city. Patient populations were characterized using socio-structural (age, gender) and health- and care-related variables (triage, transport to ED, case and discharge type, multi-morbidity). Statistical comparisons between descriptive results of primary and secondary data samples for each variable were conducted using binomial test, chi-square goodness-of-fit test, or one-sample t-test according to scale level. RESULTS: Differences in distributions of patient characteristics were found in nearly all variables in all three disease populations, especially with regard to transport to ED, discharge type and prevalence of multi-morbidity. Recruitment conditions (e.g., patient non-response), project-specific inclusion criteria (e.g., age and case type restrictions) as well as documentation routines and practices of data production (e.g., coding of diagnoses) affected the composition of primary patient samples. Time restrictions of recruitment procedures did not generate meaningful differences regarding the distribution of characteristics in primary and secondary data samples. CONCLUSIONS: Primary and secondary data types maintain their advantages and shortcomings in the context of emergency medicine health services research. However, differences in the distribution of selected variables are rather small. The identification and classification of these effects for data interpretation as well as the establishment of monitoring systems in the data collection process are pivotal. TRIAL REGISTRATION: DRKS00011930 (EMACROSS), DRKS00014273 (EMAAGE), NCT03188861 (EMASPOT).
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Medicina de Emergência , Multimorbidade , Humanos , Serviço Hospitalar de Emergência , Pesquisa sobre Serviços de Saúde , Triagem/métodosRESUMO
INTRODUCTION: It has not yet been possible to ascertain the exact proportion, characterization or impact of low-acuity emergency department (ED) attendances on the German Health Care System since valid and robust definitions to be applied in German ED routine data are missing. METHODS: Internationally used methods and parameters to identify low-acuity ED attendances were identified, analyzed and then applied to routine ED data from two EDs of the tertiary care hospitals Charité-Universitätsmedizin Berlin, Campus Mitte (CCM) and Campus Virchow (CVK). RESULTS: Based on the three routinely available parameters `disposition´, `transport to the ED´ and `triage´ 33.2% (n = 30 676) out of 92 477 presentations to the two EDs of Charité-Universitätsmedizin Berlin (CVK, CCM) in 2016 could be classified as low-acuity presentations. CONCLUSION: This study provides a reliable and replicable means of retrospective identification and quantification of low-acuity attendances in German ED routine data. This enables both intra-national and international comparisons of figures across future studies and health care monitoring.
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Serviço Hospitalar de Emergência , Triagem , Humanos , Estudos RetrospectivosRESUMO
Heart failure remains a major global burden regarding patients' morbidity and mortality and health system organization, logistics, and costs. Despite continual advances in pharmacological and resynchronization device therapy, it is currently well accepted that heart transplantation and mechanical circulatory support represent a cornerstone in the management of advanced forms of this disease, with the latter becoming an increasingly accepted treatment modality due to the ongoing shortage of available donor hearts in an ever-increasing pool of patients. Mechanical circulatory support strategies have seen tremendous advances in recent years, especially in terms of pump technology improvements, indication for use, surgical techniques for device implantation, exchange and explantation, and postoperative patient management, but not in the field of treatment of critically ill patients and those undergoing cardiac arrest. This contemporary review aims to summarize the collected knowledge of this topic with an emphasis on complications in patients with left ventricular assist devices, their treatment, and establishing a clear-cut algorithm and the latest recommendations regarding out-of-hospital or emergency department management of cardiac arrest in this patient population.
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Reanimação Cardiopulmonar , Parada Cardíaca , Insuficiência Cardíaca , Transplante de Coração , Coração Auxiliar , Humanos , Doadores de Tecidos , Reanimação Cardiopulmonar/efeitos adversos , Reanimação Cardiopulmonar/métodos , Coração Auxiliar/efeitos adversos , Parada Cardíaca/etiologiaRESUMO
A plethora of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostic tests are available, each with different performance specifications, detection methods, and targets. This narrative review aims to summarize the diagnostic technologies available and how they are best selected to tackle SARS-CoV-2 infection as the pandemic evolves. Seven key settings have been identified where diagnostic tests are being deployed: symptomatic individuals presenting for diagnostic testing and/or treatment of COVID-19 symptoms; asymptomatic individuals accessing healthcare for planned non-COVID-19-related reasons; patients needing to access emergency care (symptom status unknown); patients being discharged from healthcare following hospitalization for COVID-19; healthy individuals in both single event settings (e.g. airports, restaurants, hotels, concerts, and sporting events) and repeat access settings (e.g. workplaces, schools, and universities); and vaccinated individuals. While molecular diagnostics remain central to SARS-CoV-2 testing strategies, we have offered some discussion on the considerations for when other tools and technologies may be useful, when centralized/point-of-care testing is appropriate, and how the various additional diagnostics can be deployed in differently resourced settings. As the pandemic evolves, molecular testing remains important for definitive diagnosis, but increasingly widespread point-of-care testing is essential to the re-opening of society.
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COVID-19 , SARS-CoV-2 , Humanos , Teste para COVID-19 , COVID-19/diagnóstico , Pandemias , Testes Imediatos , Sensibilidade e EspecificidadeRESUMO
PURPOSE: This review intends to illustrate basic principles on how to apply the Fourth Universal Definition of Myocardial Infarction (UDMI) for the diagnosis of peri-procedural myocardial infarction (MI) after percutaneous coronary interventions (PCI) in clinical practice. METHODS AND RESULTS: Review of routine case-based events. Increases in cardiac troponin (cTn) concentrations are common after elective PCI in patients with chronic coronary syndrome (CCS). Peri-procedural PCI-related MI (type 4a MI) in CCS patients should be diagnosed in cases of major peri-procedural acute myocardial injury indicated by an increase in cTn concentrations of >5-times the 99th percentile upper reference limit (URL) together with evidence of new peri-procedural myocardial ischaemia as demonstrated by electrocardiography (ECG), imaging, or flow-limiting peri-procedural complications in coronary angiography. Measurement of cTn baseline concentrations before elective PCI is useful. In patients presenting with acute MI undergoing PCI, peri-procedural increases in cTn concentrations are usually due to their index presentation and not PCI-related, apart from obvious major peri-procedural complications, such as persistent occlusion of a large side branch or no-reflow after stent implantation. CONCLUSION: The distinction between type 4a MI, PCI-related acute myocardial injury, and chronic myocardial injury can be challenging in individuals undergoing PCI. Careful integration of all available clinical data is essential for correct classification.
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Cardiologia , Infarto do Miocárdio , Intervenção Coronária Percutânea , Biomarcadores , Angiografia Coronária/efeitos adversos , Humanos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea/efeitos adversosRESUMO
BACKGROUND: Only few studies of emergency department (ED) consulters include a longitudinal investigation. The EMACROSS study had surveyed 472 respiratory patients in eight inner-city EDs in Berlin in 2017/2018 for demographic, medical and consultation-related characteristics. This paper presents the results of a follow-up survey at a median of 95 days post-discharge. We aimed to explore the post hoc assessment of ED care and identify potential longitudinal trends. METHODS: The follow-up survey included items on satisfaction with care received, benefit from the ED visit, potential alternative care, health care utilization, mental and general health, and general life satisfaction. Univariable between-subject and within-subject statistical comparisons were conducted. Logistic regression was performed for multivariable investigations of determinants of dropout and of retrospectively rating the ED visit as beneficial. RESULTS: Follow-up data was available for 329 patients. Participants of lower education status, migrants, and tourists were more likely to drop out. Having a general practitioner (GP), multimorbidity, and higher general life satisfaction were determinants of response. Retrospective satisfaction ratings were high with no marked longitudinal changes and waiting times as the most frequent reason for dissatisfaction. Retrospective assessment of the visit as beneficial was positively associated with male sex, diagnoses of pneumonia and respiratory failure, and self-referral. Concerning primary care as a viable alternative, judgment at the time of the ED visit and at follow-up did not differ significantly. Health care utilization post-discharge increased for GPs and pulmonologists. Self-reported general health and PHQ-4 anxiety scores were significantly improved at follow-up, while general life satisfaction for the overall sample was unchanged. CONCLUSIONS: Most patients retrospectively assess the ED visit as satisfactory and beneficial. Possible sex differences in perception of care and its outcomes should be further investigated. Conceivable efforts at diversion of ED utilizers to primary care should consider patients' views regarding acceptable alternatives, which appear relatively independent of situational factors. Representativeness of results is restricted by the study focus on respiratory symptoms, the limited sample size, and the attrition rate. TRIAL REGISTRATION: German Clinical Trials Register ( DRKS00011930 ); date: 2017/04/25.
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Assistência ao Convalescente , Saúde Mental , Berlim , Serviço Hospitalar de Emergência , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Aceitação pelo Paciente de Cuidados de Saúde , Alta do Paciente , Encaminhamento e Consulta , Estudos RetrospectivosRESUMO
Adult congenital heart disease (ACHD) patients represent a growing population with increasing use of acute emergency department (ED) care. Providing comprehensive ED care necessitates an understanding of the most common clinical scenarios to improve morbidity and mortality in this population. The aim of this position document is to provide a consensus regarding the management of the most common clinical scenarios of ACHD patients presenting to the ED.
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Medicina de Emergência , Cardiopatias Congênitas , Cirurgia Torácica , Adulto , Consenso , Serviço Hospitalar de Emergência , Cardiopatias Congênitas/cirurgia , HumanosRESUMO
BACKGROUND: E-scooters have emerged as a frequently used vehicle in German cities due to their high availability and easy access. However, investigations about the causes and mechanisms of E-scooter incidents and their trauma-specific consequences are rare. METHODS: We analysed all patients involved in E-scooter incidents from June to December 2019 who presented to four inner-city EDs in Berlin. The prospective data included patient-related and incident-related data, information on injury patterns and therapy, responses in a voluntary questionnaire concerning E-scooter use and general traffic experience. RESULTS: 248 patients (129 males; median age 29 years (5-81)) were included: 41% were tourists and 4% were children. Most incidents (71%) occurred between July and September 2019, the majority occurring at weekends (58%). The injury pattern was mostly multifocal, affecting the lower (42%) and upper limbs (37%) and the head (40%). Traumatic brain injury was associated with alcohol consumption. Inpatient admission was recorded in 25%, surgery in 23%. CONCLUSION: This study has defined the incidence of injury related to E-scooter use in a major European city. Stricter laws governing the use of E-scooters, the wearing of helmets and technical modifications to the E-scooter platforms might decrease E-scooter-associated incidents and resulting injuries in the future. TRIAL REGISTRATION NUMBER: German Clinical Trials Registry (DRKS00018061).
Assuntos
Acidentes de Trânsito , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Berlim/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Against the backdrop of emergency department (ED) overcrowding, patients' potential redirection to outpatient care structures is a subject of current political debate in Germany. It was suggested in this context that suitable lower-urgency cases could be transported directly to primary care practices by emergency medical services (EMS), thus bypassing the ED. However, practicality is discussed controversially. This qualitative study aimed to capture the perspective of EMS personnel on potential patient redirection concepts. METHODS: We conducted qualitative, semi-structured phone interviews with 24 paramedics. Interviews were concluded after attainment of thematic saturation. Interviews were transcribed verbatim, and qualitative content analysis was performed. RESULTS: Technical and organizational feasibility of patients' redirection was predominantly seen as limited (theme: "feasible, but only under certain conditions") or even impossible (theme: "actually not feasible"), based on a wide spectrum of potential barriers. Prominently voiced reasons were restrictions in personnel resources in both EMS and ambulatory care, as well as concerns for patient safety ascribed to a restricted diagnostic scope. Concerning logistics, alternative transport options were assessed as preferable. Regarding acceptance by stakeholders, the potential for releasing ED caseload was described as a factor potentially promoting adoption, while doubt was raised regarding acceptance by EMS personnel, as their workload was expected to conversely increase. Paramedics predominantly did not consider transporting lower-urgency cases as their responsibility, or even as necessary. Participants were markedly concerned of EMS being misused for taxi services in this context and worried about negative impact for critically ill patients, as to vehicles and personnel being potentially tied up in unnecessary transports. As to acceptance on the patients' side, interview participants surmised a potential openness to redirection if this would be associated with benefits like shorter wait times and accompanied by proper explanation. CONCLUSIONS: Interviews with EMS staff highlighted considerable doubts about the general possibility of a direct redirection to primary care as to considerable logistic challenges in a situation of strained EMS resources, as well as patient safety concerns. Plans for redirection schemes should consider paramedics' perspective and ensure a provision of EMS with the resources required to function in a changing care environment.