To understand the opinions of emergency department (ED) heads in Catalonia on their support for a residency program for specializing in emergency medicine (EM) and on their beliefs about the impact such a program would have.Heads of ED were asked if there would be support (from them, their staff, and their hospital) for a residency program to train specialists in EM. They were also asked their opinion on the impact that specialization would have on quality of care and costs in their department. Responses were compared by type of hospital and ED and by affiliation or not with the Spanish Society of Emergency Medicine (SEMES).Responses were received from 79 of the 82 heads of hospital EDs in Catalonia (96%). They reported that favorable opinions toward creation of an EM specialization were held by them personally (93.7%; 95% CI, 85.8%-97.9%), by their in their departments (88.6%; 95% CI, 79.4%-94.7%), and by staff in their hospitals (48.7%; 95% CI, 36.7%-59.6%). A majority thought that the impact of specialization would be good in the short term (82.0%; 95% CI, 71.7%-89.8%) and in the medium and long term (94.8%; 95% CI, 87.2%-98.6%). The respondents were neutral about whether there would be an impact on costs (60.3%; 95% CI, 48.6%-71.2%). More heads in mid-sized hospitals, private hospitals, and nonmembers of SEMES thought that creating a specialty would raise ED costs (p<0,05).The heads of Catalan ED, their staff, and their hospitals' staffs hold favorable opinions of the proposal to create a residency program allowing specialization in EM. They foresee short-, medium-, and long-term benefits for the EDs and scarce impact on costs.Conocer la opinión de los responsables de los servicios de urgencias hospitalarios (SUH) de Cataluña respecto al soporte e impacto que tendría la creación de la especialidad primaria de Medicina de Urgencias y Emergencias (MUE).Se solicitó la opinión a los responsables de SUH respecto al respaldo a una futura especialidad primaria de MUE (personal, en su servicio y en su hospital) y la estimación del impacto (cualitativo y económico) que tendría en su SUH. Se compararon las respuestas en función del tipo de hospital y SUH y de su afiliación a la Sociedad Española de Medicina de Urgencias y Emergencias (SEMES).Contestaron 79 de los 82 responsables de los SUH de Cataluña (96%), que percibieron una posición favorable a la creación de la especialidad, tanto ellos personalmente (93,7%; IC 95%: 85,8-97,9) como en sus SUH (88,6%; 79,4- 94,7) y hospitales (48,7%; 36,7-59,6). El 82,0% (71,7-89,8) opinó que la especialidad tendría un efecto positivo a corto plazo y el 94,8% (87,2-98,6) que también lo tendría a medio-largo plazo, y respecto al impacto económico, la opinión mayoritaria fue que sería neutro (60,3%; 48,6-71,2). Los responsables de SUH con actividad media, de hospitales privados y no afiliados a SEMES consideraron más frecuentemente que la creación de la especialidad encarecería el SUH (p < 0,05).Los responsables de los SUH catalanes tienen una opinión favorable y también la perciben en su servicio y su hospital respecto a la creación de la especialidad primaria de MUE y consideran que tendría efectos beneficiosos a corto, medio y largo plazo para el SUH, con un escaso impacto económico.
INTRODUCTION AND OBJECTIVES: Cardiac troponin, a marker of myocardial injury, is frequently observed in patients with COVID-19 infection. Our objective was to analyze myocardial injury and its prognostic implications in patients with and without COVID-19 infection treated in the same period of time. METHODS: The present study included patients treated in a university hospital with cardiac troponin I measurements and with suspected COVID-19 infection, confirmed or ruled out by polymerase chain reaction analysis. The impact was analyzed of cardiac troponin I positivity on 30-day mortality. RESULTS: In total, 433 patients were distributed among the following groups: confirmed COVID-19 (n = 186), 22% with myocardial injury (n = 41); and ruled out COVID-19 (n = 247), 21.5% without myocardial injury (n = 52). The confirmed and ruled out COVID-19 groups had a similar age, sex, and cardiovascular history. Mortality was significantly higher in the confirmed COVID-19 group than in the ruled out group (19.9% vs 5.3%, P < .001). In Cox multivariate regression analysis, cardiac troponin I was a predictor of mortality in both groups (confirmed COVID-19 group: HR, 3.54; 95%CI, 1.70-7.34; P = .001; ruled out COVID-19 group: HR, 5.57; 95%CI, 1.70-18.20; P = .004). The predictive model analyzed by ROC curves was similar in the 2 groups (P = .701), with AUCs of 0.808 in the confirmed COVID-19 group (0.750-0.865) and 0.812 in the ruled out COVID-19 group (0.760-0.864). CONCLUSIONS: Myocardial injury is detected in 1 in every 5 patients with confirmed or ruled out COVID-19 and predicts 30-day mortality to a similar extent in both circumstances.
Dear Editor, The mechanistic pathways leading to immune dysregulation and complications driven by uncontrolled severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection remain major challenges.1, 2 Hence, a detailed analysis of the proteome, metabolome and lipidome profile of coronavirus disease 2019 (COVID-19) patients showing different severity grades might shed light on the disease pathophysiology and unveil new predictive biomarkers to promptly ascertain patient's outcomes. Our COVID-19 study cohort included 273 SARS-CoV-2 infected individuals recruited during the first wave (March–April 2020) in three different hospitals and grouped by the disease severity following the medical inclusion criteria3 in mild, severe or critical (Figure 1A), from whom demographic, preexisting clinical conditions and COVID-19 treatments are summarized in Table S1. The greatest significant differences were observed between mild and critically ill patients. These findings indicated that older individuals with comorbidities such as hypertension, obesity, diabetes and cardiovascular disorders, mostly presenting dyspnea (Figure 1B), may be at higher risk of suffering from severe respiratory distress with subsequent oxygen and drug requirements and, eventually, died. Similarly, the serum biochemical composition analysis revealed a well-differentiated blood pattern previously defined for critically ill patients (Figure S1). In light of the promising results already provided by omic technologies in the search for predictive biomarkers of COVID-19 severity,4, 5 we conducted a nontargeted multi-omic, including proteomic, metabolomic and lipidomic analyses, in the serum from patients of the COVID-19 study cohort. The proteomics analysis identified 65 proteins with a significant increase or decrease in abundance according to the disease severity (Figure 2A), which resulted to be highly interconnected (Figure 2B). Hence, the complement and coagulation cascades were markedly the most significantly enriched pathways related to COVID-19 severity (Figure 2C). Other protein-coding genes such as carboxypeptidases, protease inhibitors, acute phase proteins, extracellular matrix stabilizers and antimicrobial enzymes, were also significantly up-regulated in severely and critically ill patients. These results showed the essential contribution of these proteins in the coagulopathy phenomenon and hyperinflammatory state that subsequently enhances SARS-CoV-2 endocytosis and infectivity and promotes secondary bacterial infections, previously described as aggravators of severe and critical COVID-19 cases.6 Proteins with reduced abundance in critically ill patients with COVID-19 were mostly associated with lipid transport (apolipoproteins), which dysfunction seems to increase SARS-CoV-2 infectivity in patients with COVID-19.7 For the first time, fetuin-A (AHSG) and inter-α-trypsin inhibitor 3 (ITIH3) were determined as the most accurate biomarkers (random forest) of the critical clinical progression of COVID-19 (Figure 2D). The metabolomic and lipidomic analyses revealed 34 metabolites and 28 lipids that were significantly increased or decreased in relation to severity (Figure 3A). Interestingly, many of the altered metabolites were amino acids and sugars involved in central carbon metabolism. In line with previous reports,8, 9 critically ill patients showed a significant increase in glucose and glutamic acid (GA) levels but a reduction in glutamine, citrate and uric acid levels, suggesting mitochondrial dysfunction, an enhanced glutaminolysis and a shift from anaerobic to aerobic glycolysis (Warburg effect). Accordingly, D-glutamine and D-glutamate metabolism were the most significantly enriched pathways (Figure 3B, left panel), and were significantly related to seizures disorders, anoxia, heart failure, diabetes, obesity and inflammatory diseases (Figure 3B, right panel). Lipid levels that increased with severity were mainly triglycerides (TGs) and diacylglycerols, and those that decreased were predominantly sphingomyelins (SMs), cholesteryl esters (ChoEs) and lysophosphatidylcholines. Lipoproteins rich in TGs may trigger dysfunction in innate immunity and impair the defence mechanism against COVID-1910 and a reduced abundance of SMs and ChoEs may interfere in signal transduction and in key immune and cellular processes. Among them, GA and ChoE (18:0) resulted in the most powerful (random forest) predictive biomarkers for COVID-19 evolution (Figure 3C), confirmed by the prognosis accuracy determined by the receiver operating characteristic (ROC) analysis (Figure S2A–C, respectively). The highest accuracy was attained when combining both compounds in the distinction of mild from critical illnesses (Figure 2SD). To provide insights into the biological pathways related to the pathophysiology of the disease, we study the linkage and co-regulation between the distinct classes of biomolecules by integrating the most significant demographical and clinical data (Table S1 and Figure S1) and the top omic molecules determined above (Figure S3A,B) in Spearman correlation matrix analyses (Figure 4A1–3). Despite all three groups showing a similar association pattern for most of the variables analyzed, patients with mild illness (Figure 4A1) significantly differed from those of the severe and critical groups (Figure 4A2,3, respectively). In brief, significant correlations were obtained across the omic data, which were more intense between lipidomics than within the protein-encoding genes, and nearly negligible through metabolomics. The predictive power of the selected omics biomolecules as biomarkers for the severe disease was subsequently demonstrated by the high accuracy, sensitivity and specificity obtained by combining the four molecules in the ROC analysis (Figure 4B) to effectively distinguish critical COVID-19 patients from patients with mild disease (area under the curve [AUC] = 0.994). To precisely predict whether a patient will progress from severe to a life-threatening disease, not only the four but all the top-omic selected biomarkers need to be integrated into the ROC analysis (AUC = 0.811; Figure 4C). Taking a step further, the inclusion of AHSG, ITIH, GA and ChoE (18:0) in a predictive biomarker panel for COVID-19 severity was validated in a randomly selected subset of patients. The regression modelling analysis confirmed the usefulness (classification accuracy >90%) of the biomarker panel in distinguishing mild to critical COVID-19 outcomes (Figure 4D). Once more, all these findings highlighted the complex interactions between certain biological processes and the most serious complications arising from SARS-CoV-2 infections and revealed their potential as predictive biomarkers of disease severity. Limitations are the small sample size to perform subgroup analyses and the lack of a non-infected SARS-CoV-2 group of subjects. However, this study was conducted in a representative symptomatic well-characterized Spanish cohort to determine predictive biomarkers of COVID-19 severity. In conclusion, the multi-omic analysis identified new specific molecules related to complement and coagulation cascades, platelet activation, cell adhesion, acute inflammation, energy production (Krebs cycle and Warburg effect), amino acid catabolism and lipid transport as fingerprints of the acute disease. A novel biomarker panel consisting of AHSG, ITIH3, GA and ChoE (18:0) was proposed for the accurate differentiation of mild from critical COVID-19 outcomes. This study would not have been possible without the generous collaboration of all the patients and their families and medical and nursing staff who have taken part in the project. We want to particularly acknowledge the collaboration of the Departments of Preventive Medicine and Epidemiology, Internal Medicine, Critical Care, Emergency, Occupational Health, Laboratory Medicine and Molecular Biology, and BioBank-IISPV (B.0000853 and B.0000854) integrated into the Spanish National Biobanks Platform (PT20/00197) and CERCA Programme (Generalitat de Catalunya) and IISPV for their collaboration. We also thank Pol Herrero, Maria Guirro and Antoni del Pino from the Proteomics and Metabolomics facilities of the Centre for Omic Sciences (COS) Joint Unit of the Universitat Rovira i Virgili-Eurecat for their contribution to mass spectrometry analyses. This work has been developed in the framework of the COVIDOMICS' project supported by Direcció General de Recerca i Innovació en Salut (DGRIS), Departament de Salut, Generalitat de Catalunya (PoC-6-17 and PoC1-5). The research has also been funded by the Programa de Suport als Grups de Recerca AGAUR (2017SGR948), the SPANISH AIDS Research Network [RD16/0025/0006, RD16/0025/0007 and RD16/0025/0020]-ISCIII-FEDER (Spain), the Centro de Investigación Biomédica en Red de Enfermedades Infecciosas-ISCIII [CB21/13/00020], Madrid, Spain and Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades Junta de Andalucía (research Project CV20-85418). Elena Yeregui was supported by the Instituto de Salud Carlos III (ISCIII) under grant agreement "FI20/00118″ through the programme "Contratos Predoctorales de Formación en Investigación en Salud". Laia Reverté was supported by the Instituto de Salud Carlos III (ISCIII) under grant agreement "CD20/00105″ through the programme "Contratos Sara Borrell". Francesc Vidal was supported by grants from the Programa de Intensificación de Investigadores (INT20/00031)-ISCIII and by "Premi a la Trajectòria Investigadora dels Hospitals de l'ICS 2018″. Anna Rull was supported by a grant from IISPV through the project "2019/IISPV/05″ (Boosting Young Talent), by GeSIDA through the "III Premio para Jóvenes Investigadores 2019″ and by the Instituto de Salud Carlos III (ISCIII) under grant agreement "CP19/00146″ through the Miguel Servet Program. Maria José Buzón was supported by the Miguel Servet Program (CP17/00179). Ezequiel Ruiz-Mateos was supported by the Spanish Research Council (CSIC). Alicia Gutiérrez-Valencia was supported by the Instituto de Salud Carlos III, cofinanced by the European Development Regional Fund ("A way to achieve Europe"), Subprograma Miguel Servet (grant CP19/00159). This project was also funded by a donation from the city Council of Perafort (to Teresa Auguet). The authors declare that they have no conflict of interest. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
To identify patients with type 2 myocardial infarction (MI) and patients with non-ischaemic myocardial injury (NIMI) and to compare their prognosis with those of patients with type 1 MI.
Methods
A retrospective observational study was performed in 1010 patients admitted to the emergency department of a university hospital with at least one troponin I test between 2012 and 2013. Participants were identified using laboratory records and divided into three groups: type 1 MI (rupture of atheromatous plaque), type 2 MI (imbalance between myocardial oxygen supply and/or demand) and NIMI (patients who did not meet diagnostic criteria for type 1 or type 2 MI). Clinical characteristics and 2-year outcomes were analysed.
Results
Patients with type 2 MI and NIMI were older, with higher proportion of women and more comorbidities than patients with type 1 MI. Absolute mortality and the adjusted risk for all-cause mortality in both groups were significantly higher than that of patients with type 1 MI (39.7%, HR: 1.41 95% CI 1.02 to 1.94, p=0.038 and 40.0%, HR: 1.54 95% CI 1.16 to 2.04, p=0.002, respectively). Patients with type 2 MI and NIMI tended to present more readmissions due to heart failure (16.5%, HR: 1.55 95% CI 0.87 to 2.76, p=0.133 and 12.3%, HR: 1.15 95% CI 0.70 to 1.90, p=0.580) and less readmission rates due to acute coronary syndrome (ACS) than patients with type 1 MI (2.1%, HR: 0.11 95% CI 0.04 to 0.31, p<0.001 and 4.3%, HR: 0.22 95% CI 0.12 to 0.41, p<0.001),
Conclusions
Patients diagnosed with type 2 MI and NIMI have higher rates of mortality and lower readmission rates for ACS compared with patients with type 1 MI.
To study the prognostic role of elevated troponin I levels in patients discharged home directly from a hospital emergency department.Observational study of a retrospective cohort of all patients attended for any emergency for whom troponin I tests were ordered and who were discharged home directly from our hospital emergency department between January and December 2012. We collected demographic information, medical histories, symptoms related to the acute coronary event, and diagnosis on discharge. The main outcome was all-cause mortality in the year following discharge.A total of 1381 patients discharged home directly from the emergency department were studied; 1192 (86.3%) had normal troponin I results and 189 (13.7%) had elevated levels. On multivariate analysis, troponin I elevation emerged as an independent risk factor for death within a year of discharge (hazard ratio, 2.41; 95% CI, 1.40-4.22; P<.01).A raised troponin I level is an independent predictor of 1-year mortality in patients for whom this test is ordered at least once and who are discharged home directly from a hospital emergency service.Estudiar el papel pronóstico a un año de la troponina I elevada en los pacientes dados de alta directamente desde un servicio de urgencias hospitalario.Estudio observacional de cohortes retrospectivo que incluyó a todos los pacientes atendidos por cualquier causa a los que se les había solicitado al menos una determinación de troponina I y fueron dados de alta directamente desde un servicio de urgencias de un hospital universitario entre enero y diciembre de 2012. Se recogieron datos demográficos, antecedentes personales y clínicos relacionados con el episodio agudo y el diagnóstico al alta. La variable de resultado principal fue la mortalidad por cualquier causa en el primer año tras el alta.Se incluyeron 1.381 pacientes dados de alta directamente desde urgencias, de los cuales, 1.192 (86,3%) tenían troponina I negativa y 189 (13,7%) troponina I positiva. Tras un análisis multivariado, la troponina I elevada se mostró como un factor de riesgo independiente para mortalidad a un año (HR = 2,41 IC 95%: 1,40-4,22, p < 0,01).La troponina I elevada es un marcador independiente de mortalidad al año en los pacientes dados de alta directamente desde urgencias a los que se les solicitó al menos una determinación por parte del urgenciólogo.
Objetivo: Investigar las actividades formativas, docentes e investigadoras realizadas en los servicios de urgencias hospitalarios (SUH) de Cataluna, y compararlas en funcion de las caracteristicas de estos SUH y de los hospitales. Metodo: Se entrevisto a los responsables de 79 de los 82 SUH de Cataluna (96%), que respondieron a preguntas referentes a las actividades formativas en las que participan los profesionales de urgencias, las caracteristicas y resultados de las actividades docentes e investigadoras llevadas a cabo por ellos y la disponibilidad de tiempos por parte de medicos y enfermeros para realizarlas. Se excluyeron de este analisis los datos referentes a la formacion de residentes. Se analizaron las respuestas segun la actividad del SUH (alta, media, baja), el uso del hospital (privado, publico) y la complejidad del hospital publico (alta tecnologia o alta resolucion, referencia, comarcal). Resultados: El 31,6% de SUH protege parte de la jornada laboral para la formacion de sus facultativos y el 23,1% parte de la jornada de sus enfermeros, con unas medianas del 5% (p25-75: 3-10%) y el 2% (1-3%) del tiempo contratado, respectivamente. Existen sesiones propias para los facultativos y los enfermeros en el 79,7% y 94,2% de los SUH, respectivamente. La presencia de facultativos y enfermeros al congreso catalan y espanol y a congresos internacionales existio en el 79,5%, 76,9% y 25,6% de los SUH para los primeros, y en el 57,7%, 39,8% y 3,8% para los segundos (p=0,006, p Conclusiones: Los SUH catalanes tienen un elevado papel en la actividad docente de pregrado y postgrado, tanto de medicina como de enfermeria, y en cambio la actividad investigadora todavia abarca a un numero excesivamente limitado de SUH y de profesionales. Palabras clave: Urgencias, servicio de urgencias hospitalario, docencia, investigacion, formacion.