Combining loop with thiazide diuretics in patients discharged home after a heart failure decompensation: Association with 30-day outcomes.

OBJECTIVE: To investigate the association of the addition of thiazide diuretic on top of loop diuretic and standard of care with short-term outcomes of patients discharged after surviving an acute heart failure (AHF) episode. METHODS: This is a secondary analysis of 14,403 patients from three independent cohorts representing the main departments involved in AHF treatment for whom treatment at discharge was recorded and included loop diuretics. Patients were divided according to whether treatment included or not thiazide diuretics. Short-term outcomes consisted of 30-day all-cause mortality, hospitalization (with a separate analysis for hospitalization due to AHF or to other causes) and the combination of death and hospitalization. The association between thiazide diuretics on short-term outcomes was explored by Cox regression and expressed as hazard ratios (HR) with 95 % confidence intervals, which were adjusted for 18 patient-related variables and 9 additional drugs (aside from loop and thiazide diuretics) prescribed at discharge. RESULTS: The median age was 81 (interquartile range=73-86) years, 53 % were women, and patients were mainly discharged from the cardiology (42 %), internal medicine or geriatric department (29 %) and emergency department (19 %). There were 1,367 patients (9.5 %) discharged with thiazide and loop diuretics, while the rest (13,036; 90.5 %) were discharged with only loop diuretics on top of the remaining standard of care treatments. The combination of thiazide and loop diuretics showed a neutral effect on all outcomes: death (adjusted HR 1.149, 0.850-1.552), hospitalization (0.898, 0.770-1.048; hospitalization due to AHF 0.799, 0.599-1.065; hospitalization due to other causes 1.136, 0.756-1.708) and combined event (0.934, 0.811-1.076). CONCLUSION: The combination of thiazide and loop diuretics was not associated with changes in risk of death, hospitalization or a combination of both.

Chest Pain in Cancer Patients: Prevalence of Myocardial Infarction and Performance of High-Sensitivity Cardiac Troponins.

Background: Little is known about patients with cancer presenting with acute chest discomfort to the emergency department (ED). Objectives: The aim of this study was to assess the prevalence of acute myocardial infarction (AMI), outcomes, and the diagnostic utility of recommended diagnostic tools in this population. Methods: Patients presenting with chest pain to the ED were prospectively enrolled in an international multicenter diagnostic study with central adjudication. Cancer status was assessed prospectively and additional cancer details retrospectively. Findings were externally validated in an independent multicenter cohort. Results: Among 8,267 patients, 711 (8.6%) had cancer. Patients with cancer had a higher burden of cardiovascular risk factors and pre-existing cardiac disease. Total length of stay in the ED (5.2 hours vs 4.3 hours) and hospitalization rate (49.8% vs 34.3%) were both increased in patients with cancer (P < 0.001 for both). Among 8,093 patients eligible for the AMI analyses, those with cancer more often had final diagnoses of AMI (184 of 686 with cancer [26.8%] vs 1,561 of 7,407 without cancer [21.1%]; P < 0.001). In patients with cancer, high-sensitivity cardiac troponin T (hs-cTnT) but not high sensitivity cardiac troponin I (hs-cTnI) concentration had lower diagnostic accuracy for non-ST-segment elevation myocardial infarction (for hs-cTnT, area under the curve: 0.89 [95% CI: 0.86-0.92] vs 0.94 [95% CI: 0.93-0.94] [P < 0.001]; for hs-cTnI, area under the curve: 0.93 [95% CI: 0.91-0.95] vs 0.95 [95% CI: 0.94-0.95] [P = 0.10]). In patients with cancer, the European Society of Cardiology 0/1-hour hs-cTnT and hs-cTnI algorithms maintained very high safety but had lower efficacy, with twice the number of patients remaining in the observe zone. Similar findings were obtained in the external validation cohort. Conclusions: Patients with cancer have a substantially higher prevalence of AMI as the cause of chest pain. Length of ED stay and hospitalization rates are increased. The diagnostic performance of hs-cTnT and the efficacy of both the European Society of Cardiology 0/1-hour hs-cTnT and hs-cTnI algorithms is reduced. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE] Study; NCT00470587).

Sex differences in mortality of older adults with falls after emergency department consultation: FALL-ER registry.

BACKGROUND: To investigate if sex is a risk factor for mortality in patients consulting at the emergency department (ED) for an unintentional fall. METHODS: This was a secondary analysis of the FALL-ER registry, a cohort of patients ≥65 years with an unintentional fall presenting to one of 5 Spanish EDs during 52 predefined days (one per week during one year). We collected 18 independent patient baseline and fall-related variables. Patients were followed for 6 months and all-cause mortality recorded. The association between biological sex and mortality was expressed as unadjusted and adjusted hazard ratios (HR) with the 95% confidence interval (95% CI), and subgroup analyses were performed by assessing the interaction of sex with all baseline and fall-related mortality risk variables. RESULTS: Of 1315 enrolled patients (median age 81 years), 411 were men (31%) and 904 women (69%). The 6-month mortality was higher in men (12.4% vs. 5.2%, HR = 2.48, 95% CI = 1.65-3.71), although age was similar between sexes. Men had more comorbidity, previous hospitalizations, loss of consciousness, and an intrinsic cause for falling. Women more frequently lived alone, with self-reported depression, and the fall results in a fracture and immobilization. Nonetheless, after adjustment for age and these eight divergent variables, older men aged 65 and over still showed a significantly higher mortality (HR = 2.19, 95% CI = 1.39-3.45), with the highest risk observed during the first month after ED presentation (HR = 4.18, 95% CI = 1.31-13.3). We found no interaction between sex and any patient-related or fall-related variables with respect to mortality (p > 0.05 in all comparisons). CONCLUSIONS: Male sex is a risk factor for death following ED presentation for a fall in the older population adults aged 65 and over. The causes for this risk should be investigated in future studies.

Invasive bacterial infection in children with fever and petechial rash in the emergency department: a national prospective observational study.

OBJECTIVE: To determine the incidence and clinical predictors of invasive bacterial infection (IBI) in well-appearing children who present to the emergency department (ED) with fever and petechiae. DESIGN: A prospective, observational, multicentre study was conducted in 18 hospitals between November 2017 and October 2019. PATIENTS: A total of 688 patients were recruited. MAIN OUTCOME MEASURES: The primary outcome was the presence of IBI. Clinical features and laboratory test results were described and related to the presence of IBI. RESULTS: Ten IBIs were found (1.5%), comprising eight cases of meningococcal disease and two of occult pneumococcal bacteraemia. Median age was 26.2 months (IQR 15.3-51.2). Blood samples were obtained from 575 patients (83.3%). Patients with an IBI had a shorter time from fever to ED visit (13.5 hours vs 24 hours) and between fever and rash onset (3.5 hours vs 24 hours). Values for absolute leucocyte count, total neutrophil count, C reactive protein and procalcitonin were significantly higher in patients with an IBI. Significantly fewer patients with a favourable clinical status while in the observation unit were found to have an IBI (2/408 patients, 0.5%) than when clinical status was unfavourable (3/18, 16.7%). CONCLUSIONS: The incidence of IBI among children with fever and petechial rash is lower than previously reported (1.5%). The time from fever to ED visit and to rash onset was shorter in patients with an IBI. Patients with a favourable clinical course during observation in the ED are at lower risk of IBI.

Single-cell RNA sequencing identifies precise tolerogenic cellular and molecular pathways induced by depigmented-polymerized grass pollen allergen extract.

BACKGROUND: Immunologic mechanism of action of allergoids remains poorly understood. Previous models of allergenicity and immunogenicity have yielded suboptimal knowledge of these immunotherapeutic vaccine products. Novel single-cell RNA sequencing technology offers a bridge to this gap in knowledge. OBJECTIVE: We sought to identify the underpinning tolerogenic molecular and cellular mechanisms of depigmented-polymerized Phleum pratense (Phl p) extract. METHODS: The molecular mechanisms underlying native Phl p, depigmented Phl p (DPG-Phl p), and depigmented-polymerized (DPG-POL-Phl p) allergoid were investigated by single-cell RNA sequencing. Allergen-specific TH2A, T follicular helper (Tfh), and IL-10+ regulatory B cells were quantified by flow cytometry in peripheral blood mononuclear cells from 16 grass pollen-allergic and 8 nonatopic control subjects. The ability of Phl p, DPG-Phl p, and DPG-POL-Phl p to elicit FcεRI- and FcεRII-mediated IgE responses was measured by basophil activation test and IgE-facilitated allergen binding assay. RESULTS: Analysis revealed that DPG-POL-Phl p downregulated genes associated with TH2 signaling, induced functional regulatory T cells exhibiting immunosuppressive roles through CD52 and Siglec-10, modulated genes encoding immunoproteasome that dysregulate the processing and presentation of antigens to T cells and promoted a shift from IgE toward an IgA1 and IgG responses. In grass pollen-allergic subjects, DPG-POL-Phl p exhibited reduced capacity to elicit proliferation of TH2A, IL-4+ Tfh and IL-21+ Tfh cells while being the most prominent at inducing IL-10+CD19+CD5hi and IL-10+CD19+CD5hiCD38intCD24int regulatory B-cell subsets compared to Phl p (all P < .05). Furthermore, DPG-POL-Phl p demonstrated a hypoallergenic profile through basophil activation and histamine release compared to Phl p (31.54-fold, P < .001). CONCLUSIONS: Single-cell RNA sequencing provides an in-depth resolution of the mechanisms underlying the tolerogenic profile of DPG-POL-Phl p.

Análisis individualizado por sexo de los factores asociados a la clasificación inicial errónea en urgencias del dolor torácico como no coronario / Factors associated with erroneous emergency department noncardiac chest pain classifications in men and women

Introducción. Analizar de forma independiente en mujeres y hombres la frecuencia y las características clínicas asociadas a una clasificación inicial errónea (CIE) en urgencias del dolor torácico (DT) como no coronario. Método. Se analizan todas las consultas por DT atendidas en urgencias entre 2008 y 2017 clasificadas inicialmente (historia clínica y ECG) como DT no coronario. Se consideró como CIE si el diagnóstico final fue síndrome coronario agudo (SCA). Se crearon dos modelos multivariable, uno con 10 factores de riesgo, y otro con 10 características clínicas del DT, en los que se investigó la asociación de estas variables con una CIE. Se analizaron independientemente mujeres y hombres. Resultados. Se analizaron 8.093 mujeres con DT clasificado inicialmente como no coronario (edad mediana: 54 años, RIC: 38-73), 72 con CIE (0,9%). Los factores de riesgo asociados independientemente a CIE fueron obesidad (OR = 0,40; IC 95% = 0,17-0,97) y consumo de cocaína (5,18; 1,16-23,2), y las características clínicas fueron relación con el esfuerzo (2,01; 1,21-3,33), existencia de irradiación (2,05; 1,23-3,41) y síntomas vegetativos acompañantes (1,86; 1,02-3,41). Se analizaron 9.979 hombres (edad mediana: 47 años, RIC: 33-64), 83 con CIE (0,8%). Los factores de riesgo asociados a CIE fueron edad > 40 años (1,74; 1,04-2,91) e hipertensión (0,45; 0,24-0,84). No hubo características clínicas del DT asociadas a CIE. Conclusión. En las mujeres con dolor torácico, se identifican más características asociadas al error de clasificación que en los hombres. Este estudio remarca la necesidad de análisis independiente por sexo en el SCA, en el que clásica- mente se ha considerado la clínica en las mujeres como atípica. (AU)

Objective. To analyze the frequency and clinical characteristics associated with erroneous initial classifications of noncardiac chest pain (NCP) in men and women. Methods. We analyzed all case records in which chest pain was initially classified as noncardiac in origin according to clinical signs and electrocardiograms evaluated in our emergency department between 2008 and 2017. We considered the initial evaluation of NCP to be in error if the final diagnosis was acute coronary syndrome. A risk model for an erroneous initial classification of NCP was developed based on multivariable analysis of our patient data. We also used multivariable analysis to explore associations between 10 clinical signs of chest pain and an erroneous initial NCP classification. The data for men and women were analyzed separately. Results. NCP was the initial classification for 8093 women; their median (interquartile range) age was 54 (38-73) years. The classification was in error for 72 women (0.9%). Odds ratios (ORs) showed that patient risk factors associated with an erroneous NCP classification in the women in our series were obesity (OR, 0.40; 95% CI, 0.17- 0.97) and cocaine consumption (OR, 5.18; 95% CI, 1.16-23.2). Clinical risk factors associated with erroneous NCP classification in women were recent physical exertion (OR, 2.01; 95% CI, 1.21-3.33), radiation exposure (OR, 2.05; 95% CI, 1.23-3.41), and vegetative symptoms (OR, 1.86; 95% CI, 1.02-3.41). For 9979 men with a median age of 47 (33-64) years, NCP was the initial classification; in 83 of the men (0.8%) the classification was erroneous. Patient factors associated with erroneous NCP classification in men were age over 40 years (OR, 1.74; 95% CI, 1.04-2.91) and hypertension (OR, 0.45; 95% CI, 0.24-0.84). No clinical signs of chest pain in men were associated with error. Conclusions. More clinical characteristics are associated with an erroneous classification of NCP in women. [...] (AU)

Factors associated with erroneous emergency department noncardiac chest pain classifications in men and women. / Análisis individualizado por sexo de los factores asociados a la clasificación inicial errónea en urgencias del dolor torácico como no coronario.

OBJECTIVES: To analyze the frequency and clinical characteristics associated with erroneous initial classifications of noncardiac chest pain (NCP) in men and women. MATERIAL AND METHODS: We analyzed all case records in which chest pain was initially classified as noncardiac in origin according to clinical signs and electrocardiograms evaluated in our emergency department between 2008 and 2017. We considered the initial evaluation of NCP to be in error if the final diagnosis was acute coronary syndrome. A risk model for an erroneous initial classification of NCP was developed based on multivariable analysis of our patient data. We also used multivariable analysis to explore associations between 10 clinical signs of chest pain and an erroneous initial NCP classification. The data for men and women were analyzed separately. RESULTS: NCP was the initial classification for 8093 women; their median (interquartile range) age was 54 (38-73) years. The classification was in error for 72 women (0.9%). Odds ratios (ORs) showed that patient risk factors associated with an erroneous NCP classification in the women in our series were obesity (OR, 0.40; 95% CI, 0.17- 0.97) and cocaine consumption (OR, 5.18; 95% CI, 1.16-23.2). Clinical risk factors associated with erroneous NCP classification in women were recent physical exertion (OR, 2.01; 95% CI, 1.21-3.33), radiation exposure (OR, 2.05; 95% CI, 1.23-3.41), and vegetative symptoms (OR, 1.86; 95% CI, 1.02-3.41). For 9979 men with a median age of 47 (33-64) years, NCP was the initial classification; in 83 of the men (0.8%) the classification was erroneous. Patient factors associated with erroneous NCP classification in men were age over 40 years (OR, 1.74; 95% CI, 1.04-2.91) and hypertension (OR, 0.45; 95% CI, 0.24-0.84). No clinical signs of chest pain in men were associated with error. CONCLUSION: More clinical characteristics are associated with an erroneous classification of NCP in women. Our findings underline the need to assess the possibility of acute coronary syndrome differently in women, in whom the signs have usually been considered to be atypical.

OBJETIVO: Analizar de forma independiente en mujeres y hombres la frecuencia y las características clínicas asociadas a una clasificación inicial errónea (CIE) en urgencias del dolor torácico (DT) como no coronario. METODO: Se analizan todas las consultas por DT atendidas en urgencias entre 2008 y 2017 clasificadas inicialmente (historia clínica y ECG) como DT no coronario. Se consideró como CIE si el diagnóstico final fue síndrome coronario agudo (SCA). Se crearon dos modelos multivariable, uno con 10 factores de riesgo, y otro con 10 características clínicas del DT, en los que se investigó la asociación de estas variables con una CIE. Se analizaron independientemente mujeres y hombres. RESULTADOS: Se analizaron 8.093 mujeres con DT clasificado inicialmente como no coronario (edad mediana: 54 años, RIC: 38-73), 72 con CIE (0,9%). Los factores de riesgo asociados independientemente a CIE fueron obesidad (OR = 0,40; IC 95% = 0,17-0,97) y consumo de cocaína (5,18; 1,16-23,2), y las características clínicas fueron relación con el esfuerzo (2,01; 1,21-3,33), existencia de irradiación (2,05; 1,23-3,41) y síntomas vegetativos acompañantes (1,86; 1,02-3,41). Se analizaron 9.979 hombres (edad mediana: 47 años, RIC: 33-64), 83 con CIE (0,8%). Los factores de riesgo asociados a CIE fueron edad > 40 años (1,74; 1,04-2,91) e hipertensión (0,45; 0,24-0,84). No hubo características clínicas del DT asociadas a CIE. CONCLUSIONES: En las mujeres con dolor torácico, se idenfitican más características asociadas al error de clasificación que en los hombres. Este estudio remarca la necesidad de análisis independiente por sexo en el SCA, en el que clásicamente se ha considerado la clínica en las mujeres como atípica.

Risk Factors of Serious Bacterial Infection in Previously Healthy Children Older Than 90 Days Old With Fever and Neutropenia.

BACKGROUND: The main objective was to determine the clinical or analytical factors that independently predict risk of serious bacterial infection (RSBI) in immunocompetent patients older than 90 days given a diagnosis of fever and for whom neutropenia was an incidental finding. The secondary objective was to describe the prevalence of serious bacterial infections (SBIs). METHODS: This is a 3-year-long, multicenter, prospective analytical and observational study carried out at 6 pediatric emergency departments. Data for epidemiological, clinical, and analytical variables were collected. RESULTS: One hundred forty patients with febrile neutropenia (60.7% mild, 39.3% moderate to severe) were recruited. Serious bacterial infection incidence was 15.0% (95% confidence interval [CI], 9-21): 1 Invasive Bacterial Infection (Staphylococcus epidermidis bacteremia), 10 urinary tract infections, 8 pneumonias, and 2 cellulitis. Median total neutrophil counts per microliter showed no statistically significant differences (P = 0.512; 1000 [750-1200] in SBI patients vs 1100 [800-1300] in non-SBI patients). Higher RSBI was observed in patients with neutrophils less than 20% relative to total leukocytes (SBI, 15, 26.3%) than in those with neutrophils of 20% or greater (SBI, 6, 7.2%) (odds ratio, 4.6; 95% CI, 1.7-12.7). In patients with greater than 5000 leukocytes/µL, a percentage of neutrophils less than 20% was related to a greater RSBI with a trend toward statistical significance (odds ratio, 6.1; 95% CI, 0.7-51.1; P = 0.066). The clinical variables did not show a significant association with RSBI. CONCLUSIONS: None of the clinical or analytical variables assessed were associated with the RSBI. However, according to a post hoc analysis, in patients with greater than 5000 leukocytes/µL, a neutrophil percentage less than 20% could be an independent risk factor for SBI. A thorough physical examination and basic diagnostic tests (urinalysis and chest x-ray) may help to establish a diagnosis of SBI in the vast majority of cases.

Association between troponin and outcome in patients with chest pain and rapid atrial fibrillation: a retrospective study of a single-center 10-year cohort.

BACKGROUND AND OBJECTIVE: The prognosis of myocardial infarction in patients with rapid atrial fibrillation (RAF) is poorly known. We sought to ascertain if troponin concentrations are associated with a higher risk of major adverse cardiovascular events (MACE) in patients with RAF and chest discomfort suggestive of coronary origin. METHODS: We retrospectively reviewed all consecutive patients attending an emergency department of a single-center (2008-2017) with chest pain suggestive of coronary origin who had RAF and at least one troponin determination. Patients were classified as having normal/increased troponin. They were followed until December 2019 to detect MACE (primary outcome), which included acute coronary syndrome (ACS), revascularization, stroke, or all-cause death. In addition to cardiovascular death and type I myocardial infarction, these were considered secondary outcomes. The adjusted risk was determined by Cox regression, and sensitivity analysis were run. Relationship between troponin as a continuous variable and outcomes was also evaluated, as well as interaction by sex. RESULTS: We included 574 patients (median = 76.5 years, IQR = 14, women 56.8%, increased troponin 34.1%) followed by a median of 3.8 years (IQR = 4.8). MACE occurred in 200 patients (34.8%). Increased troponin was independently associated with MACE (adjusted hazard ratio, 1.502, 95% CI, 1.130-1.998), ACS (adjusted hazard ratio, 2.488, 95% CI, 1.256-4.928), type I myocardial infarction (adjusted hazard ratio, 2.771, 95% CI, 1.212-6.333) and stroke (adjusted hazard ratio, 3.580, 95% CI, 1.888-6.787) but not with death, cardiovascular death or revascularization. Sensitivity analyses were consistent with these results. There was no interaction by sex. When assessed continuously, an increase in troponin concentrations was lineally associated with a steady increase in the risk of MACE. CONCLUSIONS: In patients with RAF who complain of chest pain, increased troponin levels are related to adverse cardiovascular outcomes.

International Validation of the Canadian Syncope Risk Score : A Cohort Study.

BACKGROUND: The Canadian Syncope Risk Score (CSRS) was developed to predict 30-day serious outcomes not evident during emergency department (ED) evaluation. OBJECTIVE: To externally validate the CSRS and compare it with another validated score, the Osservatorio Epidemiologico della Sincope nel Lazio (OESIL) score. DESIGN: Prospective cohort study. SETTING: Large, international, multicenter study recruiting patients in EDs in 8 countries on 3 continents. PARTICIPANTS: Patients with syncope aged 40 years or older presenting to the ED within 12 hours of syncope. MEASUREMENTS: Composite outcome of serious clinical plus procedural events (primary outcome) and the primary composite outcome excluding procedural interventions (secondary outcome). RESULTS: Among 2283 patients with a mean age of 68 years, the primary composite outcome occurred in 7.2%, and the composite outcome excluding procedural interventions occurred in 3.1% at 30 days. Prognostic performance of the CSRS was good for both 30-day composite outcomes and better compared with the OESIL score (area under the receiver-operating characteristic curve [AUC], 0.85 [95% CI, 0.83 to 0.88] vs. 0.74 [CI, 0.71 to 0.78] and 0.80 [CI, 0.75 to 0.84] vs. 0.69 [CI, 0.64 to 0.75], respectively). Safety of triage, as measured by the frequency of the primary composite outcome in the low-risk group, was higher using the CSRS (19 of 1388 [0.6%]) versus the OESIL score (17 of 1104 [1.5%]). A simplified model including only the clinician classification of syncope (cardiac syncope, vasovagal syncope, or other) variable at ED discharge-a component of the CSRS-achieved similar discrimination as the CSRS (AUC, 0.83 [CI, 0.80 to 0.87] for the primary composite outcome). LIMITATION: Unable to disentangle the influence of other CSRS components on clinician classification of syncope at ED discharge. CONCLUSION: This international external validation of the CSRS showed good performance in identifying patients at low risk for serious outcomes outside of Canada and superior performance compared with the OESIL score. However, clinician classification of syncope at ED discharge seems to explain much of the performance of the CSRS in this study. The clinical utility of the CSRS remains uncertain. PRIMARY FUNDING SOURCE: Swiss National Science Foundation & Swiss Heart Foundation.

A case-control, multicentre study of consecutive patients with COVID-19 and acute (myo)pericarditis: incidence, risk factors, clinical characteristics and outcomes.

OBJECTIVE: To estimate incidence, risk factors, clinical characteristics and outcomes of acute (myo)pericarditis (AMP) in patients with COVID-19. METHODS: Case-control, retrospective review, consecutive case inclusion performed in 62 Spanish EDs. All COVID-19 patients with AMP (cases) were compared in clinical characteristics and outcomes with COVID-19 without AMP (control group A) and non-COVID patients with AMP (control group B). We estimated unadjusted standardised incidence (SI, not adjusted by population's age/sex) of AMP in COVID-19 and non-COVID populations (per 100 000/year). RESULTS: We identified 67 AMP in COVID-19 patients (SI=56.5, OR with respect to non-COVID patients=4.43, 95% CI=3.98 to 4.94). Remarkably, COVID-19 cases presented with chest pain less frequently than non-COVID patients and had less typical ECG changes, higher NT-proBNP (N-terminal prohormone of brain natriuretic peptide), more left and right ventricular dysfunction in echocardiography and more need of inotropic/vasopressor drugs. Admission to intensive care was higher than control group A (OR=3.22, 95% CI=1.43 to 7.23), and in-hospital mortality was higher than control group B (OR=7.75, 95% CI=2.77 to 21.7). CONCLUSION: AMP is unusual as a form of COVID-19 presentation (about 1‰ cases), but SI is more than fourfold higher than non-COVID population, and it is less symptomatic, more severe and has higher in-hospital mortality; therefore, rapid recognition, echocardiographic assessment of myopericardial inflammation/dysfunction and treatment with vasoactive drugs when needed are recommended in AMP in patients with COVID-19.

Factors associated with late presentation to the emergency department in patients complaining of chest pain.

OBJECTIVE: We investigated which factors predict late presentation (LP) to the emergency department (ED) in patients with non-traumatic chest pain (CP). METHODS: All CP cases attended at a single ED (2008-2017) were included. LP was considered if time from CP onset to ED arrival was>6 h. We analyzed associations between 42 patient/CP-related characteristics and LP in the whole cohort and in patients with CP due to acute coronary syndrome (ACS). RESULTS: The cohort included 25,693 cases (LP=50.6%; ACS=19.0%). Twenty factors were associated with LP, and 8 were also found in patients with ACS: CP of short-duration, aggravated by exertion or breathing/movement, undulating or recurrent CP increased the risk of LP, whereas CP accompanied by diaphoresis, irradiated to the throat, and chronic treatment with nitrates decreased the risk of LP. Exertional and recurrent CP were associated with both, LP and ACS. CONCLUSION: Some characteristics, mainly CP-related, may lead to LP to the ED. CP aggravated by exercise and recurrent CP were associated with both LP and a final diagnosis of ACS. PRACTICE IMPLICATIONS: Patient educational initiatives should consider these two features as potential warnings for ACS and thereby encourage patients to seek early medical consultation.

Incidence, clinical presentation, management, and outcome of acute pericarditis and myopericarditis.

AIMS: Little is known about the epidemiology, clinical presentation, management, and outcome of acute pericarditis and myopericarditis. METHODS AND RESULTS: The final diagnoses of acute pericarditis, myopericarditis, and non-ST-segment elevation myocardial infarction (NSTEMI) of patients presenting to seven emergency departments in Switzerland with acute chest pain were centrally adjudicated by two independent cardiologists using all information including serial measurements of high-sensitivity cardiac troponin T. The overall incidence of pericarditis and myopericarditis was estimated relative to the established incidence of NSTEMI. Current management and long-term outcome of both conditions were also assessed. Among 2533 chest pain patients, the incidence of pericarditis, myopericarditis, and NSTEMI were 1.9% (n = 48), 1.1% (n = 29), and 21.6% (n = 548), respectively. Accordingly, the estimated incidence of pericarditis and myopericarditis in Switzerland was 10.1 [95% confidence interval (95% CI) 9.3-10.9] and 6.1 (95% CI 5.6-6.7) cases per 100 000 population per year, respectively, vs. 115.0 (95% CI 112.3-117.6) cases per 100 000 population per year for NSTEMI. Pericarditis (85% male, median age 46 years) and myopericarditis (62% male, median age 56 years) had male predominance, and commonly (50% and 97%, respectively) resulted in hospitalization. No patient with pericarditis or myopericarditis died or had life-threatening arrhythmias within 30 days [incidence 0% (95% CI 0.0-4.8%)]. Compared with NSTEMI, the 2-year all-cause mortality adjusted hazard ratio of pericarditis and myopericarditis was 0.40 (95% CI 0.05-2.96), being 0.59 (95% CI 0.40-0.88) for non-cardiac causes of chest pain. CONCLUSION: Pericarditis and myopericarditis are substantially less common than NSTEMI and have an excellent short- and long-term outcome. CLINICAL TRIAL REGISTRATION: ClinicalTrial.gov, number NCT00470587, https://clinicaltrials.gov/ct2/show/NCT00470587.

Mortality in patients treated for COVID-19 in the emergency department of a tertiary care hospital during the first phase of the pandemic: Derivation of a risk model for emergency departments. / Análisis de mortalidad de los pacientes atendidos por COVID-19 en el servicio de urgencias de un hospital de tercer nivel en la fase incial de la pandemia. Derivación de un modelo de riesgo para urgencias.

OBJECTIVES: To develop a risk model to predict 30-day mortality after emergency department treatment for COVID-19. MATERIAL AND METHODS: Observational retrospective cohort study including 2511 patients with COVID-19 who came to our emergency department between March 1 and April 30, 2020. We analyzed variables with Kaplan Meier survival and Cox regression analyses. RESULTS: All-cause mortality was 8% at 30 days. Independent variables associated with higher risk of mortality were age over 50 years, a Barthel index score less than 90, altered mental status, the ratio of arterial oxygen saturation to the fraction of inspired oxygen (SaO2/FIO2), abnormal lung sounds, platelet concentration less than 100 000/mm3, a C-reactive protein concentration of 5 mg/dL or higher, and a glomerular filtration rate less than 45 mL/min. Each independent predictor was assigned 1 point in the score except age, which was assigned 2 points. Risk was distributed in 3 levels: low risk (score of 4 points or less), intermediate risk (5 to 6 points), and high risk (7 points or above). Thirty-day risk of mortality was 1.7% for patients who scored in the low-risk category, 28.2% for patients with an intermediate risk score, and 67.3% for those with a high risk score. CONCLUSION: This mortality risk stratification tool for patients with COVID-19 could be useful for managing the course of disease and assigning health care resources in the emergency department.

OBJETIVO: Derivar un modelo de riesgo para estimar la probabilidad de mortalidad a los 30 días de la visita a urgencias de pacientes con COVID-19. METODO: Estudio observacional de cohortes retrospectivo de 2.511 pacientes con COVID-19 atendidos en el servicio de urgencias hospitalario (SUH) del 1 de marzo al 30 de abril de 2020. Se realizó análisis de supervivencia mediante Kaplan Meier y regresión de Cox. RESULTADOS: La mortalidad por cualquier causa a los 30 días fue de un 8%. Los factores asociados de forma independiente a mayor mortalidad fueron: edad 50 años, índice de Barthel 90 puntos, alteración del nivel de consciencia, índice de SaO2/FIO2 400, auscultación respiratoria anómala, cifra de plaquetas 100.000/mm3, PCR 5 mg/dL y filtrado glomerular 45 mL/min. A estos factores se les asignó una puntuación de 1, excepto a la edad, que se le asignó un valor de 2 puntos. Se dividió el modelo de riesgo en 3 categorías: riesgo bajo (menor o igual a 4 puntos), riesgo intermedio (5-6 puntos) y riesgo alto (igual o superior a 7 puntos). Para los pacientes clasificados como de bajo riesgo la probabilidad de mortalidad a los 30 días fue del 1,7%, en los casos de riesgo intermedio fue del 28,2% y para los de alto riesgo fue del 67,3%. CONCLUSIONES: Disponer de una herramienta para estratificar el riesgo de mortalidad de los pacientes con COVID-19 que consultan a un SUH podría ser de utilidad para la gestión de los recursos sanitarios disponibles.

Clinical presentation of patients with prior coronary artery bypass grafting and suspected acute myocardial infarction.

AIMS: Diagnosis of acute myocardial infarction (AMI) can be challenging in patients with prior coronary artery bypass grafting (CABG). METHODS AND RESULTS: Final diagnoses were adjudicated by two independent cardiologists using the universal definition of AMI among patients presenting to the emergency department (ED) with suspected AMI. Diagnostic accuracy of 34 chest pain characteristics (CPCs) and four electrocardiogram (ECG) signatures stratified according to the presence or absence of prior CABG were prospectively quantified. Among 4015 patients (no prior CABG: n = 3686; prior CABG: n = 329), prevalence of AMI and unstable angina were higher in patients with prior CABG (35% vs. 18%; 26% vs. 8%; both P < 0.001). Three CPCs (9%) and two electrocardiographic findings (50%) showed a different diagnostic performance (interaction P < 0.05) with loss of diagnostic value in patients with prior CABG. The diagnostic accuracy as quantified by the area under the curve (AUC) of the integrated clinical judgement was moderate to good in patients with prior CABG, and significantly lower compared to patients without prior CABG [AUC 0.80 (95% confidence interval (CI) 0.75-0.84) vs. AUC 0.87 (95% CI 0.86-0.89); P = 0.004]. Time to discharge from the ED was significantly longer in patients with prior CABG [359 (215-525) min vs. 300 (192-435) min; P < 0.001]. Key findings were confirmed in a large independent external validation cohort (n = 13 653). CONCLUSIONS: Patients with prior CABG presenting with suspected AMI have a high prevalence of AMI and unstable angina and lower diagnostic accuracy of CPCs and the ECG, possibly justifying liberal use of early coronary angiography in these vulnerable patients. CLINICALTRIALS.GOV REGISTRY: Number NCT00470587.

The FAST-FURO study: effect of very early administration of intravenous furosemide in the prehospital setting to patients with acute heart failure attending the emergency department.

AIMS: The effect of early administration of intravenous (IV) furosemide in the emergency department (ED) on short-term outcomes of acute heart failure (AHF) patients remains controversial, with one recent Japanese study reporting a decrease of in-hospital mortality and one Korean study reporting a lack of clinical benefit. Both studies excluded patients receiving prehospital IV furosemide and only included patients requiring hospitalization. To assess the impact on short-term outcomes of early IV furosemide administration by emergency medical services (EMS) before patient arrival to the ED. METHODS AND RESULTS: In a secondary analysis of the Epidemiology of Acute Heart Failure in Emergency Departments (EAHFE) registry of consecutive AHF patients admitted to Spanish EDs, patients treated with IV furosemide at the ED were classified according to whether they received IV furosemide from the EMS (FAST-FURO group) or not (CONTROL group). In-hospital all-cause mortality, 30-day all-cause mortality, and prolonged hospitalization (>10 days) were assessed. We included 12 595 patients (FAST-FURO = 683; CONTROL = 11 912): 968 died during index hospitalization [7.7%; FAST-FURO = 10.3% vs. CONTROL = 7.5%; odds ratio (OR) = 1.403, 95% confidence interval (95% CI) = 1.085-1.813; P = 0.009], 1269 died during the first 30 days (10.2%; FAST-FURO = 13.4% vs. CONTROL = 9.9%; OR = 1.403, 95% CI = 1.146-1.764; P = 0.004), and 2844 had prolonged hospitalization (22.8%; FAST-FURO = 25.8% vs. CONTROL = 22.6%; OR = 1.189, 95% CI = 0.995-1.419; P = 0.056). FAST-FURO group patients had more diabetes mellitus, ischaemic cardiomyopathy, peripheral artery disease, left ventricular systolic dysfunction, and severe decompensations, and had a better New York Heart Association class and had less atrial fibrillation. After adjusting for these significant differences, early IV furosemide resulted in no impact on short-term outcomes: OR = 1.080 (95% CI = 0.817-1.427) for in-hospital mortality, OR = 1.086 (95% CI = 0.845-1.396) for 30-day mortality, and OR = 1.095 (95% CI = 0.915-1.312) for prolonged hospitalization. Several sensitivity analyses, including analysis of 599 pairs of patients matched by propensity score, showed consistent findings. CONCLUSION: Early IV furosemide during the prehospital phase was administered to the sickest patients, was not associated with changes in short-term mortality or length of hospitalization after adjustment for several confounders.

Induction of IL-10-producing type 2 innate lymphoid cells by allergen immunotherapy is associated with clinical response.

The role of innate immune cells in allergen immunotherapy that confers immune tolerance to the sensitizing allergen is unclear. Here, we report a role of interleukin-10-producing type 2 innate lymphoid cells (IL-10+ ILC2s) in modulating grass-pollen allergy. We demonstrate that KLRG1+ but not KLRG1- ILC2 produced IL-10 upon activation with IL-33 and retinoic acid. These cells attenuated Th responses and maintained epithelial cell integrity. IL-10+ KLRG1+ ILC2s were lower in patients with grass-pollen allergy when compared to healthy subjects. In a prospective, double-blind, placebo-controlled trial, we demonstrated that the competence of ILC2 to produce IL-10 was restored in patients who received grass-pollen sublingual immunotherapy. The underpinning mechanisms were associated with the modification of retinol metabolic pathway, cytokine-cytokine receptor interaction, and JAK-STAT signaling pathways in the ILCs. Altogether, our findings underscore the contribution of IL-10+ ILC2s in the disease-modifying effect by allergen immunotherapy.

Altered chromatin landscape in circulating T follicular helper and regulatory cells following grass pollen subcutaneous and sublingual immunotherapy.

BACKGROUND: Allergen-specific immunotherapy is a disease-modifying treatment that induces long-term T-cell tolerance. OBJECTIVE: We sought to evaluate the role of circulating CXCR5+PD-1+ T follicular helper (cTFH) and T follicular regulatory (TFR) cells following grass pollen subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) and the accompanying changes in their chromatin landscape. METHODS: Phenotype and function of cTFH cells were initially evaluated in the grass pollen-allergic (GPA) group (n = 28) and nonatopic healthy controls (NAC, n = 13) by mathematical algorithms developed to manage high-dimensional data and cell culture, respectively. cTFH and TFR cells were further enumerated in NAC (n = 12), GPA (n = 14), SCIT- (n = 10), and SLIT- (n = 8) treated groups. Chromatin accessibility in cTFH and TFR cells was assessed by assay for transposase-accessible chromatin sequencing (ATAC-seq) to investigate epigenetic mechanisms underlying the differences between NAC, GPA, SCIT, and SLIT groups. RESULTS: cTFH cells were shown to be distinct from TH2- and TH2A-cell subsets, capable of secreting IL-4 and IL-21. Both cytokines synergistically promoted B-cell class switching to IgE and plasma cell differentiation. Grass pollen allergen induced cTFH-cell proliferation in the GPA group but not in the NAC group (P < .05). cTFH cells were higher in the GPA group compared with the NAC group and were lower in the SCIT and SLIT groups (P < .01). Time-dependent induction of IL-4, IL-21, and IL-6 was observed in nasal mucosa following intranasal allergen challenge in the GPA group but not in SCIT and SLIT groups. TFR and IL-10+ cTFH cells were induced in SCIT and SLIT groups (all, P < .01). ATAC-seq analyses revealed differentially accessible chromatin regions in all groups. CONCLUSIONS: For the first time, we showed dysregulation of cTFH cells in the GPA group compared to NAC, SCIT, and SLIT groups and induction of TFR and IL-10+ cTFH cells following SCIT and SLIT. Changes in the chromatin landscape were observed following allergen-specific immunotherapy in cTFH and TFR cells.

Influence of previous coronary artery bypass grafting in the difficulty of acute coronary syndrome diagnosis.

OBJECTIVES: To investigate whether the diagnosis of acute coronary syndrome (ACS) in coronary artery bypass grafting (CABG) patients with chest pain (CP) is more difficult based on the initial clinical and electrocardiogram (ECG) findings. METHODS: We included consecutive CP patients attended at a single emergency department (ED) during a 10-year period. CABG status and the final diagnosis of ACS were considered as stated in the ED discharge report. We evaluated the frequency of 21 CP characteristics (CPC) and four ECG signatures, their individual and collective association with ACS, and ED length of stay (LOS) in CABG and non-CABG patients. RESULTS: We included 34 429 patients [median age: 61 years; female: 41.8%; CABG: 2204 patients (6.4%)], and ACS was diagnosed in 6727 (19.5%; CABG/non-CABG 37.2%/18.3%; P < 0.001). CABG patients more frequently had CPC and ECG findings typically associated with ACS, but their final association with ACS was weaker than in non-CABG patients (only significant after adjustment for attendant diaphoresis, throat irradiation, ST-segment elevation and T-wave inversion). The collective discriminative capacity was significantly lower in CABG patients (area under the curve 0.710 vs. 0.793; P < 0.001), even after adjustment (0.708 vs. 0.790; P < 0.001). ED LOS was longer for CABG patients, overall (P < 0.001) and for patients diagnosed with ACS (P = 0.008) and non-ACS (P < 0.001), but these differences disappeared after adjustment. CONCLUSION: CABG substantially reduces the diagnostic performance of CPC and ECG findings to suggest ACS. A longer LOS in the ED in CABG patients is more related to their baseline characteristics than to CABG itself.