Live Cell Imaging by Förster Resonance Energy Transfer Fluorescence to Study Trafficking of PLGA Nanoparticles and the Release of a Loaded Peptide in Dendritic Cells.

Our previous study demonstrated that a selected ß-lactoglobulin-derived peptide (BLG-Pep) loaded in poly(lactic-co-glycolic acid) (PLGA) nanoparticles protected mice against cow's milk allergy development. However, the mechanism(s) responsible for the interaction of the peptide-loaded PLGA nanoparticles with dendritic cells (DCs) and their intracellular fate was/were elusive. Förster resonance energy transfer (FRET), a distance-dependent non-radioactive energy transfer process mediated from a donor to an acceptor fluorochrome, was used to investigate these processes. The ratio of the donor (Cyanine-3)-conjugated peptide and acceptor (Cyanine-5) labeled PLGA nanocarrier was fine-tuned for optimal (87%) FRET efficiency. The colloidal stability and FRET emission of prepared NPs were maintained upon 144 h incubation in PBS buffer and 6 h incubation in biorelevant simulated gastric fluid at 37 °C. A total of 73% of Pep-Cy3 NP was internalized by DCs as quantified using flow cytometry and confirmed using confocal fluorescence microscopy. By real-time monitoring of the change in the FRET signal of the internalized peptide-loaded nanoparticles, we observed prolonged retention (for 96 h) of the nanoparticles-encapsulated peptide as compared to 24 h retention of the free peptide in the DCs. The prolonged retention and intracellular antigen release of the BLG-Pep loaded in PLGA nanoparticles in murine DCs might facilitate antigen-specific tolerance induction.

The utility of the Barthel index as an outcome predictor in older patients with acute infection attending the emergency department.

BACKGROUND: Functional decline and frailty are common in older adults and influence the risk of adverse outcomes. We aimed to assess the value of a Barthel index at the Emergency Department (ED-BI) score in predicting 30-day mortality and ED reconsultation among older patients with acute infection. METHODS: We performed a prospective multicentre cohort study of older patients (≥75 years) diagnosed with acute infection in 69 Spanish EDs. Demographic, comorbidities, functional status, clinical and analytical data were collected. Unadjusted and adjusted logistic regression models were used to assess the association between ED-BI score, mortality and ED reconsultation. RESULTS: In total 1596 patients with a mean age of 84.7 years were included in the study and 51.7% female. The most frequent focus of infection was respiratory in 918 patients (57.5%). Patients with an ED-BI< 60 points were significantly older, predominantly female, more likely institutionalized and more urinary infections. When comparing patients with an ED-BI score ≥ 60 points with those< 60 points no differences were found in ED reconsultation but in the latter group mortality at 30-days was higher (p < 0.001). CONCLUSION: An ED-BI score< 60 points appears to be a strong predictor of mortality at the 30-day follow up in older patients with acute infection. DATA AVAILABILITY: The data used to support the findings of this study are included within the article.

Emergency Department capacity to initiate thromboprophylaxis in patients with atrial fibrillation and thrombotic risk after discharge: URGFAICS cohort analysis.

Atrial fibrillation (AF) is the most prevalent heart rhythm disorder in the general population. Stroke prevention is one of the leading management objectives in the treatment of AF patients. The variables associated with the non-initiation of thromboprophylaxis in patients with thrombotic risk consulting for an episode of AF in Emergency Departments (ED) were investigated. This was a multipurpose, analytical, non-interventionist, multicenter Spanish study with a prospective 30-day follow-up. All patients ≥ 18 years of age consulting to the ED for the casual finding of AF in an electrocardiogram (ECG) performed 12 h prior to the consultation or with symptoms related to AF were enrolled from September 1, 2016 to February 28, 2017. Patients not previously received thromboprophylaxis were selected. Multivariate analysis was performed to calculate the odds ratio (OR) and the 95% confidence interval (CI). A total of 634 patients, not received thromboprophylaxis and at high thrombotic risk, were included. Of these, 251 (39.6%) did not receive thromboprophylaxis at ED discharge. In the multivariate analysis, non-initiation of anticoagulation at discharge from the ED was mostly related to cognitive impairment (OR 3.95; (95% CI 2.02-7.72), cancer history (OR 2.12; (95%CI 1.18-3.81), AF duration < 48 h (OR 2.49; (95% CI 1.48-4.21) and patients with re-establishment of sinus rhythm (OR 3.65; (95% CI 1.47-9.06). Reinforcement of the use of CHA2DS2-VASC as a stroke risk scale and empowerment of ED physicians is a must to improve this gap in care.

High-sensitivity cardiac troponin T 30 days all-come mortality in patients with acute heart failure. A Propensity Score-Matching Analysis Based on the EAHFE Registry. TROPICA4 Study.

BACKGROUND: Acute heart failure (AHF) patients with high troponin levels have a worse prognosis. High-sensitive troponin T (hs-TnT) has been used as a tool to stratify prognosis in many scales but always as a qualitative and not as a quantitative variable. OBJECTIVES: The main objective of this study was to determine the best hs-TnT cut-off for prediction of 30-day all-cause mortality. METHODS: The EAHFE registry, a prospective follow-up cohort of patients with AHF, was analysed. We performed a propensity score analysis of the optimal hs-TnT cut-off point previously determined by receiver operating characteristic (ROC) curve analysis. RESULTS: Of the 13 791 patients in the EAHFE cohort, we analysed 3190 patients in whom hs-TnT determination was available. The area under the ROC curve for 30-day all-cause mortality was 0.70 (CI95% 0.68 to 0.71; P < .001), establishing an optimal cut-off of hs-TnT of 35 ng/L. The sensitivity and specificity of this cut-off were 76.2 and 55.5%, respectively, with a negative predictive value (NPV) of 95.3%. A propensity score was made with 34 variables showing differences based on the cut-off of 35 ng/L for hs-TnT. In the analysis of the population obtained with the propensity score, patients with hs-TnT > 35 ng/L showed a greater 30-day all-cause mortality, with a HR of 2.95 (CI95% 1.83-4.75; P < .001). External validation reported similar results. CONCLUSIONS: An hs-TnT value of 35 ng/L is an adequate cut-off to evaluate the prediction of 30-day all-cause mortality with a NPV of 95.3%.

Impact of emergency department management of atrial fibrillation with amiodarone on length of stay. A propensity score analysis based on the URGFAICS registry.

OBJECTIVE: Amiodarone is a widely used drug in the emergency department (ED) for control of atrial fibrillation, but it has a delayed onset of action and slow metabolism, leading to longer length of ED stay. The aim of this study was to compare the length of ED stay of atrial fibrillation patients who were treated with or without amiodarone. METHODS: We undertook a multicenter, observational, cohort study of the URGFAICS registry of older adults with atrial fibrillation who presented to five Spanish EDs and compared patients who had received amiodarone with those who had not. Afterward, we performed a propensity score matched analysis of atrial fibrillation to determine the ED length of stay related to amiodarone. RESULTS: Of the 1199 patients included in the registry, 225 patients (18.8%) were treated with amiodarone while 974 (81.2%) were not. We performed a univariate study depending on amiodarone administration followed by propensity score calculation according to the 14 statistically different features found previously and six significant variables, obtaining 150 patients (75 for each group) suitable for the analysis. The length of ED stay was analyzed using box plot, with a P <0.001 in the crude analysis and P = 0.012 after propensity score matching and using survival curves for the analysis of prolonged ED stay, with a log rank <0.001 in the crude analysis and log rank 0.021 after the propensity score-matched analysis. CONCLUSION: Amiodarone is associated with longer length of ED stay until discharge independently of the baseline characteristics of the patients.

The environmental predictors of spatio-temporal variation in the breeding phenology of a passerine bird.

Establishing the cues or constraints that influence avian timing of breeding is the key to accurate prediction of future phenology. This study aims to identify the aspects of the environment that predict the timing of two measures of breeding phenology (nest initiation and egg laying date) in an insectivorous woodland passerine, the blue tit (Cyanistes caeruleus). We analyse data collected from a 220 km, 40-site transect over 3 years and consider spring temperatures, tree leafing phenology, invertebrate availability and photoperiod as predictors of breeding phenology. We find that mean night-time temperature in early spring is the strongest predictor of both nest initiation and lay date and suggest this finding is most consistent with temperature acting as a constraint on breeding activity. Birch budburst phenology significantly predicts lay date additionally to temperature, either as a direct cue or indirectly via a correlated variable. We use cross-validation to show that our model accurately predicts lay date in two further years and find that similar variables predict lay date well across the UK national nest record scheme. This work refines our understanding of the principal factors influencing the timing of tit reproductive phenology and suggests that temperature may have both a direct and indirect effect.

Emergency Atrial Fibrillation Registry of the Catalan Institute of Health (URGFAICS): analysis by type of atrial fibrillation and revisits within 30 days. / Registro de fibrilación auricular en servicios de urgencias del Institut Català de la Salut (URGFAICS): análisis en función del tipo de fibrilación auricular y de la reconsulta a urgencias relacionada a los 30 días.

OBJECTIVES: To study the characteristics of patients attending a hospital emergency department (ED) with de novo or previously diagnosed atrial fibrillation (AF), and to determine the rate of revisits for AF within 30 days of discharge. MATERIAL AND METHODS: Prospective multicenter, observational cohort study of patients aged 18 years or older who came to 5 Catalan EDs with symptoms of AF or who were found to have AF on examination. We recorded demographic information and data related to the acute episode and ED management on the first or other visits within 30 days. RESULTS: We had complete follow-up data for 1052 of the 1199 patients initially registered. The mean (SD) age was 73 (13) years, and 646 (53.9%) were women. AF had already been diagnosed in 652 (54.4%). Patients with diagnosed AF were older, had more concomitant conditions, and were more likely to be taking antiarrhythmic and/or anticoagulant drugs. Pharmacologic management in the ED was similar. The 30-day revisiting rate was 7.9% , and revisits were more frequent when digoxin was used in the ED and/or calcium channel blockers were prescribed on discharge. CONCLUSION: We detected differences between ED patients with de novo FA and previously diagnosed FA, but management of the 2 groups was similar. The 30-day revisiting rate was associated with use of digoxin in the ED and the prescription of calcium channel blockers on discharge.

OBJETIVO: Estudiar las características de los pacientes que consultan por un episodio de fibrilación auricular (FA) en los servicios de urgencias hospitalarios (SUH), en función de si la FA es de novo o conocida previamente, y la reconsulta relacionada con la FA a los 30 días (R30d). METODO: Estudio observacional de cohorte prospectivo y multicéntrico que incluyó a todos los pacientes 18 años que consultaron por síntomas relacionados con una FA o el hallazgo de una FA en 5 SUH catalanes. Se recogieron variables demográficas, del episodio agudo, de manejo en urgencias y la R30d. RESULTADOS: De los 1.199 pacientes, 1.052 tuvieron seguimiento a 30 días. La edad media fue de 73 (DE 13) años y 646 (53,9%) eran mujeres. Seiscientos cincuenta y dos pacientes (54,4%) tenían una FA conocida, los cuales tenían mayor edad, presencia de comorbilidades y uso de antiarrítmicos y anticoagulantes orales. Hubo escasas diferencias en el manejo farmacológico en urgencias. La R30d fue de un 7,9%, y fue más frecuente cuando se usó digoxina en urgencias y bloqueadores de los canales del calcio al alta. CONCLUSIONES: Existen diferencias basales entre los pacientes con FA de novo y conocida, pero estas son escasas en el manejo en urgencias. En pacientes atendidos por fibrilación auricular en urgencias, la R30d se relacionó con el uso de digoxina en urgencias y de bloqueadores de los canales del calcio al alta.

Registro de fibrilación auricular en servicios de urgencias del Institut Català de la Salut (URGFAICS): análisis en función del tipo de fibrilación auricular y de la reconsulta a urgencias relacionada a los 30 días / Emergency Atrial Fibrillation Registry of the Catalan Institute of Health (URGFAICS): analysis by type of atrial fibrillation and revisits within 30 days

Objetivos: Estudiar las características de los pacientes que consultan por un episodio de fibrilación auricular (FA) en los servicios de urgencias hospitalarios (SUH), en función de si la FA es de novo o conocida previamente, y la reconsulta relacionada con la FA a los 30 días (R30d). Método: Estudio observacional de cohorte prospectivo y multicéntrico que incluyó a todos los pacientes ≥ 18 años que consultaron por síntomas relacionados con una FA o el hallazgo de una FA en 5 SUH catalanes. Se recogieron variables demográficas, del episodio agudo, de manejo en urgencias y la R30d. Resultados: De los 1.199 pacientes, 1.052 tuvieron seguimiento a 30 días. La edad media fue de 73 (DE 13) años y 646 (53,9%) eran mujeres. Seiscientos cincuenta y dos pacientes (54,4%) tenían una FA conocida, los cuales tenían mayor edad, presencia de comorbilidades y uso de antiarrítmicos y anticoagulantes orales. Hubo escasas diferencias en el manejo farmacológico en urgencias. La R30d fue de un 7,9%, y fue más frecuente cuando se usó digoxina en urgencias y bloqueadores de los canales del calcio al alta. Conclusiones: Existen diferencias basales entre los pacientes con FA de novo y conocida, pero estas son escasas en el manejo en urgencias. En pacientes atendidos por fibrilación auricular en urgencias, la R30d se relacionó con el uso de digoxina en urgencias y de bloqueadores de los canales del calcio al alta

Objectives: To study the characteristics of patients attending a hospital emergency department (ED) with de novo or previously diagnosed atrial fibrillation (AF), and to determine the rate of revisits for AF within 30 days of discharge. Methods: Prospective multicenter, observational cohort study of patients aged 18 years or older who came to 5 Catalan EDs with symptoms of AF or who were found to have AF on examination. We recorded demographic information and data related to the acute episode and ED management on the first or other visits within 30 days. Results: We had complete follow-up data for 1052 of the 1199 patients initially registered. The mean (SD) age was 73 (13) years, and 646 (53.9%) were women. AF had already been diagnosed in 652 (54.4%). Patients with diagnosed AF were older, had more concomitant conditions, and were more likely to be taking antiarrhythmic and/or anticoagulant drugs. Pharmacologic management in the ED was similar. The 30-day revisiting rate was 7.9% , and revisits were more frequent when digoxin was used in the ED and/or calcium channel blockers were prescribed on discharge. Conclusions: We detected differences between ED patients with de novo FA and previously diagnosed FA, but management of the 2 groups was similar. The 30-day revisiting rate was associated with use of digoxin in the ED and the prescription of calcium channel blockers on discharge

Association of APOA5 and APOC3 Genetic Polymorphisms With Severity of Hypertriglyceridemia in Patients With Cutaneous T-Cell Lymphoma Treated With Bexarotene.

Importance: Hypertriglyceridemia is the most frequent and limiting adverse effect of bexarotene therapy in cutaneous T-cell lymphoma (CTCL). Despite standard prophylactic measures, there is a wide variability in the severity of this complication, which could be associated with both genetic and environmental factors. Objectives: To analyze the association between genetic polymorphisms of apolipoprotein genes APOA5, APOC3, and APOE and the severity of hypertriglyceridemia during bexarotene therapy and to optimize patient selection for bexarotene therapy based on adverse effect profile. Design, Setting, and Participants: This case series study was conducted in 12 university referral hospitals in Spain from September 17, 2014, to February 6, 2015. One hundred twenty-five patients with a confirmed diagnosis of CTCL who had received bexarotene therapy for at least 3 months were enrolled. Nine patients were excluded owing to missing analytic triglyceride level data, leaving a study group of 116 patients. Data on demographic and cardiovascular risk factor were collected, and a complete blood analysis, including lipid profile and genetic analysis from a saliva sample, was performed. Main Outcomes and Measures: Primary outcomes were the maximal triglyceride levels reported in association with the minor alleles of the polymorphisms studied. Results: Among 116 patients, the mean (SD) age was 61.2 (14.7) years, 69 (59.5%) were men, and 85 (73.2%) had mycosis fungoides, the most prevalent form of CTCL. During bexarotene therapy, 96 patients (82.7%) experienced hypertriglyceridemia, which was severe or extreme in 8 of these patients (8.3%). Patients who carried minor alleles of the polymorphisms did not show significant differences in baseline triglyceride concentrations. After bexarotene treatment, carriers of at least 1 of the 2 minor alleles of APOA5 c.-1131T>C and APOC3 c.*40C>G showed lower levels of triglycerides than noncarriers (mean [SD], 241.59 [169.91] vs 330.97 [169.03] mg/dL, respectively; P = .02). Conclusions and Relevance: These results indicate that the screening of APOA5 and APOC3 genotypes may be useful to estimate changes in triglyceride concentrations during bexarotene treatment in patients with CTCL and also to identify the best candidates for bexarotene therapy based on the expected adverse effect profile.

Trasplante renal no funcionante en una paciente de 76 años / Never-functioning kidney transplant in a76 - year old woman

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