Tiempo de estancia hospitalaria en pacientes ingresados por insuficiencia cardiaca aguda. Factores asociados

La presente tesis doctoral persigue los siguientes objetivos: 1. Estudiar los factores asociados con una estancia prolongada de los pacientes ingresados por insuficiencia cardiaca aguda en las unidades de corta estancia españolas; 2. Identificar los factores asociados al tiempo de estancia hospitalaria prolongada en los pacientes ingresados por insuficiencia cardiaca aguda; 3. Identificar factores asociados a un tiempo de estancia hospitalaria corto en pacientes ingresados por insuficiencia cardiaca aguda en hospitales con unidad de corta estancia; 4. Determinar si la presencia de una unidad de corta estancia en un hospital influye en el porcentaje de ingresos, en el tiempo de estancia hospitalaria y en los resultados de los pacientes atendidos con insuficiencia cardiaca aguda en un servicio de urgencias hospitalario.Departamento de Medicina, Dermatología y ToxicologíaDoctorado en Investigación en Ciencias de la Salu

Polo-like kinase 1 inhibition as a therapeutic approach to selectively target BRCA1-deficient cancer cells by synthetic lethality induction

Purpose: BRCA1 and BRCA2 deficiencies are widespread drivers of human cancers that await the development of targeted therapies. We aimed to identify novel synthetic lethal relationships with therapeutic potential using BRCA-deficient isogenic backgrounds. Experimental Design: We developed a phenotypic screening technology to simultaneously search for synthetic lethal (SL) interactions in BRCA1- and BRCA2-deficient contexts. For validation, we developed chimeric spheroids and a dualtumor xenograft model that allowed the confirmation of SL induction with the concomitant evaluation of undesired cytotoxicity on BRCA-proficient cells. To extend our results using clinical data, we performed retrospective analysis on The Cancer Genome Atlas (TCGA) breast cancer database. Results: The screening of a kinase inhibitors library revealed that Polo-like kinase 1 (PLK1) inhibition triggers strong SL induction in BRCA1-deficient cells. Mechanistically, we found no connection between the SL induced by PLK1 inhibition and PARP inhibitors. Instead, we uncovered that BRCA1 downregulation and PLK1 inhibition lead to aberrant mitotic phenotypes with altered centrosomal duplication and cytokinesis, which severely reduced the clonogenic potential of these cells. The penetrance of PLK1/BRCA1 SL interaction was validated using several isogenic and nonisogenic cellular models, chimeric spheroids, and mice xenografts. Moreover, bioinformatic analysis revealed high-PLK1 expression in BRCA1-deficient tumors, a phenotype that was consistently recapitulated by inducing BRCA1 deficiency in multiple cell lines as well as in BRCA1-mutant cells. Conclusions: We uncovered an unforeseen addiction of BRCA1-deficient cancer cells to PLK1 expression, which provides a new means to exploit the therapeutic potential of PLK1 inhibitors in clinical trials, by generating stratification schemes that consider this molecular trait in patient cohorts.Fil: Carbajosa González, Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Pansa, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Paviolo, Natalia Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Fundación Instituto Leloir; ArgentinaFil: Castellaro, Andrés Marcos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Andino, Diego Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigación y Desarrollo en Inmunología y Enfermedades Infecciosas. Universidad Católica de Córdoba. Centro de Investigación y Desarrollo en Inmunología y Enfermedades Infecciosas; ArgentinaFil: Nigra, Ayelén Denise. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: García, Iris Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Racca, Ana Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Rodriguez, María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Angiolini, Virginia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Guantay, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Villafañez, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Federico, Maria Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Rodríguez, Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Caputto, Beatriz Leonor. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Drewes, Gerard. Cellzome AG; AlemaniaFil: Madauss, Kevin P.. Global Observatory on Health Research and Development; Estados UnidosFil: Gloger, Israel. Global Observatory on Health Research and Development; Estados UnidosFil: Fernandez, Elmer Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigación y Desarrollo en Inmunología y Enfermedades Infecciosas. Universidad Católica de Córdoba. Centro de Investigación y Desarrollo en Inmunología y Enfermedades Infecciosas; ArgentinaFil: Gil, German Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Bocco, Jose Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Gottifredi, Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Soria, Ramiro Gaston. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentin

Accuracy of prehospital point-of-care lactate in early in-hospital mortality

Background: Emergency medical services (EMS) routinely face complex scenarios where decisions should be taken with limited clinical information. The development of fast, reliable and easy to perform warning biomarkers could help in such decision-making processes. The present study aims at characterizing the validity of point-of-care lactate (pLA) during prehospital tasks for predicting in-hospital mortality within two days after the EMS assistance. Materials and methods: Prospective, multicentric, ambulance-based and controlled observational study without intervention, including six advanced life support and five hospitals. The pLA levels were recorded during EMS assistance of adult patients. The validity of pLA to determine the in-hospital mortality was assessed by the area under the curve (AUC) of the receiver operating curve (ROC). Results: A total of 2997 patients were considered in the study, with a median of 69 years (IQR 54-81) and 41.4% of women. The median pLA value was 2.7 mmol/L (1.9-3.8) in survivors and 5.7 mmol/L (4.4-7.6) in nonsurvivors. The global discrimination level of pLA reached an AUC of 0.867, being 1.9 mmol/L and 4 mmol/L the cut-off point for low and high mortality. The discrimination value of pLA was not affected by sex, age or pathology. Conclusions: Our results highlight the clinical importance of prehospital pLA to determine the in-hospital risk of mortality. The incorporation of pLA into the EMS protocols could improve the early identification of risky patients, leading to a better care of such patients.Fil: Martín Rodríguez, Francisco. Universidad de Valladolid; España. Paseo Hospital Militar; EspañaFil: López Izquierdo, Raúl. Universidad de Valladolid; España. Hospital Universitario Rio Hortega; EspañaFil: Medina Lozano, Elena. Universidad de Valladolid; EspañaFil: Ortega, Guillermo José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Autonoma de Madrid. Hospital Universitario de la Princesa; EspañaFil: del Pozo Vegas, Carlos. Hospital Clínico Universitario; EspañaFil: Carbajosa Rodríguez, Virginia. Hospital Universitario Rio Hortega; EspañaFil: Castro Villamor, Miguel Ángel. Universidad de Valladolid; EspañaFil: Sánchez Soberon, Irene. Paseo Hospital Militar; EspañaFil: Sanz García, Ancor. Universidad Autonoma de Madrid. Hospital Universitario de la Princesa; Españ

Blood Biomarkers for Assessing Headaches in Healthcare Workers after Wearing Biological Personal Protective Equipment in a COVID-19 Field Hospital

The coronavirus disease 2019 (COVID-19) has led to a pandemic, which among other things, has highlighted biosafety as a key cornerstone in the management of disease transmission. The aim of this work was to analyze the role played by different blood biomarkers in predicting the appearance of headaches in healthcare workers wearing personal protective equipment (PPE) in a COVID-19 treatment unit. A prospective cohort study of 38 healthcare workers was performed during April 2020. Blood analysis, performed just before the start of a 4 hour shift, was carried out on all volunteers equipped with PPE. At the end of their shifts and after decontamination, they were asked if they had suffered from headache in order to obtain a binary outcome. The baseline creatinine value reflected a specific odds ratio of 241.36 (95% CI: 2.50–23,295.43; p = 0.019) and an area under the curve (AUC) value of 0.737 (95%CI: 0.57–0.90; p < 0.01). Blood creatinine is a good candidate for predicting the appearance of a de novo headache in healthcare workers after wearing PPE for four hours in a COVID-19 unit

Accuracy of prehospital point‐of‐care lactate in early in‐hospital mortality

Background: Emergency medical services (EMS) routinely face complex scenarios where decisions should be taken with limited clinical information. The development of fast, reliable and easy to perform warning biomarkers could help in such decision-making processes. The present study aims at characterizing the validity of point-of-care lactate (pLA) during prehospital tasks for predicting in-hospital mortality within two days after the EMS assistance. Materials and methods: Prospective, multicentric, ambulance-based and controlled observational study without intervention, including six advanced life support and five hospitals. The pLA levels were recorded during EMS assistance of adult patients. The validity of pLA to determine the in-hospital mortality was assessed by the area under the curve (AUC) of the receiver operating curve (ROC). Results: A total of 2997 patients were considered in the study, with a median of 69 years (IQR 54-81) and 41.4% of women. The median pLA value was 2.7 mmol/L (1.9-3.8) in survivors and 5.7 mmol/L (4.4-7.6) in nonsurvivors. The global discrimination level of pLA reached an AUC of 0.867, being 1.9 mmol/L and 4 mmol/L the cut-off point for low and high mortality. The discrimination value of pLA was not affected by sex, age or pathology. Conclusions: Our results highlight the clinical importance of prehospital pLA to determine the in-hospital risk of mortality. The incorporation of pLA into the EMS protocols could improve the early identification of risky patients, leading to a better care of such patients.Fil: Martín Rodríguez, Francisco. Universidad de Valladolid; España. Paseo Hospital Militar; EspañaFil: López Izquierdo, Raúl. Universidad de Valladolid; España. Hospital Universitario Rio Hortega; EspañaFil: Medina Lozano, Elena. Universidad de Valladolid; EspañaFil: Ortega, Guillermo José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Autonoma de Madrid. Hospital Universitario de la Princesa; EspañaFil: del Pozo Vegas, Carlos. Hospital Clínico Universitario; EspañaFil: Carbajosa Rodríguez, Virginia. Hospital Universitario Rio Hortega; EspañaFil: Castro Villamor, Miguel Ángel. Universidad de Valladolid; EspañaFil: Sánchez Soberon, Irene. Paseo Hospital Militar; EspañaFil: Sanz García, Ancor. Universidad Autonoma de Madrid. Hospital Universitario de la Princesa; Españ

The Value of Prehospital Early Warning Scores to Predict in - Hospital Clinical Deterioration: A Multicenter, Observational Base-Ambulance Study

Objectives: Early warning scores are clinical tools capable of identifying prehospital patients with high risk of deterioration. We sought here to contrast the validity of seven early warning scores in the prehospital setting and specifically, to evaluate the predictive value of each score to determine early deterioration-risk during the hospital stay, including mortality at one, two, three and seven- days since the index event. Methods: A prospective multicenter observational based-ambulance study of patients treated by six advanced life support emergency services and transferred to five Spanish hospitals between October 1, 2018 and December 31, 2019. We collected demographic, clinical, and laboratory variables. Seven risk score were constructed based on the analysis of prehospital variables associated with death within one, two, three and seven days since the index event. The area under the receiver operating characteristics was used to determine the discriminant validity of each early warning score. Results: A total of 3,273 participants with acute diseases were accurately linked. The median age was 69 years (IQR, 54–81 years), 1,348 (41.1%) were females. The overall mortality rate for patients in the study cohort ranged from 3.5% for first-day mortality (114 cases), to 7% for seven-day mortality (228 cases). The scores with the best performances for one-day mortality were Vitalpac Early Warning Score with an area under the receiver operating characteristic (AUROC) of 0.873 (95% CI: 0.81-0.9), for two-day mortality, Triage Early Warning Score with an AUROC of 0.868 (95% CI: 0.83-0.9), for three and seven-days mortality the Modified Rapid Emergency Medicine Score with an AUROC of 0.857 (0.82-0.89) and 0.833 (95% CI: 0.8-0.86). In general, there were no significant differences between the scores analyzed. Conclusions: All the analyzed scores have a good predictive capacity for early mortality, and no statistically significant differences between them were found. The National Early Warning Score 2, at the clinical level, has certain advantages. Early warning scores are clinical tools that can help in the complex decision-making processes during critical moments, so their use should be generalized in all emergency medical services.Fil: Martín Rodríguez, Francisco. Universidad de Valladolid; España. Servicios médicos de emergencia; EspañaFil: Sanz García, Ancor. Universidad Autonoma de Madrid. Hospital Universitario de la Princesa; EspañaFil: Medina Lozano, Elena. Universidad de Valladolid; EspañaFil: Castro Villamor, Miguel Ángel. Universidad Autonoma de Madrid. Hospital Universitario de la Princesa; EspañaFil: Carbajosa Rodríguez, Virginia. Hospital Universitario Rio Hortega; EspañaFil: del Pozo Vegas, Carlos. Hospital Clínico Universitario; EspañaFil: Fadrique Millán, Laura Natividad. Hospital Universitario Rio Hortega; EspañaFil: Ortega, Guillermo José. Universidad Autonoma de Madrid. Hospital Universitario de la Princesa; España. Universidad Nacional de Misiones. Secretaria de Ciencia y Tecnologia. Unidad de Vinculacion y Transferencias Tecnologicas.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Martín Conty, José Luis. Universidad de Castilla-La Mancha; EspañaFil: López Izquierdo, Raúl. Universidad de Valladolid; Españ

Influence of the length of hospitalisation in post-discharge outcomes in patients with acute heart failure: Results of the LOHRCA study.

To investigate the relationship between length of hospitalisation (LOH) and post-discharge outcomes in acute heart failure (AHF) patients and to ascertain whether there are different patterns according to department of initial hospitalisation. Consecutive AHF patients hospitalised in 41 Spanish centres were grouped based on the LOH (15 days). Outcomes were defined as 90-day post-discharge all-cause mortality, AHF readmissions, and the combination of both. Hazard ratios (HRs), adjusted by chronic conditions and severity of decompensation, were calculated for groups with LOH >6 days vs. LOH 6 days vs. LOH We included 8563 patients (mean age: 80 (SD = 10) years, 55.5% women), with a median LOH of 7 days (IQR 4-11): 2934 (34.3%) had a LOH 15 days. The 90-day post-discharge mortality was 11.4%, readmission 32.2%, and combined endpoint 37.4%. Mortality was increased by 36.5% (95%CI = 13.0-64.9) when LOH was 11-15 days, and by 72.0% (95%CI = 42.6-107.5) when >15 days. Conversely, no differences were found in readmission risk, and the combined endpoint only increased 21.6% (95%CI = 8.4-36.4) for LOH >15 days. Stratified analysis by hospitalisation departments rendered similar post-discharge outcomes, with all exhibiting increased mortality for LOH >15 days and no significant increments in readmission risk. Short hospitalisations are not associated with worse outcomes. While post-discharge readmissions are not affected by LOH, mortality risk increases as the LOH lengthens. These findings were similar across hospitalisation departments