Estudios sobre la tomografía óptica difusiva de fluorescencia

La Tomografía Óptica Difusiva de Fluorescencia (FDOT) es una técnica de imagen molecular de reciente creación, que ha atraído fuertemente la atención de la comunidad de investigadores biomédicos “preclínicos”, pues utiliza radiación no ionizante y su coste es muy bajo. La conjunción de estos factores la perfilan como una alternativa posible al paradigma nuclear en la investigación con animales pequeños. Debido a la juventud de la técnica, se plantean numerosos interrogantes que abarcan desde sus áreas de aplicación al discurrir de su desarrollo tecnológico. Es la intención de este trabajo dar respuesta a algunos de ellos. En lo que concierne al desarrollo tecnológico hemos construido un FDOT de geometría de placas paralelas que utiliza un reconstructor optimizado. Posteriormente el sistema ha sido clonado, incluyéndose en el gantry rotatorio de un tomógrafo de rayos X (CT). Usando estos dispositivos hemos querido resolver dos cuestiones técnicas relevantes: la primera relativa al grado de detalle necesario en el modelo matemático de transporte de luz. Este modelo alimenta el algoritmo de reconstrucción y habitualmente se construye suponiendo que los sujetos tienen propiedades ópticas homogéneas, junto con el uso de datos normalizados. Hemos demostrado que esta asunción no es válida en presencia de heterogeneidades de dispersión. La segunda cuestión hace referencia a la geometría del montaje experimental, demostrando que la adquisición en placas paralelas es capaz de proporcionar reconstrucciones de mejor calidad que la adquisición en rotación. En lo referente a las áreas de aplicación, en este documento demostramos la capacidad de la técnica para cuantificar in-vivo la concentración de células T fluorescentes en los ganglios cervicales y en el timo de ratones transgénicos

Quality control in clinical raster-scan optoacoustic mesoscopy

Optoacoustic (photoacoustic) mesoscopy bridges the gap between optoacoustic microscopy and macroscopy and enables high-resolution visualization deeper than optical microscopy. Nevertheless, as images may be affected by motion and noise, it is critical to develop methodologies that offer standardization and quality control to ensure that high-quality datasets are reproducibly obtained from patient scans. Such development is particularly important for ensuring reliability in applying machine learning methods or for reliably measuring disease biomarkers. We propose herein a quality control scheme to assess the quality of data collected. A reference scan of a suture phantom is performed to characterize the system noise level before each raster-scan optoacoustic mesoscopy (RSOM) measurement. Using the recorded RSOM data, we develop a method that estimates the amount of motion in the raw data. These motion metrics are employed to classify the quality of raw data collected and derive a quality assessment index (QASIN) for each raw measurement. Using simulations, we propose a selection criterion of images with sufficient QASIN, leading to the compilation of RSOM datasets with consistent quality. Using 160 RSOM measurements from healthy volunteers, we show that RSOM images that were selected using QASIN were of higher quality and fidelity compared to non-selected images. We discuss how this quality control scheme can enable the standardization of RSOM images for clinical and biomedical applicationsThis project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 871763 (WINTHER) and under grant agreement No 687866 (INNODERM). Dr. He would like to thank the Helmholtz Imaging Platform (HIP: Deep4OM). Dr. Aguirre would like to thank support from the Madrid Autonomous Region Talento Project 2020-T1/TIC-2066

Supervivencia en pacientes con COVID-19 ingresados en UCI en un hospital de tercer nivel de Lambayeque, Perú.

Introduction: COVID-19, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has reached pandemic proportions worldwide, persisting over time. In this context, this study aims to analyze the factors associated with mortality in hospitalized patients with COVID-19 in a third-level hospital in the Lambayeque region. Material and metodo: A retrospective cohort study was conducted on patients diagnosed with COVID-19, hospitalized at the National Hospital Almanzor Aguinaga Asenjo (HNAAA) during the months of March to September 2020. Results: Forty patients admitted to the Intensive Care Unit (ICU) were examined, of whom twenty-two required mechanical ventilation (MV). Overall mortality in the ICU was 68.7%, while mortality among patients who required mechanical ventilation was 91.6%. A statistical association was found between death and vital signs on admission to the ICU, as well as with the waiting time for admission. The probability of survival at 2 and 7 days was 90.1% and 45.5%, respectively. Conclusions: In this cohort, a mortality rate of 68.7% was observed in the ICU, with a survival rate of 45.5% at 7 days and less than 10% at 18 days. No associations were found between survival and any of the variables of interest.Introducción: La COVID-19, causada por el Coronavirus 2 del Síndrome Respiratorio Agudo Severo (SARS-CoV-2), ha alcanzado proporciones pandémicas a nivel mundial, prolongándose en el tiempo. En este contexto, el presente estudio tiene como objetivo analizar los factores asociados a la mortalidad en pacientes hospitalizados por COVID-19 en un hospital de tercer nivel de la región Lambayeque. Material y método: Se realizó un estudio de cohorte retrospectivo de los pacientes con diagnóstico de COVID-19, hospitalizados en el Hospital Nacional Almanzor Aguinaga Asenjo (HNAAA) durante los meses de marzo a septiembre del 2020.  Resultados: Se examinaron cuarenta pacientes que ingresaron en la Unidad de Cuidados Intensivos (UCI), de los cuales veintidós necesitaron ventilación mecánica (VM). La mortalidad general en la UCI fue del 68.7%, mientras que la mortalidad entre los pacientes que necesitaron ventilación mecánica fue del 91.6%. Se encontró una asociación estadística entre el fallecimiento y los signos vitales al ingreso en la UCI, así como con el tiempo de espera para el ingreso. La probabilidad de supervivencia a 2 y 7 días fue del 90.1% y del 45.5%, respectivamente. Conclusiones: En esta cohorte, se observó una tasa de mortalidad del 68.7% en UCI, con una tasa de supervivencia del 45.5% a los 7 días y menos del 10% a los 18 días. No se encontró asociaciones entre la supervivencia y ninguna de las variables de interés

Integrated flow cytometry and sequencing to reconstruct evolutionary patterns from dysplasia to acute myeloid leukemia

Clonal evolution in acute myeloid leukemia (AML) originates long before diagnosis and is a dynamic process that may affect survival. However, it remains uninvestigated during routine diagnostic workups. We hypothesized that the mutational status of bone marrow dysplastic cells and leukemic blasts, analyzed at the onset of AML using integrated multidimensional flow cytometry (MFC) immunophenotyping and fluorescence-activated cell sorting (FACS) with next-generation sequencing (NGS), could reconstruct leukemogenesis. Dysplastic cells were detected by MFC in 285 of 348 (82%) newly diagnosed patients with AML. Presence of dysplasia according to MFC and World Health Organization criteria had no prognostic value in older adults. NGS of dysplastic cells and blasts isolated at diagnosis identified 3 evolutionary patterns: stable (n = 12 of 21), branching (n = 4 of 21), and clonal evolution (n = 5 of 21). In patients achieving complete response (CR), integrated MFC and FACS with NGS showed persistent measurable residual disease (MRD) in phenotypically normal cell types, as well as the acquisition of genetic traits associated with treatment resistance. Furthermore, whole-exome sequencing of dysplastic and leukemic cells at diagnosis and of MRD uncovered different clonal involvement in dysplastic myelo-erythropoiesis, leukemic transformation, and chemoresistance. Altogether, we showed that it is possible to reconstruct leukemogenesis in ∼80% of patients with newly diagnosed AML, using techniques other than single-cell multiomics.This work was supported by grants from the Área de Oncología del Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red (CIBER-ONC) (CB16/12/00369, CB16/12/00233, CB16/12/00489, and CB16/12/00284), Instituto de Salud Carlos III/Subdirección General de Investigación Sanitaria (FIS numbers PI16/01661, PI16/00517, and PI19/01518), and the Plan de Investigación de la Universidad de Navarra (PIUNA 2014-18). This work was supported internationally by the Cancer Research UK, FCAECC, and AIRC under the Accelerator Award Program (EDITOR)

Thirty-day outcomes in frail older patients discharged home from the emergency department with acute heart failure: effects of high-risk criteria identified by the DEED FRAIL-AHF trial

Objectives: To study the effect of high-risk criteria on 30-day outcomes in frail older patients with acute heart failure (AHF) discharged from an emergency department (ED) or an ED's observation and short-stay areas. Material and methods: Secondary analysis of discharge records in the Older AHF Key Data registry. We selected frail patients (aged > 70 years) discharged with AHF from EDs. Risk factors were categorized as modifiable or nonmodifiable. The outcomes were a composite endpoint for a cardiovascular event (revisits for AHF, hospitalization for AHF, or cardiovascular death) and the number of days alive out-of-hospital (DAOH) within 30 days of discharge. Results: We included 380 patients with a mean (SD) age of 86 (5.5) years (61.2% women). Modifiable risk factors were identified in 65.1%, nonmodifiable ones in 47.8%, and both types in 81.6%. The 30-day cardiovascular composite endpoint occurred in 83 patients (21.8%). The mean 30-day DAOH observed was 27.6 (6.1) days. Highrisk factors were present more often in patients who developed the cardiovascular event composite endpoint: the rates for patients with modifiable, nonmodifiable, or both types of risk were, respectively, as follows in comparison with patients not at high risk: 25.0% vs 17.2%, P = .092; 27.6% vs 16.7%, P = .010; and 24.7% vs 15.2%, P = .098). The 30-day DAOH outcome was also lower for at-risk patients, according to type of risk factor present: modifiable, 26.9 (7.0) vs 28.4 (4.4) days, P = .011; nonmodifiable, 27.1 (7.0) vs 28.0 (5.0) days, P = .127; and both, 27.1 (6.7) vs 28.8 (3.4) days, P = .005). After multivariate analysis, modifiable risk remained independently associated with fewer days alive (adjusted absolute difference in 30-day DAOH, -1.3 days (95% CI, -2.7 to -0.1 days). Nonmodifiable factors were associated with increased risk for the 30-day cardiovascular composite endpoint (adjusted absolute difference, 10.4%; 95% CI, -2.1% to 18.7%). Conclusion: Risk factors are common in frail elderly patients with AHF discharged home from hospital ED areas. Their presence is associated with a worse 30-day prognosis

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

Objective: 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. Methods: 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 (reference), and stratified by hospitalisation in cardiology, internal medicine, geriatrics, or short-stay units. Results: 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. Conclusions: 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

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Spread of a SARS-CoV-2 variant through Europe in the summer of 2020

[EN] Following its emergence in late 2019, the spread of SARS-CoV-21,2 has been tracked by phylogenetic analysis of viral genome sequences in unprecedented detail3,4,5. Although the virus spread globally in early 2020 before borders closed, intercontinental travel has since been greatly reduced. However, travel within Europe resumed in the summer of 2020. Here we report on a SARS-CoV-2 variant, 20E (EU1), that was identified in Spain in early summer 2020 and subsequently spread across Europe. We find no evidence that this variant has increased transmissibility, but instead demonstrate how rising incidence in Spain, resumption of travel, and lack of effective screening and containment may explain the variant’s success. Despite travel restrictions, we estimate that 20E (EU1) was introduced hundreds of times to European countries by summertime travellers, which is likely to have undermined local efforts to minimize infection with SARS-CoV-2. Our results illustrate how a variant can rapidly become dominant even in the absence of a substantial transmission advantage in favourable epidemiological settings. Genomic surveillance is critical for understanding how travel can affect transmission of SARS-CoV-2, and thus for informing future containment strategies as travel resumes.S

Capitulo 2. Ciencias Naturales y Ciencias Básicas, Ingeniería y Tecnología

La diseminación de la Levitación Magnética, a pesar de lo antiguo de su tecnología, ha sido limitada. Debido a sus inconvenientes prácticos de implementación, su uso es bastante restringido, comparado con otras tecnologías (SCMaglev japonés, Transrapid alemán, o productos comerciales para ocio y entretenimiento). Con el boom de las tecnologías limpias y amigables con el medio ambiente y en concordancia con los objetivos del milenio, es pertinente plantearse el objetivo de optimizar el proceso de Levitación Magnética para generar un aprovechamiento de las ventajas de esta tecnología a nivel mecánico, eléctrico, y ambiental.&nbsp; Actualmente la UNAD adelanta un proyecto de investigación cuyo objetivo es generar un modelo físico matemático de levitación magnética para aplicaciones en ingeniería. De este proyecto se ha derivado una primera revisión sistemática de los principios físicos y los modelos vigentes en Levitación Magnética