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Several computational models, both continuum and discrete, allow for the simulation of collective cell behaviors in connection with challenges linked to disease modeling and understanding. Normally, discrete cell modelling employs quasi-infinite or boundary-less 2D lattices, hence modeling collective cell behaviors in Petri dish-like environments. The advent of lab- and organ-on-a-chip devices proves that the information obtained from 2D cell cultures, upon Petri dishes, differs importantly from the results obtained in more biomimetic micro-fluidic environments, made of interconnected chambers and channels. However, discrete cell modelling within lab- and organ-on-a-chip devices, to our knowledge, is not yet found in the literature, although it may prove useful for designing and optimizing these types of systems. Consequently, in this study we focus on the establishment of a direct connection between the computer-aided designs (CAD) of microfluidic systems, especially labs- and organs-on-chips (and their multi-chamber and multi-channel structures), and the lattices for discrete cell modeling approaches aimed at the simulation of collective cell interactions, whose boundaries are defined directly from the CAD models. We illustrate the proposal using a quite straightforward cellular automata model, apply it to simulating cells with different growth rates, within a selected set of microsystem designs, and validate it by tuning the growth rates with the support of cell culture experiments and by checking the results with a real microfluidic system.

Functional dependence for the performance of basic activities of daily living (ADLs) is one of the main causes of institutionalization. This study analyzed the interrelationships between basic and instrumental activities of daily living, use of assistive mobility devices, socioeconomic factors, changes during COVID-19 pandemic confinement, and 3-year survival in the ADL-dependent people of the Orcasitas neighborhood of Madrid (Spain). A longitudinal descriptive study, carried out on the entire population of functional dependent patients (Barthel ≤ 60) in the Orcasitas neighborhood. We included 127 patients, 78.7% women and 21.3% men, with a mean age of 86 years. Pre-pandemic, post-confinement (June 2020) and June 2023 data were contrasted. Results: The use of crutches-cane was associated with a higher probability of being independent in performing ADLs, leaving home (OR 4.848; CI 1.428-16.458), improving functional capacity during confinement (OR 3.621; CI 1.409-9.308), and even ceasing to be functionally dependent (OR 0.394; CI 0.165-0.941). Using a wheelchair was associated with a higher level of dependency (OR 2.583; CI 1.167-5.714) and higher mortality (HR 1.913; CI 1.106-3.309). After COVID-19 pandemic confinement, having a financial income of less than 11,200 euros/year (OR 2.413; CI 1.159-5.023), or using a wheelchair (OR 2.464; CI 1.009-6.017), increased the risk of living homebound. Living homebound decreased the probability of survival, while maintaining the ability to leave home increased it (OR 3.880; CI 1.834-8.211). Economic capacity modulated the results. Lower economic capacity was associated with higher mortality (HR 2.47 (Exp(B) 0.405; CI 0.232-0.708). Living in confinement and having a low economic income were associated with higher mortality (OR 0.127; CI 0.029-0.562), mortality that was also higher with respect to those who could leave their home (OR 6.697; CI 2.084-21.525). Functional ADL-dependence affects multiple facets of the person. Confinement triggered changes in the baseline conditions of this cohort, which were influenced by the level of dependency, mobility capacity and economic income level. Economic capacity modulated the results, showing that social inequalities influence survival. The ability to leave home and the use of a wheelchair should be included in the assessment of the risk level of this population group.

COVID-19 has overloaded national health services worldwide. Thus, early identification of patients at risk of poor outcomes is critical. Our objective was to analyse SARS-CoV-2 RNA detection in serum as a severity biomarker in COVID-19. Retrospective observational study including 193 patients admitted for COVID-19. Detection of SARS-CoV-2 RNA in serum (viremia) was performed with samples collected at 48–72 h of admission by two techniques from Roche and Thermo Fischer Scientific (TFS). Main outcome variables were mortality and need for ICU admission during hospitalization for COVID-19. Viremia was detected in 50–60% of patients depending on technique. The correlation of Ct in serum between both techniques was good (intraclass correlation coefficient: 0.612; p < 0.001). Patients with viremia were older (p = 0.006), had poorer baseline oxygenation (PaO 2 /FiO 2 ; p < 0.001), more severe lymphopenia (p < 0.001) and higher LDH (p < 0.001), IL-6 (p = 0.021), C-reactive protein (CRP; p = 0.022) and procalcitonin (p = 0.002) serum levels. We defined \"relevant viremia\" when detection Ct was < 34 with Roche and < 31 for TFS. These thresholds had 95% sensitivity and 35% specificity. Relevant viremia predicted death during hospitalization (OR 9.2 [3.8–22.6] for Roche, OR 10.3 [3.6–29.3] for TFS; p < 0.001). Cox regression models, adjusted by age, sex and Charlson index, identified increased LDH serum levels and relevant viremia (HR = 9.87 [4.13–23.57] for TFS viremia and HR = 7.09 [3.3–14.82] for Roche viremia) as the best markers to predict mortality. Viremia assessment at admission is the most useful biomarker for predicting mortality in COVID-19 patients. Viremia is highly reproducible with two different techniques (TFS and Roche), has a good consistency with other severity biomarkers for COVID-19 and better predictive accuracy.

Introducción: El síndrome de DRESS es una reacción mucocutánea y visceral grave provocada por fármacos que puede llegar a provocar la muerte por la afectación de hígado y riñón. Caso Clínico: Varón de 46 años que presentó un exantema generalizado no pruriginoso, junto con fiebre, síntomas digestivos, adenopatías cervicales y sudoración nocturna coincidiendo con la toma previa de alopurinol. Tras el ingreso en el hospital se le diagnostica hepatitis aguda y deterioro de la función renal con oliguria, necesitando realización de hemodiálisis urgente. Tras un tratamiento multidisciplinar entre los servicios de nefrología, digestivo y hematología, el paciente es dado de alta con mejora de su función renal, pero continúa en seguimiento ambulatorio. Conclusiones: El alopurinol, fármaco muy utilizado en la práctica clínica, puede tener reacciones adversas muy graves, poniendo en riesgo la vida del paciente. El síndrome de DRESS, al ser muy poco frecuente, no tiene un tratamiento estandarizado. En el caso concreto de nuestro paciente, una detección temprana, junto a un tratamiento efectivo, con recambios plasmáticos con albúmina, hemodiálisis y corticoides, propiciaron una evolución favorable del paciente, con recuperación de la función renal.

Purpose Whether the use of high-flow nasal oxygen in adult patients with COVID-19 associated acute respiratory failure improves clinically relevant outcomes remains unclear. We thus sought to assess the effect of high-flow nasal oxygen on ventilator-free days, compared to early initiation of invasive mechanical ventilation, on adult patients with COVID-19. Methods We conducted a multicentre cohort study using a prospectively collected database of patients with COVID-19 associated acute respiratory failure admitted to 36 Spanish and Andorran intensive care units (ICUs). Main exposure was the use of high-flow nasal oxygen (conservative group), while early invasive mechanical ventilation (within the first day of ICU admission; early intubation group) served as the comparator. The primary outcome was ventilator-free days at 28 days. ICU length of stay and all-cause in-hospital mortality served as secondary outcomes. We used propensity score matching to adjust for measured confounding. Results Out of 468 eligible patients, a total of 122 matched patients were included in the present analysis (61 for each group). When compared to early intubation, the use of high-flow nasal oxygen was associated with an increase in ventilator-free days (mean difference: 8.0 days; 95% confidence interval (CI): 4.4 to 11.7 days) and a reduction in ICU length of stay (mean difference: − 8.2 days; 95% CI − 12.7 to − 3.6 days). No difference was observed in all-cause in-hospital mortality between groups (odds ratio: 0.64; 95% CI: 0.25 to 1.64). Conclusions The use of high-flow nasal oxygen upon ICU admission in adult patients with COVID-19 related acute hypoxemic respiratory failure may lead to an increase in ventilator-free days and a reduction in ICU length of stay, when compared to early initiation of invasive mechanical ventilation. Future studies should confirm our findings.

Introducción: El acceso vascular supone un pilar fundamental en el tratamiento dialítico de los pacientes renales. El empleo de catéteres se ha incrementado en los últimos años. Caso clínico: Varón de 49 años que inició tratamiento de hemodiálisis a sus 32 años. Presentó 7 accesos registrados (tiempo medio de uso: 64 días) hasta el primer trasplante y otros 15 accesos (tiempo medio de uso: 162 días) y 11 infecciones por el germen Staphylococcus Epidermidis, hasta recibir el segundo trasplante, que perdió a los 5 días por infarto renal isquémico masivo, volviendo a hemodiálisis con la colocación de un catéter venoso central tunelizado femoral izquierdo, que dura hasta la actualidad sin complicaciones destacables, gracias al diagnóstico posterior de la mutación heterocigótica del factor V de Leiden (que provoca un trastorno de hipercoagulabilidad), comenzando anticoagulación oral con acenocumarol de forma domiciliaria y heparina de bajo peso molecular intradiálisis desde ese momento. Discusión: Tras comenzar el sellado del catéter con Citrato + Heparina sódica (inicialmente incluía también Taurolidina pero se eliminó debido a intolerancia), no presentó más infecciones. Debido al diagnóstico de la mutación heterocigótica del factor V de Leiden, nos planteamos la posibilidad de que los fracasos de los accesos anteriores sean debidos al desconocimiento de esta mutación. Ante la situación demográfica de España se pone de manifiesto la necesidad de equipos multidisciplinares más amplios e incluir un control y seguimiento del acceso tunelizado para reducir sus pérdidas y evitar situaciones altamente invasivas.

Objetivo: Analizar la percepción de las enfermeras renales en España en relación con el entorno organizacional para la práctica clínica basada en la evidencia (PCBE); y determinar qué factores profesionales y del contexto influenyen esta percepción. Material y Método: Estudio observacional transversal multiéntrico, en 15 servicios de nefrología de distitos hospitales en España y 2 centros de diálisis. Se utilizaron los instrumentos Practice Environment Scale of Nursing Work Index (PES-NWI) y Evidence Based Practice Questionnarie (EBPQ). Se realizó un análisis estadístio descriptivo, bivariado (ANOVA, Kruskall-Wallis), y regresión logística con la puntuación total del EBPQ como variable dependiente. Resultados: Se recibieron 397 encuestas (participación84,28%), tras depuración encuestas, fueron válidas 382 (81,1% población): 82,7% mujeres, edad media 42 años, media de experiencia profesional como enfermera 18,2 años (12,2 años en nefrología), 94,8% clínicas, 81,9% de hemodiálisis. Puntuación media PES-NWI 62,35±15,10 (IC:95% 60,78-48,06). Presentaron menores puntuaciones en algunos factores del PES-NWI las enfermeras de centros >500 enfermeras, que trabajan en hemodiálisis y >11 años de experiencia profesional. Las enfermeras gestoras presentaron mayores puntuaciones en todos los factores del PES-NWI. Puntuación media EBPQ 81,05±21,92 (IC:95% 78,70-83,4). Presentaron mayores puntuaciones en varios factores del EBPQ las enfermeras con menor experiencia profesional, mejor puntuación en PES-NWI y que poseían estudios de postgrado. Conclusiones: Los factores que más influyen en la percepción de las enfermeras renales en España son la experiencia profesional, el rol dentro de la organización, un contexto favorable y la formación de postgrado.

SARS-CoV-2 viral load has been related to COVID-19 severity. The main aim of this study was to evaluate the relationship between SARS-CoV-2 viremia and SNPs in genes previously studied by our group as predictors of COVID-19 severity. Retrospective observational study including 340 patients hospitalized for COVID-19 in the University Hospital La Princesa between March 2020 and December 2021, with at least one viremia determination. Positive viremia was considered when viral load was above the quantifiable threshold (20 copies/ml). A total of 38 SNPs were genotyped. To study their association with viremia a multivariate logistic regression was performed. The mean age of the studied population was 64.5 years (SD 16.6), 60.9% patients were male and 79.4% white non-Hispanic. Only 126 patients (37.1%) had at least one positive viremia. After adjustment by confounders, the presence of the minor alleles of rs2071746 ( ; T/T genotype OR 9.9  < 0.0001), rs78958998 (probably associated with expression; A/T genotype OR 2.3,  = 0.04 and T/T genotype OR 12.9,  < 0.0001), and rs713400 (eQTL for ; C/T + T/T genotype OR 1.86,  = 0.10) were associated with higher risk of viremia, whereas the minor alleles of rs11052877 ( ; A/G genotype OR 0.5, p = 0.04 and G/G genotype OR 0.3,  = 0.01), rs2660 ( ; A/G genotype OR 0.6,  = 0.08), rs896 ( ; T/T genotype OR 0.4,  = 0.02) and rs33980500 ( ; C/T + T/T genotype OR 0.3,  = 0.01) were associated with lower risk of viremia. Genetic variants in (rs2071746), (rs78958998), (rs713400), (rs11052877), (rs33980500), (rs2660) and (rs896) could explain heterogeneity in SARS-CoV-2 viremia in our population.

BackgroundInterleukin 6 (IL6) levels and SARS-CoV-2 viremia have been correlated with COVID-19 severity. The association over time between them has not been assessed in a prospective cohort. Our aim was to evaluate the relationship between SARS-CoV-2 viremia and time evolution of IL6 levels in a COVID-19 prospective cohort.MethodsSecondary analysis from a prospective cohort including COVID-19 hospitalized patients from Hospital Universitario La Princesa between November 2020 and January 2021. Serial plasma samples were collected from admission until discharge. Viral load was quantified by Real-Time Polymerase Chain Reaction and IL6 levels with an enzyme immunoassay. To represent the evolution over time of both variables we used the graphic command twoway of Stata.ResultsA total of 57 patients were recruited, with median age of 63 years (IQR [53–81]), 61.4% male and 68.4% Caucasian. The peak of viremia appeared shortly after symptom onset in patients with persistent viremia (more than 1 sample with > 1.3 log10 copies/ml) and also in those with at least one IL6 > 30 pg/ml, followed by a progressive increase in IL6 around 10 days later. Persistent viremia in the first week of hospitalization was associated with higher levels of IL6. Both IL6 and SARS-CoV-2 viral load were higher in males, with a quicker increase with age.ConclusionIn those patients with worse outcomes, an early peak of SARS-CoV-2 viral load precedes an increase in IL6 levels. Monitoring SARS-CoV-2 viral load during the first week after symptom onset may be helpful to predict disease severity in COVID-19 patients.