Exosomal Osteoclast-Derived miRNA in Rheumatoid Arthritis: From Their Pathogenesis in Bone Erosion to New Therapeutic Approaches

Rheumatoid arthritis (RA) is an autoimmune disease that causes inflammation, pain, and ultimately, bone erosion of the joints. The causes of this disease are multifactorial, including genetic factors, such as the presence of the human leukocyte antigen (HLA)-DRB1*04 variant, alterations in the microbiota, or immune factors including increased cytotoxic T lymphocytes (CTLs), neutrophils, or elevated M1 macrophages which, taken together, produce high levels of pro-inflammatory cytokines. In this review, we focused on the function exerted by osteoclasts on osteoblasts and other osteoclasts by means of the release of exosomal microRNAs (miRNAs). Based on a thorough revision, we classified these molecules into three categories according to their function: osteoclast inhibitors (miR-23a, miR-29b, and miR-214), osteoblast inhibitors (miR-22-3p, miR-26a, miR-27a, miR-29a, miR-125b, and miR-146a), and osteoblast enhancers (miR-20a, miR-34a, miR-96, miR-106a, miR-142, miR-199a, miR-324, and miR-486b). Finally, we analyzed potential therapeutic targets of these exosomal miRNAs, such as the use of antagomiRs, blockmiRs, agomiRs and competitive endogenous RNAs (ceRNAs), which are already being tested in murine and ex vivo models of RA. These strategies might have an important role in reestablishing the regulation of osteoclast and osteoblast differentiation making progress in the development of personalized medicine.This research was supported by the grant CIGE/2021/162 funded by Generalitat Valenciana and by University of Alicante, grant number GRE21-17, both as the Emerging Research Groups Grants

Early mobilisation in critically ill COVID-19 patients: a subanalysis of the ESICM-initiated UNITE-COVID observational study

Background Early mobilisation (EM) is an intervention that may improve the outcome of critically ill patients. There is limited data on EM in COVID-19 patients and its use during the first pandemic wave. Methods This is a pre-planned subanalysis of the ESICM UNITE-COVID, an international multicenter observational study involving critically ill COVID-19 patients in the ICU between February 15th and May 15th, 2020. We analysed variables associated with the initiation of EM (within 72 h of ICU admission) and explored the impact of EM on mortality, ICU and hospital length of stay, as well as discharge location. Statistical analyses were done using (generalised) linear mixed-effect models and ANOVAs. Results Mobilisation data from 4190 patients from 280 ICUs in 45 countries were analysed. 1114 (26.6%) of these patients received mobilisation within 72 h after ICU admission; 3076 (73.4%) did not. In our analysis of factors associated with EM, mechanical ventilation at admission (OR 0.29; 95% CI 0.25, 0.35; p = 0.001), higher age (OR 0.99; 95% CI 0.98, 1.00; p ≤ 0.001), pre-existing asthma (OR 0.84; 95% CI 0.73, 0.98; p = 0.028), and pre-existing kidney disease (OR 0.84; 95% CI 0.71, 0.99; p = 0.036) were negatively associated with the initiation of EM. EM was associated with a higher chance of being discharged home (OR 1.31; 95% CI 1.08, 1.58; p = 0.007) but was not associated with length of stay in ICU (adj. difference 0.91 days; 95% CI − 0.47, 1.37, p = 0.34) and hospital (adj. difference 1.4 days; 95% CI − 0.62, 2.35, p = 0.24) or mortality (OR 0.88; 95% CI 0.7, 1.09, p = 0.24) when adjusted for covariates. Conclusions Our findings demonstrate that a quarter of COVID-19 patients received EM. There was no association found between EM in COVID-19 patients' ICU and hospital length of stay or mortality. However, EM in COVID-19 patients was associated with increased odds of being discharged home rather than to a care facility. Trial registration ClinicalTrials.gov: NCT04836065 (retrospectively registered April 8th 2021)

Early high protein provision and mortality in ICU patients including those receiving continuous renal replacement therapy

Background: Findings on the association between early high protein provision and mortality in ICU patients are inconsistent. The relation between early high protein provision and mortality in patients receiving CRRT remains unclear. The aim was to study the association between early high protein provision and hospital and ICU mortality and consistency in subgroups. Methods: A retrospective cohort study was conducted in 2618 ICU patients with a feeding tube and mechanically ventilated ≥48 h (2003–2016). The association between early high protein provision (≥1.2 g/kg/day at day 4 vs. 50%, results remained robust in all groups except for patients receiving CRRT. Conclusions: Early high protein provision is associated with lower hospital and ICU mortality in ICU patients, including CRRT-receiving patients. There was no association for septic patients

Indirect calorimetry in critically ill mechanically ventilated patients: Comparison of E-sCOVX with the deltatrac

Background & aims: Indirect calorimetry is recommended to measure energy expenditure (EE) in critically ill, mechanically ventilated patients. The most validated system, the Deltatrac® (Datex-Ohmeda, Helsinki, Finland) is no longer in production. We tested the agreement of a new breath-by-breath metabolic monitor E-sCOVX® (GE healthcare, Helsinki, Finland), with the Deltatrac. We also compared the performance of the E-sCOVX to commonly used predictive equations. Methods: We included mechanically ventilated patients eligible to undergo indirect calorimetry. After a stabilization period, EE was measured simultaneously with the Deltatrac and the E-sCOVX for 2 h. Agreement and precision of the E-sCOVX was tested by determining bias, limits of agreement and agreement rates compared to the Deltatrac. Performance of the E-sCOVX was also compared to four predictive equations: the 25 kcal/kg, Penn State University 2003b, Faisy, and Harris–Benedict equation. Results: We performed 29 measurements in 16 patients. Mean EE-Deltatrac was 1942 ± 274 kcal/day, and mean EE-E-sCOVX was 2177 ± 319 kcal/day (p < 0.001). E-sCOVX overestimated EE with a bias of 235 ± 149 kcal/day, being 12.1% of EE-Deltatrac. Limits of agreement were −63 to +532 kcal/day. The 10% and 15% agreement rates of EE-E-sCOVX compared to the Deltatrac were 34% and 72% respectively. The bias of E-sCOVX was lower than the bias of the 25 kcal/kg-equation, but higher than bias of the other equations. Agreement rates for E-sCOVX were similar to the equations. The Faisy-equation had the highest 15% agreement rate. Conclusion: The E-sCOVX metabolic monitor is not accurate in estimating EE in critically ill mechanically ventilated patients when compared to the Deltatrac, the present reference method. The E-sCOVX overestimates EE with a bias and precision that are clinically unacceptable

Procesos de Cocreación que Contribuyen al Impacto Social de la Ciencia: Aportaciones de la Red Net4Impact

Meaningful citizen participation throughout the development of research projects has increased the societal impact of science. Co-creation processes promote a more significant societal impact by aligning research with societal needs. In recent years, essential advances in citizen participation in science have been identified. However, there are still critical challenges that limit citizen interaction with scientific creations. This article provides some of the contributions made by the Net4Impact network in the face of these challenges. Specifically, we analyse co-creation processes developed by those projects that have demonstrated societal impact. This qualitative study is based on the analysis of Webinars, meetings with researchers from different scientific areas and Communicative Content Analysis. As a result, this work provides six examples of societal impact in three scientific areas: social sciences, humanities, and engineering. In addition, we analyse the characteristics and implications of the different co-creation processes developed by these successful projects.La participación ciudadana a lo largo del desarrollo de los proyectos de investigación ha demostrado aumentar el impacto social de la ciencia. Los procesos de cocreación promueven un impacto social más significativo al alinear la investigación con las necesidades sociales. En los últimos años se han identificado importantes avances en materia de participación ciudadana en la ciencia. Sin embargo, todavía existen importantes retos que limitan la interacción de la ciudadanía con las creaciones científicas. Este artículo recoge algunas de las aportaciones de la red Net4Impact frente a estos retos. Concretamente, analizamos los procesos de cocreación desarrollados por proyectos que han demostrado impacto social. Este estudio cualitativo se basa en el análisis de Webinars, reuniones con investigadores de diferentes áreas científicas y en el Análisis de Contenido Comunicativo. Como resultado, este trabajo ofrece seis ejemplos de impacto social en tres áreas científicas: ciencias sociales, humanidades e ingeniería. Además, se analizan las características e implicaciones de los distintos procesos de cocreación desarrollados por estos proyectos exitosos

Early high protein provision and mortality in ICU patients including those receiving continuous renal replacement therapy

Background: Findings on the association between early high protein provision and mortality in ICU patients are inconsistent. The relation between early high protein provision and mortality in patients receiving CRRT remains unclear. The aim was to study the association between early high protein provision and hospital and ICU mortality and consistency in subgroups. Methods: A retrospective cohort study was conducted in 2618 ICU patients with a feeding tube and mechanically ventilated ≥48 h (2003–2016). The association between early high protein provision (≥1.2 g/kg/day at day 4 vs. 50%, results remained robust in all groups except for patients receiving CRRT. Conclusions: Early high protein provision is associated with lower hospital and ICU mortality in ICU patients, including CRRT-receiving patients. There was no association for septic patients

Early high protein provision and mortality in ICU patients including those receiving continuous renal replacement therapy

BACKGROUND: Findings on the association between early high protein provision and mortality in ICU patients are inconsistent. The relation between early high protein provision and mortality in patients receiving CRRT remains unclear. The aim was to study the association between early high protein provision and hospital and ICU mortality and consistency in subgroups. METHODS: A retrospective cohort study was conducted in 2618 ICU patients with a feeding tube and mechanically ventilated ≥48 h (2003-2016). The association between early high protein provision (≥1.2 g/kg/day at day 4 vs. 50%, results remained robust in all groups except for patients receiving CRRT. CONCLUSIONS: Early high protein provision is associated with lower hospital and ICU mortality in ICU patients, including CRRT-receiving patients. There was no association for septic patients