Diseño in silico de un vector de expresión que contiene un poli-mir-122 para el tratamiento del hepatocarcinoma por terapia génica

El uso de microRNAs (miRNAs) en terapia génica, ha surgido como una poderosa herramienta para la regulación de genes implicados en enfermedades genéticas adquiridas como el cáncer, con lo que se pretende diseñar tratamientos que eliminen selectivamente a las células cancerosas. El miR-122 es específico de hígado y el más abundante en este órgano, se ha demostrado su función como supresor de tumores, pues participa en la represión de algunos genes implicados en el proceso de tumorigénesis. Se sabe que los niveles de este miRNA se encuentran significativa y específicamente disminuidos en el hepatocarcinoma (HCC). Por tal motivo, en este trabajó se diseñó una construcción genética que contiene un poli-miR-122, regidos bajo el promotor de la α-fetoproteína (AFP), que está activo exclusivamente en las células de este carcinoma. Con esta construcción genética, se pretende dirigir la expresión únicamente en las células del HCC y por tanto, su eliminación selectiva, sin afectar a los hepatocitos sanos.Use of microRNAs (miRNAs) in gene therapy has emerged as a powerful tool for regulation of genes involved in genetic diseases such as cancer, with which it is intended to design treatments selectively eliminating cancer cells. The miR-122 is a liver-specific miRNA and the most abundant within this organ from which has been shown to function as a tumor suppressor since it participates in the repression of some genes involved in the tumorigenesis process. It is known that levels of this miRNA decrease significant and specifically in hepatocellular carcinoma (HCC). In this work it was designed a genetic construct containing poly-miR-122 governed under the α-fetoprotein promoter (AFP), which is active exclusively in this carcinoma cells. With this construction it is intended to direct the expression only in HCC cells and to eliminate them selectively

The Impact of COVID-19 on Sport in Twitter: A Quantitative and Qualitative Content Analysis

[EN] The spread of the SARS-CoV-2 virus has transformed many aspects of people's daily life, including sports. Social networks have been flooded on these issues. The present study aims to analyze the tweets produced relating to sports and COVID-19. From the end of January to the beginning of May 2020, over 4,000,000 tweets on this subject were downloaded through the Twitter search API. Once the duplicates, replicas, and retweets were removed, 119,253 original tweets were analyzed. A quantitative-qualitative content analysis was used to study the selected tweets. Posts dynamics regarding sport and exercise evolved according to the COVID-19 pandemic and subsequent lockdown, shifting from considering sport as a healthy bastion to an activity exposed to disease like any other. Most media professional sporting events received great attention on Twitter, while grassroots and women's sport were relegated to a residual role. The analysis of the 30 topics identified focused on the social, sporting, economic and health impact of the pandemic on the sport. Sporting cancellations, leisure time and socialization disruptions, club bankruptcies, sports training and athletes' uncertain career development were the main concerns. Although general health measures appeared in the tweets analyzed, those addressed to sports practice were relatively scarce. Finally, this study shows the importance of Twitter as a means of conveying social attitudes towards sports and COVID-19 and its potential to generate alternative responses in future stages of the pandemic.González, L.; Devis-Devis, J.; Pellicer-Chenoll, M.; Pans, M.; Pardo-Ibáñez, A.; García-Massó, X.; Peset Mancebo, MF.... (2021). The Impact of COVID-19 on Sport in Twitter: A Quantitative and Qualitative Content Analysis. International Journal of Environmental research and Public Health (Online). 18(9):1-20. https://doi.org/10.3390/ijerph18094554S12018

Meta-analysis of individual patient data of albumin dialysis in acute-on-chronic liver failure:focus on treatment intensity

Background: Acute-on-chronic liver failure (ACLF) is a common complication of cirrhosis characterized by single or multiple organ failures and high short-term mortality. Treatment of ACLF consists of standard medical care (SMC) and organ(s) support. Whether the efficacy of artificial liver support (ALS) depends on the severity of ACLF or on the intensity of this treatment, or both, is unclear. This study aimed to further assess these issues. Methods: We performed an individual patient data meta-analysis assessing the efficacy of Molecular Adsorbent Recirculating System (MARS) in ACLF patients enrolled in prior randomized control trials (RCTs). The meta-analysis was designed to assess the effect of patient severity (ACLF grade) and treatment intensity [low-intensity therapy (LIT), SMC alone or SMC plus ⩽ 4 MARS sessions, high-intensity therapy (HIT), SMC plus > 4 MARS sessions] on mortality. Results: Three RCTs suitable for the meta-analysis (n=285, ACLF patients=165) were identified in a systematic review. SMC plus MARS (irrespective of the number of sessions) did not improve survival compared with SMC alone, neither in the complete population nor in the ACLF patients. Survival, however, was significantly improved in the subgroup of patients receiving HIT both in the entire cohort (10-day survival: 98.6% versus 82.8%, p=0.001; 30-day survival: 73.9% versus 64.3%, p=0.032) and within the ACLF patients (10-day survival: 97.8% versus 78.6%, p=0.001; 30-day survival: 73.3% versus 58.5%, p=0.041). Remarkably, HIT increased survival independently of ACLF grade. Independent predictors of survival were age, Model for End-Stage Liver Disease (MELD), ACLF grade, number of MARS sessions received, and intensity of MARS therapy. Conclusion: HIT with albumin dialysis may improve survival in patients with ACLF. Appropriate treatment schedules should be determined in future clinical trials

Randomized-controlled trial of the DIALIVE liver dialysis device vs. standard of care in patients with acute-on-chronic liver failure

BACKGROUND AND AIMS: Acute on chronic liver failure (ACLF) is characterized by severe systemic inflammation, multi-organ failure and high mortality rates. Its treatment is an urgent unmet need. DIALIVE is a novel liver dialysis device that aims to exchange d ysfunctional albumin and remove damage- and pathogen-associated molecular patterns. This first-in-man randomized, controlled clinical trial was performed with the primary aim of assessing its safety in ACLF patients with secondary aims to evaluate its clinical effects, device performance and effect on pathophysiologically-relevant biomarkers. METHODS: 32 alcoholic cirrhosis patients with ACLF were included. Patients were treated with DIALIVE for up to 5-days and end points were assessed at Day-10. Safety was assessed in all patients (n=32). The secondary aims were assessed in a pre-specified subgroup that had at least 3-treatment sessions with DIALIVE (n=30). RESULTS: There were no significant differences in 28-day mortality or occurrence of serious adverse events between the groups. Significant reduction in the severity of endotoxemia and improvement in albumin function was observed in DIALIVE group, which translated into a significant reduction in the CLIF-C (Chronic Liver Failure consortium) organ failure (p=0.018) and CLIF-C ACLF scores (p=0.042) at Day-10. Time to resolution of ACLF was significantly faster in DIALIVE group (p=0.036). Biomarkers of systemic inflammation such as IL-8 (p=0.006), cell death [cytokeratin-18: M30 (p=0.005) and M65 (p=0.029)], endothelial function [asymmetric dimethylarginine (p=0.002)] and, ligands for toll-like receptor 4 (p=0.030) and inflammasome (p=0.002) improved significantly in DIALIVE group. CONCLUSIONS: These data indicate that DIALIVE appears to be safe and impacts positively on prognostic scores and pathophysiologically relevant biomarkers in patients with ACLF. Larger, adequately powered studies are warranted to further confirm its safety and efficacy. LAY SUMMARY: This is the first-in-man clinical trial which tested DIALIVE, a novel liver dialysis device for the treatment of liver cirrhosis and acute on chronic liver failure, a condition associated with severe inflammation, organ failures and a high risk of death. The study met the primary end point confirming DIALIVE system to be safe. Additionally, it reduced inflammation with improved clinical parameters. It did not, however, reduce mortality in this small study and requires further larger clinical trials to re-confirm its safety and evaluate efficacy. CLINICAL TRIAL NUMBER: NCT03065699

New Insight on the Increasing Seismicity during Tenerife's 2004 Volcanic Reactivation

Starting in April 2004, unusual seismic activity was observed in the interior of the island of Tenerife (Canary Islands, Spain) with much evidence pointing to a reawakening of volcanic activity. This seismicity is now analyzed with techniques unprecedented in previous studies of this crisis. The 200 earthquakes located onshore during 2004 and 2005 have been classified by cross-correlation, resulting in a small number of significant families. The application of a relative location algorithm (hypoDD) revealed important features about the spatial distribution of the earthquakes. The seismic catalogue has been enhanced with more than 800 additional events, detected only by the closest seismic station. These events were assigned to families by correlation and as a consequence their hypocentral location and magnitude were estimated by comparing them to the earthquakes of each family. The new catalogue obtained by these methods identifies two major seismogenic zones, one to the northwest and the other to the southwest of the Teide-Pico Viejo complex and having a separation of at least 10 km between them. These regions alternate their activity starting in January 2004, i.e., three months earlier than previously thought. We propose a simple model based on the results of this work which will also concur with all previous geophysical and geochemical studies of the 2004 crisis. The model proposes a single magma intrusion affecting the central part of the island with lateral dikes driven by the rifts to the northwest and southwest.Comment: 20 pages, 15 figure

Predictive Power of the "Trigger Tool" for the detection of adverse events in general surgery: a multicenter observational validation study

Background In spite of the global implementation of standardized surgical safety checklists and evidence-based practices, general surgery remains associated with a high residual risk of preventable perioperative complications and adverse events. This study was designed to validate the hypothesis that a new “Trigger Tool” represents a sensitive predictor of adverse events in general surgery. Methods An observational multicenter validation study was performed among 31 hospitals in Spain. The previously described “Trigger Tool” based on 40 specific triggers was applied to validate the predictive power of predicting adverse events in the perioperative care of surgical patients. A prediction model was used by means of a binary logistic regression analysis. Results The prevalence of adverse events among a total of 1,132 surgical cases included in this study was 31.53%. The “Trigger Tool” had a sensitivity and specificity of 86.27% and 79.55% respectively for predicting these adverse events. A total of 12 selected triggers of overall 40 triggers were identified for optimizing the predictive power of the “Trigger Tool”. Conclusions The “Trigger Tool” has a high predictive capacity for predicting adverse events in surgical procedures. We recommend a revision of the original 40 triggers to 12 selected triggers to optimize the predictive power of this tool, which will have to be validated in future studies

Healthcare workers hospitalized due to COVID-19 have no higher risk of death than general population. Data from the Spanish SEMI-COVID-19 Registry

Aim To determine whether healthcare workers (HCW) hospitalized in Spain due to COVID-19 have a worse prognosis than non-healthcare workers (NHCW). Methods Observational cohort study based on the SEMI-COVID-19 Registry, a nationwide registry that collects sociodemographic, clinical, laboratory, and treatment data on patients hospitalised with COVID-19 in Spain. Patients aged 20-65 years were selected. A multivariate logistic regression model was performed to identify factors associated with mortality. Results As of 22 May 2020, 4393 patients were included, of whom 419 (9.5%) were HCW. Median (interquartile range) age of HCW was 52 (15) years and 62.4% were women. Prevalence of comorbidities and severe radiological findings upon admission were less frequent in HCW. There were no difference in need of respiratory support and admission to intensive care unit, but occurrence of sepsis and in-hospital mortality was lower in HCW (1.7% vs. 3.9%; p = 0.024 and 0.7% vs. 4.8%; p<0.001 respectively). Age, male sex and comorbidity, were independently associated with higher in-hospital mortality and healthcare working with lower mortality (OR 0.211, 95%CI 0.067-0.667, p = 0.008). 30-days survival was higher in HCW (0.968 vs. 0.851 p<0.001). Conclusions Hospitalized COVID-19 HCW had fewer comorbidities and a better prognosis than NHCW. Our results suggest that professional exposure to COVID-19 in HCW does not carry more clinical severity nor mortality

Randomized, controlled clinical trial of the DIALIVE liver dialysis device versus standard of care in patients with acute-on- chronic liver failure

Background & Aims Acute-on-chronic liver failure (ACLF) is characterized by severe systemic inflammation, multi-organ failure and high mortality rates. Its treatment is an urgent unmet need. DIALIVE is a novel liver dialysis device that aims to exchange dysfunctional albumin and remove damage- and pathogen-associated molecular patterns. This first-in-man randomized-controlled trial was performed with the primary aim of assessing the safety of DIALIVE in patients with ACLF, with secondary aims of evaluating its clinical effects, device performance and effect on pathophysiologically relevant biomarkers. Methods Thirty-two patients with alcohol-related ACLF were included. Patients were treated with DIALIVE for up to 5 days and end points were assessed at Day 10. Safety was assessed in all patients (n = 32). The secondary aims were assessed in a pre-specified subgroup that had at least three treatment sessions with DIALIVE (n = 30). Results There were no significant differences in 28-day mortality or occurrence of serious adverse events between the groups. Significant reduction in the severity of endotoxemia and improvement in albumin function was observed in the DIALIVE group, which translated into a significant reduction in the CLIF-C (Chronic Liver Failure consortium) organ failure (p = 0.018) and CLIF-C ACLF scores (p = 0.042) at Day 10. Time to resolution of ACLF was significantly faster in DIALIVE group (p = 0.036). Biomarkers of systemic inflammation such as IL-8 (p = 0.006), cell death [cytokeratin-18: M30 (p = 0.005) and M65 (p = 0.029)], endothelial function [asymmetric dimethylarginine (p = 0.002)] and, ligands for Toll-like receptor 4 (p = 0.030) and inflammasome (p = 0.002) improved significantly in the DIALIVE group. Conclusions These data indicate that DIALIVE appears to be safe and impacts positively on prognostic scores and pathophysiologically relevant biomarkers in patients with ACLF. Larger, adequately powered studies are warranted to further confirm its safety and efficacy. Impact and implications This is the first-in-man clinical trial which tested DIALIVE, a novel liver dialysis device for the treatment of cirrhosis and acute-on-chronic liver failure, a condition associated with severe inflammation, organ failures and a high risk of death. The study met the primary endpoint, confirming the safety of the DIALIVE system. Additionally, DIALIVE reduced inflammation and improved clinical parameters. However, it did not reduce mortality in this small study and further larger clinical trials are required to re-confirm its safety and to evaluate efficacy. Clinical trial number NCT03065699

Evolution of the use of corticosteroids for the treatment of hospitalised COVID-19 patients in Spain between March and November 2020: SEMI-COVID national registry

Objectives: Since the results of the RECOVERY trial, WHO recommendations about the use of corticosteroids (CTs) in COVID-19 have changed. The aim of the study is to analyse the evolutive use of CTs in Spain during the pandemic to assess the potential influence of new recommendations. Material and methods: A retrospective, descriptive, and observational study was conducted on adults hospitalised due to COVID-19 in Spain who were included in the SEMI-COVID- 19 Registry from March to November 2020. Results: CTs were used in 6053 (36.21%) of the included patients. The patients were older (mean (SD)) (69.6 (14.6) vs. 66.0 (16.8) years; p < 0.001), with hypertension (57.0% vs. 47.7%; p < 0.001), obesity (26.4% vs. 19.3%; p < 0.0001), and multimorbidity prevalence (20.6% vs. 16.1%; p < 0.001). These patients had higher values (mean (95% CI)) of C-reactive protein (CRP) (86 (32.7-160) vs. 49.3 (16-109) mg/dL; p < 0.001), ferritin (791 (393-1534) vs. 470 (236- 996) µg/dL; p < 0.001), D dimer (750 (430-1400) vs. 617 (345-1180) µg/dL; p < 0.001), and lower Sp02/Fi02 (266 (91.1) vs. 301 (101); p < 0.001). Since June 2020, there was an increment in the use of CTs (March vs. September; p < 0.001). Overall, 20% did not receive steroids, and 40% received less than 200 mg accumulated prednisone equivalent dose (APED). Severe patients are treated with higher doses. The mortality benefit was observed in patients with oxygen saturation </=90%. Conclusions: Patients with greater comorbidity, severity, and inflammatory markers were those treated with CTs. In severe patients, there is a trend towards the use of higher doses. The mortality benefit was observed in patients with oxygen saturation </=90%