Lipoma parostal de fémur: Aportación de un caso

Describimos un caso de lipoma parostal de fémur, un tumor benigno poco frecuente formado por tejido adiposo maduro en relación con el periostio. Nuestro objetivo es documentar el caso, comentando los hallazgos radiológicos, histológicos y el tratamiento y realizar una revisión bibliográfica.We describe a case of parosteal lipoma of the femur. It is an infrequent benign neoplasm composed of mature fat, intermately connected with the periosteum. Our aim is to document the case, and comment the radiological, histological findings, and treatment, and review the literature

Glioblastoma: Vascular Habitats Detected at Preoperative Dynamic Susceptibility-weighted Contrast-enhanced Perfusion MR Imaging Predict Survival

[EN] Purpose: To determine if preoperative vascular heterogeneity of glioblastoma is predictive of overall survival of patients undergoing standard-of-care treatment by using an unsupervised multiparametric perfusion-based habitat-discovery algorithm. Materials and Methods: Preoperative magnetic resonance (MR) imaging including dynamic susceptibility-weighted contrast material-enhanced perfusion studies in 50 consecutive patients with glioblastoma were retrieved. Perfusion parameters of glioblastoma were analyzed and used to automatically draw four reproducible habitats that describe the tumor vascular heterogeneity: high-angiogenic and low-angiogenic regions of the enhancing tumor, potentially tumor-infiltrated peripheral edema, and vasogenic edema. Kaplan-Meier and Cox proportional hazard analyses were conducted to assess the prognostic potential of the hemodynamic tissue signature to predict patient survival. Results: Cox regression analysis yielded a significant correlation between patients' survival and maximum relative cerebral blood volume (rCBV(max)) and maximum relative cerebral blood flow (rCBF(max)) in high-angiogenic and low-angiogenic habitats (P < .01, false discovery rate-corrected P < .05). Moreover, rCBF(max) in the potentially tumor-infiltrated peripheral edema habitat was also significantly correlated (P < .05, false discovery rate-corrected P < .05). Kaplan-Meier analysis demonstrated significant differences between the observed survival of populations divided according to the median of the rCBV(max) or rCBF(max) at the high-angiogenic and low-angiogenic habitats (log-rank test P < .05, false discovery rate-corrected P < .05), with an average survival increase of 230 days. Conclusion: Preoperative perfusion heterogeneity contains relevant information about overall survival in patients who undergo standard-of-care treatment. The hemodynamic tissue signature method automatically describes this heterogeneity, providing a set of vascular habitats with high prognostic capabilities.Study supported by H2020 European Institute of Innovation and Technology (POC-2016.SPAIN-07) and Universitat Politecnica de Valencia (PAID-10-14). J.J.A., E.F.G., and J.M.G.G. supported by Secretaria de Estado de Investigacion, Desarrollo e Innovacion (DPI2016-80054-R, TIN2013-43457-R). E.F.G. supported by CaixaImpulse program from Fundacio Bancaria "la Caixa" (LCF/TR/CI16/10010016). E.F.G and A.A.B. supported by the Universitat Politecnica de Valencia Instituto Investigacion Sanitaria de La Fe (C05).Juan -Albarracín, J.; Fuster García, E.; Pérez-Girbés, A.; Aparici-Robles, F.; Alberich Bayarri, A.; Revert Ventura, AJ.; Martí Bonmatí, L.... (2018). Glioblastoma: Vascular Habitats Detected at Preoperative Dynamic Susceptibility-weighted Contrast-enhanced Perfusion MR Imaging Predict Survival. Radiology. 287(3):944-954. https://doi.org/10.1148/radiol.2017170845S944954287

La producción de mensajes escritos en estudiantes de enseñanza secundaria: diálogo entre alfabetización en información y prácticas letradas

A partir de una investigación realizada en centros de enseñanza secundaria pública de Montevideo (Uruguay) que consistió en la elaboración de un diagnóstico sobre alfabetización en información en estudiantes de primer año, proponemos abordar la producción de textos en base al análisis de mensajes producidos por los estudiantes. La consigna involucra la información recabada durante un proceso de búsqueda de información, la cual deberá ser compartida con el destinatario del mensaje. A partir del análisis mencionado esperamos indagar sobre la relación entre la alfabetización en información y las prácticas letradas de los estudiantes de secundaria y conocer qué criterios consideran de relevancia para elaborar los textos, y cómo seleccionaron la información encontrada. Para la elaboración del diagnóstico construimos un formulario basado en las etapas del Modelo Pindó de alfabetización en información, donde se plantea un problema de información a resolver y desde allí se abordan elementos relacionados con la búsqueda, selección, evaluación y comunicación de la información. Para la determinación de la muestra seleccionamos trece liceos del departamento de Montevideo. En los resultados compartimos una aproximación al proceso de comprensión que realizan los estudiantes sobre lo leído y cómo lo traducen en un mensaje

Determinants of Progression and Regression of Subclinical Atherosclerosis Over 6 Years.

BACKGROUND Atherosclerosis is a systemic disease that frequently begins early in life. However, knowledge about the temporal disease dynamics (ie, progression or regression) of human subclinical atherosclerosis and their determinants is scarce. OBJECTIVES This study sought to investigate early subclinical atherosclerosis disease dynamics within a cohort of middle-aged, asymptomatic individuals by using multiterritorial 3-dimensional vascular ultrasound (3DVUS) imaging. METHODS A total of 3,471 participants from the PESA (Progression of Early Subclinical Atherosclerosis) cohort study (baseline age 40-55 years; 36% female) underwent 3 serial 3DVUS imaging assessments of peripheral arteries at 3-year intervals. Subclinical atherosclerosis was quantified as global plaque volume (mm3) (bilateral carotid and femoral plaque burden). Multivariable logistic regression models for progression and regression were developed using stepwise forward variable selection. RESULTS Baseline to 6-year subclinical atherosclerosis progression occurred in 32.7% of the cohort (17.5% presenting with incident disease and 15.2% progressing from prevalent disease at enrollment). Regression was observed in 8.0% of those patients with baseline disease. The effects of higher low-density lipoprotein cholesterol (LDL-C) and elevated systolic blood pressure (SBP) on 6-year subclinical atherosclerosis progression risk were more pronounced among participants in the youngest age stratum (Pinteraction = 0.04 and 0.02, respectively). CONCLUSIONS Over 6 years, subclinical atherosclerosis progressed in one-third of middle-age asymptomatic subjects. Atherosclerosis regression is possible in early stages of the disease. The impact of LDL-C and SBP on subclinical atherosclerosis progression was more pronounced in younger participants, a finding suggesting that the prevention of atherosclerosis and its progression could be enhanced by tighter risk factor control at younger ages, with a likely long-term impact on reducing the risk of clinical events. (Progression of Early Subclinical Atherosclerosis [PESA; also PESA-CNIC-Santander]; NCT01410318).S

A deep learning system to obtain the optimal parameters for a threshold-based breast and dense tissue segmentation

[EN] Background and Objective: Breast cancer is the most frequent cancer in women. The Spanish healthcare network established population-based screening programs in all Autonomous Communities, where mammograms of asymptomatic women are taken with early diagnosis purposes. Breast density assessed from digital mammograms is a biomarker known to be related to a higher risk to develop breast cancer. It is thus crucial to provide a reliable method to measure breast density from mammograms. Furthermore the complete automation of this segmentation process is becoming fundamental as the amount of mammograms increases every day. Important challenges are related with the differences in images from different devices and the lack of an objective gold standard. This paper presents a fully automated framework based on deep learning to estimate the breast density. The framework covers breast detection, pectoral muscle exclusion, and fibroglandular tissue segmentation. Methods: A multi-center study, composed of 1785 women whose "for presentation" mammograms were segmented by two experienced radiologists. A total of 4992 of the 6680 mammograms were used as training corpus and the remaining (1688) formed the test corpus. This paper presents a histogram normalization step that smoothed the difference between acquisition, a regression architecture that learned segmentation parameters as intrinsic image features and a loss function based on the DICE score. Results: The results obtained indicate that the level of concordance (DICE score) reached by the two radiologists (0.77) was also achieved by the automated framework when it was compared to the closest breast segmentation from the radiologists. For the acquired with the highest quality device, the DICE score per acquisition device reached 0.84, while the concordance between radiologists was 0.76. Conclusions: An automatic breast density estimator based on deep learning exhibits similar performance when compared with two experienced radiologists. It suggests that this system could be used to support radiologists to ease its work.This work was partially funded by Generalitat Valenciana through I+D IVACE (Valencian Institute of Business Competitiviness) and GVA (European Regional Development Fund) supports under the project IMAMCN/2019/1, and by Carlos III Institute of Health under the project DTS15/00080.Perez-Benito, FJ.; Signol, F.; Perez-Cortes, J.; Fuster Bagetto, A.; Pollan, M.; Pérez-Gómez, B.; Salas-Trejo, D.... (2020). A deep learning system to obtain the optimal parameters for a threshold-based breast and dense tissue segmentation. Computer Methods and Programs in Biomedicine. 195:123-132. https://doi.org/10.1016/j.cmpb.2020.105668S123132195Kuhl, C. K. (2015). The Changing World of Breast Cancer. 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Global parenchymal texture features based on histograms of oriented gradients improve cancer development risk estimation from healthy breasts. Computer Methods and Programs in Biomedicine, 177, 123-132. doi:10.1016/j.cmpb.2019.05.022Ciatto, S., Houssami, N., Apruzzese, A., Bassetti, E., Brancato, B., Carozzi, F., … Scorsolini, A. (2005). Categorizing breast mammographic density: intra- and interobserver reproducibility of BI-RADS density categories. The Breast, 14(4), 269-275. doi:10.1016/j.breast.2004.12.004Skaane, P. (2009). Studies comparing screen-film mammography and full-field digital mammography in breast cancer screening: Updated review. Acta Radiologica, 50(1), 3-14. doi:10.1080/02841850802563269Van der Waal, D., den Heeten, G. J., Pijnappel, R. M., Schuur, K. H., Timmers, J. M. H., Verbeek, A. L. M., & Broeders, M. J. M. (2015). Comparing Visually Assessed BI-RADS Breast Density and Automated Volumetric Breast Density Software: A Cross-Sectional Study in a Breast Cancer Screening Setting. PLOS ONE, 10(9), e0136667. doi:10.1371/journal.pone.0136667Kim, S. H., Lee, E. H., Jun, J. K., Kim, Y. M., Chang, Y.-W., … Lee, J. H. (2019). Interpretive Performance and Inter-Observer Agreement on Digital Mammography Test Sets. Korean Journal of Radiology, 20(2), 218. doi:10.3348/kjr.2018.0193Miotto, R., Wang, F., Wang, S., Jiang, X., & Dudley, J. T. (2017). Deep learning for healthcare: review, opportunities and challenges. Briefings in Bioinformatics, 19(6), 1236-1246. doi:10.1093/bib/bbx044LeCun, Y., Bengio, Y., & Hinton, G. (2015). Deep learning. Nature, 521(7553), 436-444. doi:10.1038/nature14539Hinton, G., Deng, L., Yu, D., Dahl, G., Mohamed, A., Jaitly, N., … Kingsbury, B. (2012). Deep Neural Networks for Acoustic Modeling in Speech Recognition: The Shared Views of Four Research Groups. 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K., Yuan, Y., Scheckel, C., … Troyanskaya, O. G. (2019). Whole-genome deep-learning analysis identifies contribution of noncoding mutations to autism risk. Nature Genetics, 51(6), 973-980. doi:10.1038/s41588-019-0420-0Kallenberg, M., Petersen, K., Nielsen, M., Ng, A. Y., Diao, P., Igel, C., … Lillholm, M. (2016). Unsupervised Deep Learning Applied to Breast Density Segmentation and Mammographic Risk Scoring. IEEE Transactions on Medical Imaging, 35(5), 1322-1331. doi:10.1109/tmi.2016.2532122Lecun, Y., Bottou, L., Bengio, Y., & Haffner, P. (1998). Gradient-based learning applied to document recognition. Proceedings of the IEEE, 86(11), 2278-2324. doi:10.1109/5.726791P. Sermanet, D. Eigen, X. Zhang, M. Mathieu, R. Fergus, Y. LeCun, Overfeat: integrated recognition, localization and detection using convolutional networks, arXiv:1312.6229 (2013).Dice, L. R. (1945). Measures of the Amount of Ecologic Association Between Species. Ecology, 26(3), 297-302. doi:10.2307/1932409Pollán, M., Llobet, R., Miranda-García, J., Antón, J., Casals, M., Martínez, I., … Salas-Trejo, D. (2013). Validation of DM-Scan, a computer-assisted tool to assess mammographic density in full-field digital mammograms. SpringerPlus, 2(1). doi:10.1186/2193-1801-2-242Llobet, R., Pollán, M., Antón, J., Miranda-García, J., Casals, M., Martínez, I., … Pérez-Cortés, J.-C. (2014). Semi-automated and fully automated mammographic density measurement and breast cancer risk prediction. Computer Methods and Programs in Biomedicine, 116(2), 105-115. doi:10.1016/j.cmpb.2014.01.021He, L., Ren, X., Gao, Q., Zhao, X., Yao, B., & Chao, Y. (2017). The connected-component labeling problem: A review of state-of-the-art algorithms. Pattern Recognition, 70, 25-43. doi:10.1016/j.patcog.2017.04.018Wu, K., Otoo, E., & Suzuki, K. (2008). Optimizing two-pass connected-component labeling algorithms. Pattern Analysis and Applications, 12(2), 117-135. doi:10.1007/s10044-008-0109-yShen, R., Yan, K., Xiao, F., Chang, J., Jiang, C., & Zhou, K. (2018). Automatic Pectoral Muscle Region Segmentation in Mammograms Using Genetic Algorithm and Morphological Selection. Journal of Digital Imaging, 31(5), 680-691. doi:10.1007/s10278-018-0068-9Yin, K., Yan, S., Song, C., & Zheng, B. (2018). A robust method for segmenting pectoral muscle in mediolateral oblique (MLO) mammograms. International Journal of Computer Assisted Radiology and Surgery, 14(2), 237-248. doi:10.1007/s11548-018-1867-7James, J. . (2004). The current status of digital mammography. Clinical Radiology, 59(1), 1-10. doi:10.1016/j.crad.2003.08.011Sáez, C., Robles, M., & García-Gómez, J. M. (2016). Stability metrics for multi-source biomedical data based on simplicial projections from probability distribution distances. Statistical Methods in Medical Research, 26(1), 312-336. doi:10.1177/0962280214545122Jain, A. K. (2010). 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Evaluating the impact of existing legislation in Europe with regard to Female Genital Mutilation

The Spanish Report on the evaluation of existing legislation with regard to Female Genital Mutilation (FGM) is the result of a research project supported by the European Commision Daphne Programme. The project Evaluating the impact of existing legislation in Europe with regard to female genital mutilation, has been coordinated by the International Centre for Reproductive Health of Ghent University (Belgium) from january 2003 to march 2004. The project included as partners the Foundation for Women’s Health, Research and Development (FORWARD, United Kingdom); Lund University (Sweden); Commission pour l'Abolition des Mutilations Sexuelles, (CAMS, France), the Centre of Studies on Citizenship, Migration and Minorities of the University of Valencia (GECIM, Spain), and the above mentioned ICRH (Ghent University, Belgium) . The Spanish report is an interdisciplinary research done by the Centre of Studies on Citizenship, Migration and Minorities (University of València), directed by professor Javier De Lucas, and which counts with researchers and collaborators both, from the University of Valencia and other Universities such as University of Barcelona and University Rovira i Virgili of Tarragona; in the fields of Law (Penal Law, Constitutional Law, Theory and Philosophy of Law), Sociology and Antropology. The Group of researchers includes as well lawyers and public prosecutors. Practice of Female Genital Mutilation in Spain, like other european countries, address this rite that is introduced by immigrants from countries where the practice is prevalent (as we may see in chapter 3), as a violation of women’s rights and consider that such violation cannot be justified by respect of cultural traditions or initiation ceremonies. The increasing of immigration in Spain, has been a fact in last years, and it would be an important issue in future, increasing too the number of girls at risk in our country. In Spain, since october 2003, we have anew specific legislation, but before Female Genital Mutilation was liable too under the general offence of injuries in the Penal Code. In this Report, like in the other of the project, we have examined the possibilities and difficulties in the implementation of the spanish national legislation, in order to recommend a legislative and political strategy through Europe. page4image1440 The research methodology, common to all reports, was designed by the ICRH in its cooordination task, but was as well discussed by all the partners along the six steering commitee meetings we have had. The structure and content of report reflects the answers to following questions: 1. What is the legislation with regard to FGM in your country? Description of the legislation.; 2. What is the number of published court cases/suspected cases related to FGM in your country? What is the number of “hearsay” cases?; 3. Brief description of the practising community and the corresponding jurisdiction: number of Africans per country in the geographic area where the cases that you describe are located; 4. What is the procedure to be followed in case of a legal intervention to prevent or to penalise the performance of FGM?; 5. Is legislation applicable on FGM being implemented?; 6.What are the obstructing (favouring) factors for the implementation of legislation applicable to FGM? First of all we have compiled information about legislation applied with regard to FGM: not only general or specific criminal law, (in the case of Spain both because we have a change of law since october 2003), but also child protection procedures. In chapter 1, you may find the result: a Constitutional analysis, changes in Criminal Law, ans an introduction to Minor protection Laws. The second issue was the knowledge of court cases, police and judicial investigation in order to study how justice works. In this part, we contact key-informants, review archival records and study other reports: usually sociological, anthropological and health reports. In chapter 2 we have selected and summarized seven court cases in which we hace found enough relevant information to other parts of the report. At the same time, we need to identify the practicing communities to estimate the prevalence of women with FGM and the number of girls at risk of FGM. This was interesting not only to limit the research but to focus on a territory where there was a probability of cases in Court. We have choosen Catalonia: a community with court cases (in Barcelona and Girona) and prevalence of FGM; and Valencia, a territory without known cases and with no prevalence of FGM. This analysis is shown in chapter 3. In order to detect factors that hamper the implementation of existing legisaltion we need to know how procedures works at different levels: health services, social assistance, police, prosecution office and courts. Examining procedure laws, referral procedures, guidelines or ruled practices was not enough. We had to know what happen, who know a case, which institution examine it, which real mens they have.... To complete this, we have performe a study, interviewing key-informants with an standard interview: police, prosecutors, judges, doctors, nurses, social assistants and immigrants. Interviews were fulfilled in Valencia, Tarragona, Barcelona and Girona. Results are in Chapter 4 (procedure followed); Chapter 5 (implementation of appllicable legislation) and Chapter 6 (obstructing and favouring factors for the implementation of legislation). We had three main meetings to design the research and discuss texts and provissional results. Some of conclusions of provissional spanish report were discused in two seminars: “Ciudadania europea y conflictos culturales”, [european citizenship and cultural conflicts] (Valencia, 29, 30 and 31 october 2003); and “Violencia de género: instrumentos jurídicos en la lucha contra la discriminación de las mujeres”[Gender violence: legal instruments fighting agains women discrimination] (Valencia, 26, 27 and 28 november 2003) The study was financed by the European Commission, Daphne programme, and ran from January 2003 to March 2004 (EC-CONTRACT no 02/058/WYC). In additon, in the period we have done this study, the Centre of Studies on Citizenship, Migration and Minorities was financed with other projects related: “Indicadores y medidas para el desarrollo de políticas públicas de integración social de los inmigrantes y la garantía de sus derechos en la Comunidad Valenciana”, [indicators and measures to develop public policies for social integration of immigrants and the protection of their fundamental rights in the Land of Valencia], Project I+D “Generalitat Valenciana”; 2002-2003; "Los derechos fundamentales en las sociedades multiculturales" [fundamental rights in multicultural societies], project I+D, Subdirección General de Proyectos de Investigación, Dirección General de Investigación, Ministerio de Ciencia y Tecnología, november 2002-october 2005; “Los derechos de participación como elemento de integración de los inmigrantes” [participation rights as a element of the integration of immigrants], II Convocatoria de Ayudas a la Investigación en Economía, Demografía y Estudios de Población y Estudios Europeos de la Fundacion BBVA; 2004-2005. We wish to thank all who have collaborated in this study, specially we remark the collaboration and contributions of Elena Gascón Sorribas (Sociology of Law Laboratory; University of Zaragoza); María Heras García (Public Prosecutor); Dolores Gisbert Millet (Doctor, Health Service, Valencia); Ignacio de Lucas (Public Prosecutor); Laura Matilla (Lawyer, city council of Cullera); Joan Mayoral Simón (Justice Evaluating the impact of existing legislation with regard to Female Genital Mutilation..Spanish National Report. Daphne Programme Department, Regional Government of Catalonia); Xavier Montagud (Social Services, Regional Government of Valencia); and Dolores Sabater Collado (Court Secretary). With the results of the five National Report analysis and the information about legislation in all European Union member States, the coordinators, Els Leye and Jessika Deblonde, have elaborated A comparative analysis of the different legal approaches in the 15 EU Member States, and the respective judicial outcomes in Belgium, France, Spain, Sweden and the United Kingdom (ICRH, 2004)

Granger Causality and Jensen-Shannon Divergence to Determine Dominant Atrial Area in Atrial Fibrillation

[EN] Atrial fibrillation (AF) is already the most commonly occurring arrhythmia. Catheter pulmonary vein ablation has emerged as a treatment that is able to make the arrhythmia disappear; nevertheless, recurrence to arrhythmia is very frequent. In this study, it is proposed to perform an analysis of the electrical signals recorded from bipolar catheters at three locations, pulmonary veins and the right and left atria, before to and during the ablation procedure. Principal Component Analysis (PCA) was applied to reduce data dimension and Granger causality and divergence techniques were applied to analyse connectivity along the atria, in three main regions: pulmonary veins, left atrium (LA) and right atrium (RA). The results showed that, before the procedure, patients with recurrence in the arrhythmia had greater connectivity between atrial areas. Moreover, during the ablation procedure, in patients with recurrence in the arrhythmial both atria were more connected than in patients that maintained sinus rhythms. These results can be helpful for procedures designing to end AF.This work has been supported by the Spanish Government, under the grant DPI2015-70821-R received from the research program Retos de la Sociedad' by the Ministry of Economics and Competitiveness.Cervigón, R.; Castells, F.; Gómez-Pulido, JM.; Pérez-Villacastín, J.; Moreno, J. (2018). Granger Causality and Jensen-Shannon Divergence to Determine Dominant Atrial Area in Atrial Fibrillation. Entropy. 20(1):1-14. https://doi.org/10.3390/e20010057S11420

Three-dimensional cardiac fibre disorganization as a novel parameter for ventricular arrhythmia stratification after myocardial infarction

Aims: Myocardial infarction (MI) alters cardiac fibre organization with unknown consequences on ventricular arrhythmia. We used diffusion tensor imaging (DTI) of three-dimensional (3D) cardiac fibres and scar reconstructions to identify the main parameters associated with ventricular arrhythmia inducibility and ventricular tachycardia (VT) features after MI. Methods and results: Twelve pigs with established MI and three controls underwent invasive electrophysiological characterization of ventricular arrhythmia inducibility and VT features. Animal-specific 3D scar and myocardial fibre distribution were obtained from ex vivo high-resolution contrast-enhanced T1 mapping and DTI sequences. Diffusion tensor imaging-derived parameters significantly different between healthy and scarring myocardium, scar volumes, and left ventricular ejection fraction (LVEF) were included for arrhythmia risk stratification and correlation analyses with VT features. Ventricular fibrillation (VF) was the only inducible arrhythmia in 4 out of 12 infarcted pigs and all controls. Ventricular tachycardia was also inducible in the remaining eight pigs during programmed ventricular stimulation. A DTI-based 3D fibre disorganization index (FDI) showed higher disorganization within dense scar regions of VF-only inducible pigs compared with VT inducible animals (FDI: 0.36; 0.36-0.37 vs. 0.32; 0.26-0.33, respectively, P = 0.0485). Ventricular fibrillation induction required lower programmed stimulation aggressiveness in VF-only inducible pigs than VT inducible and control animals. Neither LVEF nor scar volumes differentiated between VF and VT inducible animals. Re-entrant VT circuits were localized within areas of highly disorganized fibres. Moreover, the FDI within heterogeneous scar regions was associated with the median VT cycle length per animal (R2 = 0.5320). Conclusion: The amount of scar-related cardiac fibre disorganization in DTI sequences is a promising approach for ventricular arrhythmia stratification after MI.The CNIC (Madrid, Spain) is supported by the Ministry of Science, Innovation and Universities and the Pro CNIC Foundation. The CNIC and the BSC (Barcelona, Spain) are Severo Ochoa Centers of Excellence (SEV-2015-0505 and SEV-2011-0067, respectively). This study was supported by grants from Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional (RD12/0042/0036, CB16/11/00458), Spanish Ministry of Science, Innovation and Universities (SAF2016-80324-R, PI16/02110, and DTS17/00136), and by the European Commission [ERA-CVD Joint Call (JTC2016/APCIN-ISCIII-2016), grant#AC16/00021]. The study was also partially supported by the Fundacion Interhospitalaria para la Investigacion Cardiovascular (FIC, Madrid, Spain), the Spanish Society of Cardiology (Dr. Pedro Zarco award) and the Heart Rhythm section of the Spanish Society of Cardiology (DFR). J.J. is supported by R01 Grant HL122352 from the National Heart Lung and Blood Institute, USA National Institutes of Health. J.A.S. is funded by the CompBioMed project, H2020-EU.1.4.1.3 European Union's Horizon 2020 research and innovation programme, grant#675451. D.G.L. has received financial support through the 'la Caixa' Fellowship Grant for Doctoral Studies, 'la Caixa' Banking Foundation, Barcelona, Spain.S

Metoprolol in Critically Ill Patients With COVID-19.

Severe coronavirus disease-2019 (COVID-19) can progress to an acute respiratory distress syndrome (ARDS), which involves alveolar infiltration by activated neutrophils. The beta-blocker metoprolol has been shown to ameliorate exacerbated inflammation in the myocardial infarction setting. The purpose of this study was to evaluate the effects of metoprolol on alveolar inflammation and on respiratory function in patients with COVID-19-associated ARDS. A total of 20 COVID-19 patients with ARDS on invasive mechanical ventilation were randomized to metoprolol (15 mg daily for 3 days) or control (no treatment). All patients underwent bronchoalveolar lavage (BAL) before and after metoprolol/control. The safety of metoprolol administration was evaluated by invasive hemodynamic and electrocardiogram monitoring and echocardiography. Metoprolol administration was without side effects. At baseline, neutrophil content in BAL did not differ between groups. Conversely, patients randomized to metoprolol had significantly fewer neutrophils in BAL on day 4 (median: 14.3 neutrophils/µl [Q1, Q3: 4.63, 265 neutrophils/µl] vs median: 397 neutrophils/µl [Q1, Q3: 222, 1,346 neutrophils/µl] in the metoprolol and control groups, respectively; P = 0.016). Metoprolol also reduced neutrophil extracellular traps content and other markers of lung inflammation. Oxygenation (PaO2:FiO2) significantly improved after 3 days of metoprolol treatment (median: 130 [Q1, Q3: 110, 162] vs median: 267 [Q1, Q3: 199, 298] at baseline and day 4, respectively; P = 0.003), whereas it remained unchanged in control subjects. Metoprolol-treated patients spent fewer days on invasive mechanical ventilation than those in the control group (15.5 ± 7.6 vs 21.9 ± 12.6 days; P = 0.17). In this pilot trial, intravenous metoprolol administration to patients with COVID-19-associated ARDS was safe, reduced exacerbated lung inflammation, and improved oxygenation. Repurposing metoprolol for COVID-19-associated ARDS appears to be a safe and inexpensive strategy that can alleviate the burden of the COVID-19 pandemic.Mr Clemente-Moragón is supported by a fellowship from the Ministerio de Ciencia e Innovación (FPU2017/01932). The CNIC is supported by the ISCIII, the Ministerio de Ciencia e Innovación, and the Pro CNIC Foundation. Dr Ibáñez is supported by the European Commission (ERC-CoG grant No 819775) and by the Spanish Ministry of Science and Innovation (MCN; “RETOS 2019” grant No PID2019- 107332RB-I00). Dr Oliver is supported by funds from the Comunidad de Madrid Programa de Atracción de Talento (2017-T1/BMD-5185). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.S

Remote ischemic preconditioning ameliorates anthracycline-induced cardiotoxicity and preserves mitochondrial integrity

Aims: Anthracycline-induced cardiotoxicity (AIC) is a serious adverse effect among cancer patients. A central mechanism of AIC is irreversible mitochondrial damage. Despite major efforts, there are currently no effective therapies able to prevent AIC. Methods and results: Forty Large-White pigs were included. In Study 1, 20 pigs were randomized 1:1 to remote ischaemic preconditioning (RIPC, 3 cycles of 5 min leg ischaemia followed by 5 min reperfusion) or no pretreatment. RIPC was performed immediately before each intracoronary doxorubicin injections (0.45 mg/kg) given at Weeks 0, 2, 4, 6, and 8. A group of 10 pigs with no exposure to doxorubicin served as healthy controls. Pigs underwent serial cardiac magnetic resonance (CMR) exams at baseline and at Weeks 6, 8, 12, and 16, being sacrifice after that. In Study 2, 10 new pigs received 3 doxorubicin injections (with/out preceding RIPC) and were sacrificed at week 6. In Study 1, left ventricular ejection fraction (LVEF) depression was blunted animals receiving RIPC before doxorubicin (RIPC-Doxo), which had a significantly higher LVEF at Week 16 than doxorubicin treated pigs that received no pretreatment (Untreated-Doxo) (41.5 ± 9.1% vs. 32.5 ± 8.7%, P = 0.04). It was mainly due to conserved regional contractile function. In Study 2, transmission electron microscopy (TEM) at Week 6 showed fragmented mitochondria with severe morphological abnormalities in Untreated-Doxo pigs, together with upregulation of fission and autophagy proteins. At the end of the 16-week Study 1 protocol, TEM revealed overt mitochondrial fragmentation with structural fragmentation in Untreated-Doxo pigs, whereas interstitial fibrosis was less severe in RIPC+Doxo pigs. Conclusion: In a translatable large-animal model of AIC, RIPC applied immediately before each doxorubicin injection resulted in preserved cardiac contractility with significantly higher long-term LVEF and less cardiac fibrosis. RIPC prevented mitochondrial fragmentation and dysregulated autophagy from AIC early stages. RIPC is a promising intervention for testing in clinical trials in AIC.Fil: Galán Arriola, Carlos. Centro de Investigacion Biomedica En Red.; EspañaFil: Villena Gutiérrez, Rocio. Centro de Investigacion Biomedica En Red.; EspañaFil: Higuero Verdejo, María I.. Centro Nacional de Investigaciones Cardiovasculares; EspañaFil: Díaz Rengifo, Iván A.. Centro Nacional de Investigaciones Cardiovasculares; EspañaFil: Pizarro, Gonzalo. Centro de Investigacion Biomedica En Red.; EspañaFil: López, Gonzalo J.. Centro Nacional de Investigaciones Cardiovasculares; EspañaFil: de Molina Iracheta, Antonio. Centro Nacional de Investigaciones Cardiovasculares; EspañaFil: Pérez Martínez, Claudia. Universidad de Leon. Facultad de Veterinaria; ArgentinaFil: García, Rodrigo Damián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: González Calle, David. Centro de Investigacion Biomedica En Red.; EspañaFil: Lobo, Manuel. Centro de Investigacion Biomedica En Red.; EspañaFil: Sánchez, Pedro L.. Centro de Investigacion Biomedica En Red.; EspañaFil: Oliver, Eduardo. Centro de Investigacion Biomedica En Red.; EspañaFil: Córdoba, Raúl. Hospital Fundacion Jimenez Diaz; EspañaFil: Fuster, Valentin. Centro Nacional de Investigaciones Cardiovasculares; EspañaFil: Sánchez González, Javier. No especifíca;Fil: Ibanez, Borja. Centro de Investigacion Biomedica En Red.; Españ