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Abstract Adopting a multi-criteria approach in forest management is essential for preserving or improving specific benefits while minimizing negative environmental impacts. Determining the appropriate long-term management approach for a forest requires considering heterogeneous environmental and social factors, as well as changes in forest characteristics over time. Conducting a strategic assessment of forest use suitability (FUS), namely productive, protective, conservation-oriented, social and multifunctional, at the national level, taking into account the dynamics in the provision of forest ecosystem services and the trade-offs between FUS alternatives, can guide the development of customized management strategies and policies that align with the specific requirements and conditions of the forest. In this study, we evaluate the supply and simulation-based changes over time of diverse ecosystem services of Pinus sylvestris stands in Spain and utilize a decision model to determine the most suitable FUS alternative that enhances the provision of these services. The assignment of the most appropriate FUS alternative aims to help in decision-making processes and in the selection of the most adequate management strategies. To achieve this, we utilize the last version of ecosystem management decision support (EMDS) system, a spatially focused decision support tool capable of generating precise results for multi-criteria assessment. Participatory planning actions based on Delphi principles and Analytic Hierarchy Process (AHP) analysis were applied and combined with geospatial logic-based modelling. According to the results, the dominant FUS is protective, followed by productive alternative, exhibiting high levels of multifunctionality.

Sr. Editor: La canulación coronaria sigue siendo todo un desafío tras un implante percutáneo de válvula aórtica (TAVI). El alineamiento comisural de la prótesis valvular facilita la canulación coronaria, especialmente en prótesis autoexpandibles1. Además, para ciertos dispositivos, pueden hacerse necesarias diferentes técnicas de canulación coronaria si la prótesis valvular previamente implantada presenta un alineamiento comisural incorrecto2. Analizando las proyecciones de 3 cúspides y solapamiento de 2 cúspides izquierda a derecha (2 cúspides) tras el TAVI, es posible calcular el grado de alineamiento comisural de las prótesis valvulares con los postes comisurales identificables en la fluoroscopia3,4. El objetivo de este estudio fue describir las proyecciones óptimas para la canulación de la arteria coronaria izquierda (CI) y coronaria derecha (CD) en pacientes con TAVI previo. Se analizaron las imágenes tomográficas computarizadas pre-TAVI de 105 pacientes consecutivos derivados a nuestro centro para recibir un TAVI. Cinco casos fueron descartados por su mala calidad del estudio o por el reemplazo previo de la válvula aórtica. Las proyecciones óptimas para cateterizar la CI y la CD se identificaron con el software 3mensio (Pie Medical Imaging, Países Bajos) y definieron como proyecciones coplanares con el plano trasversal de la aorta a nivel de cada ostium coronario y ortogonales...

To the Editor, Coronary re-access continues to be a challenge following transcatheter aortic valve implantation (TAVI). Commissural alignment of the prosthesis facilitates coronary re-access, especially in self-expanding prostheses.1 Additionally, for certain devices, different techniques for coronary cannulation might be necessary if the previously implanted prosthesis has commissural misalignment.2 By analyzing 3-cusp and left-to-right 2-cusp overlap (2-cusp) projections after TAVI, it is possible to estimate the degree of commissural alignment in prostheses with identifiable commissural posts on fluoroscopy.3,4 This study aimed to describe the optimal projections for left and right coronary artery (LCA, RCA) cannulation in patients with previous TAVI. We analyzed the pre-TAVI computed tomography scans of 105 consecutive patients referred to our center for TAVI implantation. Of these scans, 5 were excluded due to their poor quality or previous aortic valve replacement. The ideal projections for LCA and RCA catheterization were identified by using 3mensio software (Pie Medical Imaging, The Netherlands) and were defined as projections coplanar with the cross-sectional transverse plane of the aorta at the level of each coronary ostium and orthogonal to them, respectively. An en-face projection to the aortic annulus can be established intraprocedurally as a projection where the prosthesis is foreshortened, usually in a cranial (CRA)...

Abstract Mixed forests play a fundamental ecological role increasing biodiversity and providing ecosystem services; it has been suggested they have higher resilience and resistance against disturbances, particularly fire. Here, we compare tree mortality in post-fire mixed and pure stands in Spain, on 2,782 plots and 30,239 trees during the period 1986 to 2007. We show evidence that mixed stands can have higher post-fire mortality than pure stands, and specific mixtures of species with different fire-related strategies increase the stand's vulnerability to fire damage versus pure stands of either species, such is the case of Pinus halepensis—Pinus nigra mixtures. Mixtures of two species often had higher mortality than species growing in pure stands. Combinations of species with different fire-related strategies can both enhance or reduce forest resistance. The role and management of mixed forests should be reconsidered after these findings, in order to enhance forest resilience to fires.

Management of forest lands considering multi-functional approaches is the basis to sustain or enhance the provision of specific benefits, while minimizing negative impacts to the environment. Defining a desired management itinerary to a forest depends on a variety of factors, including the forest type, its ecological characteristics, and the social and economic needs of local communities. A strategic assessment of the forest use suitability (FUS) (namely productive, protective, conservation-oriented, social and multi-functional) at regional level, based on the provision of forest ecosystem services and trade-offs between FUS alternatives, can be used to develop management strategies that are tailored to the specific needs and conditions of the forest. The present study assesses the provision of multiple forest ecosystem services and employs a decision model to identify the FUS that supports the most present and productive ecosystem services in each stand in Catalonia. For this purpose, we apply the latest version of the Ecosystem Management Decision Support (EMDS) system, a spatially oriented decision support system that provides accurate results for multi-criteria management. We evaluate 32 metrics and 12 associated ecosystem services indicators to represent the spatial reality of the region. According to the results, the dominant primary use suitability is social, followed by protective and productive. Nevertheless, final assignment of uses is not straightforward and requires an exhaustive analysis of trade-offs between all alternative options, in many cases identifying flexible outcomes, and increasing the representativeness of multi-functional use. The assignment of forest use suitability aims to significantly improve the definition of the most adequate management strategy to be applied.

Abstract Aims This study aims to investigate the clinical and biochemical characteristics of patients with atrial fibrillation (AF) referred for ablation who develop arrhythmia‐induced cardiomyopathy (AiCM) as well as their long‐term outcomes after catheter ablation (CA). Methods and results A prospective multicentre study was conducted on consecutive AF patients who underwent CA. AiCM was defined as the development of heart failure in the presence of AF and an improvement of left ventricular fraction by at least 10% at 6 months after ablation. A subgroup of patients underwent peripheral and left atrial blood samples [galectin‐3, fatty acid‐binding protein 4 (FABP4), and soluble receptor for advanced glycation end products (sRAGE)] at the time of the procedure. Of the 769 patients who underwent AF ablation, 135 (17.56%) met the criteria for AiCM. Independent predictors of AiCM included persistent AF, male gender, left atrial volume, QRS width, active smoking, and chronic kidney disease (CKD). Biomarker analysis revealed that sRAGE, FABP4, and galectin‐3 levels were not predictive of AiCM development nor did they differ between groups or predict recurrence. There were no differences in AF recurrence between patients with and without AiCM (30.83% vs. 27.77%; P = 0.392) during a median follow‐up of 23.83 months (inter‐quartile range 9–36). Conclusions In the subset of patients referred for AF ablation, the development of AiCM was associated with persistent AF and CKD. Biomarker analysis was not different between groups nor predicted recurrence. Patients with AiCM benefited from ablation, with a significant improvement in left ventricular ejection fraction and similar AF recurrence rates to those without AiCM.

Process-based forest models combine biological, physical, and chemical process understanding to simulate forest dynamics as an emergent property of the system. As such, they are valuable tools to investigate the effects of climate change on forest ecosystems. Specifically, they allow testing of hypotheses regarding long-term ecosystem dynamics and provide means to assess the impacts of climate scenarios on future forest development. As a consequence, numerous local-scale simulation studies have been conducted over the past decades to assess the impacts of climate change on forests. These studies apply the best available models tailored to local conditions, parameterized and evaluated by local experts. However, this treasure trove of knowledge on climate change responses remains underexplored to date, as a consistent and harmonized dataset of local model simulations is missing.Here, our objectives were (i) to compile existing local simulations on forest development under climate change in Europe in a common database, (ii) to harmonize them to a common suite of output variables, and (iii) to provide a standardized vector of auxiliary environmental variables for each simulated location to aid subsequent investigations. Our dataset of European stand- and landscape-level forest simulations contains over 1.1 million simulation runs representing 135 million simulation years for more than 13,000 unique locations spread across Europe. The data were harmonized to consistently describe forest development in terms of stand structure (dominant height), composition (dominant species, admixed species), and functioning (leaf area index). Auxiliary variables provided include consistent daily climate information (temperature, precipitation, radiation, vapor pressure deficit) as well as information on local site conditions (soil depth, soil physical properties, soil water holding capacity, plant-available nitrogen). The present dataset facilitates analyses across models and locations, with the aim to better harness the valuable information contained in local simulations for large-scale policy support, and for fostering a deeper understanding of the effects of climate change on forest ecosystems in Europe.

Large forest fires are one of the most common environmental issues in the Mediterranean region. In this study, we defined a set of indicators and criteria based on available spatial data to assess and prioritize management zones for preventing large forest fires in Catalonia (NE Spain). In total, 22 indicators were defined and grouped into 5 criteria. The process involved geospatial modelling using a Geographical Information System (GIS) and the Multi-Attribute Utility Theory (MAUT) analysis. The conducted MAUT analysis resulted in the development of rules for a more standardized assessment of priority management areas. This assessment is based on participatory evaluation and introduces a utility-function-based hierarchical spatial model. Within the model, each of the 5 criteria contains relevant information, including fuel hazard, potential fire behaviour, fire extinction accessibility, valuable resources at risk, and historical fire data, serving as the foundation for a comprehensive analysis of fire prevention measures. During the assessment, two distinct sets of weights were applied: one based on expert evaluation and another using equal weights. These weights describe the relative importance of the indicators within each criterion in the assessment of fire prevention measures. Our results reveal noticeable differences between the two applied approaches. In general terms, management priority levels showcase certain spatial aggregation patterns and spatial polarization characteristics. Our study underscores the importance of participatory planning for prioritizing forest management areas to reduce fire impacts and presents a methodological framework that facilitates such spatial assessments, utilizing tools that combine expert knowledge and scientific expertise. Therefore, the main focus of this study is not on the obtained results, but on the novel methodological framework used, which consists in combining geospatial modelling with MAUT and the participatory workshops for generating the utility rules. This framework allows participation of stakeholders which at the same time enlarges credibility and acceptance of the methodology and results.

Resumen: A pesar de los tratamientos actuales, que incluyen los inhibidores del sistema renina angiotensina y los inhibidores SGLT2, el riesgo de progresión de la enfermedad renal en los sujetos con diabetes y enfermedad renal crónica (ERC) continúa inaceptablemente alto. La patogenia de la ERC en el paciente con diabetes es compleja e incluiría factores hemodinámicos, metabólicos y de inflamación y fibrosis. La finerenona es un antagonista no esteroideo altamente selectivo del receptor mineralocorticoide que, a diferencia de los tratamientos actuales, podría disminuir directamente la inflamación y la fibrosis, aportando un valor añadido al abordaje de estos pacientes. De hecho, la finerenona disminuye la albuminuria y enlentece la progresión de la ERC en personas con diabetes. La presente revisión aborda el mecanismo de acción de la finerenona, los resultados de ensayos clínicos recientes y la integración en práctica clínica de la nefroprotección y cardioprotección de la finerenona en el abordaje terapéutico integral del paciente diabético con ERC. Abstract: Despite current treatments, that include renin angiotensin system blockers and SGLT2 inhibitors, the risk of renal disease progression among patients with diabetes and chronic kidney disease (CKD) remains unacceptably high. The pathogenesis of CKD in patients with diabetes is complex and includes hemodynamic and metabolic factors, as well as inflammation and fibrosis. Finerenone is a nonsteroidal highly selective mineralocorticoid antagonist that, in contrast to current therapies, may directly reduce inflammation and fibrosis, supporting an added value in the management of these patients. In fact, finerenone decreased albuminuria and slowed CKD progression in persons with diabetes. We now review the mechanisms of action of finerenone, the results of recent clinical trials and a practical approach to integrate the kidney and cardiovascular protection afforded by finerenone in the routine care of patients with diabetes and CKD.

Despite current treatments, which include renin angiotensin system blockers and SGLT2 inhibitors, the risk of progression of kidney disease among patients with diabetes and chronic kidney disease (CKD) remains unacceptably high. The pathogenesis of CKD in patients with diabetes is complex and includes hemodynamic and metabolic factors, as well as inflammation and fibrosis. Finerenone is a highly selective nonsteroidal mineralocorticoid antagonist that, in contrast to current therapies, may directly reduce inflammation and fibrosis, thus adding value in the management of these patients. In fact, finerenone decreases albuminuria and slows CKD progression in persons with diabetes. We now review the mechanisms of action of finerenone, the results of recent clinical trials, and the integration of the kidney and cardiovascular protection afforded by finerenone in the routine care of patients with diabetes and CKD. Resumen: A pesar de los tratamientos actuales, que incluyen los inhibidores del sistema renina angiotensina y los inhibidores SGLT2, el riesgo de progresión de la enfermedad renal en los sujetos con diabetes y enfermedad renal crónica (ERC) continúa inaceptablemente alto. La patogenia de la ERC en el paciente con diabetes es compleja, e incluiría factores hemodinámicos, metabólicos, y de inflamación y fibrosis. La finerenona es un antagonista no esteroideo altamente selectivo del receptor mineralocorticoide que, a diferencia de los tratamientos actuales, podría disminuir directamente la inflamación y la fibrosis, aportando un valor añadido al abordaje de estos pacientes. De hecho, finerenona disminuye la albuminuria y enlentece la progresión de la ERC en personas con diabetes. La presente revisión aborda el mecanismo de acción de la finerenona, los resultados de ensayos clínicos recientes y la integración en práctica clínica de la nefroprotección y cardioprotección de la finerenona en el abordaje terapéutico integral del paciente diabético con ERC.

Abstract Relaxin-2 exerts many favourable cardiovascular effects in pathological circumstances such as atrial fibrillation (AF) and heart failure, but the mechanisms underlying its actions are not completely understood. Since inflammation and fibrosis are pivotal processes in the pathogenesis of AF, our aim was to study the relationship between relaxin-2 plasma levels in left atrium (LA) and peripheral vein with molecules implicated in fibrosis, inflammation and oxidative stress in AF patients, and to evaluate the anti-fibrotic ability of relaxin-2 in normal human atrial cardiac fibroblasts (NHCF-A). Peripheral vein relaxin-2 plasma levels were higher than LA relaxin-2 plasma levels in men while, in women, peripheral vein relaxin-2 levels were increased compared to men. AF patients with higher levels of relaxin-2 exhibited a reduction in H2O2 plasma levels and in mRNA levels of alpha-defensin 3 (DEFA3) and IL-6 in leucocytes from LA plasma. Relaxin-2-in-vitro treatment inhibited NHCF-A migration and decreased mRNA and protein levels of the pro-fibrotic molecule transforming growth factor-β1 (TGF-β1). Our results support an association between relaxin-2 and molecules involved in fibrosis, inflammation and oxidative stress in AF patients, and reinforce an anti-fibrotic protective role of this hormone in NHCF-A; strengthening the relevance of relaxin-2 in AF physiopathology, diagnosis and treatment.

Sr. Editor: Una novedosa vertiente en la visualización de imágenes médicas son las conocidas como realidades extendidas, término que engloba distintas tecnologías: realidad virtual, realidad aumentada y realidad mixta. De ellas, la más reciente es la realidad mixta. La característica distintiva de los visores de realidad mixta es su capacidad para percibir el mundo real y fusionar en él modelos virtuales que pueden complementar las fuentes de información disponibles de forma habitual. A priori, las posibilidades de su aplicación en el campo de la medicina son múltiples, siendo especialmente interesante su integración en procedimientos quirúrgicos e intervencionistas. En la actualidad, la principal limitación para su aplicación clínica es que no hay en el mercado presentaciones comerciales para usuario y en cada caso de uso concreto se deben desarrollar soluciones específicas. En el contexto del proyecto de investigación «sala de HemodinÁMica auMentada cON 3D» (Proyecto HAMMOND) se ha realizado una experiencia clínica preliminar de integración de las gafas de realidad mixta HoloLens 2 (Microsoft, Estados Unidos) (figura 1) en la práctica del intervencionismo cardiaco. Previa aprobación del comité de ética de la investigación (CASVE-PI-GR-20-2001), se desarrolló una aplicación de realidad mixta para la asistencia en cateterismos cardiacos y se ensayó su uso en...

To the Editor, A novel aspect of medical imaging visualization are the so-called extended realities, a term that includes a plethora of very different technologies such as virtual, augmented, and mixed reality. The latter being the most recent one of all. The ultimate feature of mixed reality headsets is their capacity to perceive the real world while mixing virtual models to complement the sources of information traditionally available. In principle, there are multiple possible applications to the medical field being particularly interesting their integration into surgical and interventional procedures. Currently, the main limitation preventing their clinical applicability is that no commercial applications remain available in the market for users. Also that, for every specific new case, specific solutions need to be developed. In the context of the «3D Augmented Reality Cath Lab» research project (the HAMMOND project) only 1 preliminary clinical experience integrating the mixed reality HoloLens 2 headset (Microsoft, United States) has taken place (figure 1) in the percutaneous coronary intervention setting. Prior to the research ethics committee approval (CASVE-PI-GR-20-2001) a mixed reality application was developed for cardiac catheterization care that was tried in 9 patients treated with transcatheter aortic valve implantation (TAVI). Figure 1. HoloLens extended mixed reality headset 2. The descriptive...

Background Congenitally corrected transposition of the great arteries (ccTGA) is a rare congenital heart defect that is frequently associated with ventricular septal defects (VSDs) and valvular abnormalities. Advanced cardiac imaging techniques are often needed for early detection and detailed study of potential complications during long-term follow-up in these patients. Case summary A 20-year-old male, asymptomatic during regular follow-ups, with ccTGA, restrictive subpulmonary VSD, and mild pulmonary stenosis. Latest outpatient evaluations showed progressive biventricular dilation, particularly in the subpulmonary left ventricle. Advanced cardiac imaging, including magnetic resonance imaging (MRI), identified an imbalance in flow between pulmonary and systemic circulations, indicated by a Qp/Qs ratio of 2.6, which could not be attributed to the known restrictive VSD. Additionally, 4D-flow MRI sequences detected low-velocity interatrial flow in the lower atrial segment. Subsequent targeted cardiac computed tomography (CT) confirmed extensive unroofing of the coronary sinus, revealing an unrecognized shunt contributing to the patient's haemodynamic imbalance. Discussion Coronary sinus unroofing is exceedingly rare and often clinically silent, complicating diagnosis. Advanced cardiac imaging (MRI, CT) plays a pivotal role in detecting such anomalies. This case underscores the challenges of diagnosing subtle shunts in complex congenital heart disease and highlights the importance of comprehensive imaging for timely intervention and management. [ABSTRACT FROM AUTHOR]

Prophylaxis to prevent bleeding is highly recommended for hemophilia patients. The development of new drugs and tools for modeling personalized prophylaxis provides the means for people with hemophilia to lead active lives with a quality of life comparable to that of nonhemophilic individuals. The choice of regimens must be made on a highly individual basis. Unfortunately, reference guides neither always concur in their recommendations nor provide directions to cover all possible scenarios. In this review, a group of experts identify the significant limitations and unmet needs of prophylaxis, taking advantage of their clinical experience in the disease, and supported by a rigorous literature update. To perform a more systematic and comprehensive search for gaps, the main cornerstones that influence decisions regarding prophylactic patterns were first identified. Bleeding phenotype, joint status, physical activity, pharmacokinetics/medication properties, and adherence to treatment were considered as the primary mainstays that should allow physicians guiding prophylaxis to secure the best outcomes. Several challenges identified within each of these topics require urgent attention and agreement. The scores to assess severity of bleeding are not reliable, and lead to no consensus definition of severe bleeding phenotype. The joint status is to be redefined in light of new, more efficient treatments with an agreement to establish one scale as the unique reference for joint health. Further discussion is needed to establish the appropriateness of high-intensity physical activities according to patient profiles, especially because sustaining trough factor levels within the safe range is not always warranted for long periods. Importantly, many physicians do not benefit from the advantages provided by the programs based on population pharmacokinetic models to guide individualized prophylaxis through more efficient and cost-saving strategies. Finally, ensuring correct adherence to long-term treatments may be time-consuming for practitioners, who often have to encourage patients and review complex questionnaires. In summary, we identify five cornerstones that influence prophylaxis and discuss the main conflicting concerns that challenge the proper long-term management of hemophilia. A consensus exercise is warranted to provide reliable guidelines and maximize benefit from recently developed tools that should notably improve patients' quality of life.

Objective: PCSK9 inhibitors have been shown to reduce LDLc by up to about 60% and 85% when used with high doses of statins and ezetimibe (2019 ESC/EAS Guidelines). These therapies may lead to very low levels of LDLc and have been associated with possible cognitive deterioration. No significant differences were found in the only specific study (EBBINGHAUS). The objective is to prospectively evaluate cognitive deterioration and its repercussion on quality of life and changes in LDLc in patients starting treatment with PCKS9 inhibitors.Method: It is a postauthorization, multicentre, non-randomized, prospective study. Patients starting treatment for the first time with PCSK9 inhibitors will be recruited in 11 Galician Hospitals over a period of 12 months and with 24 months of follow-up. The primary outcome will be to evaluate changes in cognitive function using the Montreal Cognitive Assessment (MOCA) questionnaire. The secondary outcome will be to evaluate changes in quality of life using the EuroQol-5D. Changes in LDLc will be assessed. The sample size will be 275 patients, taking into account a loss to follow-up of no more than 10%. The primary outcome will be studied through the dichotomous variable cognitive deterioration (0/1). Cognitive changes over the follow-up period will be analysed using the McNemar test. In addition, an analytical approach using logistic regression will be followed to identify patients at risk of cognitive deterioration. As a result, this analysis will obtain a frequency measurement: the odds ratio (OR). The specific objectives will be studied using bivariate analysis. Continuous contrast variables will be studied using the t-test or ANOVA and categorical variables will be studied using the chi- square test.Conclusions: The MEMOGAL study will provide information on safety in terms of cognitive deterioration in patients starting treatment with PCSK9 inhibitors.

Resumen: Antecedentes y objetivo: El objetivo del estudio fue caracterizar el perfil clínico y terapéutico de los pacientes con cardiopatía isquémica en España en los pacientes (grupo 1) al alta tras un síndrome coronario agudo, (grupo 2) en primera visita post-alta y (grupo 3) entre uno o 2 años tras el síndrome coronario agudo. Materiales y métodos: Estudio observacional, multicéntrico, transversal, de ámbito nacional, realizado en condiciones de práctica clínica habitual. Resultados: Se incluyeron 1.018 pacientes: 354 (34,8%) del grupo 1, 326 (32,0%) del 2 y 338 (33,2%) del 3. En comparación con el grupo 3, en el grupo 1 había un porcentaje significativamente mayor de pacientes fumadores (32,2 contra 10,9%), que consumían alcohol (28,2 contra 19,5%), que no realizaba ejercicio físico (61,0 contra 38,2%) o que no seguían una dieta (57,1 contra 32,5%). El 65,4% de los pacientes del grupo 1 no fue derivado a un programa de rehabilitación cardiaca (PRC). Del grupo 2, el 53,1% no tenía cita prevista para comenzar un PRC. Respecto al grupo 3, al 58,3% no se le recomendó nunca hacer rehabilitación cardiaca. Las variables asociadas al control de los factores de riesgo cardiovascular fueron la ausencia de obesidad y la asistencia a un PRC. Conclusiones: En el momento actual, menos de la mitad de los pacientes con cardiopatía isquémica en España son remitidos a un PRC, aunque estos programas se asocian a un mejor control de los factores de riesgo cardiovascular. Abstract: Introduction and objectives: The objective of the study was to characterize the clinical and therapeutic profile of patients with ischemic cardiopathy (IC) in Spain in patients (group 1) at the time of hospital discharge after an acute coronary syndrome (ACS), (group 2) at the first post-discharge follow-up visit, and (group 3) after one year of the ACS. Patients and methods: Observational, multicenter, cross-sectional, nationwide, performed in conditions of routine clinical practice. Results: A total of 1018 patients were included: 354 (34.8%) in the group 1, 326 (32.0%) in the 2, and 338 (33.2%) in the 3. Compared with group 3, a higher percentage of patients from group 1 were smokers (32.2% versus 10.9%), consumed alcohol (28.2% versus 19.5%), did not do any physical exercise (61.0% versus 38.2%) or followed a diet (57.1% versus 32.5%). Of patients in group 1, 65.4% were referred to a cardiac rehabilitation program (CRP). Of those in group 2, 53.1% had not a scheduled appointment to initiate a CRP. Regarding group 3, 58.3% did not receive the recommendation of doing a CRP. Absence of obesity and attendance to a CRP were variables associated with the control of cardiovascular risk factors. Conclusions: Currently, less than 50% of patients with IC in Spain are remitted to a CRP despite being associated with an improved control of cardiovascular risk factors.

Objective: Splenectomy, thrombopoietin receptor agonists and rituximab are the second-line treatments for steroid-resistant adult primary immune thrombocytopenia. The last two are becoming the most widely used treatments to avoid splenectomy adverse effects and inconveniences. However, the choice between rituximab and thrombopoietin receptor agonists is unclear. Therefore, the treatment cost may be of particular interest to prioritize the therapy option. Our aim is to determine the cost per responding-patient after 6 months of use of rituximab compared to thrombopoietin receptor agonists eltrombopag in the treatment of chronic primary immune thrombocytopenia in the Spanish National Health Service. Method: A 26-week decision tree model was developed to assess the cost of treatment response of adult patients with chronic-refractory primary immune thrombocytopenia to eltrombopag and rituximab from the perspective of the Spanish National Health System. Effectiveness was obtained from the literature, and cost was obtained from the official rates. Costs were expressed in € (2018). Due to the short period of assessment, no discount rate was applied. Results: The average cost per patient after 6 months of treatment was slightly higher for eltrombopag (€13,089.40) than for rituximab (€11,852.60). However, the greater response rate of eltrombopag decreases the bleeding costs, resulting in a 29% higher cost per responding-patient with rituximab (€18,964.15) than for eltrombopag (€14,732.65). This result is consistent with the results of the 15 sensitivity analyses carried out where eltrombopag always represents a lower cost per responding patient, except in the sensitivity analysis in which treatment with eltrombopag is performed at its maximum dose (75mg). Only in this case, the cost per responder of eltrombopag is €48 more expensive than that of rituximab. Likewise, the greatest difference in favor of eltrombopag occurs in the scenario that uses the minimum dose of this drug —25mg— (eltrombopag €7,622.14 compared to €18,964.15 for rituximab). Thus, the cost per responding patient is lower in eltrombopag even if a second cycle of retreatment with rituximab is not performed (€14,732.65 versus €15,298.61). Conclusions: The treatment cost of rituximab, including monitoring and bleeding costs, is higher than eltrombopag, favoring the latter over rituximab treatment.

In the last years, the use of thrombopoietin receptor agonists (TPO-RA), eltrombopag and romiplostim, has improved the management of immune thrombocytopenia (ITP). Moreover, eltrombopag is also active in patients with aplastic anemia and myelodysplastic syndrome. However, their mechanisms of action and signaling pathways still remain controversial. In order to gain insight into the mechanisms underlying eltrombopag therapy, a gene expression profile (GEP) analysis in patients treated with this drug was carried out. Fourteen patients with chronic ITP were studied by means of microarrays before and during eltrombopag treatment. Median age was 78 years (range, 35–87 years); median baseline platelet count was 14 × 109/L (range, 2–68 × 109/L). Ten patients responded to the therapy, two cases relapsed after an initial response and the remaining two were refractory to the therapy. Eltrombopag induced relevant changes in the hematopoiesis, platelet activation and degranulation, as well as in megakaryocyte differentiation, with overexpression of some transcription factors and the genes PPBP, ITGB3, ITGA2B, F13A1, F13A1, MYL9 and ITGA2B. In addition, GP1BA, PF4, ITGA2B, MYL9, HIST1H4H and HIST1H2BH, genes regulated by RUNX1 were also significantly enriched after eltrombopag therapy. Furthermore, in non-responder patients, an overexpression of Bcl-X gene and genes involved in erythropoiesis, such as SLC4A1 and SLC25A39, was also observed. To conclude, overexpression in genes involved in megakaryopoiesis, platelet adhesion, degranulation and aggregation was observed in patients treated with eltrombopag. Moreover, an important role regarding heme metabolism was also present in non-responder patients.

Abstract Background Cardio myoblast generation from conventional approaches is laborious and time-consuming. We present a bioelectronics on-a-chip for stimulating cells cardio myoblast proliferation during culture. Method The bioelectronics chip fabrication methodology involves two different process. In the first step, an aluminum layer of 200 nm is deposited over a soda-lime glass substrate using physical vapor deposition and selectively removed using a Q-switched Nd:YVO4 laser to create the electric tracks. To perform the experiments, we developed a biochip composed of a cell culture chamber fabricated with polydimethylsiloxane (PDMS) with a glass coverslip or a cell culture dish placed over the electric circuit tracks. By using such a glass cover slip or cell culture dish we avoid any toxic reactions caused by electrodes in the culture or may be degraded by electrochemical reactions with the cell medium, which is crucial to determine the effective cell-device coupling. Results The chip was used to study the effect of electric field stimulation of Rat ventricular cardiomyoblasts cells (H9c2). Results shows a remarkable increase in the number of H9c2 cells for the stimulated samples, where after 72 h the cell density double the cell density of control samples. Conclusions Cell proliferation of Rat ventricular cardiomyoblasts cells (H9c2) using the bioelectronics-on-a-chip was enhanced upon the electrical stimulation. The dependence on the geometrical characteristics of the electric circuit on the peak value and homogeneity of the electric field generated are analyzed and proper parameters to ensure a homogeneous electric field at the cell culture chamber are obtained. It can also be observed a high dependence of the electric field on the geometry of the electrostimulator circuit tracks and envisage the potential applications on electrophysiology studies, monitoring and modulate cellular behavior through the application of electric fields.

ABSTRACT Introduction and objectives: Complex calcified lesions can affect stent expansion and lead to stent failure and adverse outcomes. Intracoronary lithotripsy (ICL) has emerged as a new tool that enables calcium modification. The Disrupt CAD II clinical trial has recently evaluated the safety and feasibility of ICL in patients with stable coronary disease and calcified coronary lesions. Although its use has increased rapidly, the experience already reported with this new device is limited. We report the results in real-life complex patients with heavy coronary calcification. Methods: From October 2018 to March 2019, 25 patients (37 calcified lesions) were treated in 2 Spanish centers, which accounted for 2.7% of the patients treated with percutaneous coronary intervention. Results: The device and clinical success rates were 84% and 95%, respectively. No procedure-related complications were seen. The crossing rate of the ICL balloon was 100% and balloon rupture during inflation occurred in 8%. The ICL was performed in a subset of highly complex lesions like left main coronary artery lesions and chronic total coronary occlusions. Compared to the Disrupt CAD II trial, our patients were younger but their clinical scenario was worse with a higher prevalence of diabetes (68%), renal failure (22%), and up to 76% suffered from acute coronary syndrome. The ICL failed to reach proper expansion in 3 out of 4 cases of stent underexpansion. The procedure was performed safely, and clinical and device success were high with no in-hospital mortality. One patient died of non-cardiac causes at the 30-day follow-up. Conclusions: The ICL-assisted percutaneous coronary intervention was performed safely and effectively in a real-life cohort of patients with calcified and highly complex lesions.

Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal-dominant genetic disorder involving defects in two predominant genes known as endoglin (ENG; HHT-1) and activin receptor-like kinase 1 (ACVRL1/ALK1; HHT-2). It is characterized by mucocutaneous telangiectases that, due to their fragility, frequently break causing recurrent epistaxis and gastrointestinal bleeding. Because of the severity of hemorrhages, the study of the hemostasis involved in these vascular ruptures is critical to find therapies for this disease. Our results demonstrate that HHT patients with high bleeding, as determined by a high Epistaxis Severity Score (ESS), do not have prolonged clotting times or alterations in clotting factors. Considering that coagulation is only one of the processes involved in hemostasis, the main objective of this study was to investigate the overall mechanisms of hemostasis in HHT-1 (Eng+/−) and HHT-2 (Alk1+/−) mouse models, which do not show HHT vascular phenotypes in the meaning of spontaneous bleeding. In Eng+/− mice, the results of in vivo and in vitro assays suggest deficient platelet-endothelium interactions that impair a robust and stable thrombus formation. Consequently, the thrombus could be torn off and dragged by the mechanical force exerted by the bloodstream, leading to the reappearance of hemorrhages. In Alk1+/− mice, an overactivation of the fibrinolysis system was observed. These results support the idea that endoglin and Alk1 haploinsufficiency leads to a common phenotype of impaired hemostasis, but through different mechanisms. This contribution opens new therapeutic approaches to HHT patients' epistaxis.

In this study, we evaluated alternative methods for comparing the provision of ecosystem services among urban areas, stressing how the choice of comparison method affects the ability to compare the ecosystem service outcomes, in order to improve the management actions in urban green areas, reduce environmental inequality, and ensure satisfactory levels of human well-being. For the analysis, ten spatial indicators were quantified to assess the provision of urban ecosystem services in Barcelona, Spain, and Santiago, Chile. Two comparison methods were applied in both cities to evaluate the differences in their provision scores. The analysis was performed using the Ecosystem Management Decision Support (EMDS) system, a spatially enabled decision support framework for environmental management. The results depicted changes in the values of the provision of ecosystem services depending on the methodological approach applied. When the data were analysed separately for each city, both cities registered a wide range of provision values across the city districts, varying from very low to very high values. However, when the analysis was based on the data for both cities, the provision scores in Santiago decreased, while they increased in Barcelona, showing relativeness and a discrepancy in their provisions, hindering an appropriate planning definition. Our results emphasise the importance of the choice of comparison approach in the analyses of urban ecosystem services and the need for further studies on these comparison methods.

The EMPA-REG OUTCOME (Empagliflozin, Cardiovascular Outcome Event Trial in patients with Type 2 Diabetes Mellitus (T2DM)) trial evidenced the potential of sodium-glucose cotransporter 2 (SGLT2) inhibitors for the treatment of patients with diabetes and cardiovascular disease. Recent evidences have shown the benefits of the SGLT2 inhibitor empagliflozin on improving liver steatosis and fibrosis in patients with T2DM. Metabolomic studies have been shown to be very useful to improve the understanding of liver pathophysiology during the development and progression of metabolic hepatic diseases, and because the effects of empagliflozin and of other SGLT2 inhibitors on the complete metabolic profile of the liver has never been analysed before, we decided to study the impact on the liver of male Zucker diabetic fatty (ZDF) rats of a treatment for 6 weeks with empagliflozin using an untargeted metabolomics approach, with the purpose to help to clarify the benefits of the use of empagliflozin at hepatic level. We found that empagliflozin is able to change the hepatic lipidome towards a protective profile, through an increase of monounsaturated and polyunsaturated glycerides, phosphatidylcholines, phosphatidylethanolamines, lysophosphatidylinositols and lysophosphatidylcholines. Empagliflozin also induces a decrease in the levels of the markers of inflammation IL-6, chemerin and chemerin receptor in the liver. Our results provide new evidences regarding the molecular pathways through which empagliflozin could exert hepatoprotector beneficial effects in T2DM.

Atrial fibrillation is the most prevalent tachyarrhythmia in clinical practice, with very high cardiovascular morbidity and mortality with a high-cost impact in health systems. Currently, it is one of the main causes of stroke and subsequent heart failure and sudden death. miRNAs mediate in several processes involved in cardiovascular disease, including fibrosis and electrical and structural remodeling. Several studies suggest a key role of miRNAs in the course and maintenance of atrial fibrillation. In our study, we aimed to identify the differential expression of circulating miRNAs and their predictive value as biomarkers of recurrence in atrial fibrillation patients undergoing catheter pulmonary vein ablation. To this effect, 42 atrial fibrillation patients were recruited for catheter ablation. We measured the expression of 84 miRNAs in non-recurrent and recurrent groups (45.2%), both in plasma from peripheral and left atrium blood. Expression analysis showed that miRNA-451a is downregulated in recurrent patients. Receiver operating characteristic curve analysis showed that miR-451a in left atrium plasma could predict atrial fibrillation recurrence after pulmonary vein isolation. In addition, atrial fibrillation recurrence is positively associated with the increment of scar percentage. Our data suggest that miRNA-451a expression plays an important role in AF recurrence by controlling fibrosis and progression.

In this review, the authors describe evolving alternative strategies for the management of AF, focusing on non-invasive and percutaneous autonomic modulation. This modulation can be achieved – among other approaches – via tragus stimulation, renal denervation, cardiac afferent denervation, alcohol injection in the vein of Marshall, baroreceptor activation therapy and endocardial ganglionated plexi ablation. Although promising, these therapies are currently under investigation but could play a role in the treatment of AF in combination with conventional pulmonary vein isolation in the near future.

Se aportan algunas claves para comprender las principales tensiones y contradicciones que se están produciendo en el modelo hegemónico de protección alimentaria. Para ello se analizan dinámicas y discursos de diversas experiencias puestas en marcha para afrontar el hambre y la Inseguridad Alimentaria en la Comunidad de Madrid. Para cubrir estos objetivos, se parte del análisis del material cualitativo procedente de un Proyecto de Aprendizaje Colaborativo desarrollado entre la Universidad Complutense de Madrid, la Carta contra el Hambre y el Observatorio para la Garantía del Derecho a la Alimentación en la Comunidad de Madrid entre 2019 y 2021. Se comprueba cómo el modelo hegemónico de reparto de alimentos a partir de los Bancos de Alimentos asistenciales provistos, fundamentalmente, desde el Estado en la sombra y desde iniciativas filantrópicas, se va viendo progresivamente tensionado y cuestionado tanto interna, como externamente. Al mismo tiempo, se observa la enorme potencialidad de los grupos vecinales y de apoyo para proponer experiencias innovadoras que suponen un aprendizaje fundamental en el objetivo de la protección alimentaria, al mismo tiempo que generan bienestar y fortalecen el tejido social y la identidad barrial.

Resumen: Como bien se ha expresado a lo largo de este documento, la diabetes mellitus es una epidemia en salud pública, la cual se ha relacionado con complicaciones macrovasculares y microvasculares que llevan a una alta morbilidad y mortalidad cardiovascular. A partir del 2008, la Administración de Drogas y Alimentos (FDA, su sigla en inglés por Food and Drug Administration), ente regulatorio en los Estados Unidos, determinó la evaluación de la seguridad cardiovascular para todas las moléculas antidiabéticas. Esto ha generado gran número de nuevos estudios con nuevos medicamentos que buscan demostrar protección cardiovascular más allá del control glicémico. Este artículo describe los principales estudios que se están realizando con los inhibidores del cotransportador de sodio-glucosa tipo 2 (i-SGLT2) en pacientes con insuficiencia cardiaca con y sin diabetes. Abstract: As has been shown throughout this article, diabetes mellitus is a public health epidemic. It has been associated with macrovascular and microvascular complications that have a high cardiovascular morbidity and mortality. Since 2008, the American Food and Drug Administration (FDA) evaluated the cardiovascular safety of all the anti-diabetic drugs. This has led to a large number of studies with new drugs that seek to demonstrate cardiovascular protection beyond that of glycaemic control. A description is presented of the principal studies that are being carried out with sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients with heart failure and with and without diabetes. Palabras clave: Diabetes, Insuficiencia cardiaca, Tratamiento, Keywords: Diabetes, Heart failure, Treatment

Abstract Accumulating evidence has confirmed that the expression of sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) is downregulated in heart failure and cardiac allograft rejection. Although many SERCA2a-related genes and proteins involved in the regulation of myocardial Ca2+ fluxes have been explored, its related metabolites remain poorly studied. Our main objective was to identify circulating SERCA2a-related metabolites altered in cardiac allograft rejection and to determine whether these could serve as non-invasive biomarkers. Sixty plasma samples from adult heart transplant were included in a metabolomic analysis. Sphingosine-1 phosphate (S1P), metabolite closely related with SERCA, were increased in patients with cardiac rejection (p

Telemedicine (TM) is potentially a way of escalating heart failure (HF) multidisciplinary integrated care. Despite the initial efforts to implement TM in HF management, we are still at an early stage of its implementation. The coronavirus disease 2019 pandemic led to an increased utilisation of TM. This tendency will probably remain after the resolution of this threat. Face-to-face medical interventions are gradually transitioning to the virtual setting by using TM. TM can improve healthcare accessibility and overcome geographic inequalities. It promotes healthcare system efficiency gains, and improves patient self-management and empowerment. In cooperation with human intervention, artificial intelligence can enhance TM by helping to deal with the complexities of multicomorbidity management in HF, and will play a relevant role towards a personalised HF patient approach. Artificial intelligence-powered/telemedical/heart team/multidisciplinary integrated care may be the next step of HF management. In this review, the authors analyse TM trends in the management of HF patients and foresee its future challenges within the scope of HF multidisciplinary integrated care.