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Sr. Editor: La administración de tratamiento anticoagulante solo ha demostrado ser eficaz contra la embolia pulmonar (EP) aguda de riesgo bajo y de bajo a intermedio1. No obstante, la EP de riesgo intermedio-alto y alto está asociada a un riesgo considerablemente alto de colapso circulatorio a corto plazo, muerte o hipertensión pulmonar tromboembólica crónica de entre el 3 y el 10% cuando se trata solo con anticoagulación1. Aunque la fibrinólisis sistémica reduce este riesgo en un 50%, este tratamiento aumenta significativamente el riesgo de sangrado mayor, tal y como describió el ensayo PEITHO2, lo cual ha limitado el uso de la fibrinólisis sistémica a pacientes de alto riesgo, tal y como recomienda la guía vigente3. Esta limitación ha generado un interés creciente en las terapias dirigidas por catéter (TDC) en pacientes con EP aguda de alto riesgo y una contraindicación o fracaso de la fibrinolisis sistémica, así como en pacientes de riesgo intermedio-alto que desarrollan deterioro hemodinámico a pesar de la anticoagulación3. Las TDC permiten una resolución más rápida de los defectos de perfusión y una mejora hemodinámica sin los efectos hemorrágicos sistémicos asociados a la trombolisis sistémica. A pesar del mayor uso de estas TDC, la evidencia clínica sobre sus beneficios sigue...

To the Editor, Anticoagulation alone has proven efficacy for the treatment of low- and low-to-intermediate- -risk acute pulmonary embolism (PE) patients.1 Nonetheless, intermediate-high and high-risk PE are associated with a considerable risk of short-term circulatory collapse, death or chronic thromboembolic pulmonary hypertension, ranging from 3% to 10%, when treated with anticoagulation alone.1 Although systemic fibrinolysis decreases this risk by 50%, this treatment significantly increases the risk of major bleeding, as seen in PEITHO trial (Fibrinolysis for patients with intermediate-risk pulmonary embolism),2 which has limited the use of systemic fibrinolysis to high-risk patients, as recommended in the current guidelines.3 This limitation has led to growing interest in catheter-directed therapies (CDT) for patients with high-risk acute PE and a contraindication or failure of systemic fibrinolysis and patients with intermediate-high risk who develop worsening hemodynamics despite anticoagulation.3 CDT allow faster resolution of perfusion defects and hemodynamic improvement without the systemic hemorrhagic effects of systemic thrombolysis. Despite an increasing use of CDT, the clinical evidence of its benefits remains scarce, as there are no adequately powered randomized controlled trials and current studies have been limited to immediate hemodynamic improvement or imaging surrogate markers.4-6 This study aimed to assess the safety, feasibility, and mid-term effects of CDT. Between 2020...

ABSTRACT Introduction and objectives: Transfemoral access is globally accepted as the preferential access route for transcatheter aortic valve implantation (TAVI). However, in up to 15% of the patients, this access is considered inadequate. Considering the various alternatives available, the fully percutaneous access routes have been chosen preferentially. This analysis aims to compare outcomes and complications of 3 alternative access routes for transfemoral, trans-subclavian and transcaval TAVI. Methods: Retrospective analysis of patients referred for TAVI using transfemoral, trans-subclavian, and transcaval accesses in a single tertiary center from 2008 through 2021. The primary endpoints were 30-day and 1-year all-cause mortality rates. The secondary endpoints were technical success, residual moderate-to-severe paravalvular leak, major vascular complication, 30-day stroke, 30-day Valve Academic Research Consortium-2 (VARC-2) major bleeding, and 30-day acute kidney injury (AKIN criteria 2 or 3). Results: A total of 642 TAVIs were performed (601 transfemoral, 24 trans-subclavian, and 10 transcaval). A total of 7 patients treated via transapical access were excluded. As expected, baseline comorbidities like left ventricular dysfunction, coronary artery disease, atrial fibrillation, chronic kidney disease, and previous stroke were more frequent in the non-femoral groups. The 1-year and 30-day all-cause mortality rates were higher in the non-transfemoral population (HR, 2.88 and HR, 3.53, respectively). The rates of 30-day stroke and acute kidney injury (AKIN 2 or 3) were also significantly lower in transfemoral patients, but similar between trans-subclavian and transcaval patients. The rates of 30-day major bleeding showed a statistically significant tendency towards lower rates in the transfemoral group. The rates of technical success, major vascular complications, and residual moderate or severe perivalvular leak were similar among the 3 groups. Conclusions: After careful selection, transfemoral access is the preferential access route for TAVI procedures. In intermediate surgical risk patients with severe symptomatic aortic stenosis, non-transfemoral TAVI approaches have poorer outcomes. The worse outcomes of percutaneous alternative access routes are partially associated with worse baseline characteristics.

RESUMEN Introducción y objetivos: El acceso transfemoral (aTF) es el de elección para el implante percutáneo de válvula aórtica (TAVI). Sin embargo, hasta en el 15% de los pacientes este acceso es inadecuado. De las alternativas disponibles, el acceso totalmente percutáneo es el preferido. El objetivo del estudio es comparar los resultados clínicos de los pacientes tratados por aTF frente a los de aquellos con acceso transubclavio (aTS) o transcava (aTCv). Métodos: Análisis retrospectivo de los pacientes tratados con TAVI (2008-2021) en un centro terciario mediante aTF, aTS y aTCv. El objetivo primario fue la mortalidad por cualquier causa a 30 días y 1 año. Los objetivos secundarios fueron el éxito técnico, la regurgitación perivalvular moderada o grave, las complicaciones vasculares mayores, el accidente vascular cerebral, el sangrado mayor y el daño renal agudo a 30 días (Valve Academic Research Consortium II [VARC-2]). Resultados: Se realizaron 642 TAVI (601 por aTF, 24 por aTS y 10 por aTCv). Fueron excluidos 7 pacientes tratados por vía transapical. En los pacientes con acceso alternativo fue más frecuente la comorbilidad, incluyendo disfunción ventricular izquierda, enfermedad coronaria, fibrilación auricular, enfermedad renal e ictus previo. La mortalidad a 1 año y a 30 días fue también más alta en este grupo de pacientes (hazard ratio [HR] = 2,88 y 3,53, respectivamente). A 30 días, las tasas de ictus y daño renal (grado 2 o 3) fueron significativamente más bajas para el aTF, y similares en los pacientes con aTS y aTCv. Hubo también una tendencia a menor sangrado en el grupo de aTF. El éxito técnico, las complicaciones vasculares mayores y la regurgitación perivalvular moderada o grave fueron similares en los tres grupos. Conclusiones: Tras una adecuada selección, el aTF es el preferido para el TAVI. En pacientes de riesgo intermedio con estenosis aórtica grave sintomática, un acceso no transfemoral tiene peores resultados. Los inferiores resultados del uso de vías percutáneas alternativas están parcialmente relacionados con las peores características clínicas basales.

Introduction and objectives: Patients with hypertrophic obstructive cardiomyopathy (HOCM) that remain symptomatic despite optimized medical therapy often undergo alcohol septal ablation (ASA). One of the most frequent complications is complete heart block (CHB), requiring a permanent pacemaker (PPM) in variable rates of up to 20% of patients. The long-term impact of PPM implantation in these patients remains unclear. This study aimed to evaluate the long-term clinical outcomes in patients who implant PPM after ASA. Methods: Patients who underwent ASA at a tertiary center were consecutively and prospectively enrolled. Patients with previous PPM or implantable cardio-defibrillator were excluded from this analysis. Patients with and without PPM implantation after ASA were compared based on their baseline characteristics, procedure data and three-year primary endpoint of composite of all-cause mortality and hospitalization and secondary endpoint of composite of all-cause mortality and cardiac cause hospitalization. Results: Between 2009 and 2019, 109 patients underwent ASA, 97 of whom were included in this analysis (68% female, mean age 65.2 years old). 16 patients (16.5%) required PPM implantation for CHB. In these patients, no vascular access, pacemaker pocket or pulmonary parenchyma complications were noted. The baseline characteristics of comorbidities, symptoms, echocardiographic and electrocardiographic findings were identical in the two groups, with higher mean age (70.6±10.0 years vs. 64.1±11.9 years) and lower beta-blocker therapy rate (56% vs. 84%) in the PPM group. Procedure-related data showed higher creatine kinase (CK) peaks in the PPM group (1692 U/L vs. 1243 U/L), with no significant difference in the alcohol dose. At three years after ASA procedure, there were no differences in the primary and secondary endpoints between the two groups. Conclusions: Permanent pacemaker after ASA induced CHB do not affect long term prognosis in hypertrophic obstructive cardiomyopathy patients. Resumo: Introdução e objetivos: Doentes com miocardiopatia hipertrófica obstrutiva (MCHO) sintomáticos apesar de terapêutica médica otimizada são frequentemente submetidos a ablação septal alcoólica (ASA). O bloqueio atrioventricular (BAV) completo é uma complicação frequente, requerendo implantação de pacemaker definitivo em taxas variáveis que podem ir até 20% dos doentes. O impacto a longo prazo da implantação de pacemaker nestes doentes permanente mal-esclarecido. Esta análise pretende avaliar os outcomes clínicos a longo prazo nestes doentes. Métodos: Doentes consecutivos submetidos a ASA num centro terciário foram incluídos e seguidos prospetivamente. Pacientes com pacemaker ou cardiodesfibrilhador prévio foram excluídos desta análise. Os doentes com e sem implantação de pacemaker após a ASA foram caracterizados e comparados relativamente aos endpoints primário (composto de mortalidade e hospitalização por todas as causas) e secundário (composto de mortalidade por todas as causas e hospitalização de causa cardíaca) a três anos. Resultados: Entre 2009 e 2019, 109 pacientes foram submetidos a ASA e 97 foram incluídos nesta análise (68% sexo feminino, idade media 65,2 anos). Implantaram pacemaker 16 doentes (16,5%) após a ASA por BAV completo. Não se registaram complicações vasculares, da loca ou parenquimatosas pulmonares. As características basais foram semelhantes entre os grupos, com maior idade média (70,6 ± 10,0 anos versus 64,1 ± 11,9 anos) e menor taxa de terapêutica beta-bloqueante (56% versus 84%) no grupo de pacemaker. Dados do periprocedimento revelaram maior pico de creatina cinase (CK) no grupo de pacemaker, sem diferença na dose de álcool usado. Aos três anos, os endpoints primário e secundário não mostraram diferenças entre os dois grupos. Conclusão: A implantação de pacemaker definitivo por BAV completo induzido por ablação septal alcoólica não afeta o prognóstico de pacientes com MCHO.

The number of migrant children in Lithuania is increasing every year. For many years, the majority of migrants (around 82%) were returning Lithuanians, but since 2022, due to the ongoing war between Ukraine and Russia, a large influx of Ukrainian immigrants has been observed: 7761 children have arrived in Lithuania since the outbreak of the full-scale invasion. This study aims to highlight the integration-related challenges that educators face in the context of the increasing number of migrant children. Qualitative, semi-structured interviews (N = 9) were applied to investigate the issue and outline possible solutions from the point of view of educators. The study was conducted in a school with 875 students, including 31 (3.5%) immigrants. The empirical study revealed that the school implements the integration of migrant children in accordance with the recommendations issued by the Ministry of Education, Science, and Sport. Upon the arrival of a migrant child, the committee assesses the child’s knowledge, interviews the parents, and determines the appropriate class placement and learning methods. An individual education plan is then devised based on the expectations of both the child and their parents. Teachers face challenges related to language barriers and cultural differences. The provision of courses developing intercultural competence, more language lessons, and training for both children and their parents are considered to be the most important conditions for the successful integration of migrant children into the education system.

The article emphasizes the critical importance of language generation today, particularly focusing on three key aspects: Multitasking, Multilinguality, and Multimodality, which are pivotal for the Natural Language Generation community. It delves into the activities conducted within the Multi3Generation COST Action (CA18231) and discusses current trends and future perspectives in language generation.

BackgroundThe Danish cardiovascular screening (DANCAVAS) trial, a nationwide trial designed to investigate the impact of cardiovascular screening in men, did not decrease all-cause mortality, an outcome decided by the investigators. However, the target group may have varied preferences. In this study, we aimed to evaluate whether men aged 65 to 74 years requested a CT-based cardiovascular screening examination and to assess its impact on outcomes determined by their preferences.Methods and findingsThis is a post hoc study of the randomised DANCAVAS trial. All men 65 to 74 years of age residing in specific areas of Denmark were randomised (1:2) to invitation-to-screening (16,736 men, of which 10,471 underwent screening) or usual-care (29,790 men). The examination included among others a non-contrast CT scan (to assess the coronary artery calcium score and aortic aneurysms). Positive findings prompted preventive treatment with atorvastatin, aspirin, and surveillance/surgical evaluation. The usual-care group remained unaware of the trial and the assignments. The user-defined outcome was based on patient preferences and determined through a survey sent in January 2023 to a random sample of 9,095 men from the target group, with a 68.0% response rate (6,182 respondents). Safety outcomes included severe bleeding and mortality within 30 days after cardiovascular surgery. Analyses were performed on an intention-to-screen basis. Prevention of stroke and myocardial infarction was the primary motivation for participating in the screening examination. After a median follow-up of 6.4 years, 1,800 of 16,736 men (10.8%) in the invited-to-screening group and 3,420 of 29,790 (11.5%) in the usual-care group experienced an event (hazard ratio (HR), 0.93 (95% confidence interval (CI), 0.88 to 0.98; p = 0.010); number needed to invite at 6 years, 148 (95% CI, 80 to 986)). A total of 324 men (1.9%) in the invited-to-screening group and 491 (1.7%) in the usual-care group had an intracranial bleeding (HR, 1.17; 95% CI, 1.02 to 1.35; p = 0.029). Additionally, 994 (5.9%) in the invited-to-screening group and 1,722 (5.8%) in the usual-care group experienced severe gastrointestinal bleeding (HR, 1.02; 95% CI, 0.95 to 1.11; p = 0.583). No differences were found in mortality after cardiovascular surgery. The primary limitation of the study is that exclusive enrolment of men aged 65 to 74 renders the findings non-generalisable to women or men of other age groups.ConclusionIn this comprehensive population-based cardiovascular screening and intervention program, we observed a reduction in the user-defined outcome, stroke and myocardial infarction, but entail a small increased risk of intracranial bleeding.Trial registrationISRCTN Registry number, ISRCTN12157806 https://www.isrctn.com/ISRCTN12157806.

Author(s): Axel Cosmus Pyndt Diederichsen 1,*, Anna Mejldal 2, Rikke Søgaard 3, Jesper Hallas 4, Jess Lambrechtsen 5, Flemming Hald Steffensen 6, Lars Frost 7, Kenneth Egstrup 5, Martin Busk [...], Background The Danish cardiovascular screening (DANCAVAS) trial, a nationwide trial designed to investigate the impact of cardiovascular screening in men, did not decrease all-cause mortality, an outcome decided by the investigators. However, the target group may have varied preferences. In this study, we aimed to evaluate whether men aged 65 to 74 years requested a CT-based cardiovascular screening examination and to assess its impact on outcomes determined by their preferences. Methods and findings This is a post hoc study of the randomised DANCAVAS trial. All men 65 to 74 years of age residing in specific areas of Denmark were randomised (1:2) to invitation-to-screening (16,736 men, of which 10,471 underwent screening) or usual-care (29,790 men). The examination included among others a non-contrast CT scan (to assess the coronary artery calcium score and aortic aneurysms). Positive findings prompted preventive treatment with atorvastatin, aspirin, and surveillance/surgical evaluation. The usual-care group remained unaware of the trial and the assignments. The user-defined outcome was based on patient preferences and determined through a survey sent in January 2023 to a random sample of 9,095 men from the target group, with a 68.0% response rate (6,182 respondents). Safety outcomes included severe bleeding and mortality within 30 days after cardiovascular surgery. Analyses were performed on an intention-to-screen basis. Prevention of stroke and myocardial infarction was the primary motivation for participating in the screening examination. After a median follow-up of 6.4 years, 1,800 of 16,736 men (10.8%) in the invited-to-screening group and 3,420 of 29,790 (11.5%) in the usual-care group experienced an event (hazard ratio (HR), 0.93 (95% confidence interval (CI), 0.88 to 0.98; p = 0.010); number needed to invite at 6 years, 148 (95% CI, 80 to 986)). A total of 324 men (1.9%) in the invited-to-screening group and 491 (1.7%) in the usual-care group had an intracranial bleeding (HR, 1.17; 95% CI, 1.02 to 1.35; p = 0.029). Additionally, 994 (5.9%) in the invited-to-screening group and 1,722 (5.8%) in the usual-care group experienced severe gastrointestinal bleeding (HR, 1.02; 95% CI, 0.95 to 1.11; p = 0.583). No differences were found in mortality after cardiovascular surgery. The primary limitation of the study is that exclusive enrolment of men aged 65 to 74 renders the findings non-generalisable to women or men of other age groups. Conclusion In this comprehensive population-based cardiovascular screening and intervention program, we observed a reduction in the user-defined outcome, stroke and myocardial infarction, but entail a small increased risk of intracranial bleeding. Trial registration ISRCTN Registry number, ISRCTN12157806 https://www.isrctn.com/ISRCTN12157806.

In the original publication [...]

Background: Gaucher disease (GD) is a lysosomal storage disorder caused by mutations in the GBA1 gene, leading to β-glucocerebrosidase deficiency and glucosylceramide accumulation. Methods: We analyzed short- and long-term dynamics of lyso-glucosylceramide (lyso-Gb1) in a large cohort of GD patients undergoing enzyme replacement therapy (ERT). Results: Eight-years analysis of lyso-Gb1 revealed statistically insignificant variability in the biomarker across the years and relatively high individual variability in patients’ results. GD type 1 (GD1) patients exhibited higher variability compared to GD type 3 (GD3) patients (coefficients of variation: 34% and 23%, respectively; p-value = 0.0003). We also investigated the short-term response of the biomarker to enzyme replacement therapy (ERT), measuring lyso-Gb1 right before and 30 min after treatment administration. We tested 20 GD patients (16 GD1, 4 GD3) and observed a rapid and significant reduction in lyso-Gb1 levels (average decrease of 17%; p-value < 0.0001). This immediate response reaffirms the efficacy of ERT in reducing substrate accumulation in GD patients but, on the other hand, suggests the biomarker’s instability between the infusions. Conclusions: These findings underscore lyso-Gb1’s potential as a reliable biomarker for monitoring efficacy of treatment. However, individual variability and dry blood spot (DBS) testing limitations urge a further refinement in clinical application. Our study contributes valuable insights into GD patient management, emphasizing the evolving role of biomarkers in personalized medicine.

As world populations are ageing, more attention is given to the social and digital inclusion of older people. The level of ICT non-use among older adults in Lithuania is significantly higher than in Western European countries. In 2023, 29% of the Lithuanian population aged 65–74 had never used the Internet, while in most Western countries, this share varied between 2 and 8%. Insufficient research efforts in Eastern and Central Europe prompted this study to explore the barriers to ICT use in Lithuania based on qualitative semi-structured interviews with older users (N=36) and their facilitators (N=9). The difficulties revealed by the study are divided into three groups. First, the participants found it difficult to adjust to the technologies as a unique system (to understand its specific principles of functioning, to deal with information on English and technical language). Second, their psychological relationship with the unknown and complex subject have caused some problems, as they faced a spectrum of fears, insecurity, the shame of not knowing, the experience of one’s limitations, lack of patience. Third, changes that informants relate to old age like diminishing motivation to engage with innovations, learning difficulties, and bodily changes (sensitivity of fingers, weakening sight and memory) constituted additional barriers for older ICT users. To overcome the barriers, access to mentoring and consulting would be beneficial.

The purpose of this article is to highlight the critical importance of language generation today. In particular, language generation is explored from the following three aspects: multi-modality, multilinguality, which play crucial role for NLG community. We present the activities conducted within the Multi3Generation COST Action (CA18231), as well as current trends and future perspectives for multitask, multilingual and multimodal language generation.

The important thing for teachers is to solve conflicts with students correctly and effectively without damaging the relationship, losing the cooperation with students or disrupting educational process. Although there is a great concern about the way a teacher manages students' behaviour, there is very little relevant data concerning teacher-student conflict. The article aims at revealing the characteristics of conflict resolution between students and teachers from the students' point of view. To investigate the process of conflict between a teacher and a student, a case study method was used. Respondents were asked to recall a conflict occurring between them and a teacher during the school years, describe how the incident was handled, and the consequences of it. The number of respondents constituted 30 students. Students and teachers actually engage in a range of behaviours. In accordance with the theoretical framework, the four behavioural categories were grouped. Students reported that during the teacher-students conflict a full palette of strategies (dominating, integrating, accommodating and avoiding strategies) was used. Findings revealed that forcing was expressed by arguments, involving a third party and aggression. Avoiding was expressed by crying, avoiding the contact. Accommodating was expressed by pretending and giving in. Apologising, making a compromise, compensation, talking about the problem were examples of an integrating strategy. The results indicated that participants reported 28 behavioural reactions to a classroom conflict. Among them, 12 were those of teacher engagement, and 16 of student engagement. In line with the conglomerated conflict behaviour framework, students reported that both conflict parties (students and teachers) in the case of active student position engaged in more than one type of behaviour in response to a single incident. Understanding students' experience would allow teachers to better respond and manage students' reactions, as well as help teachers prevent behaviours such as aggression and promote other behaviours such as motivation.

Continuous agricultural activities lead to soil organic carbon (SOC) depletion, and agroecological intensification practices (i.e., reduced soil disturbance and crop diversification) have been suggested as strategies to increase SOC storage. The study aims to assess the effect of agroecological intensification levels (lower (T1) and highest (T2)) on the soil C pool and aggregate stability and validate the correlation between different variables compared to the control (lowest/none (T3), where agroecological intensification was not applied. The C-stock, soil microbial biomass carbon (SMB-C), SOC, water extractable organic carbon (WEOC) in bulk soil, fine and coarse soil aggregates, and water-stable aggregates (WSA) were measured during maximum nutrient uptake in plants under diversified agroecological practices across different environmental conditions (core sites: Italy (CS1), France (CS2), Denmark (CS4), Spain (CS5), Netherlands (CS6), Lithuania (CS7), Turkey (CS8), and Belgium (CS9)). The soil aggregate stability varied among the CSs and treatments. At sites CS7 and CS9, WSA was higher in T1 and T2 compared to the control; a similar trend was observed at other sites, except CS1. SMB-C differed among the core sites, with the lowest value obtained in CS5 (52.3 μg g−1) and the highest in CS6 (455.1 μg g−1). The highest average contents of SOC and WEOC were obtained in bulk soil at CS2 (3.1 % and 0.3 g kg−1 respectively). Positive and statistically significant (p < 0.001) correlations were detected among all variables tested with SOC in bulk soil and WSA. This study demonstrates the significance of agroecological practices in improving soil carbon stock and optimizing plant–soil–microbe interactions. [ABSTRACT FROM AUTHOR]