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Publication
Emergency Department Workflow Times of Intravenous Thrombolysis with Tenecteplase versus Alteplase in Acute Ischemic Stroke: A Prospective Cohort Study before and during the COVID-19 Pandemic
(2025) Guzmán, Matías; Lavados, Pablo; Cavada, Gabriel; Brunser, Alejandro M.; Olavarría, Verónica
Introduction: Tenecteplase (TNK) has demonstrated to be non-inferior to alteplase (ALT) for intravenous thrombolysis (IVT) in acute ischemic stroke (AIS). There are potential workflow benefits associated with TNK use, aiming to reduce patient length of stay in the emergency department. Our aim was to investigate whether the routine use of TNK during the COVID-19 pandemic influenced workflow times compared to historical use of ALT, while maintaining non-inferior clinical outcomes in a non-drip and ship scenario of a comprehensive stroke center. Methods: We included patients with AIS admitted from September 2019 to September 2022 and compared those treated with TNK during the COVID-19 pandemic to those treated with ALT in the period immediately before. We compared emergency department length of stay (EDLOS), door-to-needle time (DTN), door-to-groin puncture time (DTG), clinical and safety outcomes with adjusted general linear regression models. Results: 110 patients treated with TNK and 111 with ALT were included in this study. Mean EDLOS was 251 (SD = 164) min for TNK users versus 240 (SD = 148) min for ALT (p = 0.62). Mean DTN was 43 (SD = 25) min for TNK versus 46 (SD = 27) min for ALT users (p = 0.39). Mean DTN under 60 min was achieved in 86 (78.2%) patients and in 85 (76.5%) patients of the TNK and ALT groups, respectively (p = 1.0). DTN under 45 min was achieved in 65.4% and 58.6% (p = 0.65) of the TNK and ALT groups, respectively. DTG time was 114 (SD = 43) min for TNK versus 111 (58 = SD) min in the ALT group (p = 0.88). DTG under 90 min was achieved in 32% of the TNK group and 35% of the ALT group (p = 0.69). There were no differences in any of the clinical or safety outcomes between groups at 90 days. Conclusions: The adoption of TNK during COVID-19 pandemic did not result in a change in EDLOS, DTN, or DTG times when compared to ALT in this cohort. Safety and clinical outcomes were similar between groups. Probably a greater benefit could have been seen in a drip and ship thrombolysis setting. Further research is needed to assess the potential advantages of TNK in drip and ship scenarios of IVT.
Publication
Polygenic score analysis identifies distinct genetic risk profiles in Alzheimer’s disease comorbidities
(2025) Hernández, Carlos F.; Villaman, Camilo; Leu, Costin; Lal, Dennis; Mata, Ignacio; Klein, Andrés; Pérez-Palma, Eduardo
Alzheimer’s disease (AD) is usually accompanied by comorbidities such as type 2 diabetes (T2D), epilepsy, major depressive disorder (MDD), and migraine headaches (MH) that can significantly affect patient management and progression. As AD, these comorbidities have their own cumulative common genetic risk component that can be explored in a single individual through polygenic scores. Utilizing data from the UK Biobank, we investigated the correlation between polygenic scores (PGS) for these comorbidities and their actual presentation in AD patients. We show that individuals with higher PGS values showed an elevated risk of developing T2D (OR 2.1, p = 1.07 × 10−11) and epilepsy (OR 1.5, p = 0.0176). High T2D-PGS is also associated with an earlier AD onset in individuals at high genetic risk for AD (AD-PGS). In contrast, no significant genetic associations were found for MDD and MH. Our findings show distinct common genetic risk factors for T2D and epilepsy carried by AD patients that are associated with increased prevalence and earlier disease onset. These results highlight the contribution of common genetic variation to the broader clinical landscape of AD and will contribute to future tailored patient management strategies for individuals at high genetic risk.
Publication
Machine learning‑based identification of efficient and restrictive physiological subphenotypes in acute respiratory distress syndrome
(2025) Meza‑Fuentes, Gabriela; Delgado, Iris; Barbé, Mario; Sánchez‑Barraza, Ignacio; Retamal, Mauricio; López, René
Introduction Acute respiratory distress syndrome (ARDS) is a severe condition with high morbidity and mortality, characterized by significant clinical heterogeneity. This heterogeneity complicates treatment selection and patient inclusion in clinical trials. Therefore, the objective of this study is to identify physiological subphenotypes of ARDS using machine learning, and to determine ventilatory variables that can effectively discriminate between these sub‑phenotypes in a bedside setting with high performance, highlighting potential utility for future clinical stratification approaches. Methodology A retrospective cohort study was conducted using data from our ICU, covering admissions from 2017 to 2021. The study included 224 patients over 18 years of age diagnosed with ARDS according to the Berlin criteria and undergoing invasive mechanical ventilation (IMV). Data on physiological and ventilatory variables were collected during the first 24 h IMV. We applied machine learning techniques to categorize subphenotypes in ARDS patients. Initially, we employed the unsupervised Gaussian Mixture Classification Model approach to group patients into sub‑phenotypes. Subsequently, we applied supervised models such as XGBoost to perform root cause analysis, evaluate the classification of patients into these subgroups, and measure their performance. Results Our models identified two ARDS subphenotypes with significant clinical differences and significant outcomes. Subphenotype Efficient (n = 172) was characterized by lower mortality, lower clinical severity and presented a less restrictive pattern with better gas exchange compared to Subphenotype Restrictive (n = 52), which showed the opposite. The models demonstrated high performance with an area under the ROC curve of 0.94, sensitivity of 94.2% and specificity of 87.5%, in addition to an F1 score of 0.85. The most influential variables in the discrimination of subphenotypes were distension pressure, respiratory frequency and exhaled carbon dioxide volume. Conclusion This study presents an approach to improve subphenotype categorization in ARDS. The generation of clustering and prediction models by machine learning involving clinical, ventilatory mechanics, and gas exchange variables allowed for more accurate stratification of patients. These findings have the potential to optimize individualized treatment selection and improve clinical outcomes in patients with ARDS.
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Conocimientos sobre cuidados paliativos en internos de medicina de universidades chilenas: Un diagnóstico necesario
(2026) Riveros, Francisco; Faúndez, María; Rodríguez, Felipe; González, Sebastián; Cortés, Marcela
Introducción: Los cuidados paliativos son esenciales en la formación médica actual. Objetivo: Determinar conocimientos de los internos de medicina en universidades chilenas respecto a los cuidados paliativos. Metodología: Diseño convergente paralelo, descriptivo, transversal y multicéntrico. Se aplicó un cuestionario validado, evaluando dimensiones conceptuales, clínicas y legales. Se contó con la autorización de un comité de ética y los participantes firmaron consentimiento informado. Resultado: Se analizaron las respuestas de 346 internos. El 87% considera que los cuidados paliativos son esenciales en la atención médica. Existen brechas en el conocimiento específico: un porcentaje relevante asocia cuidados paliativos al final de la vida o hay dudas sobre el uso de morfina y adicción (11%). El 93% identifica que los cuidados paliativos no deben retrasarse. Discusión: Aunque existe una actitud positiva y un conocimiento conceptual general adecuado. Existen mitos y brechas de conocimiento técnico que sugieren la necesidad de fortalecer las competencias curriculares en cuidados paliativos. Conclusión: Los internos de medicina en Chile muestran actitud favorable y base conceptual adecuada en cuidados paliativos. Se requiere fortalecer la formación curricular y continua para garantizar una atención oportuna, integral y acorde a la legislación vigente. Introduction: Palliative care is essential in current medical education. Objective: To determine the knowledge of medical interns in Chilean universities regarding palliative care. Methodology: A convergent parallel, descriptive, cross-sectional, and multicenter design was used. A validated questionnaire was administered to assess conceptual, clinical, and legal dimensions. The study was approved by an ethics committee and the participants signed informed consent. Result: Responses from 346 interns were analyzed. Eighty-seven percent consider palliative care to be essential in medical care. There are gaps in specific knowledge: a significant percentage associates palliative care with end-of-life care, or there are doubts regarding the use of morphine and addiction (11%). 93% agree that palliative care should not be delayed. Discussion: Although there is a positive attitude and adequate general conceptual knowledge. There are myths and gaps in technical knowledge that suggest the need to strengthen palliative care competencies. Conclusion: Medical interns in Chile demonstrate a positive attitude and a solid conceptual foundation in palliative care. There is a need to strengthen both curricular and continuing education to ensure timely, comprehensive care that complies with current legislation.
Publication
Efficacy of an avocado-based Mediterranean diet on serum lipids for secondary prevention after ischemic stroke: a randomized phase 2 controlled pilot trial
(2025) Olavarría, Verónica V.; Campodónico, Paola R.; Vollrath, Valeska; Geldern, Paula von; Velásquez, Carolina; Pavez, Patricia; Valente, Barbara; Donoso, Pamela; Ginesta, Alexandra; Cavada, Gabriel; Mazzon, Enrico; Navia, Víctor; Guzmán, Matías; Brinck, Pablo; Gallardo, Andrés; Gonzalez, González; Lavados, Pablo
Background The impact of a healthy diet on the secondary prevention of ischemic stroke (IS) remains uncertain. Levels of low-density lipoprotein cholesterol (LDL-C) are inversely associated with the risk of IS recurrence. A Mediterranean diet (MeDi), consisting of a preference for fish/poultry, monosaturated fats from olive oil, fruit, vegetables, whole grains, legumes/nuts and limited red meats, animal fats and sweetened beverages, reduces metabolic syndrome, LDL-C levels and stroke risk. Avocados also reduce metabolic syndrome and LDL-C levels but are not part of the traditional MeDi diet. The effects of an avocado-based Mediterranean diet on LDL-C were investigated and compared to those of a low-fat diet in patients with previous IS. Methods The Avocado-Based Mediterranean Diet on Serum Lipids for Secondary Prevention after Ischemic Stroke (ADD-SPISE) was a prospective, randomized, open-label, blinded outcome assessment, phase 2, clinical trial. The participants were adults with an IS in the previous month who were randomly assigned at a 1:1 ratio to a MeDi or a low-fat diet for three months. Outcome assessors of laboratory results and data analysts were masked. The primary outcome was the mean difference in LDL-C between groups at 90 days, adjusted by statin use. Safety, feasibility and acceptability (assessed through a 14-item questionnaire administered to all patients who completed the follow-up) were also evaluated. Results From August 2018 to October 2022, 200 participants were enrolled (97 randomized to the low-fat diet and 103 to the MeDi), with 189 (94.5%) completing the study. There were no significant differences in LDL-C levels between the MeDi group and the low-fat group at 90 days: 66.5 mg/dL (95% confidence interval [CI] 59.6, 73.4) in the MeDi group and 69.9 mg/dL (62.6, 77.2) in the low-fat group at the end of follow-up. The adjusted difference was − 3.4 mg/dL (-13.4, -6.62); P = 0.50. The intervention group showed significant improvements in Mediterranean diet adherence (P < 0.01). Moreover, no significant differences in adverse events were observed between the groups. Conclusion Compared with a low-fat diet, the avocado-based MeDi did not significantly lower LDL-C in IS patients after three months. The intervention was safe, feasible, and well accepted. Larger trials should establish whether longer dietary interventions could yield clinically significant benefits in these patients. The study is registered under ADD-SPISE at www.clinicaltrials.gov. Identifier: NCT03524742.
Publication
Navigating disruption in the PID landscape: embracing opportunities and anticipating threats in the next ten years
(2025) Mamede, Lúcia; Cantenys, Roser; Van Coillie, Samya; Prévot, Johan; Sánchez, Silvia; Poli Harlowe, María Cecilia; Barasa, Anne; Schuller, Björn; Hendel, Ayal; Garcelon, Nicolas; Boersma, Cornelis; Lee, Pamela; Booth, Claire; Notarangelo, Luigi; Drabwell, Jose; Rider, Nicholas; Staal, Frank; O Burns, Siobhan; Van Hagen, Martin; Pergent, Martine; Rivière, Jacques; Mahlaoui, Nizar
Introduction: The International Patient Organisation for Primary Immunodeficiencies (IPOPI) held its third edition of the Global Multi-Stakeholders' Summit, gathering key primary immunodeficiencies (PID) stakeholders and experts to discuss and foment global collaboration. Methods: This edition focused on the impact of genomic medicine in PID treatment, the role of digital health, including artificial intelligence, in PID care, and how to anticipate and minimise risks to ensure optimal patient access to care. Results: These discussions aimed to examine current hurdles and brainstorm feasible solutions and priorities for the PID community in these areas in the next ten years. Discussion: These discussions led to recommendations for comprehensive approaches to care and access to treatment for PID patients, suggesting actions that will bring the community closer to treatments based on real-world evidence and adjusted to patient's needs. To accomplish this, collaboration between academia, industry, regulatory authorities, and patients is crucial.
Publication
Characterizing adolescent vaccination in publicly funded national immunization programs in Latin America and the Caribbean: A review of the literature
(2025) Rojas, Monica; Lución, Maria; Becker, Ricardo; Luevanos, Antonio; Gutierrez, Ivan; Estripeaut, Dora; Schilling Redlich, Andrea; Webster, Jessica; Perez, Maria; Hirata, Luciana; Orengo, Juan; Parellada, Cintia
This review aimed to characterize adolescent vaccination schedules in publicly funded national immunization programs in Latin America and the Caribbean. The initial review identified vaccine type, target age and gender, dose schedule, and vaccination coverage rate (VCR) across 50 countries/territories in the region. A systematic review from January 2010-October 2023 was then conducted to identify primary data collection studies reporting VCRs. Overall, 42 webpages and 23 primary studies were identified. Among 47 countries/territories with ≥1 vaccine for adolescent immunization, human papillomavirus (HPV) vaccine was included in 45, tetanus component vaccines in 43, and meningococcal vaccines in 10. Catch-up vaccination for hepatitis B in 17, and yellow fever in all 13 endemic countries/territories. VCRs were primarily available for HPV. The findings of this review underscore the need to prioritize adolescent vaccination, improve accessibility, and strengthen tracking infrastructure to ensure comprehensive protection of this age group across the region.
Publication
BugBuster: a novel automatic and reproducible workflow for metagenomic data analysis
(2025) Fuentes, Francisco; Curiqueo, Carolina; Araos Bralic, Rafael Ignacio; Ugalde, Juan
Phages are the most abundant biological entities on the planet, and they play an important role in controlling density, diversity, and network interactions among bacterial communities through predation and gene transfer. To date, a variety of bacteriophage identification tools have been developed that differ in the phage mining strategies used, input files requested, and results produced. However, new users attempting bacteriophage analysis can struggle to select the best methods and interpret the variety of results produced. Here, we present MetaPhage, a comprehensive reads-to-report pipeline that streamlines the use of multiple phage miners and generates an exhaustive report. The report both summarizes and visualizes the key findings and enables further exploration of key results via interactive filterable tables. The pipeline is implemented in Nextflow, a widely adopted workflow manager that enables an optimized parallelization of tasks in different locations, from local server to the cloud; this ensures reproducible results from containerized packages. MetaPhage is designed to enable scalability and reproducibility; also, it can be easily expanded to include new miners and methods as they are developed in this continuously growing field. MetaPhage is freely available under a GPL-3.0 license at https://github.com/MattiaPandolfoVR/MetaPhage. IMPORTANCE Bacteriophages (viruses that infect bacteria) are the most abundant biological entities on earth and are increasingly studied as members of the resident microbiota community in many environments, from oceans to soils and the human gut. Their identification is of great importance to better understand complex bacterial dynamics and microbial ecosystem function. A variety of metagenome bacteriophage identification tools have been developed that differ in the phage mining strategies used, input files requested, and results produced. To facilitate the management and the execution of such a complex workflow, we developed MetaPhage (MP), a comprehensive reads-to-report pipeline that streamlines the use of multiple phage miners and generates an exhaustive report. The pipeline is implemented in Nextflow, a widely adopted workflow manager that enables an optimized parallelization of tasks. MetaPhage is designed to enable scalability and reproducibility and offers an installation-free, dependency-free, and conflict-free workflow execution.
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Evaluación preoperatoria en anestesia: Revisión de la Guía 2017 de la Sociedad de Anestesiología de Chile
(2026) Acuña, María; Alarcón, Asunción; Hidalgo, Valeria; Norero, Sofía
Introducción: Las guías de evaluación preanestésica estandarizan el manejo perioperatorio para disminuir la morbimortalidad. En 2017, la Sociedad de Anestesiología de Chile (SACh) publicó sus recomendaciones nacionales. Sin embargo, la constante evolución de la evidencia científica exige analizar su vigencia frente a las nuevas publicaciones internacionales. Objetivo: Describir los pilares de la guía SACh 2017 (momento de evaluación, historia clínica, examen físico y exámenes complementarios) y analizar los aportes de la literatura actualizada en la planificación anestésica. Metodología: Revisión narrativa desarrollada en tres etapas: categorización de los ejes temáticos de la guía SACh 2017, análisis de su bibliografía de respaldo y búsqueda bibliográfica en bases de datos indexadas publicadas en el período 2018–2026. Resultado: La evaluación se sustenta en anamnesis detallada, examen físico dirigido y exámenes complementarios selectivos. Se destaca la importancia de realizar la valoración con antelación suficiente para permitir la optimización de patologías y hábitos. El examen físico debe ser centrado en el área cardiopulmonar, y agregar otra en caso de síntomas. La indicación de pruebas de laboratorio e imágenes no debe realizarse de manera rutinaria, sino basarse estrictamente en las comorbilidades del paciente y la invasividad del procedimiento, garantizando así la costo-efectividad del sistema de salud. La nueva evidencia introduce actualizaciones críticas, como la telemedicina, protocolos de suspensión de agonistas GLP-1 y SGLT2, y nuevos biomarcadores. Conclusión: La evaluación preoperatoria es un acto médico crítico y personalizado. Los fundamentos centrales de la guía SACh 2017 continúan vigentes; no obstante, es indispensable integrar los nuevos consensos. Introduction: Preoperative evaluation guidelines standardize perioperative management to reduce morbidity and mortality. In 2017, the Chilean Society of Anesthesiology (SACh) published its national recommendations. However, the continuous evolution of scientific evidence requires an analysis of their current validity in light of recent international publications. Objective: To describe the core pillars of the 2017 SACh guidelines (timing of evaluation, medical history, physical examination, and complementary tests) and to analyze the contributions of updated literature to anesthetic planning. Methodology: A narrative review conducted in three stages: categorization of the main thematic axes of the 2017 SACh guidelines, analysis of its supporting literature, and a literature search in indexed databases published between 2018 and 2026. Result: Preoperative evaluation relies on a detailed medical history, a targeted physical examination, and selective complementary testing. Early evaluation is essential to allow time for the optimization of medical conditions and lifestyle habits. The physical examination should focus on the cardiopulmonary system, adding other systems if symptoms are present. Laboratory tests and imaging should not be requested routinely; instead, they must be strictly based on patient comorbidities and procedural invasiveness to ensure healthcare system cost- effectiveness. Recent evidence introduces critical updates, such as telemedicine, discontinuation protocols for GLP-1 receptor agonists and SGLT2 inhibitors, and new biomarkers. Conclusion: Preoperative evaluation is a critical and personalized medical act. While the core principles of the 2017 SACh guidelines remain valid, integrating these new consensus guidelines is essential.
Publication
Early Integration of Clinical Simulation in Medical Students: A Progressive Experience Using SimZones
(2025) Medel Rodríguez, Karen Alejandra; Benaglio, Carla; Ortega Sepúlveda, José Ignacio
BackgroundEarly clinical training in undergraduate medical education often occurs in unstructured environments, limiting student participation and competency development. The SimZones framework offers a progressive approach to simulation-based education, yet evidence for its implementation in first-year medical students remains limited. ObjectiveTo describe the design, implementation, and outcomes of a structured clinical simulation program for first-year medical students using the SimZones framework. MethodsA descriptive study with mixed-methods analysis was conducted in 2024 with 116 first-year medical students at a Chilean medical school. Students participated in structured Zone 1 simulation activities throughout the academic year in small groups (5-6 students), using 12 validated assessment instruments developed and validated by a multidisciplinary expert panel comprising 202 specific procedural steps including 30 critical safety steps. Activities focused on technical, communication, and attitudinal skills with study guides, pre-tests, and formative rubrics. The program culminated with a Zone 2 integrative activity simulating primary care consultations using standardized patients, clinical documentation, and faculty debriefing using the Plus/Delta model. Performance was assessed using standardized rubrics, and qualitative observations were analyzed thematically. ResultsAll 116 students completed the program. High performance was observed in attitudinal competencies (≥97%) and communication domains (≥89%), while technical skills showed variable achievement rates (range 63%-78%). Qualitative analysis identified strengths in empathy, professionalism, and teamwork, with areas for improvement in procedural technique, interview sequencing, and time management. ConclusionsEarly progressive simulation using the SimZones framework effectively develops foundational competencies in first-year medical students. The structured approach, combining deliberate practice with formative assessment and guided debriefing, supports competency-based medical education objectives while identifying specific areas requiring additional reinforcement in technical skill training.
Publication
Enfoque clínico del paciente con síndrome de Stevens-Johnson y necrólisis epidérmica tóxica: Parte II
(2025) Lobos, Nelson; Valenzuela, Fernando; López, Valeska; Alfaro-Fierro, Valeria; Palisson, Francis
El SSJ, SSJ/NET y NET son reacciones adversas graves e infrecuentes a medicamentos, que representan distintas manifestaciones de una misma enfermedad caracterizada por el denudamiento de piel y mucosas. En la literatura se han reportado resultados con corticoides sistémicos, inmunoglobulina endovenosa, ciclosporina, inhibidores de TNF-alfa, plasmaféresis e inhibidores de la Janus quinasa. Objetivo: Ser una puesta al día en el manejo integral del SJS/NET. Para aumentar la sobrevida, disminuir la aparición de secuelas y mejorar la calidad de vida. Métodos: Se realizó una búsqueda sistemática entre septiembre de 2024 y abril de 2025 en bases de datos indexadas y literatura gris, seleccionando 55 artículos y 3 guías clínicas relacionadas. Resultados: El diagnóstico de SSJ/NET debe plantearse frente a fiebre, linfopenia, lesiones cutáneas atípicas y signo de Nikolsky, siendo prioritario suspender de inmediato los medicamentos sospechosos y realizar biopsia cutánea. Se recomienda aplicar escalas que estimen mortalidad, tales como SCORTEN, ABCD-10 y CRISTEN. Hospitalizar en UCI o unidad de quemados bajo estrictas medidas de soporte vital y aislamiento. El manejo debe ser multidisciplinario e implica medidas de soporte, como reposición de fluidos, control térmico, nutrición, analgesia, tromboprofilaxis y prevención de infecciones. El tratamiento sistémico se recomienda siempre, según respuesta y evolución puede incluir corticoides, inmunoglobulina, ciclosporina, inhibidores de TNF-alfa, plasmaféresis, o en casos excepcionales JAKi. Se sugiere seguimiento durante el primer año para controlar posibles secuelas cutáneas, mucosas, visuales y psicológicas. Conclusiones: Este estudio aporta recomendaciones prácticas y actualizadas para un diagnóstico precoz, priorizar medidas de soporte vital y la elección de alternativas terapéuticas, con el fin de mejorar la sobrevida y la calidad de vida de los pacientes. El tratamiento sistémico precoz es fundamental para mejorar el pronóstico de los pacientes.
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Dupilumab en el tratamiento de pacientes pediátricos con dermatitis atópica moderada a severa en Chile. Serie de 10 casos clínicos
(2025) Fuentes Escobar, Ignacia; Caussade, Marie-Chantal; Lecaros Cornejo, Cristóbal; Hasbún Zegpi, María Trinidad
La dermatitis atópica (DA) es una enfermedad inflamatoria crónica, de curso variable, que se presenta con alta frecuencia en la edad pediátrica. Las terapias dirigidas, como los anticuerpos monoclonales (mAb) o los inhibidores de la enzima Janus quinasa, representan nuevas alternativas terapéuticas. Dupilumab, un anticuerpo monoclonal, fue el primer fármaco aprobado por la Administración de Alimentos y Medicamentos (FDA) de los Estados Unidos para el tratamiento de la DA severa. Objetivo: Describir una serie de casos de pacientes menores de 12 años con DA moderada a severa tratados con dupilumab, y aportar consideraciones prácticas para su uso en este grupo etario. Métodos: Estudio observacional, retrospectivo, descriptivo y multicéntrico que incluyó pacientes pediátricos con DA moderada a severa tratados con dupilumab. Se recopilaron variables demográficas, clínicas y de respuesta al tratamiento. Resultados: Se incluyeron 10 pacientes con DA moderada a severa, con un puntaje EASI inicial promedio de 24,4 (DE 12), y antecedente de fracaso a tratamientos previos. A los 6 meses de iniciado el tratamiento con dupilumab, se observó una reducción media del puntaje EASI de 13,5 puntos [rango intercuartílico: 5,9–25,8], junto con una disminución progresiva del puntaje individual. El tiempo de seguimiento varió entre 12 y 24 meses. Los efectos adversos observados fueron menores y no motivaron la suspensión del tratamiento. Conclusiones: Los resultados de este estudio son concordantes con la literatura existente, que respalda la eficacia y el perfil de seguridad de dupilumab en pacientes menores de 12 años con DA moderada a severa. Además, este trabajo entrega orientación práctica para su uso en la práctica clínica.
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Complicaciones del uso del balón gástrico como terapia para control de peso
(2025) Camus, Cristobal; Radic, Nicolás; Campos, Oscar; Urnía, Nicolás; Labra, Andrés; Schiappacasse, Giancarlo
El balón intragástrico es una opción no quirúrgica para la pérdida de peso, sin embargo, existen complicaciones que pueden ser leves, como náuseas y dolor epigástrico, o graves, incluyendo perforación gástrica, obstrucción intestinal y pancreatitis. Factores de riesgo, como cirugías gástricas previas, uso prolongado del balón e incluso el no utilizar inhibidores de bomba de protones, aumentan la probabilidad de complicaciones serias. El diagnóstico temprano es fundamental y la tomografía computada es una herramienta muy útil para hacerlo. El pronóstico varía según la presencia de infecciones y comorbilidades. La experiencia médica y el seguimiento del paciente son clave para minimizar riesgos. Esta revisión narrativa se fundamenta en la literatura científica que encontramos sobre las complicaciones del balón gástrico como tratamiento para el control del peso. Para ilustrar las diversas manifestaciones clínicas y hallazgos imagenológicos documentados, se presentan imágenes de casos observados en nuestra institución que evidencian dichas complicaciones.
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Severe acneiform eruption associated with TNFRSF13B mutation: Clinical response to adalimumab
(2025) Joo Hu, Ka Wei Katty; Karsulovic, Claudio; Hojman, Lia
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Tobacco imagery in prime-time television in Spain: A content analysis
(2025) Peruga, Armando; Tigova, Olena; Feliu, Ariadna; Carnicer, Dolors; Anton, Laura; Bosch, Félix; Rey, Juan; Salto, Esteve; Fernández, Esteve; Martínez, Cristina
Introduction: Exposure to tobacco content in media among youth is a well-established risk factor for smoking initiation and continued use. This study assessed the prevalence and nature of tobacco imagery on Spanish prime-time television (TV) programming and its associations with program characteristics: genre, production nationality, and broadcast timing. Methods: A content analysis of 63959 minutes of TV programming in 2021, excluding advertisements and trailers, across 18 broadcast channels examined the presence of tobacco imagery: actual tobacco use, tobacco cultural cues, smoking ban violations, tobacco brand appearances, or any of these. Results: The analysis revealed that 2.4% of the TV programming time contained at least one instance of tobacco imagery, resulting in 8.5 million impressions for viewers aged 4-24 years. Feature films had the highest prevalence of tobacco-related content (adjusted prevalence ratio, APR=11.9; 95% CI: 9.5-14.9). Tobacco-related content appeared more frequently outside designated children's protection hours (PR=0.7; 95% CI: 0.6-0.80). However, its presence within the designated children's protection schedule remains a significant concern, generating 15.6 million tobacco impressions for young viewers. Conclusions: The seemingly modest content level of tobacco imagery (2.4%) translates into a substantial number of impressions for young viewers aged 4-24 years, including during the designated children's protection schedule. Reducing tobacco imagery in films and TV series represents a promising strategy for curbing youth smoking. However, the current reliance on youth protection schedules is inadequate. To better protect children from tobacco imagery, policies should mandate strong anti-tobacco disclaimers preceding programs featuring tobacco and certificates of No Pay-off for tobacco portrayals.
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Exploring the Impact of Mitonuclear Discordance on Disease in Latin American Admixed Populations
(2025) Ruiz, Mauricio; Böhme, Daniela; Repetto, Gabriela; Rebolledo, Boris; Rebolledo Jaramillo, Boris
Background. The coevolution of nuclear and mitochondrial genomes has guaranteed mitochondrial function for millions of years. The introduction of European (EUR) and African (AFR) genomes into the Ameridian continent during the Columbus exchange in Latin America created an opportunity to naturally test different combinations of nuclear and mitochondrial genomes. However, the impact of potential "mitonuclear discordance" (MND, differences in ancestries) has not been evaluated in Latin American admixed individuals (AMR) affected with developmental disorders, even though MND alters mitochondrial function and reduces viability in other organisms. Methods. To characterize MND in healthy and affected AMR individuals, we used AMR genotype data from the 1000 Genomes Project (n = 385), two cohorts of 22q.11 deletion syndrome patients 22qDS-ARG (n = 26) and 22qDS-CHL (n = 58), and a cohort of patients with multiple congenital anomalies and/or neurodevelopmental disorders (DECIPHERD, n = 170). Based on their importance to mitochondrial function, genes were divided into all mitonuclear genes (n = 1035), high-mt (n = 167), low-mt (n = 793), or OXPHOS (n = 169). We calculated local ancestry using FLARE and estimated MND as the fraction of nuclear mitochondrial genes ancestry not matching the mtDNA ancestry and ∆MND as (MNDoffspring-MNDmother)/MNDmother. Results. Generally, MND showed distinctive population and haplogroup distributions (ANOVA p < 0.05), with haplogroup D showing the lowest MND of 0.49 ± 0.17 (mean ± s.d.). MND was significantly lower in 22qDS-ARG patients at 0.43 ± 0.24 and DECIPHERD patients at 0.56 ± 0.12 compared to healthy individuals at 0.60 ± 0.09 (ANOVA p < 0.05). OXPHOS and high-mt showed the same trend, but with greater differences between healthy and affected individuals. Conclusions. MND seems to inform population history and constraint among affected individuals, especially for OXPHOS and high-mt genes.
Publication
NLC-Based Rifampicin Delivery System: Development and Characterization for Improved Drug Performance Against Staphylococcus aureus
(2025) Carrasco, Javiera; Sandoval, Felipe; Schuh, Christina; Lagos, Carlos; Morales, Javier; Arriagada, Francisco; Ortiz, Andrea
Background/Objectives: Rifampicin is a typical antibiotic used for the treatment of Staphylococcus aureus (S. aureus) infections; however, its clinical utility is limited by poor aqueous solubility, chemical instability, and increasing bacterial resistance. Nanostructured lipid carriers (NLCs) offer a promising strategy to improve drug solubility, stability, and antimicrobial performance. Methods: In this study, rifampicin-loaded NLC (NLC-RIF) was developed using a hot homogenization with a low energy method and characterized in terms of particle size, polydispersity index, zeta potential, encapsulation efficiency, colloidal stability, and drug loading. Results: In vitro release studies under sink conditions demonstrated a biphasic release pattern, best described by the Korsmeyer-Peppas model, suggesting a combination of diffusion and matrix erosion mechanisms. Antimicrobial activity against S. aureus revealed a substantial increase in potency for NLC-RIF, with an IC50 of 0.46 ng/mL, approximately threefold lower than that of free rifampicin. Cytotoxicity assays in HepG2 cells confirmed over 90% cell viability across all tested concentrations. Conclusions: These findings highlight the potential of NLC-RIF as a biocompatible and effective nanocarrier system for enhancing rifampicin delivery and antibacterial activity.
Publication
Norma técnica de prevención de transmisión vertical de hepatitis B. 2022
(2022) González, Fernando; Contreras, Patricia; Peña, Andrea; Izquierdo, Giannina; Zamora, Francisco; Zapata, Rodrigo; Muñoz, María; Peña, Andrea; Jara, Ana; Torres, Claudio; Alicia, Ribes; Torrealba, Paulina
La infección por el virus de la hepatitis B (VHB) es un problema de gran impacto en la salud pública en el mundo1. Aproximadamente un tercio de la población mundial ha estado expuesta al virus y entre 250 a 290 millones de personas tienen infección crónica por VHB (persistencia de HBsAg por al menos 6 meses). La Organización Mundial de la Salud estimó para el año 2019 aproximadamente 820.000 defunciones, debido a complicaciones del VHB como cirrosis o carcinoma hepatocelular2.
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Betulinic Acid ω-Triphenylphosphonium Alkyl Esters: Antiproliferative Activities and In Silico Pharmacokinetic Profiles
(2025) Suárez, Cristian; Duarte, Claudia; Gajardo, Javier; Salgado, Paola; Salas, Julio; Cassels, Bruce; Theoduloz, Cristina; Jara, José; Fuentes, Sebastián; Campodónico, Paola; Soto, Jorge; Catalán, Mabel
Betulinic acid (BA) and some derivatives are well-known antiproliferative compounds. Literature precedents suggest that incorporating triphenylphosphonium (TPP+) salts on this triterpenoid scaffold enhances its biological activity. In the present study, we carried out a simple synthesis of C-28 ester derivatives of this triterpenoid conjugated with TPP+ bromide salts through 4- to 6-carbon chains via nucleophilic substitution of the corresponding ω-TPP+bromoalkanes. Tests for antiproliferative activity in nine cancer cell lines and normal human fibroblasts showed that TPP+ incorporation enhanced the potency of BA by more than an order of magnitude, up to 100-fold. BA-C4-TPP+Br-, with a four-carbon chain separating the TPP+ moiety from the BA, showed remarkable antiproliferative effects, sometimes more potent than the reference drug (Etoposide). This compound exhibited the strongest mitochondrial uncoupling effect in human cancer cells. No significant LDH release was noted in colorectal carcinoma cells at low micromolar concentrations of BA-C4-TPP+Br-, and sub-micromolar concentrations were sufficient for inducing apoptosis. The in silico prediction of pharmacokinetic properties suggested high oral absorption (88%), as well as a non-inhibitor and non-substrate profile vs. cytochrome isoenzymes. These results point to this compound as a promising lead for the development of novel anticancer drugs.
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Antimicrobial Resistance in the Aconcagua River, Chile: Prevalence and Characterization of Resistant Bacteria in a Watershed Under High Anthropogenic Contamination Pressure
(2025) González, Nicolás; Lira, Diego; Covarrubia, Richard; Plaza, Johan; Munita, Jose M.; Carter, Mauricio; Olivares, Jorge
Background: Antimicrobial resistance (AMR) is a growing global health concern, driven in part by the environmental release of antimicrobial-resistant bacteria (ARB) and antimicrobial resistance genes (ARGs). Aquatic systems, particularly those exposed to urban, agricultural, and industrial activity, are recognized as hotspots for AMR evolution and transmission. In Chile, the Aconcagua River-subject to multiple anthropogenic pressures-offers a representative model for studying the environmental dimensions of AMR. Methods: Thirteen surface water samples were collected along the Aconcagua River basin in a single-day campaign to avoid temporal bias. Samples were filtered through 0.22 μm membranes and cultured on MacConkey agar, either unsupplemented or supplemented with ceftazidime (CAZ) or ciprofloxacin (CIP). Isolates were purified and identified using MALDI-TOF mass spectrometry. Antibiotic susceptibility was evaluated using the Kirby-Bauer disk diffusion method in accordance with CLSI guidelines. Carbapenemase activity was assessed using the Blue-Carba test, and PCR was employed for the detection of the blaVIM, blaKPC, blaNDM, and blaIMP genes. Results: A total of 104 bacterial morphotypes were isolated; 80 were identified at the species level, 5 were identified at the genus level, and 19 could not be taxonomically assigned using MALDI-TOF. Pseudomonas (40 isolates) and Aeromonas (25) were the predominant genera. No growth was observed on CIP plates, while 24 isolates were recovered from CAZ-supplemented media, 87.5% of which were resistant to aztreonam. Five isolates exhibited resistance to carbapenems; two tested positive for carbapenemase activity and carried the blaVIM gene. Conclusions: Our results confirm the presence of clinically significant resistance mechanisms, including blaVIM, in environmental Pseudomonas spp. from the Aconcagua River. These findings highlight the need for environmental AMR surveillance and reinforce the importance of adopting a One Health approach to antimicrobial stewardship and wastewater regulation.