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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.
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.
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.
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.
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.
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.
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.
Severe acneiform eruption associated with TNFRSF13B mutation: Clinical response to adalimumab
(2025) Joo Hu, Ka Wei Katty; Karsulovic, Claudio; Hojman, Lia
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.
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.
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.
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.
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.
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.
Conserved missense variant pathogenicity and correlated phenotypes across paralogous genes
(2025) Brünger, Tobias; Ivaniuk, Alina; Pérez Palma, Eduardo; Montanucci, Ludovica; Cohen, Stacey; Smith, Lacey; Parthasarathy, Shridhar; Helbig, Ingo; Nothnagel, Michael; May, Patrick; Lal, Dennis
Background: The majority of missense variants in clinical genetic tests are classified as variants of uncertain significance. Prior research shows that the deleterious effects and the subsequent molecular consequences of variants are often conserved among paralogous protein sequences within a gene family. Here, we systematically quantify on an exome-wide scale whether the existence of pathogenic variants in paralogous genes at a conserved position can serve as evidence for the pathogenicity of a new variant. For the gene family of voltage-gated sodium channels, where variants and expert-curated clinical phenotypes are available, we also assess whether phenotype patterns of multiple disorders for each gene are conserved across variant positions within the gene family.
Results: Mapping 590,000 pathogenic and 1.9 million population variants onto 9928 genes grouped into 2054 paralogous families increases the number of residues with classifiable evidence 5.1-fold compared with gene-specific data alone. The presence of a pathogenic variant in a paralogous gene is associated with a positive likelihood ratio of 13.0 for variant pathogenicity. Across ten genes encoding voltage-gated sodium channels and 22 expert-curated disorders, we identify cross-paralog correlated phenotypes based on 3D structure spatial position. For example, multiple established loss-of-function related disorders across SCN1A, SCN2A, SCN5A, and SCN8A show overlapping spatial variant clusters. Finally, we show that phenotype integration in paralog variant selection improves variant classification.
Conclusion: Conserved pathogenic missense variants in paralogous genes provide robust, quantifiable support for clinical variant interpretation, and phenotype-informed mapping further improves predictions.
Long-term effects of COVID-19 in patients with primary immunodeficiency: An IPOPI worldwide survey
(2025) Van Leeuwen, Leanne; Van Coillie, Samya; Prévot, Johan; Drabwell, Jose; Mahlaoui, Nizar; Sánchez-Ramón, Silvia; Poli Harlowe, María Cecilia; Meyts, Isabelle; Ali, Adli; Lowe, David; Dalm, Virgil; Pergent, Martine
Background: During the coronavirus disease 2019 (COVID-19) pandemic, many individuals developed persistent symptoms after COVID-19. The data on these long-term effects in the primary immunodeficiency (PID) community are limited.
Objective: This study aimed to understand long-term symptoms after COVID-19 in patients with PID, focusing on prevalence, risk factors, viral persistence, and the impact of COVID-19 on their health-related quality of life (HR-QoL).
Methods: A global, multilingual web-based survey was conducted by the International Patient Organization for Primary Immunodeficiencies between July and October 2023. Self-reported data on demographics, PID diagnosis, comorbidities, COVID-19, and HR-QoL were collected using the EuroQol 5-Dimensions 5-Level (EQ-5D-5L) survey and analyzed.
Results: Of the 1160 respondents, 25% reported persistent symptoms after COVID-19. Common symptoms included fatigue, headache, and nasal symptoms. Compared with those respondents without persistent symptoms, those with persistent symptoms after COVID-19 reported a significantly higher prevalence of symptoms across all categories-systemic, pain, cardiopulmonary, gastrointestinal, neurologic, psychological, neurocognitive, and others-except for upper respiratory tract symptoms. Independent risk factors for development of persistent symptoms included female sex, asthma, neurologic diseases, and predominantly antibody deficiency other than common variable immunodeficiency or agammaglobulinemia. In 30% of patients with persistent symptoms, viral clearance was not achieved within 1 month. During the pandemic, HR-QoL declined across all PID categories-even in those without COVID-19, but especially in those with a symptom duration of more than 6 months.
Conclusion: Persistent symptoms after COVID-19 are prevalent among patients with PID, with various risk factors identified. The COVID-19 pandemic had a considerable impact on the HR-QoL of patients with PID regardless of COVID-19 status.
Case-fatality of acute ischemic stroke in stroke units of Latin American hospitals
(2025) Vences, Miguel; Barboza, Miguel; Carbonera, Leonardo; Failoc, Virgilio; Rosales, Julieta; Amaya, Pablo; Lavados, Pablo; FAICAM Registry Group
Background and purpose: The Case-fatality of acute ischemic stroke in stroke units of Latin American hospitals is a multicenter registry from various stroke centers in Latin America, exploring demographic, clinical, imaging, and functional outcomes in acute ischemic stroke (AIS) patients, with the intention of determining case-fatality rates (in-hospital, 30 and 90 days follow up) and analyzing associated risk factors.
Methods: We conducted a retrospective cohort study using data from hospitalized AIS patients over 18 years of age, collected from 27 centers in 11 Latin American countries between January 1 and December 31, 2022. The effect size was estimated using the hazard ratio (HR) and 95 % confidence intervals (95 % CI) through Cox regression models to assess the association between time to 30-day fatality event and covariates.
Results: A total of 2,997 patients were included. The mean age was 68.7 years and 48.1 % were women. In-hospital case-fatality was 9.42 %, 277 patients (10.2 %) died within 30 days, and 90-day case-fatality was relatively close at 353 patients (13.3 %). Complications were reported in 31.3 % of cases, most frequently infections (18.5 %). Age over 75 years (HRa=2.28), hyperglycemia (HRa=1.28), baseline status (HRa=1.61), stroke severity according to NIHSS >26 (HRa=6.11) and the presence of neurological complications (HRa=3.2) were risk factors for 30-day follow up case-fatality in these patients.
Conclusion: AIS patients in Latin America stroke centers had an in-hospital case-fatality of 9.42 % and the 30-day case-fatality was 10.2 %. Older age, hyperglycemia, baseline status, stroke severity and neurological complications were the strongest predictors of early case-fatality. The findings underscore the need to optimize stroke management protocols in the region.
Colonization with antibiotic resistant bacteria in communities and hospitals across six countries, including Bangladesh, Botswana, Chile, Guatemala, India, and Kenya
(2025) Parra, Gemma; Lautenbach, Ebbing; Mosepele, Mosepele; Mannathoko, Naledi; Gross, Robert; Call, Douglas; Ramay, Brooke; Omulo, Sylvia; Girish, C P; Bhatnagar, Tarun; Chowdhury, Fahmida; Syeda Mah-E-Muneer; Araos Bralic, Rafael Ignacio; Munita, Jose M.; Acevedo, Johanna; Mahon, Garrett; Smith, Rachel; Styczynski, Ashley
The recognized burden of antimicrobial resistance (AR) is greatest in low- and middle-income countries (LMICs), but limitations in surveillance preclude accurate estimates of AR. We aimed to evaluate colonization in communities and hospitals across six LMICs for two clinically-important pathogens: extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) and carbapenem-resistant Enterobacterales (CRE). Participants in hospitals and communities provided rectal swabs or stool samples for ESCrE and CRE identification. Isolates recovered from selective agars underwent confirmatory identification and antibiotic susceptibility testing (AST) using Vitek® 2, MALDI-TOF, and/or disc diffusion testing. ESCrE and CRE were defined based on established breakpoints of phenotypic resistance to third-generation cephalosporins and carbapenems, respectively, to calculate prevalence of colonization. Community prevalence estimates were weighted to account for sampling design differences. A total of 10,139 participants across the 6 countries provided samples; 63% were females with a median age of 35 years (range: 0-99). Colonization with ESCrE in hospitals was high in all sites (range 34-84%). In communities, ESCrE colonization ranged from 22 to 77%. Prevalence of CRE colonization in hospitals ranged from 7 to 36% and in communities ranged from < 1 to 14%. These findings reveal a high burden of AR colonization in LMICs in both communities and hospitals. Cost-effective strategies to reduce AR colonization burden are needed in LMICs.
HSV-1 alters lipid metabolism and induces lipid droplet accumulation in functionally impaired mouse dendritic cells
(2025) Farías, Mónica; Cancino, Felipe; Navarro, Areli; Duarte, Luisa; Soto, Abel; Tognarelli, Eduardo; Ramm, Maximiliano; Alarcón, Bárbara; Cordero, José; San Martín, Sergio; Agurto, Cristian; Retamal, Angello; Riedel, Claudia; Barrera, Nelson; Bustamante, Luis; Bueno, Susan; Kalergis, Alexis; González, Pablo
Herpes simplex virus type 1 (HSV-1) significantly impairs dendritic cell (DC) function, ultimately eliciting the death of these cells. Here, we sought to assess whether HSV-1 modulates lipid metabolism in mouse DCs as a mechanism of immune evasion. For this, we performed RT-qPCR gene arrays with ingenuity pathway analysis (IPA), RNA sequencing (RNA-seq) and gene set enrichment analysis (GSEA), confocal microscopy, transmission electron microscopy, ultra-high-performance liquid chromatography-quadrupole time-of-flight (UHPLC-QTOF) analysis, pharmacological inhibition of eight lipid-metabolism-related enzymes in HSV-1-infected DCs, co-cultures between virus-specific transgenic CD4+ and CD8+ T cells and HSV-1-infected DCs, and in vivo assays with mice. We found that HSV-1 significantly alters lipid metabolism in DCs and induces lipid droplet (LD) accumulation in these cells. Pharmacological inhibition of two particular lipid metabolism enzymes was found to partially restore DC function. Overall, these results suggest that lipid metabolism plays an important role in the impairment of DC function by HSV-1.
Pericarditis constrictiva tuberculosa de rápida progresión y fatal
(2026) Sanhueza, Renato; Di Giammarino, Antonia; Fuentes, Cristóbal; Descalzi, Sofía; Follegati, Micaela; Roca, Felipe; Saldias, Roberto
Objetivo: Describir caso de pericarditis constrictiva secundaria a tuberculosis de evolución fulminante, destacando hallazgos clínicos, microbiológicos, imagenológicos e histopatológicos. Metodología: Estudio observacional, descriptivo y retrospectivo, consistente en un reporte de caso. La información se obtuvo de fuentes como ficha clínica, exámenes de laboratorio, estudios microbiológicos e imagenológicos, entre otros. Los antecedentes se ordenaron cronológicamente y analizaron descriptivamente. Se obtuvo firma de consentimiento informado del representante legal. Desarrollo: Hombre de 28 años con consumo perjudicial de alcohol y policonsumo de sustancias, con lesión cervical abscedada crónica interpretada como probable escrófula. Consultó por ascitis progresiva, edema periférico, pérdida de peso, sudoración nocturna y disnea. La tomografía computarizada evidenció derrame pericárdico y pleural bilateral, además de congestión hepática. Inicialmente fue manejado como pericarditis viral; luego presentó tromboembolismo pulmonar, shock refractario y falla respiratoria, requiriendo ventilación mecánica y soporte vasoactivo. La ecocardiografía mostró fisiología constrictiva y engrosamiento pericárdico. Durante la toracotomía se observó un pericardio tabicado con contenido hemopurulento. La PCR para Mycobacterium tuberculosis en líquido pericárdico fue positiva y la biopsia evidenció inflamación granulomatosa. Pese al drenaje quirúrgico y al tratamiento antituberculoso, el paciente falleció. Discusión: La presentación inespecífica y el bajo rendimiento microbiológico de las muestras pericárdicas pueden retrasar el diagnóstico. Los síntomas constitucionales, el derrame pericárdico y las manifestaciones extrapulmonares deben aumentar la sospecha de tuberculosis. Conclusión: La integración precoz de antecedentes clínicos y hallazgos imagenológicos, microbiológicos e histopatológicos son fundamental para establecer el diagnóstico e iniciar tratamiento oportuno, aunque las formas avanzadas de tuberculosis pueden evolucionar fatalmente.