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Biofilm formation on collagen substrates modulates Streptococcus mutans bacterial extracellular nanovesicle production and cargo
(2025) Leiva, Camila; Berríos, Pablo; Saavedra, Paula; Carrasco, Javiera; González, José; Vera, Mario; Tarifeño, Estefanía; Schuh, Christina; Aguayo, Sebastian
Streptococcus mutans is the major microbial etiological agent of dental caries and can adhere to surfaces such as type-I collagen, which is present in dentin and periodontal tissues. Recent studies have characterized planktonic S. mutans bacterial extracellular vesicles (bEVs) at the nanoscale range and demonstrated environmental-induced changes due to sugar presence or pH alterations. However, to date, no studies have explored whether surface-derived changes can modulate bEV production in the context of oral biofilm formation in the elderly. Therefore, this work aimed to determine the role of biofilm formation and collagen glycation on the nanoscale morphology and proteomic composition of S. mutans bEVs. For this, bEVs from S. mutans biofilms on native and glycated collagen surfaces were isolated, characterized, and compared to bEVs from planktonic cells. Nanoparticle tracking analysis (NTA), atomic force microscopy (AFM), and electron microscopy confirmed bEV production and showed that bEVs from biofilms are smaller in size and less abundant than those from planktonic cells. Furthermore, proteome analysis revealed that S. mutans biofilm formation on native and glycated collagen led to the enrichment of several key virulence proteins. Also, a shift towards proteins involved in metabolic processes was found in bEVs following biofilm formation on collagen surfaces, whereas glucan metabolism proteins were overexpressed in vesicles from the planktonic state. These results demonstrate that biofilm formation, as well as the glycation of collagen associated with aging and hyperglycaemia, can modulate bEV characteristics and cargo and could play a central role in S. mutans virulence and the development of diseases such as dental caries and periodontal disease.
Incontinencia fecal femenina: una condición silenciada en el discurso de salud pélvica
(2026) Cárdenas, Valentina; Soto, Javiera; Comicheo, Nelly; Paredes, Natalia; Ñanco, Lisset; Rojas, Daniela; Hernández, Alejandro
La incontinencia fecal es una disfunción de suelo pélvico que ha permanecido invisibilizada en el ámbito clínico y científico a pesar de que la salud pélvica femenina se ha tratado históricamente desde una perspectiva predominantemente fisiopatológica, lo que ha limitado la comprensión integral de sus implicancias biopsicosociales. Esta condición, a menudo silenciada debido al estigma, la falta de información y la vergüenza, presenta un impacto considerable en la calidad de vida de las mujeres. La incontinencia fecal, además de su dimensión clínica, tiene un fuerte impacto a nivel psicosocial, afectando la autopercepción, la salud mental, las relaciones interpersonales y la vida social. Este artículo reflexivo tiene por objetivo sugerir una perspectiva integral que conecte lo fisiológico con lo psicosocial, enfatizando la importancia de visibilizar este problema en la conversación sanitaria y fomentar un cuidado empático e interdisciplinario.
Fecal incontinence is a pelvic floor dysfunction that has remained invisible in the clinical and scientific fields, despite the fact that female pelvic health has historically been treated from a predominantly pathophysiological perspective, which has limited the comprehensive understanding of its biopsychosocial implications. This condition, often silenced due to stigma, lack of information, and shame, has a considerable impact on women's quality of life. Fecal incontinence, in addition to its clinical dimension, has a strong psychosocial impact, affecting self-perception, mental health, interpersonal relationships, and social life. Thisreflective article aims to suggests a comprehensive perspective that connects the physiological with the psychosocial, emphasizing the importance of making this problem visible in healthcare conversations and fostering empathetic and interdisciplinary care.
Estrategias para aumentar la autoeficacia frente al dolor en pacientes con dolor musculoesquelético cróActividad de Grado presentada a la Facultad de Medicina de la Universidad del Desarrollo para optar al grado académico de Magíster en Terapia Física y Rehabilitación (MAKI)nico de hombro: Scoping review
(Universidad del Desarrollo. Facultad de Medicina, 2026) Fuentes Werlinger, Nicolas; Araya Castro, Paulina
Antecedentes/Objetivo: El dolor musculoesquelético crónico de hombro persiste más de seis meses en aproximadamente el 50% de los casos, afectando significativamente la funcionalidad, el trabajo y la calidad de vida. La autoeficacia frente al dolor es considerada el mediador psicológico más potente de la discapacidad y la respuesta al tratamiento en poblaciones con dolor crónico. Sin embargo, la evidencia que describe estrategias para mejorar la autoeficacia frente al dolor específicamente en personas con dolor crónico de hombro es limitada. Este scoping review tuvo como objetivo mapear y describir las estrategias dirigidas a aumentar la autoeficacia frente al dolor en personas con dolor musculoesquelético crónico de hombro.
Métodos: Se realizó un scoping review siguiendo las directrices del Joanna Briggs Institute (JBI), reportado según la declaración PRISMA-ScR. Se realizó una búsqueda en cuatro bases de datos (PubMed, EBSCOhost, SciELO y Science Direct). Dos revisores independientes seleccionaron los estudios aplicando criterios de elegibilidad predefinidos, con discrepancias resueltas por un tercer revisor. Los diseños elegibles incluyeron ensayos clínicos aleatorizados, estudios cuasiexperimentales, de cohorte y series de casos.
Resultados: Se identificaron 4603 registros; tras eliminar 406 duplicados y evaluar 109 textos completos, se incluyeron 4 estudios que abarcaron desde 2011 hasta 2022, con 492 participantes. Las estrategias fueron clasificadas como multicomponentes o de terapia física, todos los estudios utilizaron el PSEQ como medida de autoeficacia frente al dolor. Las estrategias multicomponentes mostraron mejoras significativas en autoeficacia frente al dolor junto a cambios en múltiples variables psicológicas. El entrenamiento neuromuscular supervisado también mejoró significativamente la autoeficacia frente al dolor, mientras que un programa domiciliario no supervisado no mostró cambios en esta variable.
Conclusión: La evidencia disponible sobre estrategias para mejorar la autoeficacia frente al dolor en personas con dolor crónico de hombro sigue siendo escasa y se encuentra en una etapa inicial. Los hallazgos sugieren que las intervenciones supervisadas en formato grupal, especialmente las multicomponentes, se asocian a mejores resultados.
Capture and detection of extracellular vesicles derived from human breast cancer cells using a 3D self-assembled nanostructured SiO2 microfluidic chip
(2025) Cabeza, Carolina; Rojas, Felipe; Lobos, Lorena; Lemaitre, Dominique; Villena, Juan; Cordero, María; Hassan, Natalia; Ortiz, Rina
Background: Tumor-derived extracellular vesicles offer a minimally invasive approach to evaluate tumor progression and metastasis. However, detecting biomarkers, such as extracellular vesicles in body fluids during the early stages of disease, remains a significant challenge. Conventional methods like ultracentrifugation-based isolation or Western blot protein quantification are time-consuming, require large sample volumes, and offer low yield and sensitivity. Therefore, the development of new biosensors for the specific and efficient analysis of tumor extracellular vesicles is urgently needed.
Methods: Microfluidic devices provide extraordinary benefits for bioanalysis, offering a large surface area for the contact between target molecules and the biosensor, significantly enhancing the specificity, efficiency, and speed. These devices also enable nanoscale and microscale work using reduced sample volumes. In this study, we developed a three-dimensional self-assembled SiO2-based nanostructured microfluidic chip, bioconjugated with specific antibodies targeting exosomal markers for the selective capture of CD63- and CD81-positive extracellular vesicles from breast cancer-derived conditioned cell culture media.
Results: The three-dimensional SiO2-based microfluidic chip effectively captured extracellular vesicles expressing CD63 and CD81 antigens from breast cancer cell culture media. This evidence demonstrates the potential of this platform to detect extracellular vesicles as biomarkers for cancer, providing a specific and efficient, non-invasive approach for cancer diagnostics.
Conclusions: This study highlights the potential application of three-dimensional SiO2-based microfluidic chips for detecting extracellular vesicles as a non-invasive liquid biopsy tool for breast cancer. The findings show a specific and efficient device as an alternative to conventional biomarker detection techniques.
Surgical outcomes from haematoma evacuation for intracerebral haemorrhage in the INTERACT3 study
(2025) Hu, Xin; Ouyang, Menglu; Xu, Jianguo; Liu, Yi; Li, Xi; Jiang, Yan; Chen, Xiaoying; Billot, Laurent; Qiang, Li; Malavera, Alejandra; Munoz Venturelli, Paula; Thang, Nguyen; Wahab, Kolawole; Pandian, Jeyaraj; Wasay, Mohammad; Pontes-Neto, Octavio; Abanto, Carlos; Arau, Antonio; Li, Zongping; Chen, Minhui; Wang, Xiaofeng; Yang, Chengyi; Xin, Xiaodong; Jiang, Dehua; Zheng, Jun; Yu, Zhiyuan; Xiao, Anqi; Tao, Chuanyuan; Chen, Lei; Wu, Bo; Li, Hao; Anderson, Craig; You, Chao; Song, Lili; Ma, Lu; INTERACT3 Investigators
Background: There is ongoing controversy as to whether surgical intervention to haematoma evacuation benefits patients with acute intracerebral haemorrhage (ICH). This study aimed to evaluate the association of surgical intervention to evacuate the haematoma and 6-month functional outcome in participants of the third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT3).
Methods: This was a secondary analysis of INTERACT3, which enrolled adults (age ≥18 years) spontaneous ICH patients within 6 h after onset. INTERACT3 was an international, multicentre, prospective, stepped-wedge, cluster randomised, blinded outcome assessed, clinical trial undertaken at 121 hospitals in 10 countries between December 12, 2017 and December 31, 2021. To limit heterogeneity in the results, we restricted analyses to participants in China. The primary outcome was poor functional outcome, defined by a score of 5-6 on the modified Rankin scale (mRS), at 6 months. Secondary outcomes include a mRS score of 4-6 and mortality at 6 months. Sensitivity analysis included propensity score matched analysis and the imputation of missing outcome variables. The effect of timing on surgical outcome was also evaluated. The INTERACT3 trial was registered at ClinicalTrials.gov (NCT03209258) and CHiCTR.org.cn (ChiCTR-IOC-17011787).
Findings: Of 5772 participants (mean age 62.0 ± 12.5 years) at 82 sites in China, 1411 (24.4%) received surgery in which craniotomy (72.6%) was the most common approach. After adjustment for confounding variables, surgery to evacuate the haematoma was associated with lower odds of a poor functional outcome (odds ratio 0.71, 95% CI 0.55-0.92; p = 0.010) and mortality (odds ratio 0.55, 95% CI 0.40-0.75; p = 0.0001) at 6 months. The association was consistent in propensity score matching analysis and sensitivity analysis by imputation. We did not detect significant differences in outcome between those who received surgery on the same day of hospital arrival compared to those who received surgery on the second or later days. In analysis limited to participants with supratentorial ICH and with a haematoma volume 30 mL or more, evacuation of the haematoma was associated with lower odds of poor functional outcome (n = 1234, odds ratio 0.68, 95% CI 0.46-0.99; p = 0.042) and mortality (n = 1291, OR 0.45, 95% CI 0.29-0.69; p = 0.0003).
Interpretation: This secondary analysis of the INTERACT3 indicates that evacuation of the haematoma is associated with better chances of surviving free of severe disability after acute ICH. With the evolution of instrument and techniques, further trial should address the role of haematoma evacuation in deep ICH patients, the time window and difference between mini-invasive techniques.
Funding: Joint Global Health Trials (JGHT) funding scheme from the Department of Health and Social Care, the Foreign, Commonwealth & Development Office, the Medical Research Council and Wellcome Trust; the West China Hospital Outstanding Discipline Development 1-3-5 programme; National Health and Medical Research Council of Australia; Sichuan Credit Pharmaceutical; and Takeda (China).
Intracerebral haemorrhage management practices and adherence to the INTERACT3 care bundle in Latin America: Results from an international survey
(2025) Rosales, Julieta; Carbonera, Leonardo; De Souza, Ana; Rocha, Eva; Cano, Vanessa; Orjuela, Karen; Guerrero, Rodrigo; Delfino, Carlos; Nuñez, Marilaura; Munoz Venturelli, Paula; Gonzalez, Alejandro
Objective: To assess intracerebral hemorrhage (ICH) management practices and adherence to the INTERACT3 care bundle across Latin American countries.
Methods: We conducted a multi-national survey among neurologists, neurosurgeons, intensive care specialists, and emergency physicians. From August to December 2024, the survey was distributed across 19 Latin American countries. It assessed hospital characteristics, availability of an ICH code, adherence to INTERACT3 measures, and resource availability. Stroke leaders from the surveyed countries were involved in developing and disseminating the survey.
Results: Out of 580 respondents (mean age 40.25 years; 61.6% male), most worked in teaching (86%) and public hospitals (53.6%). Only 27.9% reported an ICH code at their institution. Adherence to INTERACT3 measures ranged from 57.2% (anticoagulation reversal) to 84.7% (blood pressure control), with just 44.5% reporting adherence to all four measures. Time-to-target was not measured by 65%, and only 53.9% maintained interventions for one week. Neuroimaging, neurosurgery, and hematology services were higher in private compared to public and mixed hospitals (p<0.001). ICH code availability was associated with private hospitals and emergency care specialists, while full adherence was more likely among intensive care specialists.
Conclusions: ICH management in Latin America is evolving, with increasing adoption of evidence-based practices. However, variability in adherence underscores the need for regional initiatives to standardize ICH care and ensure equitable implementation of best practices.
Vancomycin levels for Bayesian dose-optimization in critical care: a prospective cohort study
(2025) Dreyse, Natalia; Salazar, Nicole; Munita, Jose M.; Rello, Jordi; López, René
Background: Vancomycin dosing in critically ill patients typically requires monitoring the area under the concentration-time curve/minimum inhibitory
concentration (AUC/MIC), often using at least two vancomycin levels (VLs). However, the optimal number of VLs needed for accurate AUC/MIC estimation in
this population remains uncertain. This study aimed to determine the minimum number of VLs required to accurately estimate the AUC/MIC in critically ill
patients treated with intermittent infusion of vancomycin.
Methods: A prospective cohort study was conducted in critically ill patients, where VLs were obtained at peak, beta, and trough phases. Five AUC estimates were derived using PrecisePK™, a Bayesian software: AUC-1 [peak, beta (2 h after the end infusion), trough], AUC-2 (beta, trough), AUC-3 (peak, trough), AUC-4 (trough), and AUC-5 (only Bayesian prior, without VL). These estimates were compared for accuracy and bias (mean ± SEM) against the reference AUC calculated via the trapezoidal model (AUCRef).
Results: We enrolled 36 adult patients with age of 65 (52–77) years, moderate severity [APACHE II 10 (5–14) and SOFA 5 (4–6)], 6 of them in ECMO and 4 in renal replacement therapy. A total of 108 blood samples for VL were analyzed. The AUC-3 (0.976 ± 0.012) showed greater accuracy compared to AUC-4 (1.072 ± 0.032, p = 0.042) and AUC-5 (1.150 ± 0.071, p = 0.042). AUC-3 also demonstrated lower bias (0.053 ± 0.009) than AUC-4 (0.134 ± 0.026, p = 0.036) and AUC-5 (0.270 ± 0.060, p = 0.003). Bland–Altman analysis indicated better agreement between AUC-3 and AUC-2 with AUCRef.
Conclusion: Bayesian software using two vancomycin levels provides a more accurate and less biased AUC/MIC estimation in critically ill patients.
Assessing the impact of a single qualitative fecal immunochemical test on colonoscopy prioritization and mortality in risk-stratified patients with suspected colorectal cancer: a retrospective cohort study
(2025) Quezada, Felipe; Acevedo, Johanna; González, Maite; Tello, Andrea; Castillo, Richard; Morales, Carlos; Manríquez. Erik; Duran, Valentina; Mena, Felipe; Le-Bert, Catherine; Cabreras, Manuel; Fulle, Ángelo; Carvajal, Gonzalo; Briones, Pamela; Nervi, Bruno; Kusanovich, Rodrigo
Background: Performing fecal immunochemical tests in symptomatic individuals at low-or moderate risk for suspected colorectal cancer could help prioritize candidates for colonoscopies. The objective of this study was to assess the diagnostic accuracy of the fecal immunochemical test (FIT) in symptomatic individuals at low-or moderate risk of colorectal cancer and explore association with survival.
Methods: We conducted a retrospective cohort study between December 2016 and July 2024 from a single-center, public hospital in Chile. Adults (≥18 years-old) individuals were included, those with symptoms suggestive of colorectal cancer and set for evaluation via colonoscopy. Symptomatic individuals with suspected colorectal cancer were stratified as high risk or low/moderate risk by a trained nurse according to 2015 NICE guidelines. Subsequently, high risk patients were directly referred for colonoscopies, while low/moderate risk patients underwent a single qualitative FIT and prioritized to colonoscopy based on results. Main outcomes were FIT diagnostic accuracy for colorectal cancer, overall mortality, and colorectal cancer-specific mortality.
Findings: A total of 394 out of 1304 participants (30%) were classified as high risk. The remaining 910 (70%) were categorized as low/moderate risk and were referred for FIT. From these, 808 (89%) individuals were tested and had results for FIT. Regarding the diagnostic accuracy of the FIT, sensitivity was 96% and specificity reached 66.8%, with a negative value of 99.8%. Low/moderate risk positive FIT (FIT+) and high-risk participants had higher mortality rates vs. low/moderate risk negative FIT (FIT-) individuals. Time-to-event analysis confirmed a lower cumulative mortality in low/moderate risk FIT- patients. A multivariable Cox regression model showed a consistently lower risk of death in this group, while a non-significant trend towards increased mortality was observed in low/moderate risk FIT+ individuals after 30 months.
Interpretation: In symptomatic individuals at low or moderate risk, a single qualitative FIT was associated with high sensitivity and moderate specificity for colorectal cancer detection. FIT may help prioritize colonoscopy in low-resource settings, but further prospective validation is warranted.
Funding: This research was partially funded by ANIDFONDAP152220002 (CECAN).
Causas del abandono de embarazadas a la atención odontológica en atención primaria en chile. Un estudio cualitativo
(2026) Soto, Monserrat; Cantarutti, Cynthia; Pardo, Antonia; Ortúzar, Isabel; Jordán, Valentina; Moneva, Mariana; Madariaga, Pablo; Véliz, Claudia
Introducción: En Chile la atención odontológica para embarazadas está garantizada mediante Garantías Explícitas en Salud. Sin embargo, muchas mujeres que inician el tratamiento no lo completan. Las razones de este abandono han sido escasamente estudiadas desde la experiencia de las usuarias. Objetivo: Comprender el significado atribuido al tratamiento odontológico durante el embarazo y las razones que llevan a su abandono, desde la experiencia de mujeres que accedieron a las garantías. Metodología: Estudio cualitativo con análisis de contenido inductivo de entrevistas semiestructuradas a mujeres que no finalizaron el tratamiento odontológico en Atención Primaria de Salud. El muestreo fue por conveniencia. El análisis fue manual, independiente e incluyó validación de hallazgos con participantes. Resultado: Se realizaron once entrevistas, desde las cuales emergieron siete temas. El abandono se asoció a la dificultad para compatibilizar las horas con las exigencias cotidianas, agravada por la escasa flexibilidad horaria, los cambios de hora y la exclusión tras inasistencias. Se sumó un débil vínculo con el centro, con ausencia de rescate, rotación de profesionales y escasa información. Discusión: El abandono no se explicó por barreras clásicas
como el costo, el miedo o la baja valoración de la salud bucal, sino por la dificultad para compatibilizar las exigencias cotidianas con un programa poco flexible y por un vínculo institucional débil. Conclusión: Los programas para gestantes deberían asignar horas compatibles con la vida cotidiana, fortaleciendo el vínculo y seguimiento con el centro.
Introduction: In Chile dental care for pregnant women is guaranteed through the Explicit Health Guarantees system. However, many women who initiate treatment do not complete it. The reasons underlying treatment abandonment have been scarcely studied from the perspective of users. Objective: To understand the meaning attributed to dental treatment during pregnancy and the reasons leading to its abandonment, based on the experiences of women who accessed the guarantees. Methodology: A qualitative study was conducted using inductive content analysis of semi- structured interviews with women who did not complete dental treatment in Primary Healthcare. Convenience sampling was used; the analysis was performed manually and independently, and included validation of findings with participants. Result: Eleven interviews were conducted, from which seven themes emerged. Treatment abandonment was associated with difficulties in reconciling appointments with daily life demands, exacerbated by limited scheduling flexibility, appointment changes, and exclusion from the program after missed visits. A weak connection with the healthcare center was also identified, characterized by the absence of follow-up strategies, professional turnover, and limited information. Discussion: Treatment abandonment was not explained by traditional barriers such as cost, fear, or low oral health valuation, but rather by the difficulty of reconciling daily demands with an inflexible program and by a weak institutional relationship. Conclusion: Programs targeting pregnant women should provide appointment schedules compatible with daily life and strengthen patient–center follow-up and relationships to promote treatment continuity.
Gut Microbiota-Derived Extracellular Vesicles Influence Alcohol Intake Preferences in Rats
(2025) Díaz-Ubilla, Macarena; Figueroa-Valdés, Aliosha I.; Tobar, Hugo E.; Quintanilla, María Elena; Díaz, Eugenio; Morales, Paola; Berríos-Cárcamo, Pablo; Santapau, Daniela; Gallardo, Javiera; Gregorio, Cristian de; Ugalde, Juan; Rojas, Carolina; Gonzalez-Madrid, Antonia; Ezquer, Marcelo; Israel, Yedy; Alcayaga-Miranda, Francisca; Ezquer, Fernando
Growing preclinical and clinical evidence suggests a link between gutmicrobiota dysbiosis and problematic alcohol consumption.
Extracellular vesicles (EVs) are key mediators involved in bacteria-to-host communication. However, their potential role in mediating addictive behaviour remains unexplored. This study investigates the role of gut microbiota-derived bacterial extracellular vesicles (bEVs) in driving high alcohol consumption. bEVs were isolated from the gut microbiota of a high alcoholdrinking rat strain (UChB rats), either ethanol-naïve or following chronic alcohol consumption and administered intraperitoneally or orally to alcohol-rejecting male and femaleWistar rats. Both types of UChB-derived bEVs increased Wistar’s voluntary alcohol consumption (three bottle choice test) up to 10-fold (p < 0.0001), indicating that bEVs are able and sufficient to transmit drinking behaviour across different rat strains. Molecular analysis revealed that bEVs administration did not induce systemic or brain inflammation in the recipient animals, suggesting that the increased alcohol intake triggered by UChB-derived bEVs operates through an inflammation-independent mechanism. Furthermore,we demonstrate that the vagus nerve mediates the bEV-induced increase in alcohol consumption, as bilateral vagotomy completely abolished the high drinking behaviour induced by both intraperitoneally injected and orally administered bEVs. Thus, this study identifies bEVs as a novel mechanism underlying gut microbiota-induced high alcohol intake in a vagus nerve-dependent manner.
Candidate Interventions for Integrating Hypertension and Cardiovascular-Kidney-Metabolic Care in Primary Health Settings: HEARTS 2.0 Phase 1
(2025) Rosende, Andres; Romero, Cesar; DiPette, Donald; Brettler, Jeffrey; Van der Stuyft, Patrick; Satheesh, Gautam; Perel, Pablo; Chapman, Niamh; Moran, Andrew; Schutte, Aletta; Sharman, James; Irazola, Vilma; Huffman, Mark; Campbell, Norm; Salam, Abdul; Lanas, Fernando; Coca, Antonio; Garcia, Sebastian; Ferreiro, Alejandro; Lopez, Patricio; Rico, Jorge; Ridley, Emily; Picone, Dean; Flood, David; Piñeiro, Daniel; Neira, Carolina; Rodriguez, Gonzalo; Wellmann, Irmgardt; Orias, Marcelo; Rivera, Marcela; Villatoro, Matías; Onuma, Oyere; Ramroop, Shaun; Khan, Taskeen; Valdes, Yamile; Kunz, Weimar; Plavnik, Frida; Zuniga, Eric; Grassani, Ana; Tajer, Carlos; Zaidel, Ezequiel; Marin, Marcos; Cyr-Philbert, Shana; Amorin, Ignacio; Diaz, Miguel; Bortolotto, Luiz; Avezum, Alvaro; Ribeiro, Antonio; Tobe, Sheldon; Aumala, Teresa; Angell, Sonia; Lavados, Pablo; Ouriques, Sheila; Munera, Ana; Jaffe, Marc; Prabhakaran, Dorairaj; Parati, Gianfranco; Zhang, Xin Hua; Rodgers, Anthony; Yusuf, Salim; Whelton, Paul; Ordunez, Pedro
Background: HEARTS in the Americas is the regional adaptation of the WHO Global HEARTS Initiative, aimed at helping countries enhance hypertension and cardiovascular disease (CVD) risk management in primary care settings. Its core implementation tool, the HEARTS Clinical Pathway, has been adopted by 28 countries. To improve the care of hypertension, diabetes, and chronic kidney disease (CKD), HEARTS 2.0 was developed as a three-phase process to integrate evidence-based interventions into a unified care pathway, ensuring consistency across fragmented guidelines. This paper focuses on Phase 1, highlighting targeted interventions to improve and update the HEARTS Clinical Pathway.
Methods: First, the coordinating group defined the project's scope, objectives, principles, methodological framework, and tools. Second, international experts from different disciplines proposed interventions to enhance the HEARTS Clinical Pathway. Third, the coordinating group harmonized these proposals into unique interventions. Fourth, experts appraised the appropriateness of the proposed interventions on a 1-to-9 scale using the adapted RAND/UCLA Appropriateness Method. Finally, interventions with a median score above 6 were deemed appropriate and selected as candidates to enhance the HEARTS Clinical Pathway.
Results: Building on the existing HEARTS Clinical Pathway, 45 unique interventions were selected, including community-based screening, early detection and management of risk factors, lower blood pressure thresholds for diagnosing hypertension in high-CVD-risk patients, reinforcement of single-pill combination therapy, inclusion of sodium-glucose cotransporter-2 inhibitors for patients with diabetes, CKD, or heart failure, expanded roles for non-physician health workers in team-based care, and strengthened clinical documentation, monitoring, and evaluation.
Conclusion: HEARTS 2.0 Phase 1 identifies key interventions to integrate and improve hypertension and cardiovascular-kidney-metabolic care within primary care, enabling their seamless incorporation into a unified and effective clinical pathway. This process will inform an update to the HEARTS Clinical Pathway, optimizing resources, reducing care fragmentation, improving care delivery, and advancing health equity, thereby supporting global efforts to combat the leading causes of death and disability.
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.
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.
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.
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.
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.
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.
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.