Artículos Medicina y Ciencias de la Salud

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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).
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.
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.
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.

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