Artículos Medicina y Ciencias de la Salud

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The proportion of genetic similarity for liability for neuroticism in mother-child and mother-father dyads is associated with reported relationship quality
(2025) Pearson, Rebecca; Braithwaite, Elizabeth; Cadman, Tim; Culpin, Iryna; Costantini, Ilaria; Cordero, Miguel; Bornstein, Marc; James, Deborah; Kwong, Alex; Jones, Hannah; Sallis, Hannah
This study aims to explore the influence of genetic similarity for neuroticism liability in mother's reported quality of relationship with her child and partner. Such understanding could provide insight into the role of genetic similarity in neuroticism liability in close relationships. Molecular genetic data in 4,704 mothers, partners, and children in the Avon Longitudinal Study Parents And Children (ALSPAC) study were used to derive the proportion of genetic similarity in neuroticism liability between mother and child, and mother and partner, for genetic variants associated with neuroticism. Associations between genetic similarity in neuroticism liability scores and mothers' reported enjoyment and conflict in the parenting relationship (child ages 0-3) and her reported partner relationship were examined. For a one standard deviation (SD) increase in similarity in mother and child genetic variants associated with neuroticism, there was a 0.15SD (95%CI = 0.003 to 0.500, p = 0.046) increase in maternal reported enjoyment in their relationship. This association was greater where mother and child were both in the top quartile for high neuroticism (standardised beta = 0.29, 95%CI = 0.02 to 0.56, p = 0.034). Similar patterns of results emerged for similarity for genetic variants associated with neuroticism between mothers and partners, and the quality of the mother-partner relationship. These results highlight how phenotypic variation (i.e. the link between PGS scores and mothers reported enjoyment) linked to genetic liability in one individual may be linked with the genetic liability of those around them (i.e. the genetic liability of the infant). In other words, parenting and intimate partner relationships as perceived by the mother were explained not by one or the other's genetic score, but by the similarity between them These exploratory findings present an intriguing mechanism by which similarity between genetic liability might be linked to family relationships.
No evidence for exosome treatment in reducing alcohol relapse – a failed confirmatory multi-center study
(2025) Meinhardt, Marcus; Habelt, Bettina; Skorodumov, Ivan; Schwarz, Cindy; Bernhardt, Nadine; Winter, Christine; Hardar, Ravit; Müller, Christian; Israel, Yedy; Ezquer, Fernando; Spanagel, Rainer
Preclinical studies have suggested that intranasal administration of mesenchymal stem cell-derived exosomes can reduce alcohol intake and relapse-like behavior in rodents. To assess the translational potential of these findings, we conducted a preregistered, multi-center preclinical randomized controlled trial (preRCT) across several German research sites. Using the alcohol deprivation effect (ADE) model in both male and female Wistar rats, we evaluated whether exosome treatment attenuates relapse-like drinking behavior following repeated deprivation phases. Given the hurdles in standardizing exosome isolation, dosage, and intranasal delivery into the brain, we performed first a functional validation experiment of intranasally delivered exosomes. For providing such a functional proof, we conducted electrocorticography (ECoG) recording and showed that exosomes are capable of mitigating impaired electrophysiological activity in the prefrontal cortex in rats that underwent the ADE procedure. However, contrary to previously published positive findings, our confirmatory multi-site preRCT results did not demonstrate a significant reduction in ethanol consumption during an ADE in Wistar rats following exosome treatment. No sex or site-specific effects were observed. Given the absence of efficacy, the study was terminated early in alignment with the 3R principles of animal research ethics. These findings suggest that the previously reported benefits of exosome treatment may be model-specific and do not generalize to a broader genetic background or experimental model. Our results emphasize the necessity of replication across diverse preclinical models and rat lines prior to clinical translation and highlight the importance of publishing null results to improve transparency and reproducibility in addiction research.
Characterization of Hydrogel Beads for the Gradual Release of Origanum vulgare L. Essential Oil and Evaluation of Their Antifungal Activity Against Candida albicans
(2025) Concha, Victoria; Díaz, Mario; Duarte, Luisa; Jara, José; Molina, Alfredo
Candida albicans infections are associated with high morbidity and mortality worldwide. Current antifungal therapies are limited by adverse effects and the emergence of resistant strains, which compromise long-term efficacy. Previous studies have shown that Origanum vulgare L. essential oil (OvEO) possesses strong antifungal activity; however, its volatility and physicochemical instability hinder clinical application. The aim of this study was to encapsulate OvEO in a hydrogel and evaluate its release kinetics, chemical composition, structural properties, and antifungal activity. We assessed its release kinetics, chemical composition, structural characteristics (FTIR; SEM), and antifungal activity against C. albicans. OvEO was successfully encapsulated into hydrogel beads, enabling a gradual release profile, with in vitro release of phenolic compounds reaching 100% at 48 min. SEM revealed an irregular surface with small pores and crystalline aggregates distributed across the bead surface. OvEO-loaded hydrogel beads inhibited C. albicans growth with an IC50 of 0.15 ± 0.05 mg/L for strain 90029 and 0.2 ± 0.06 mg/L for strain 10231. At these concentrations, adhesion to abiotic surfaces was reduced by 60–80%. These findings support the potential of OvEO-loaded hydrogel beads as an alternative approach for the treatment of fungal infections, offering a complementary strategy to current antifungal agents.
Polygenic scores contribution to Parkinson's disease comorbidities
(2025) Hernández, Carlos; Villaman, Camilo; Tejos, Cristian; Repetto, Gabriela; Leu, Costin; Lal, Dennis; Mata, Ignacio; Klein, Andrés; Pérez Palma, Eduardo
Comorbidities are common in Parkinson's disease and significantly impact the disease progression and management. While polygenic scores have been widely used to assess genetic risk for complex diseases, their role in comorbidity presentation in Parkinson's disease remains unclear. This study investigates whether genetic predisposition to comorbidities, as measured by polygenic scores, differs between individuals with Parkinson's disease and the general population and explores how genetic risk influences disease onset and sex-related differences. We analysed data from 4144 individuals with Parkinson's disease and 370 480 individuals from the general population in the UK Biobank, focusing on four comorbidities with high-quality genome-wide association study data: Type 2 diabetes, major depressive disorder, migraine headaches and epilepsy. We first compared polygenic score distributions between individuals with Parkinson's disease and the general population. While our findings indicate that comorbidities and polygenic risk scores do not significantly differ between individuals with Parkinson's disease and the general population, we show an association with disease onset and sex-specific differences. Individuals with earlier disease onset (50-70 years old) had higher genetic risk for major depressive disorder (odds ratio: 2.19, P-value: 1.27 × 10⁻¹⁵) and epilepsy (odds ratio: 1.58, P-value: 0.00845). Additionally, a female participant with Parkinson's disease exhibited higher genetic risk scores for major depressive disorder (odds ratio: 1.5, P-value: 0.0119) and migraine headaches (odds ratio: 2.1, P-value: 0.0155), while a male participant displayed higher genetic risk scores for Type 2 diabetes (odds ratio: 2.7, P-value: 2.11 × 10⁻¹⁷). Comorbidity-polygenic score did not differ between people with versus without Parkinson's disease, yet within Parkinson's disease, a higher genetic burden for specific comorbidities was linked to earlier onset and sex-specific presentation, implicating common variants as modifiers of clinical heterogeneity rather than the primary disease risk. These results enhance our understanding of the genetic influences shaping the broader clinical presentation of Parkinson's disease and highlight the need for further research into the interplay between genetic risk factors, comorbidities and disease heterogeneity.
Therapeutic Effects of Intranasal Administration of Mesenchymal Stem Cell-Derived Secretome in Rats Exposed to Chronic Unpredictable Mild Stress
(2025) Ávila, Alba; Riveros, María; Adasme, Sofía; Guevara, Coram; Del Rio, Rodrigo; Ortiz, Fernando; Leibold, Nicole; Ezquer, Fernando
Background: Major depression is a significant source of suffering and economic loss. Despite efforts to understand this condition and find better treatments, the burden imposed by this disease continues to rise. Most approved pharmacological treatments for depression focus on controlling the availability of monoamines in synapses. However, accumulating evidence suggests that neuroinflammation, oxidative stress, and reduced hippocampal neurogenesis play key roles as causal factors in the development of major depression symptoms. Therefore, preclinical testing of pharmacological approaches targeting these factors is essential. Mesenchymal stem cells (MSCs) are known for their potential as powerful antioxidants and anti-inflammatory agents, exerting neuroprotective actions in the brain. They produce various therapeutic molecules in a paracrine manner, collectively known as secretome. Methods: In this work, we evaluated the antidepressant potential of repeated intranasal administration of MSC-derived secretome in an animal model of major depressive disorder induced by chronic mild unpredictable stress. Results: We observed that intranasal administration of MSC-derived secretome reduced the appearance of some of the behavioral parameters commonly associated with major depression, including anhedonic, apathetic, and anxious behaviors, inducing a strong reduction in the overall depression score compared to vehicle-treated animals. At the structural level, secretome administration prevented increased astrocyte density and the atrophy of astrocyte processes observed in vehicle-treated stressed animals. Additionally, secretome administration induced an increase in myelin levels and oligodendroglia in the cortex. Conclusions: Our data suggests that intranasal administration of MSC-derived secretome may represent a potential therapeutic alternative to current treatments for this devastating pathology.
Ultra-Processed Foods and Markers of Systemic Inflammation in Children
(2026) Awad, Camila; Rubilar, Paola; Hirmas Adauy, Macarena; Iglesias, Verónica; Muñoz, María; Retamal, Mauricio A.; Carvajal, Cristóbal; Dadvand, Payam; Lassale, Camille
Diets high in ultra-processed foods (UPF) have been associated with negative health outcomes in adults; however, UPF's impact on children's health and their underlying mechanisms remain underexplored, despite the rising prevalence of their intake in younger populations. We aimed to investigate the association between UPF intake and systemic inflammation in primary school children. This study included 450 children aged 7–10 years participating in a birth cohort in Arica, Chile (2023). Using the NOVA food classification system, we calculated the intake of UPF (expressed in %kcal) from a 44-item food frequency questionnaire (FFQ). The associations between UPF intake (exposure) and an array of cytokine levels (IL-6, IL-8, IL-10, IL-12, IL1β, TNF-α) were assessed using multiple linear regression models, adjusted for relevant covariates. The mean (SD) UPF intake was 29% (10.5%) of the total energy intake. Some of the associations appeared non-linear; therefore, participants were grouped into tertiles of UPF intake. In adjusted models, a suggestive trend across tertiles was observed for IL-1β (trend p-value 0.01). Stratified analyses by age suggested an association between UPF intake and IL-6 in older children (≥9 years) only (p-value for interaction=0.02). We found potential associations between UPF intake and cytokine levels in school-aged children. These results may suggest inflammation as a mechanism underlying the adverse health consequences of UPF consumption in children.
Cost-effectiveness of strategies using preventive interventions to protect infants in Chile from respiratory syncytial virus
(2025) Bolanos, Rafael; Araos Bralic, Rafael Ignacio; Gonzalez, Cecilia; Sepulveda, Dino; Falconi, Juan; Averin, Ahuva; Atwood, Mark; Quinn, Erin; Law, Amy; Mendes, Diana
Background: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract illness (LRTI; RSV-LRTI) among infants in Chile; young infants and infants born prematurely are at greatest risk. Research design and methods: A cohort model was developed to evaluate cost-effectiveness of strategies preventing RSV-LRTI in infants. Using the model, we calculated the economically justifiable price (EJP) of maternal RSVpreF vaccination (MV) versus no intervention and then evaluated the cost-effectiveness of MV (cost/dose assumed at EJP) with complementary use of monoclonal antibody nirsevimab for unprotected infants (MV+N) versus nirsevimab alone (NA) to prevent RSV-LRTI. Nirsevimab published price was $260.00; costs/prices reported in 2023 US$. Results: NA yielded 20,247 cases (hospital: 3,773, emergency ward: 16,474) and $57.2 million (M) in total costs (medical: $6.3 M, intervention: $48.7 M, indirect: $2.2 M). MV+N yielded 23,906 cases (hospital: 3,137, emergency ward: 20,769) and $28.7 M in costs (medical: $4.8 M, intervention: $21.7 M [RSVpreF assumed $75.77/dose; nirsevimab procured $260.00/dose], indirect: $2.2 M). With costs lower by $28.4 M and increased quality-adjusted life-years, MV+N would be cost-saving versus NA. Conclusions: RSVpreF vaccination among pregnant women along with nirsevimab for unprotected infants in Chile would be the most efficient use of resources, yielding substantial cost savings compared to use of nirsevimab alone. Trial registration: ClinicalTrials.gov NCT04424316 NCT03979313.
Genetics services in Latin America: a descriptive study of availability and utilization of genetics in healthcare
(2025) German, Ryan; Atkinson, Erin; Storch, Eric; Soler, Claudia; Margarit, Sonia; Lupo, Philip; Pereira, Stacey
Genetic services are expanding globally, but access remains limited in low-resource regions such as Latin America. Understanding current service availability, barriers, and facilitators is critical to guide capacity building and improve patient care. We conducted a cross-sectional survey of healthcare professionals providing genetic services in Latin America. The survey, available in Spanish and English, assessed genetic services, referral patterns, testing availability, barriers, facilitators, and perceived needs. Descriptive statistics summarized quantitative data, and thematic analysis was applied to openended responses. Eighty-five respondents from 18 countries reported broad clinical activity across pediatric, cancer, and adult-onset genetic conditions. Commonly ordered tests included karyotype, gene panels, and exome sequencing, with many sending samples abroad. Key barriers included high costs, workforce shortages, and limited clinician familiarity with testing. Facilitators included clinician interest and laboratory partnerships. Respondents emphasized the need for expanded test access, workforce development, and increased training opportunities. Genetic services in Latin America show substantial growth but face persistent barriers. Strengthening local infrastructure, training, and collaborative efforts is essential to improve access, reduce diagnostic delays, and enhance patient outcomes.
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.
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.

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