Hantavirus cardiopulmonary syndrome (HCPS) is a severe respiratory illness primarily associated with microvascular endothelial changes, particularly in the lungs. However, the role of the pulmonary epithelium in HCPS pathogenesis remains unclear. This study explores the potential of soluble Receptors for Advanced Glycation End-products (sRAGE) as a biomarker for assessing pulmonary epithelial damage in severe HCPS, challenging the prevailing view that endothelial dysfunction is the sole driver of this syndrome. We conducted a cross-sectional study on critically ill HCPS patients, categorizing them into mild HCPS, severe HCPS, and negative control groups. Plasma sRAGE levels were measured, revealing significant differences between the severe HCPS group and controls. Our findings suggest that sRAGE holds promise as an indicator of pulmonary epithelial injury in HCPS and may aid in tracking disease progression and guiding therapeutic strategies. This study brings clarity on the importance of investigating the pulmonary epithelium’s role in HCPS pathogenesis, offering potential avenues for enhanced diagnostic precision and support in this critical public health concern.

Background: Acute respiratory distress syndrome (ARDS) is characterised by substantial physiological heterogeneity, which contribute to a very variable clinical outcomes and therefore inconsistent responses to ventilatory strategies. We aimed to externally validate physiological ARDS subphenotypes previously identified using routine ventilatory and gas-exchange variables, assess their prognostic relevance across independent cohorts, and examine heterogeneity of treatment effect according to PEEP strategy. Methods: Unsupervised Gaussian Mixture Modelling was used to identify physiological subphenotypes based on ventilatory mechanics and gas-exchange parameters. Labels were subsequently used to train and validate supervised classifiers using XGBoost. Prognostic relevance was assessed across three independent cohorts, including two randomised controlled trials (ALVEOLI and LOVS). Predictive enrichment for PEEP strategy was evaluated using individual patient data from ALVEOLI and LOVS (n = 1,532) using intention-to-treat analyses, applying both one-stage and two-stage fixed-effects IPD meta-analytic approaches to test for interaction between physiological subphenotype and PEEP strategy. Results: Two distinct physiological subphenotypes, termed Efficient and Restrictive, were replicated across independent cohorts. Across each cohort, patients classified as Restrictive consistently exhibited higher all-cause 28-day mortality compared to Efficient patients. When pooled across studies, the Restrictive subphenotype was associated with a significantly increased risk of death (pooled odds ratio 1.75, 95% CI 1.36–2.24), with no evidence of between-study heterogeneity. Predictive analyses showed a statistically significant interaction between physiological subphenotype and PEEP strategy in the one-stage IPD model (p for interaction = 0.037), with concordant findings in the two-stage fixed-effects IPD meta-analysis (interaction OR 1.91, 95% CI 1.00–3.66; I² = 0%). Higher PEEP was associated with increased mortality in Efficient patients and reduced mortality in Restrictive patients, indicating effect modification by physiological subphenotype. Interpretation: Physiological ARDS subphenotypes derived from routinely collected bedside data provide robust and externally validated prognostic stratification across observational and randomised trial cohorts. The observed interaction with PEEP strategy suggests that underlying physiological profiles may influence treatment response, supporting the concept that physiology-based be a starting point for personalized medicine and therefore better ventilatory strategies in future clinical trials.

Background/objective: Lung cancer (LC) remains the leading cause of cancer-related death worldwide. However, population-level evidence on long-term mortality trends and hospital outcomes in Latin America remains limited. This study aimed to analyze long-term mortality trends from LC in Chile and characterize hospitalization patterns and factors associated with in-hospital mortality. Methods: We conducted a population-based cross-sectional study using two independent administrative databases. Population-level lung cancer mortality trends were analyzed using national mortality records from DEIS (1997–2024), whereas hospitalization patterns and in-hospital mortality were analyzed using hospitalization episodes from the GRD-FONASA database (2019–2024). LC deaths were identified using ICD-10 codes C34. Hospitalizations were analyzed by demographics, primary diagnosis, and discharge status. Logistic regression models were used to evaluate factors associated with in-hospital mortality. Results: Age-adjusted mortality declined substantially among men (−35.5%) but increased slightly among women (+9%). Among hospitalization episodes recorded in the GRD-FONASA database, in-hospital mortality was 17.4%. In-hospital mortality was higher among men than women (18.7% vs. 15.8%), and male sex remained associated with increased odds of in-hospital death after adjustment for age (aOR 1.22; 95% CI 1.13–1.31). Lung cancer or metastasis was the principal diagnosis in 10,986/14,778 hospitalizations (74.3%) included in the selected diagnostic analysis. However, pneumonia and acute respiratory complications were disproportionately more frequent among hospitalizations ending in death. In multivariable analysis, pneumonia (aOR 2.05; 95% CI 1.77–2.38) and acute respiratory complications (aOR 2.13; 95% CI 1.83–2.48) were independently associated with in-hospital death. Conclusions: LC mortality trends in Chile diverged by sex, with declining age-adjusted mortality among men but increasing mortality among women. Respiratory infections and acute respiratory complications were strongly associated with in-hospital mortality, highlighting their importance as key targets for prevention and clinical management.