Barcelona Institute for Global Health

Systemic inflammation during pregnancy is associated with adverse health outcomes for both mother and child. C-reactive protein (CRP) is a widely used biomarker of inflammation, and its levels may be influenced by environmental factors. This study examined the association between 26 components of the external urban exposome-including air pollutants, land use, and access to green and blue spaces-and CRP concentrations in 1547 pregnant women from the INMA birth cohort in Spain (Gipuzkoa, Sabadell, and Valencia). Environmental exposures during the first trimester were assessed using GIS-based indicators and land-use regression models, and were grouped into low, moderate, and high exposome clusters using hierarchical clustering on principal components. Associations between exposome clusters and CRP were evaluated using multivariable linear regression models and meta-analyses, adjusting for maternal and lifestyle covariates. No significant associations were found between exposome clusters and CRP levels. However, specific air pollutants-fine particulate matter (PM2.5: 1.08% increase per unit; 95% CI: 1.02-1.15) and nitrogen oxides (NOx: 1.03%; 95% CI: 1.00-1.06)-were positively associated with CRP. No associations were observed for green space indicators or other built environment variables. CRP concentrations also varied by region, with the highest levels observed in Valencia (3.2±4.6mg/dL). These findings suggest that while overall urban exposome profiles may not predict systemic inflammation, individual air pollutants such as PM2.5 and NOx are key contributors. Targeting these exposures in maternal health strategies may help mitigate inflammation-related risks during pregnancy, supporting the need for more detailed and component-specific exposome assessments.

Temperature extremes and air pollution are major environmental drivers of mortality. Although several studies have examined the joint health effects of heat and air pollution, the evidence remains largely confined to the summer season, and synergistic effects throughout the year are poorly understood. In particular, the combined effects of air pollution with cold temperatures, as well as how these interactions vary across population subgroups and over time, have received little attention. This study provides a comprehensive continental-scale assessment of the synergistic effects of temperature and air pollution on mortality across both warm and cold seasons in Europe during 2003-2019.We analyzed daily temperature and mortality data from the EARLY-ADAPT project, covering 654 contiguous regions across 32 European countries and a population of 539 million people, combined with daily estimates of PM2.5, PM10, NO2, and O3 at 10 km spatial resolution. Region-specific analyses were conducted using over-dispersed Poisson regression models, followed by a multilevel random-effects meta-analysis. Joint associations were modelled using product terms between non-linear functions of temperature and linear functions of air pollutants. Relative risks and attributable numbers were estimated, with stratified analyses by sex, age group, cause of death, and time period.Our findings provide robust evidence of substantial synergistic effects between temperature extremes and air pollution, with pronounced heterogeneity across demographic groups, causes of death, and over time. These results highlight the importance of accounting for compound climate-air pollution risks in public health surveillance. Integrating temperature and air quality information into early warning systems and climate adaptation strategies is essential to reduce preventable mortality and protect vulnerable populations in a changing climate.

To describe (1) the proportion of deaths that were in recently hospitalised children and (2) causes of mortality among deceased children aged 0-59 months with preceding hospitalisations who enrolled in a mortality surveillance programme. Descriptive study using prospectively collected data. Eight Child Health and Mortality Prevention Surveillance (CHAMPS) community and healthcare sites in sub-Saharan Africa and South Asia. Deaths among children aged 0-59 months enrolled in CHAMPS 2016-2023. None. Deaths with antecedent hospitalisations within 180 days of death. Causes of death determined by expert panels who reviewed clinical data and histopathologic and microbiologic results from postmortem minimally invasive tissue sampling. CHAMPS enrolled 8548 deaths; we excluded 3688 neonates who died before discharge or ≤24 hours of birth and 482 with unclear information on antecedent hospitalisations. Out of the 4378 remaining deaths, 16.7% (95% CI 15.7% to 17.9%) were deaths that occurred within 180 days of a hospitalisation (n=733/4378). Of these, 55.7% (95% CI 52.0% to 59.3%) occurred outside healthcare facilities. Among included deaths with minimally invasive tissue sampling completed (n=337), lower respiratory tract infections (41.2%, 95% CI 36.0% to 46.7%), sepsis (39.8%, 95% CI 34.5% to 45.2%) and undernutrition (n=92, 27.3%, 95% CI 22.7% to 32.4%) were most common causes of death among cases with antecedent hospitalisations. The greatest proportion of deaths with antecedent hospital admissions occurred among cases aged 1-11 months (48.0%, 95% CI 44.4% to 51.7%), compared with those aged 0-1 months (21.7%, 95% CI 18.8% to 24.9%) and those aged 1-5 years (30.3%, 95% CI 27.0% to 33.8%). Moreover, the greatest proportion of deaths with antecedent hospital admissions occurred among infants/children with weight-for-age Z-score of <-3 (62.5%, 95% CI 56.5% to 68.0%) compared with those with weight-for-age Z-score of ≥-3 (37.5%, 95% CI 32.0% to 43.5%). We observed a high proportion of deaths with antecedent hospitalisations within 180 days among young children across eight sites in sub-Saharan Africa and Asia. Among those deaths, children aged 1-11 months and undernourished infants were over-represented, suggesting early follow-up as a potential point to focus targeted support and future research.

INTRODUCTION:Bilingualism is among several lifestyle factors associated with protection against cognitive decline, yet the biological mechanisms through which it exerts these effects remain poorly understood.METHODS:We compared neuropsychological functioning and biofluid markers of brain health between active (n = 280) and passive (n = 287) Spanish-Catalan bilinguals with biomarker-confirmed Alzheimer’s disease (AD).RESULTS:Active bilinguals outperformed passive bilinguals on tests assessing attention/executive functions, language, and visuospatial/visuomotor functioning, demonstrating resilience given the same AD biological stage across participants. Active bilinguals also exhibited significant differences in cerebrospinal fluid and plasma biomarkers of amyloid burden and neuroinflammation, suggesting both resilience and resistance to AD pathophysiologic mechanisms.DISCUSSION:The protective effects of bilingual experience may engage both resilience and resistance to AD pathophysiology mechanisms. These results underscore the importance of capturing bilingualism in aging cohorts and the study of how lifestyle and sociocultural factors shape the biological expression of neurodegenerative disease.

<h2>Abstract</h2> Steatotic liver disease (SLD) is a spectrum of highly prevalent liver disease that is encountered at many different healthcare levels. Awareness about metabolic dysfunction-associated SLD (MASLD), MetALD (MASLD and increased alcohol intake) and ALD (alcohol-related liver disease) is increasing beyond hepatology, as highlighted by the various SLD guidelines that have been issued by scientific societies from different disciplines, such as endocrinology. The guidance presented here aims to improve cross-disciplinary knowledge and know-how by providing guidance to healthcare professionals from a global, holistic, multi-society and -stakeholder perspective. The patient trajectory was used as an overarching anchor point to ensure uniform guidance at all points along the SLD spectrum, with the ultimate goal of improving patient identification and optimising their care. This consensus guidance covers patient identification and risk stratification, relevant cross-disciplinary primary and secondary care approaches, referral to and from tertiary care and strategies for disease management and monitoring. Strategies at each point of the patient trajectory are recommended and stratified as optimal (i.e., "nice-to-have") or minimal (i.e., "must-have"), per expert-opinion, making them adaptable to differences in healthcare settings, levels of resource availability and policies.

In 2020, COVID-19 caused a global health crisis, prompting research efforts and accelerating drug development. As part of this response, we conducted a phase 2b, multicentre, open-label, randomized (1:1) clinical trial to compare the effects of siltuximab versus corticosteroids on disease progression in hospitalized adults with COVID-19 pneumonia. Between April 2020 and January 2021, 82 patients were randomized to receive siltuximab and 80 corticosteroids (20 methylprednisolone and 60 dexamethasone). Median (IQR) age was 61 years (50-72). Nineteen patients allocated to siltuximab were admitted to the intensive care unit compared to eight receiving corticosteroids (p = 0.025). Corticosteroid treatment was independently associated with a higher risk of avoiding intensive care unit admission (2.7; 95% CI, 1.11-6.62), lower risk of requiring mechanical ventilation (0.43; 95% CI, 0.20-0.93) and shorter hospitalization duration (p = 0.008). Mortality was similar between arms (p = 0.675). Twenty-eight patients receiving siltuximab required rescue therapy while only 5 receiving corticosteroids (p < 0.001). Furthermore, patients receiving corticosteroids had a 53% lower risk of confirmed bacterial or fungal invasive infections (RR 0.47; 95% CI, 0.23-0.95; p = 0.0096). Our results show that initial treatment with corticosteroids was more effective than siltuximab in preventing disease progression, reducing intensive care unit admission, mechanical ventilation, with shorter hospital stays, and fewer infection in COVID-19 pneumonia. Despite numerous challenges, these findings provide valuable insights into optimizing therapeutic strategies, supporting corticosteroids as a preferred treatment over siltuximab in this setting.

Adolescence is a critical period for brain development, during which dietary patterns may influence neuropsychological functioning. To examine cross-sectional associations and determine if baseline adherence to the Mediterranean diet (MD) and ultra-processed food (UPF) consumption is associated with changes in adolescent neuropsychological outcomes over 6months. This study represents a secondary analysis of the WALNUTs Smart-Snack Trial. We evaluated 653 adolescents (aged 12-16years) from Barcelona at baseline and at 6-month follow-up. All dietary data used for these analyses were collected at the baseline timepoint only. MD adherence was measured with the KIDMED index and UPF consumption was assessed using a food frequency questionnaire and classified using the NOVA system. Cognitive domains were assessed at both time points using standardised computer-based tasks: attention (alerting, orienting, executive control) with the Attention Network Test; working memory (4-back) with the N-back task; fluid intelligence with the Primary Mental Abilities-Revised; decision-making with the Roulettes Task; and emotion recognition with the Emotion Recognition Task. Behavioural outcomes were also evaluated at both time points using the self-reported Strengths and Difficulties Questionnaire and teacher-reported Attention-Deficit/Hyperactivity Disorder-DSM-IV scales. Associations were examined using multivariable generalised linear models. To further validate UPF consumption estimations, polyphenol biomarkers were measured in urine in a subsample of 257 participants. Greater adherence to the MD was cross-sectionally linked to fewer behavioural problems and higher scores of executive functioning, while higher UPF consumption was associated with poorer emotion recognition, reduced alerting attention, less advantageous decision-making, more behavioural problems and internalising symptoms. Longitudinally, higher UPF consumption was associated with more internalising symptoms and less advantageous decision-making, whereas MD adherence showed no associations. Greater MD adherence appears associated with more favourable behavioural and cognitive profiles. In contrast, higher UPF consumption seems to be associated with less favourable profiles across multiple neuropsychological domains in adolescents. However, the limited longitudinal evidence points to complex relationships that warrant further investigation. Overall, these findings highlight the importance of promoting healthier dietary habits during adolescence.