The chronic heart failure evolutions: Different fates and routes

Abstract Aims Individual prognostic assessment and disease evolution pathways are undefined in chronic heart failure (HF). The application of unsupervised learning methodologies could help to identify patient phenotypes and the progression in each phenotype as well as to assess adverse event risk. Methods and results From a bulk of 7948 HF patients included in the MECKI registry, we selected patients with a minimum 2‐year follow‐up. We implemented a topological data analysis (TDA), based on 43 variables derived from clinical, biochemical, cardiac ultrasound, and exercise evaluations, to identify several patients' clusters. Thereafter, we used the trajectory analysis to describe the evolution of HF states, which is able to identify bifurcation points, characterized by different follow‐up paths, as well as specific end‐stages conditions of the disease. Finally, we conducted a 5‐year survival analysis (composite of cardiovascular death, left ventricular assist device, or urgent heart transplant). Findings were validated on internal ( n  = 527) and external ( n  = 777) populations. We analyzed 4876 patients (age = 63 [53–71], male gender n  = 3973 (81.5%), NYHA class I–II n  = 3576 (73.3%), III–IV n  = 1300 (26.7%), LVEF = 33 [25.5–39.9], atrial fibrillation n  = 791 (16.2%), peak VO 2 % pred = 54.8 [43.8–67.2]), with a minimum 2‐year follow‐up. Nineteen patient clusters were identified by TDA. Trajectory analysis revealed a path characterized by 3 bifurcation and 4 end‐stage points. Clusters survival rate varied from 44% to 100% at 2 years and from 20% to 100% at 5 years, respectively. The event frequency at 5‐year follow‐up for each study cohort cluster was successfully compared with those in the validation cohorts ( R  = 0.94 and R  = 0.84, P  < 0.001, for internal and external cohort, respectively). Finally, we conducted a 5‐year survival analysis (composite of cardiovascular death, left ventricular assist device, or urgent heart transplant observed in 22% of cases). Conclusions Each HF phenotype has a specific disease progression and prognosis. These findings allow to individualize HF patient evolutions and to tailor assessment.

Economic burden of heart failure in Europe: A systematic review of costs and cost‐effectiveness

Abstract Heart failure (HF) affects over 64 million individuals worldwide and is a major cause of hospitalization and mortality, particularly among older adults. In Europe, HF imposes a significant and growing economic burden. This systematic review aimed to evaluate the economic impact of HF diagnosis, treatment and management across European healthcare systems. A systematic literature search was conducted using PubMed, Cochrane Library and Econlit databases including the terms ‘heart failure’ AND ‘costs’ OR ‘cost of illness’ OR ‘cost analysis’ OR ‘economic burden’ OR ‘cost effectiveness’ OR ‘primary care’ OR ‘secondary care’. Studies published between January 2000 and January 2024 were included. A total of 49 studies were included: 17 on resource use, 11 on costs, 15 on resource use and costs, 1 on costs and cost‐effectiveness, and 5 on resource use, costs and cost‐effectiveness. Hospitalizations and medication use were the most frequently reported resource parameters. Annual HF‐related costs varied widely across countries, ranging from €613 to €22,647 per patient. Hospitalizations represented the primary cost driver, accounting for 15% to 92% of total HF costs. Cost‐reduction strategies included multidisciplinary care, telemonitoring and pharmacologic interventions. Several disease management programmes reduced hospital admissions and emergency visits. Cost‐effectiveness analyses supported the use of certain HF therapies, with incremental cost‐effectiveness ratios ranging from €1490 to €9406 per QALY gained. F imposes a substantial economic burden in Europe, largely driven by hospitalizations. Cost‐effective interventions such as remote monitoring and integrated care programmes can reduce this burden. Broader adoption of these strategies may improve outcomes and optimize resource allocation across healthcare systems.

Incorporating soil‐structure interaction into simplified numerical models for fragility analysis of RC structures

Abstract Simplified building models are a valuable option for seismic assessment at the regional scale. These models often use calibrated springs to model column behaviour, and recent advances have made them suitable for capturing torsional response in Reinforced‐Concrete Moment‐Resisting‐Frames. Nevertheless, their validation is typically achieved using fixed‐base models, which do not include the influence of soil‐structure interaction (SSI). This study introduces a novel approach to quantify the accuracy of a recently developed simplified model while accounting for dynamic SSI, using a newly implemented, refined 3D Finite Element non‐linear soil model in OpenSees. The accuracy of the simplified structural model is assessed by comparing the results of non‐linear dynamic analyses with those of a refined model in terms of (i) a peak structural demand parameter such as the interstorey‐drift ratio and (ii) fragility curves computed from cloud analysis and accounting for collapse cases. The study presents details of the proposed refined approach for 3D soil modelling in OpenSees, focusing on implementing free‐field boundary conditions and structure‐to‐soil connections. Results show that the accuracy of the simplified model is maintained, even in the presence of SSI, and it successfully captures the overall structural response measured at peak demand. For the proposed case study, the difference between the simplified and refined models’ fragility curves’ medians is 4% and 2% for fixed and SSI models, respectively. The simplified structural model, combined with the refined soil model for SSI effects, presents an innovative and conservative, yet computationally efficient, alternative for seismic risk analysis, even in the presence of structural irregularity.

Techno‐Economic and Lifecycle Analysis of Green Colloidal Silver: Moving toward Scale‐Up

Abstract Silver particles (AgPs) are increasingly used across a range of industries, including personal care, household, and food packaging, but conventional synthesis methods involve high production costs and negative environmental impacts. Green synthesis using plant extracts offers a sustainable alternative, though limited comparative data on economic and environmental performance exist. This study evaluates three green methods—BX3 (a patented extract), lemon juice (LJ), and green tea (GT)—against a conventional method using sodium borohydride (NaBH₄). Equal‐volume reactions are analyzed via ICP‐MS, UV–vis spectroscopy, and dynamic light scattering. Techno‐economic analysis and life cycle assessment (LCA) assessed costs and environmental impact. BX3 emerged as the most cost‐effective and environmentally friendly option, producing AgPs at $13,000/kg with a 75% yield and a global warming potential of 1,900 kg CO₂‐Eq/kg. In contrast, NaBH₄ yielded 7.35% at $195,000/kg, 15x more expensive than the BX3 method, and a global warming potential of 74,000 kg CO₂‐Eq/kg. GT, while a green method, has the highest cost $690,000/kg, the lowest yield (1.13%), and the worst environmental impact, including a human toxicity value of 92,000 kg 1,4‐DCB‐Eq/kg‐even surpassing the toxic NaBH₄ process. These findings highlight BX3's promise for scalable, low‐impact AgP production and broader industrial use.

Cover Image, Volume 73, Issue 6

Cover Illustration: Mouse oligodendroglia (O4+ in green and nuclei in white) co‐cultured with primary microglia (not shown in this image) after exposure to corticosterone.(See Madeira, M., et al, https://doi.org/10.1002/glia.24661 )

Oligodendroglia Are Primed for Antigen Presentation in Response to Chronic Stress‐Induced Microglial‐Derived Inflammation

ABSTRACT Chronic stress is a major contributor to the development of major depressive disorder, one of the leading causes of disability worldwide. Using a model of repeated social defeat stress in mice, we and others have reported that neuroinflammation plays a dynamic role in the development of behavioral deficits consistent with social avoidance and impaired reward responses. Animals susceptible to the model also exhibit hypomyelination in the medial prefrontal cortex, indicative of changes in the differentiation pathway of cells of the oligodendroglial lineage (OLN). We computationally confirmed the presence of immune oligodendrocytes, a population of OLN cells, which express immune markers and myelination deficits. In the current study, we report that microglia are necessary to induce expression of antigen presentation markers (and other immune markers) on oligodendroglia. We further associate the appearance of these markers with changes in the OLN and confirm that microglial changes precede OLN changes. Using co‐cultures of microglia and OLN, we show that under inflammatory conditions the processes of phagocytosis and expression of MHCII are linked, suggesting potential priming for antigen presentation by OLN cells. Our findings provide insights into the nature of these OLN cells with immune capabilities, their obligatory interaction with microglia, and identify them as a potential cellular contributor to the pathological manifestations of psychosocial stress.

Primary Care Provider Perspectives on Depression Management in Older Adults With Multimorbidity

Associations of Device‐Measured Physical Activity and Sedentary Time With Neural Responses to Visual Food Cues in Adults: A Functional Magnetic Resonance Imaging Study

ABSTRACT Self‐reported physical activity is associated with lower brain food cue responsiveness in reward‐related regions, but relationships utilizing objective physical activity measurement tools have not been explored. This cross‐sectional study examined whether device‐measured moderate‐to‐vigorous intensity physical activity and sedentary time are related to neural responses to visual food cues using functional magnetic resonance imaging. Fifty‐one healthy adults (30 men, 21 women; mean ± SD: age 26 ± 6 years; body mass index 24.1 ± 3.0 kg/m 2 ) underwent a functional magnetic resonance imaging scan after an overnight fast while viewing images of high/very high‐energy density foods (HED), very low/low‐energy density foods (LED) and non‐food objects. Free‐living moderate‐to‐vigorous intensity physical activity and sedentary time were measured for seven consecutive days using an ActiGraph wGT3X‐BT and activPAL4 accelerometer, respectively. Associations of behavioural variables with brain food cue reactivity were examined in regression models controlling for physiological and behavioural covariates. After adjusting for age, sex, body mass index and device weartime, moderate‐to‐vigorous intensity physical activity was negatively associated with reactivity to LED versus non‐food cues in the precentral gyrus, hippocampus, posterior insula, and amygdala, which may diminish inhibitory‐related responses towards healthier lower energy value foods. Time spent in moderate‐to‐vigorous intensity physical activity was positively associated with reactivity to LED versus non‐food cues in the dorsal striatum, a region implicated in food motivation. A positive association was identified between sedentary time and reactivity to HED versus non‐food cues in the dorsal division of the posterior cingulate gyrus that has been implicated in attention allocation. These findings suggest that moderate‐to‐vigorous intensity physical activity may enhance the appeal of and motivation to consume LED foods, whereas sedentary time may promote attention towards HED foods, highlighting the potential for engaging in greater physical activity and less sedentary time to positively influence the central (brain) appetite control system.

The implications of non‐synchronous trading in G‐7 financial markets

Abstract We investigate the effects of non‐synchronous trading on volatility spillover for the G‐7 equity markets during the Eurozone sovereign debt crisis (ESDC) and the Covid‐19 pandemic crisis. For data synchronisation we utilise ΜΑ(1) adjusted return series to estimate the Baba‐Engle‐Kraft‐Kroner (BEKK) and the dynamic conditional correlation (DCC) models. We also consider the use of realised kernels as explanatory variables in the variance equation. In this set up, the contagion effects during crises periods are more perceptible, as the spikes are easier to interpret. We also check the robustness of our main results by applying, wavelet coherence analysis to G‐7 major equity indices with realised kernels, as well as local Gaussian correlations (LGC). Our findings suggest the empirical significance of the synchronisation effects for the US and the other G‐7 equity markets. We also conclude that realised kernels is an effective tool for mitigating non‐synchronous effects. These results underline the significance of quantifying the synchronisation effects in equity markets as well as international portfolio diversification strategies.

Sovereign bonds' risk‐based heterogeneity

Abstract Are sovereign risk premia subject to heterogeneous effects from their drivers, associated with the risk class each sovereign bond belongs to? In the paper at hand, effects on sovereign bond risk premia stemming from macroeconomic, fiscal, and volatility factors, are examined by considering the classification of sovereign riskiness. Panel data estimation techniques are used, for 30 countries, with data in quarterly frequency for the period 2001Q1 to 2019Q4. Sovereign spreads are found to be subject to heterogeneous effects associated with their credit ratings; spreads on sovereign bonds considered low‐risk increase with higher growth rates and inflation, while spreads on highly risky bonds decrease with higher growth rates and are more sensitive to idiosyncratic and global volatility. Primary fiscal surpluses indeed lower spreads but cannot counterbalance the effects of volatility episodes and the prospects for low growth. Our results provide support for countercyclical fiscal policies, suggesting that spreads can be expected to be reduced by primary surpluses, under the condition that the economy expands and market volatility is low. Our main findings are robust to various alternative setups, samples, and control variables such as central banks' asset purchases.