Intensive care is under increasing pressure due to demographic changes, availability of new complex therapies, and workforce shortages, resulting in a relative reduction in resources. Technological advances such as digitalization, wearable sensors, and artificial intelligence promise to improve care delivery, enabling providers to offer equal or higher-quality care at lower costs. However, no healthcare system has yet demonstrated large-scale gains in the efficiency of intensive care delivery. A central requirement is the capacity to translate ideas and concepts into value, providing changes that make services, products, and optimal care more accessible and affordable to a larger population, generating value. Innovation should thus be acknowledged as a fourth principal pillar of intensive care, alongside clinical excellence, research, and teaching. This paper presents the opinion of a multidisciplinary expert panel, proposing a framework to support the generation, implementation, and evaluation of innovation in intensive care. We identify and examine key areas and applications where innovation is urgently needed, including workforce development, technology adoption, environmental sustainability, and the transformation of medical education. We also highlight barriers and concerns that must be addressed when implementing innovation in ICUs. We integrate these into a comprehensive framework illustrated through concrete examples. Finally, we argue that innovation should not be driven solely by academia or industry, but strategically led by healthcare professionals and patients’ representatives, grounded in ethics and data, interdisciplinary, and centered on patients’ and society’s needs. This framework offers a pathway for innovation, supporting a more inclusive, effective, and sustainable future for intensive care.
Background:3D printing enables the fabrication of customized breast phantoms for image quality assessment in digital mammography (DM) and digital breast tomosynthesis (DBT). A major challenge is the absence of standardized, accessible methods to characterize the attenuation properties of 3D-printed materials under clinical DM/DBT spectra. Methods:An experimental framework was implemented to determine the effective X-ray attenuation coefficient (μ eff ) of six 3D-printed polymers (PLA, PET, resin, ABS, ABS+, HIPS) and reference breast tissue-equivalent materials (CIRS plates simulating different breast glandular/adipose ratios (BR) and PMMA) using two commercial DM/DBT systems, with and without anti-scatter grid. Step-wedges (0.5-5.5 cm) were imaged across multiple kVp and filter settings. The μ eff were obtained from measurements on images and fitted to an empirical model yielding μ 0 (attenuation at thickness tending to zero) and k (decay rate) to characterize beam hardening and scatter influences. 3D-reference material equivalences were evaluated based on μ eff and μ 0 . Results:Beam hardening and scatter reduced μ eff with thickness, by 6%-14% with grid and 12%-28% without grid, with scatter contributing 47%-76% of the reduction in no-grid acquisitions. No significant differences were observed between the two mammography systems. Based on μ eff values, attenuation equivalences (within ±6%) were identified between 3D-printed and reference breast tissue-equivalent materials: PLA with BR 100/0; PET and resin with BR 70/30 and PMMA; ABS+ with BR 30/70 and BR 50/50. ABS and HIPS showed larger mismatches. The empirical model achieved excellent fits (R2 > 0.99), with μ 0 values preserving attenuation ranking and enabling derivation of equivalent glandular proportions. Conclusion:This framework demonstrates that routine clinical mammography systems can be used directly, without specialized instrumentation, to characterize 3D-printed materials as tissue surrogates. Several low-cost, widely available polymers were shown to reproduce breast tissue attenuation, supporting the local fabrication of anthropomorphic breast phantoms for realistic and clinically relevant image quality evaluation.
Background and objective Cholangiocarcinoma (CCA) is a heterogeneous neoplasm of the biliary epithelium that easily infiltrates, metastasises and recurs. Magnesium disbalance is a hallmark of CCA, with the magnesium transporter cyclin M4 (CNNM4) being a key driver of various hepatic diseases. This study aims to unravel the role of CNNM4 in the initiation and progression of CCA. Design CNNM4 protein and gene expression were assessed in vitro, in vivo and in patients with CCA. Silencing of CNNM4 was effectively achieved by using small interfering RNA (siRNA) or short hairpin RNA in CCA cell lines and GalNAc-conjugated siRNA in a transposon-based CCA mice model. The impact of CNNM4 on tumour cell proliferation, migration and invasion to the lungs was evaluated using the chicken chorioallantoic membrane model. Proteomic analysis was employed to elucidate the underlying molecular mechanisms. Results CNNM4 was upregulated in CCA samples from humans, mice and cell lines. Functional studies demonstrated that CNNM4 deficiency attenuates cell growth, chemoresistance, migration, invasion, cancer stem cell properties and Warburg effect in vitro and in vivo. Proteomic analysis identified nuclear protein 1 as an upstream regulator of CNNM4-induced ferroptosis in CCA, ultimately leading to cell death. The iron chelator deferiprone could reverse the decreased proliferation induced by CNNM4 silencing, while inhibition of the heme oxygenase-1 by zinc protoporphyrin IX affected only the growth of cells with no targeted CNNM4 inhibition, highlighting the specificity of ferroptosis in CNNM4-associated effects. Conclusion This study reveals that increased CNNM4 expression drives CCA progression and malignancy and that its inhibition may be an effective therapeutic strategy to limit proliferation and metastasis in patients with CCA.
Background:Frailty assessment has emerged as a key component of pre-transplant evaluation. We aimed to validate, across international cohorts, the Hematopoietic Cell Transplantation Frailty Scale (HCT-FS) for the assessment of frailty in adult candidates for allogenic hematopoietic cell transplantation (allo-HCT). HCT-FS is designed for integration into routine workflows using existing resources. Methods:In this prospective, observational cohort study, we evaluated the performance of HCT-FS, a frailty scale that categorises patients as fit, pre-frail, or frail based on a cumulative weighted score derived from eight variables. We enrolled participants across 16 allo-HCT programmes (one in Canada, 15 in Spain). Eligible participants were all adult patients evaluated for frailty at the centres during the time frames: from the Hans Messner Allo-HCT Program at Princess Margaret Cancer Center (PMCC) in Toronto, Canada (2018-2024; where HCT-FS was developed) and from 15 Grupo Español de Trasplante Hematopoyético y Terapia Celular (GETH-TC) centres across Spain (2022-2023). Frailty was systematically assessed in all candidates for a median of 10 min at the first allo-HCT consultation by haematologists or trained nurses using the HCT-FS. The prognostic accuracy of the HCT-FS was assessed by evaluating its ability to discriminate clinical outcomes across frailty categories in the overall cohort and by testing the consistency of these associations within specific patient subgroups. Data were prospectively updated until February 2025. Findings:Overall, 1077 consecutive adult allo-HCT candidates were enrolled and evaluated across the PMCC (n = 734) and GETH-TC (n = 343) cohorts. The median age was 56 years (range 18-76); 411 patients (38.2%) were over 60, and 640 (59.4%) were male. Based on the HCT-FS, 33.4% patients were fit, 53.7% pre-frail, and 12.8% frail. Frailty was associated with longer hospital stays (23, 25, and 28 days for fit, pre-frail, and frail patients, respectively; p = 0.003) and higher ICU admission rates (Day +180: 7.0%, 10.8%, and 20.3% for fit, pre-frail, and frail patients, respectively; p = 0.002). 2-year OS decreased progressively with increasing frailty: 77.2% for fit, 65.7% for pre-frail, and 52.8% for frail (p < 0.001). Corresponding NRM rates were 11.7%, 19.5%, and 32.2%, respectively (p = 0.001). Multivariable analysis confirmed frailty as a predictor of inferior OS and increased NRM, when adjusting for age, comorbidities, performance status, DRI, and donor type. The HCT-FS maintained robust prognostic accuracy across subgroups stratified by age and comorbidity burden. Interpretation:The HCT-FS provided reliable measures of the frailty status of allo-HCT candidates that are informative for transplant outcomes, supporting its potential applicability in clinical practice. Notably, this tool was successfully integrated into clinical practice without additional resources. Future work is needed to further evaluate the applicability of the scale in transplant settings and whether targeted interventions based on can improve transplant outcomes. Funding:None.
Chronic obstructive pulmonary disease (COPD) is a progressive lung condition associated with high morbidity and mortality. Single-inhaler triple therapy (SITT), such as budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF), is recommended for patients with COPD who are not adequately controlled by dual therapy (DT). Escalation from DT or switching from triple therapy (TT)—SITT or multiple-inhaler TT (MITT)—are key real-world treatment pathways. The observational, retrospective, multicenter ORESTES study included adults (≥ 40 years) with COPD initiating BGF in routine clinical practice. This secondary analysis focuses on the following treatment pathways: escalation from DT and switch from TT. Patients’ characteristics, exacerbations, additional COPD treatments, and healthcare resource utilization (HCRU) were assessed. A total of 295 patients escalated from DT and 356 switched from TT (SITT: 147; MITT: 209) to BGF. 66.8
