About 10% of all decedents in the population die after admission to an intensive care unit (ICU). These patients often have distressing symptoms and may receive more intense life-prolonging treatment than they would have chosen, their family members often experience lasting distress from the experience and many ICU physicians and nurses are burdened by their perception of potentially non-beneficial care. The EPIC project aims to sustainably improve palliative care for critically ill patients and their families in the ICU. An interdisciplinary consortium collaborates to provide a novel harmonized palliative care practice model using telemedicine. The project is the first European interventional study on palliative care in the ICU, using a systems-based approach with proactive patient identification, checklist and blended learning targeted to specific requirements of ICU clinicians. Effectiveness of the new model is assessed through a stepped wedge randomized trial with 7 clinical centers from 5 European countries, 23 multi-disciplinary ICUs and enrolment of 2001 patients. Primary outcome is a reduction in ICU stay to relieve suffering. Cost implications and cost effectiveness will be assessed from different perspectives. An evidence-based patient decision aid for critically ill patients is developed. Additional outcomes serve deepen our understanding of barriers and facilitators and provide ethical recommendations for the use of telepalliative care in civic society. The vision of EPIC is to contribute to a mind shift from a narrow focus on prolonging life towards more holistic care. A European patient and family advisory group is implemented to engage patients and family members from the start and co-create open-access information to increase acceptance of palliative care. Telemedicine offers a low-cost solution to spread the model to all regions in Europe and open new avenues for patient-centered care.

Recent evidence demonstrates that cancer is overtaking cardiovascular disease as the number one cause of mortality in Europe. This is largely due to the lack of preventative measures for common (e.g. breast) or highly fatal (e.g. ovarian) human cancers. Most cancers are multifactorial in origin. The core hypothesis of this research programme is that the extremely high risk of BRCA1/2 germline mutation carriers to develop breast and ovarian cancer is a net consequence of cell-autonomous (direct effect of BRCA mutation in cells at risk) and cell non-autonomous (produced in distant organs and affecting organs at risk) factors which both trigger epigenetic, cancer-initiating effects. The project’s aims are centered around the principles of systems medicine and built on a large cohort of BRCA mutation carriers and controls who will be offered newly established cancer screening programmes. We will uncover how ‘cell non-autonomous’ factors work, provide detail on the epigenetic changes in at-risk tissues and investigate whether these changes are mechanistically linked to cancer, study whether we can neutralise this process and measure success in the organs at risk, and ideally in easy to access samples such as blood, buccal and cervical cells. In my Department for Women’s Cancer we have assembled a powerful interdisciplinary team including computational biologists, functionalists, immunologists and clinician scientists linked to leading patient advocacy groups which is extremely well placed to lead this pioneering project to develop the fundamental understanding of cancer development in women with BRCA mutations. To reset the epigenome, re-establishing normal cell identity and consequently reducing cancer risk without the need for surgery and being able to monitor the efficacy using multicellular epigenetic outcome predictors will be a major scientific and medical breakthrough and possibly applicable to other chronic diseases.

Ovarian cancer (OC) is the most lethal of female cancers, often termed a “silent killer”. DISARM’s overall approach to tackle the significant gaps in hereditary OC management lies in tackling both key elements of risk assessment and early detection. The project will investigate multifactorial risk assessment versus standard practices in 4 EU Member States (MS) (Lithuania, Portugal, Czech Republic, and Greece), and will upscale and validate a set of easy-to-use, highly accurate and affordable technologies in five countries (UK, Lithuania, Portugal, Czech Republic, and Greece). Several intelligent digital assets will optimally support and enhance our clinical studies, while a range of multifaceted activities will ensure the future uptake and adoption of DISARM solutions. The project aligns with the Innovation Action character of this topic by focusing on both mature technologies that can be upscaled in routine healthcare and on emerging technologies that have already shown a potential to justify larger scale validation activities. Our ultimate ambition is to holistically investigate the preconditions and set the stage for rolling out proven solutions in routine OC risk assessment, and in parallel to create further evidence for the introduction of novel promising elements in early detection programmes. DISARM gathers 26 partners from 12 countries (10 EU MS, the UK and Canada), thereby exhibiting a significant geographic coverage, strengthening European and international collaboration and ensuring widespread diffusion of the project results. This action is part of the Cancer Mission cluster of projects on ‘Prevention and Early Detection (early detection heritable cancers)

GRIP on MASH will address the unmet public health need of reducing disease burden and comorbidities associated with Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD). Together with seven medical technology, pharmaceutical and biotechnology companies, we will devise a sustainable and scalable GRIP on MASH Platform that will enable access to at-risk patients developing or having MASLD through the early detection of this condition at the primary care level. This Platform will allow A) the early detection of patients with MASLD: distributed in 12 European Centers of Excellence (CoEs), 10,000 patients at high risk of MASLD - defined as patients with type-2 diabetes mellitus, metabolic syndrome, obesity or arterial hypertension - will be screened and characterized; B) better patients’ stratification: the Platform will comprise artificial intelligence-based decision support tools that will make use of existing and novel biomarkers/biomarker combinations. Their predictive accuracy will be tested at the primary care level; there we will perform multi-OMICs analysis (proteomics, lipidomics, metabolomics, genomics, metagenomics and fluxomics) in fasted blood samples and we will explore imaging biomarkers/organ-on-a-chip to find future non-invasive diagnostic alternatives for the current standard (liver biopsies); and C) personalized lifestyle advice, by exploring evidence-based lifestyle features and the effect of nutritional recommendations: among the cohorts at the CoEs, we will use validated questionnaires to assess physical activity, diet, sleep, smoking, alcohol consumption, and perception of stress. Integrating patients’ perspectives with the participation of two patient organizations, the trustworthiness and sustainability of our GRIP on MASH Platform will be assessed by investigating potential economic, ethical and regulatory barriers to its future adoption. GRIP on MASH will change healthcare practice in MASLD and reduce the disease burden for patients.