Since 1858, human atherosclerotic plaques have been shown to contain immune cells. But are these cells suitable therapeutic targets? Dozens of clinical trials of anti-inflammatory agents other than colchicine have been performed in patients with clinically evident atherosclerosis. None of these trials led any regulatory body in any jurisdiction to allow a cardiovascular indication for any of these agents. This discouraging work provides a background to evaluate new data on colchicine. In 2024-2025, new clinical trials of colchicine in patients with atherosclerosis showed benefit, no benefit, or harm. In 2025-2026, over a dozen meta-analyses so far have appeared, drawing on ∼34 trials, but do not agree with each other. One of these meta-analyses, Xie et al.'s in the Journal of Internal Medicine, provides a compelling graphical display of the pre-specified primary outcomes of six long-term clinical trials as they were published over time. The pattern of early positive trials, then newer negative (null) trials, suggests regression to the truth. Jeon and Cho et al.'s population-wide study in the Journal of Internal Medicine of patients with Type 2 diabetes and gout found no benefit from colchicine over nonsteroidal anti-inflammatory drugs on major adverse cardiovascular events. This information suggests several areas for reform of research on inflammation in atherosclerosis. Fully informed consent should require that clinical trials of anti-inflammatory agents in atherosclerotic arterial disease must disclose to trial participants the failures of this approach in over 50 clinical trials to date, spanning decades. Additionally, the field might reconsider its commitment to the Big Idea that inflammation must be a definitive therapeutic target in atherosclerosis. The track record so far for inflammation inhibition in atherosclerosis is extensive and disappointing-a fact that merits wider discussion. Therapeutic successes from targeting cholesterol-rich, apolipoprotein-B-containing lipoproteins-the proven causative agents of this disease-provide extraordinary evidence. Current data for colchicine and other anti-inflammatory therapies do not.

High-throughput sequencing has transformed clinical diagnostics of rare diseases (RD), cancer and infectious diseases by enabling the identification of disease-causing genetic alterations and facilitating individualised treatment and care. In response to these advances, Genomic Medicine Sweden (GMS) was established in 2017 as a national collaborative effort to accelerate implementation of genomics-based precision medicine within Sweden's regionally organized, publicly funded healthcare system. GMS brings together the seven university healthcare regions and their associated medical faculties, in collaboration with healthcare regions across Sweden, Science for Life Laboratory, patient organizations, industry and governmental agencies. Activities are coordinated through national disease-specific expert groups, supported by cross-cutting functions in bioinformatics, health economics, ethics, education and patient engagement. At the operational level, seven Genomic Medicine Centres, embedded at university hospitals, develop and deliver harmonised genomic diagnostics nationwide. The National Genomics Platform provides secure infrastructure for large-scale data storage, analysis, and national and international data sharing. Following initial project-based funding, GMS now receives long-term governmental support. This review describes the national implementation of genomic-based precision diagnostics, discusses challenges and lessons learnt, and highlights key milestones across disease areas, including whole-genome sequencing in RD and paediatric cancer, comprehensive genomic profiling of haematological malignancies and solid tumours, pathogen genomics in microbiology, pharmacogenomic testing and emerging applications of polygenic risk scores in complex diseases. Collectively, these efforts have contributed to more than 500,000 genomic tests being performed within Swedish healthcare between 2017 and 2025. Finally, we outline future diagnostic needs and priority areas to ensure sustainable, scalable and equitable access to precision medicine.

Type 2 diabetes (T2D) is a major global health concern strongly associated with atherosclerosis and subsequent macrovascular complications. These complications are the leading cause of death among T2D patients. Despite a decline in cardiovascular events over the last decade, individuals with T2D still have an approximately doubled risk compared to those without diabetes. This shows an urgent need for therapies targeting biological processes specific to T2D-associated atherosclerosis. Nevertheless, more research is needed to identify exactly which processes can be targeted therapeutically. Current therapies either target lipid metabolism or inflammation, two processes commonly considered important in T2D-associated atherosclerosis. However, more recent human plaque tissue studies show no differences in plaque levels of lipids nor inflammatory markers, possibly reflecting improved clinical treatment strategies. Other distinct differences in plaque tissue composition in T2D have been put forward, including thin fibrous caps and large necrotic cores. Moreover, T2D may influence several biological processes affecting both plaque formation and progression (such as oxidative stress and efferocytosis). These mechanisms could potentially also be targeted to prevent atherosclerotic cardiovascular complications. This review focuses on the shifting epidemiology of T2D-associated cardiovascular complications, as well as biological changes in T2D plaques, and how these changes can guide future clinical approaches to further reduce atherosclerotic complications.

Several somatic diseases have been consistently linked with an increased dementia risk. However, the underlying neuropathological substrates remain poorly characterized. This narrative review aims to summarize evidence on the association between common age-related somatic conditions (i.e., heart diseases, type 2 diabetes, kidney disease, liver diseases, lung disease, and anemia) and neuropathological findings, encompassing both Alzheimer's disease (AD)-related pathology (amyloid and tau deposition) and non-AD co-pathologies (i.e., neuronal loss, neuroinflammation, cerebrovascular lesions, and non-AD proteinopathies). We conducted a PubMed search for human studies examining these associations using postmortem data, brain imaging, or cerebrospinal fluid biomarkers. Evidence was qualitatively synthesized and graded according to its strength. Strong and consistent associations were observed between most examined somatic diseases and global neuronal loss or brain atrophy, as well as cerebrovascular lesions. In contrast, evidence associating these conditions with amyloid and tau pathology was limited and inconsistent. No studies systematically examined neuroinflammation or non-AD proteinopathies in relation to somatic diseases. Together, the available evidence suggests that somatic diseases are unlikely to primarily drive AD pathology but instead contribute to brain damage through a combination of non-AD processes, particularly cerebrovascular injury and diffuse neuronal loss. These findings highlight the need to increase our knowledge of "mixed dementia" and move beyond a purely brain-centric view of dementia, especially in older adults with complex clinical profiles.