Prader-Willi syndrome (PWS) is a rare, neurodevelopmental, multisystemic syndrome caused by lack of expression of paternal genes on chromosome 15q11.2-13. PWS is characterized by muscular hypotonia, abnormal body composition, hormone deficiencies, cognitive dysfunction and behavioural issues, including hyperphagia, increasing the risk of severe obesity. A single causative gene for hyperphagia has not been identified, and regulation of hunger and satiety is complex and multifactorial, making it difficult to identify a specific neuropeptide or hormone as the most important. Cornerstone treatments are a strict, controlled diet and regular physical activity. Several clinical trials with different pharmacological agents have been performed attempting to reduce or treat hyperphagia and obesity. However, many drug programmes have been discontinued due to adverse events or not reaching endpoints. In this review, we have focused on phenomenology and management of hyperphagia, treatment with oxytocin (OT), glucagon-like-peptide-1 receptor agonists (GLP-1RA) and diazoxide choline. We conclude that controlled food access is crucial; managing expectations about food mitigates food-related behaviour; OT treatment of infants with PWS results in less severe hyperphagia at ages 3 and 4 years old; and that the effects of GLP-1RA on body weight seem modest. Studies of diazoxide choline extended-release (DCCR), the first approved treatment of hyperphagia in PWS, have shown promising results, particularly in managing severe hyperphagia, reducing fat mass and improving behavioural issues. Thus, although progress is being made in targeted pharmacological therapies to control hyperphagia, controlled food access remains crucial to prevent obesity but is not sufficient for management of food and behaviour.

Glucagon-like peptide-1 (GLP-1) receptor agonists provide benefits in weight reduction, glycaemic control in Type 2 diabetes, and cardiovascular and renal outcomes. Their widespread use has given rise to concerns regarding rare but potentially serious adverse events. This narrative review appraises evidence regarding seven serious adverse events linked to GLP-1 receptor agonists: thyroid cancer, non-arteritic anterior ischaemic optic neuropathy (NAION), suicidal behaviours and self-harm, diabetic retinopathy complications, acute pancreatitis, gallbladder and biliary disease and intestinal obstruction. Evidence from mechanistic studies, spontaneous reports, randomized trials and cohort studies is considered. Gallbladder and biliary disease has the most consistent evidence supporting a causal association. Worsening of diabetic retinopathy appears most consistent with early worsening after rapid glycaemic improvement in patients with pre-existing retinopathy. For thyroid cancer, NAION, suicidal behaviour and self-harm, acute pancreatitis and intestinal obstruction, evidence regarding causality remains uncertain. Rare events, incomplete ascertainment in trials and residual confounding in observational studies limit inference. Because these events are rare, even substantial relative risk increases generally correspond to small absolute risk increases in broad populations but may become relevant in patients with high baseline risk. Treatment decisions should consider the strength and uncertainty of safety evidence, individual baseline risk, expected benefits relative to available alternatives and patient preferences.

Vascular Ehlers-Danlos syndrome (vEDS), caused by likely pathogenic COL3A1 variants, carries a high risk of arterial dissection or rupture, intestinal perforation and uterine rupture, and a median survival near 51 years. It is often recognized only at a catastrophe, and its acute management is deliberately counter-intuitive. The therapeutic landscape changed in 2025 with the first randomized evidence for an angiotensin-receptor blocker. We provide a clinical, practice-oriented review for internists and the multidisciplinary team. As is appropriate for a rare disease, case-level evidence was considered alongside cohorts and trials. Suspicion is the rate-limiting step, and we set out speciality-specific red flags. Diagnosis requires molecular confirmation, with differentiation from other heritable arteriopathies. Genotype is a probabilistic predisposition, not a deterministic predictor: there is ascertainment bias, reduced penetrance and intrafamilial variability temper inference. Emergency care is harm-avoidant-catheter angiography, elective endoscopy and unnecessary surgery should be avoided, and endovascular and tissue-sparing techniques preferred. Pharmacological prevention rests on celiprolol, with randomized evidence now supporting irbesartan added to background celiprolol, and expert-centred consideration of angiotensin-receptor blockade when celiprolol is not tolerated. Surveillance should be individualized along the European Reference Network on Rare Multisystemic Vascular Diseases logic. Pregnancy, psychosocial care and cascade testing complete lifelong management. In vEDS, earlier recognition and the avoidance of iatrogenic harm-not new molecules-offer the largest near-term gains in survival and quality of life.

Population ageing is portrayed as a threat to the sustainability of health and welfare systems. This narrative-grounded in static chronological definitions of old age-risks overstating the burden of increasing longevity while overlooking changes in survival, health and population composition. In this article, we adopt a demographic perspective to rethink longevity and healthspan through the lens of positive demography, which reframes ageing as a structural transformation that can generate opportunities if institutions, health systems and policies adapt accordingly. Using prospective measures that define old age by remaining life expectancy (LE), we show that population ageing appears less burdensome than conventional indicators suggest (e.g., dynamic dependency ratios fluctuate around 20% compared with 40% under fixed thresholds). Nonetheless, challenges persist, including growing heterogeneity and inequalities in late-life health and care needs (with healthcare workforce demand by 2071 ranging from a 33% increase to a 16% decrease depending on morbidity trends) and a widening gap between lifespan and healthspan (LE at age 60 has risen at double the rate of healthy LE), resulting in more prolonged dependency and complex end-of-life trajectories. Prevention (primordial, primary, secondary and tertiary) and palliative care emerge as crucial but insufficiently integrated components of ageing societies' health systems. We conclude that a forward-looking demographic framework-integrating dynamic age thresholds, cohort-specific health profiles, and equitable access to care across the full continuum-is essential to align societies with realities of longer lives. Population ageing is not a problem to be solved but a context within which health systems and policies must evolve.

Conventional Swedish snus is used by millions in Scandinavia and increasingly worldwide, yet its cardiovascular effects remain poorly characterized. The emergence of nicotine pouches-commonly referred to as 'white snus' in Sweden-that deliver comparable nicotine without tobacco constituents adds complexity to a heterogeneous landscape and raises questions about whether cardiovascular risk follows nicotine exposure regardless of product type. We explore epidemiological and mechanistic evidence on snus and cardiovascular disease, the contributions of nicotine versus tobacco-specific nitrosamines (TSNAs) to risks, and identify knowledge gaps, with focus on novel nicotine products and the research opportunity offered by the Swedish Tobacco Cohort (SWETOC). Epidemiological evidence suggests elevated cardiovascular disease (CVD) mortality among snus users, with the most consistent signals for fatal myocardial infarction and heart failure. Associations with incident atherosclerotic events are more heterogeneous. Mechanistic evidence points to nicotine-mediated pathways, including sympathetic activation, endothelial dysfunction and increased arterial stiffness, whereas evidence for TSNA-driven CVD risk remains sparse, and declining TSNA levels in modern Swedish snus make that path less likely and harder to study. Nicotine pouches deliver comparable or higher systemic nicotine than conventional snus but lack long-term cardiovascular outcome data. Real-world cessation data from Denmark suggest structured programmes can achieve 6-month abstinence rates of approximately 53% among non-smoking nicotine users. The evidence supports nicotine as the primary driver of snus-associated CVD risk, with important implications for the cardiovascular safety of novel nicotine products. Evidence is needed to inform public health guidance, clinical advice and regulatory decisions. SWETOC represents a unique infrastructure to generate this evidence.

Lipodystrophy comprises a heterogeneous group of disorders characterized by reduced adipose tissue often associated with severe metabolic complications. Lipodystrophy may be genetic, acquired, or secondary to medical therapies initiated for other conditions. Despite major advances in understanding adipose tissue biology and in human genetic technologies, diagnosis of lipodystrophy is still commonly delayed or missed. Conversely, increasing use of next-generation sequencing has led to proliferation of proposed new genetic causes of lipodystrophy with variable supporting evidence. To address these challenges, an international expert working group from the European Consortium for Lipodystrophies first developed a consensus definition of lipodystrophy as deficient development and/or inadequate maintenance of adipose tissue not attributable to nutritional deprivation or a systemic catabolic state. Anatomical adipose deficiency alone is generally insufficient for diagnosis, with evidence of adipose tissue dysfunction or pathology also usually required. Building on this definition, a framework for evaluating candidate monogenic lipodystrophy syndromes is suggested, based on the strength of human phenotypic, genetic, and biological evidence. Primacy was assigned to direct evidence from affected individuals, with genetic and biological evidence considered supportive but not determinative. This approach accommodates both the variable penetrance and expressivity characteristic of many lipodystrophy syndromes and potential discrepancies between human observations and experimental models. Although the proposed definition is applicable across all forms of lipodystrophy, the classification system described here is restricted to monogenic disorders. Together, these tools aim to improve clinical recognition, promote diagnostic consistency, and provide a robust and adaptable framework for evaluating emerging gene-disease associations in lipodystrophy.