Atrial fibrillation affects approximately 37·6 million people worldwide, with the prevalence predicted to double over the next 35 years. The ubiquitous use of wearable devices and other technologies with inbuilt diagnostic algorithms allows greater detection of atrial fibrillation among the general public than previously. Atrial fibrillation increases the risk of stroke and thromboembolism, heart failure, and death, and is associated with reductions in quality of life. Patients with atrial fibrillation frequently have comorbidities, and the accumulation of risk factors, including lifestyle factors associated with poorer health outcomes, and increasing age, often adds to the complexity of managing such patients. All major clinical guidelines advocate that stroke prevention, symptom relief, identification of risk factors, and optimisation of risk factor management, incorporated into an integrated care approach, with multidisciplinary input as required, are essential elements of atrial fibrillation management. Avoidance of stroke with oral anticoagulation remains the default for most patients with atrial fibrillation and, more recently, catheter ablation has been reconsidered as an initial treatment option for symptom relief. The dynamic nature of risk factors requires early identification and appropriate management of new and existing risk factors to optimise atrial fibrillation care. Patient-centred care and better health literacy can empower patients to take a more active role in their atrial fibrillation management.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of chronic kidney disease, resulting in substantial morbidity and mortality globally. Advances in molecular genetics and deep-phenotype imaging techniques have refined existing diagnostic and prognostic tools. The strong evidence-base for tolvaptan as a disease-modifying treatment supports its early use in groups at high risk of kidney failure. Screening and management of potentially serious complications including cyst infection, intracranial aneurysms, and polycystic liver disease are important components of a comprehensive care plan. This Review focuses on current approaches to diagnosis, risk assessment, treatment, and specific aspects of clinical management in ADPKD. An updated understanding of the genetic basis of disease, pathobiology with respect to potential therapeutic targets, and promising therapies now in clinical trials are summarised. We propose a holistic patient-centred care pathway that emphasises shared decision-making with a multidisciplinary clinical team to address the individual needs of patients throughout their lifelong journey.

Sepsis is defined as a dysregulated host response to infection that leads to life-threatening organ dysfunction. The infectious insult triggers a dysregulated immune response that variably activates and suppresses multiple body system functions. Susceptibility to either developing or succumbing to sepsis is influenced by pathogen load and virulence; site of infection; host factors, including genetics, biological variability, comorbidities, immunosuppression, and extremes of age; and a wide range of external influences, such as social deprivation and local environment. Increasing appreciation of the underlying pathobiology has identified differing biological signatures with variable temporal evolution. This variability highlights the requirement to individualise treatment with targeted interventions guided by rapidly accessible biomarkers. Although improved outcomes have been obtained with better prevention, early recognition, and treatment, sepsis is a major cause of global mortality and morbidity. All populations having the benefits currently enjoyed by a privileged few is imperative. This Seminar aims to unravel the complexity of the condition, describing epidemiology and pathophysiology, evolving fundamental shifts, patient management, current challenges, and future developments.

Orforglipron is a novel non-peptide (GLP-1) receptor agonist designed for daily oral administration without food or water restrictions. This study aimed to compare the efficacy and safety of orforglipron with oral semaglutide in individuals with type 2 diabetes inadequately controlled with metformin.

Adding hormone therapy to definitive radiotherapy in localised prostate cancer improves overall survival, but whether it similarly improves overall survival in the context of postoperative radiotherapy (PORT) after radical prostatectomy is unclear. Herein, we report an individual patient data (IPD) meta-analysis of randomised trials aimed at quantifying the benefit of adding hormonal therapy to PORT.