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.

Antipsychotic drugs are the established treatment for acute schizophrenia but differ in receptor-binding profiles. In 2024, a new-in-class muscarinic receptor agonist (xanomeline-trospium) was licenced, acting upstream of antidopaminergic agents, and providing hope to decrease the adverse effects burden of antipsychotics. We aimed to compare the efficacy and tolerability of antipsychotics by performing network meta-analysis of randomised controlled trials (RCTs).

The Management of Myelomeningocele Study (MOMS) trial established the benefit of in-utero repair of myelomeningocele, with a decreased need for ventriculoperitoneal shunt placement. However, although there was some improvement of motor function, over half of the patients were unable to ambulate independently. Live placenta-derived mesenchymal stem cells (PMSCs) seeded on an extracellular matrix have shown promise in rescuing neurological function in the fetal ovine model of myelomeningocele. We aimed to evaluate the safety of this novel, living, stem cell product to augment the prenatal repair of myelomeningocele.

Total hip replacement is a successful operation that aims to restore function and quality of life to millions of people globally. Knowing how long a total hip replacement might last is important for patients, surgeons, and health-care institutions for planning and resource allocation. Over the past 20 years, the use of contemporary bearing surfaces for total hip replacement has substantially altered implant wear and, possibly, longevity. To date, there has been no large-scale study that examines survivorship of these modern implants. We aimed to determine the survivorship of contemporary total hip replacements and bearing materials.