The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides a comprehensive assessment of health and risk factor trends at global, regional, national, and subnational levels. This study aims to examine the burden of diseases, injuries, and risk factors in the USA and highlight the disparities in health outcomes across different states.

Patients with severe aortic stenosis present frequently (∼50%) with concomitant obstructive coronary artery disease. Current guidelines recommend combined surgical aortic valve replacement (SAVR) and coronary artery bypass grafting (CABG) as the preferred treatment. Transcatheter aortic valve implantation (TAVI) and fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) represent a valid treatment alternative. We aimed to test the non-inferiority of FFR-guided PCI plus TAVI versus SAVR plus CABG in patients with severe aortic stenosis and complex coronary artery disease.

Allogeneic haematopoietic stem-cell transplantation is the standard treatment for bone marrow failure (BMF) in patients with Fanconi anaemia, but transplantation-associated complications such as an increased incidence of subsequent cancer are frequent. The aim of this study was to evaluate the safety and efficacy of the infusion of autologous gene-corrected haematopoietic stem cells as an alternative therapy for these patients.

Sudden cardiac arrest and death occur among competitive and recreational athletes across the entire spectrum of age, sex, and level of competition. These events are tragic, potentially preventable, and represent a global public health concern. Currently, the precise incidence of sudden cardiac arrest and death among all athletes is uncertain due to the lack of both mandatory case reporting and the infrastructure to process all cases that occur within the general population. Disparities in outcomes between Black and White athletes also exist without explanation. Causes of sudden cardiac arrest and death are age-dependent, with genetic heart conditions and unexplained cases (ie, normal autopsy) predominant among younger athletes, and coronary artery disease accounting for most cases among veteran Masters athletes. Determining best practices for prevention of primary sudden cardiac arrest and death, including preparticipation screening, remains controversial. However, secondary prevention grounded in an emergency action plan incontrovertibly represents a fundamental aspect of comprehensive cardiac care for all athletes.

Hand eczema is a highly prevalent skin disease and one of the most common work-related disorders. In up to two-thirds of individuals affected by hand eczema, the disease becomes chronic and results in substantial personal and occupational disability. Manifestations of chronic hand eczema vary in severity and appearance over time, and people with eczema typically experience itch, pain, and a burning sensation. The pathophysiology of chronic hand eczema is multifactorial. Major risk factors are current or past atopic dermatitis and excessive or prolonged exposure to irritants or allergens. Based on the suspected main causes, chronic hand eczema is commonly classified into irritant, allergic, and atopic hand eczema. Diagnosis and assessment can be complex, and management is often challenging. Strategies include structured education, avoidance of trigger factors, primary to tertiary prevention, topical anti-inflammatory treatment with glucocorticosteroids, calcineurin inhibitors, or januskinase inhibitors, phototherapy, systemic retinoids, and off-label use of immunosuppressive drugs. Topical and systemic immunomodulatory therapies approved for atopic dermatitis could be used in severe atopic hand eczema and some of them are under clinical development for chronic hand eczema. Additional research is needed to better understand chronic hand eczema subtypes and underlying mechanisms, and the comparative effectiveness and safety of therapies. This Review combines established knowledge with ongoing changes in our understanding of the disease and their implications for prevention, management, and future research.

Landscape fire-sourced (LFS) air pollution is an increasing public health concern in the context of climate change. However, little is known about the attributable global, regional, and national mortality burden related to LFS air pollution.

Nearly two decades ago, the Eight Americas study offered a novel lens for examining health inequities in the USA by partitioning the US population into eight groups based on geography, race, urbanicity, income per capita, and homicide rate. That study found gaps of 12·8 years for females and 15·4 years for males in life expectancy in 2001 across these eight groups. In this study, we aimed to update and expand the original Eight Americas study, examining trends in life expectancy from 2000 to 2021 for ten Americas (analogues to the original eight, plus two additional groups comprising the US Latino population), by year, sex, and age group.

Although death in old age is unavoidable, premature death-defined here as death before age 70 years-is not. To assess whether halving premature mortality by 2050 is feasible, we examined the large variation in premature death rates before age 70 years and trends over the past 50 years (1970-2019), covering ten world regions and the 30 most-populous nations. This analysis was undertaken in conjunction with the third report of The Lancet Commission on Investing in Health: Global Health 2050: the path to halving premature death by mid-century.

Mirikizumab, a humanised monoclonal antibody that inhibits IL-23p19, is effective in moderate-to-severe ulcerative colitis. We aimed to evaluate the efficacy and safety of mirikizumab in patients with moderately-to-severely active Crohn's disease.

The 2 × 2 PEACE-1 study showed that combining androgen-deprivation therapy with docetaxel and abiraterone improved overall and radiographic progression-free survival in patients with de novo metastatic castration-sensitive prostate cancer. We aimed to examine the efficacy and safety of adding radiotherapy in this population.

The effectiveness of using a balloon guide catheter during endovascular thrombectomy in patients with acute ischaemic stroke due to large vessel occlusion of the anterior circulation remains uncertain. We aimed to assess the effectiveness and safety of using a balloon guide catheter during endovascular thrombectomy, compared with using a conventional guide catheter, in this patient population.

Since the discovery of statins and the Scandinavian Simvastatin Survival Study (4S) results three decades ago, remarkable advances have been made in the treatment of dyslipidaemia, a major risk factor for atherosclerotic cardiovascular disease. Safe and effective statins remain the cornerstone of therapeutic approach for this indication, including for children with genetic dyslipidaemia, and are one of the most widely prescribed drugs in the world. However, despite the affordability of generic statins, they remain underutilised worldwide. The use of ezetimibe to further decrease plasma LDL cholesterol and the targeting of other atherogenic lipoproteins, such as triglyceride-rich lipoproteins and lipoprotein(a), are likely to be required to further reduce atherosclerotic cardiovascular disease events. Drugs directed at these lipoproteins, including gene silencing and editing methods that durably suppress the production of proteins, such as PCSK9 and ANGPTL3, open novel therapeutic options to further reduce the development of atherosclerotic cardiovascular disease.

Building on the evidence from the first paper in this Series highlighting the fundamental importance of healthy and nurturing environments for children's growth and development in the next 1000 days (ages 2-5 years), this paper summarises the benefits and costs of key strategies to support children's development in this age range. The next 1000 days build on the family-based and health-sector based interventions provided in the first 1000 days and require broader multisectoral programming. Interventions that have been shown to be particularly effective in this age range are the provision of early childhood care and education (ECCE), parenting interventions, and cash transfers. We show that a minimum package of 1 year of ECCE for all children would cost on average less than 0·15% of low-income and middle-income countries' current gross domestic product. The societal cost of not implementing this package at a national and global level (ie, the cost of inaction) is large, with an estimated forgone benefit of 8-19 times the cost of investing in ECCE. We discuss implications of the overall evidence presented in this Series for policy and practice, highlighting the potential of ECCE programming in the next 1000 days as an intervention itself, as well as a platform to deliver developmental screening, growth monitoring, and additional locally required interventions. Providing nurturing care during this period is crucial for maintaining and further boosting children's progress in the first 1000 days, and to allow children to reach optimal developmental trajectories from a socioecological life-course perspective.

Following the first 1000 days of life that span from conception to two years of age, the next 1000 days of a child's life from 2-5 years of age offer a window of opportunity to promote nurturing and caring environments, establish healthy behaviours, and build on early gains to sustain or improve trajectories of healthy development. This Series paper, the first of a two-paper Series on early childhood development and the next 1000 days, focuses on the transition to the next 1000 days of the life course, describes why this developmental period matters, identifies the environments of care, risks, and protective factors that shape children's development, estimates the number of children who receive adequate nurturing care, and examines whether current interventions are meeting children's needs. Paper 2 focuses on the cost of inaction and the implications of not investing in the next 1000 days. In low-income and middle-income countries (LMICs), only 62 million children aged 3 and 4 years (25·4%) currently receive adequate nurturing care during the next 1000 days, leaving 181·9 million children exposed to risks that jeopardise their healthy development. Inputs across nurturing care dimensions of health, nutrition, protection, responsive care, and learning vary substantially across countries. In LMICs, although 86·2% of children have a healthy weight in this period, less than one in three children have access to developmental stimulation or are protected from physical punishment, and only 38·8% have access to early childhood care and education services. Intervention research in LMICs in the next 1000 days is scarce. The continuity of developmentally appropriate nurturing care, coordination across health, education, and protection sectors, and the implementation of interventions to support caregivers and improve the quality of education and care remain top priorities in this period. These sectors play key roles in promoting quality early care and education for this age group, which will help maximise developmental potential and opportunities of children globally and help progress towards the achievement of the Sustainable Development Goals.

Over the past several decades, the overweight and obesity epidemic in the USA has resulted in a significant health and economic burden. Understanding current trends and future trajectories at both national and state levels is crucial for assessing the success of existing interventions and informing future health policy changes. We estimated the prevalence of overweight and obesity from 1990 to 2021 with forecasts to 2050 for children and adolescents (aged 5-24 years) and adults (aged ≥25 years) at the national level. Additionally, we derived state-specific estimates and projections for older adolescents (aged 15-24 years) and adults for all 50 states and Washington, DC.

Cardiogenic shock is a complex syndrome defined by systemic hypoperfusion and inadequate cardiac output arising from a wide array of underlying causes. Although the understanding of cardiogenic shock epidemiology, specific subphenotypes, haemodynamics, and cardiogenic shock severity staging has evolved, few therapeutic interventions have shown survival benefit. Results from seminal randomised controlled trials support early revascularisation of the culprit vessel in infarct-related cardiogenic shock and provide evidence of improved survival with the use of temporary circulatory support in selected patients. However, numerous questions remain unanswered, including optimal pharmacotherapy regimens, the role of mechanical circulatory support devices, management of secondary organ dysfunction, and best supportive care. This Review summarises current definitions, pathophysiological principles, and management approaches in cardiogenic shock, and highlights key knowledge gaps to advance individualised shock therapy and the evidence-based ethical use of modern technology and resources in cardiogenic shock.

Oesophageal cancer is the seventh leading cause of cancer mortality worldwide. Two major pathological subtypes exist: oesophageal squamous cell carcinoma and oesophageal adenocarcinoma. Epidemiological studies in the last decade have shown a gradual increase in the incidence of oesophageal adenocarcinoma worldwide. The prognosis of oesophageal cancer has greatly improved due to breakthroughs in screening, surgical procedures, and novel treatment modalities. The success achieved with combined modality therapies, including surgery, chemotherapy, and radiotherapy, to treat locally advanced oesophageal cancer is particularly notable. Immunotherapy has become a crucial treatment for oesophageal cancer, with immune checkpoint inhibitor-based therapies now established as the standard of care in adjuvant and metastatic first-line settings. This Seminar provides an overview of advances in the screening, diagnosis, and treatment of oesophageal squamous cell carcinoma and oesophageal adenocarcinoma, with a particular focus on neoadjuvant therapies for locally advanced oesophageal cancer and immune checkpoint inhibitor-based therapies.

Glofitamab monotherapy induces durable remission in patients with relapsed or refractory diffuse large B-cell lymphoma after two or more previous therapies, but has not previously been assessed as a second-line therapy. We investigated the efficacy and safety of glofitamab plus gemcitabine-oxaliplatin (Glofit-GemOx) versus rituximab (R)-GemOx in patients with relapsed or refractory diffuse large B-cell lymphoma.

Diabetes can be detected at the primary health-care level, and effective treatments lower the risk of complications. There are insufficient data on the coverage of treatment for diabetes and how it has changed. We estimated trends from 1990 to 2022 in diabetes prevalence and treatment for 200 countries and territories.

With the advent of the first disease-modifying, anti-amyloid β-directed passive immunotherapy for Alzheimer's disease, questions arise who, when, and how to treat. This paper describes shortly the pathogenic basis of and preclinical data, which have, more than two decades ago, initiated the development of this vaccination therapy. We discuss clinical trial results of aducanumab, lecanemab, and donanemab. We also review appropriate use recommendations of these novel treatments on patient selection and safety monitoring. Furthermore, estimations of numbers of patient who will qualify for treatment regarding inclusion and exclusion criteria and estimations on readiness of health-care systems for identifying the right patients and for providing the treatment are reported. In our view, we are experiencing a fundamental shift from syndrome-based Alzheimer's dementia care to early, biomarker-guided treatment of Alzheimer's disease. This shift requires substantial adjustments of infrastructure and resources, but also holds promise of eventually achieving substantial slowing of disease progression and delaying dementia.