Haemophilia A and B are congenital X-linked bleeding disorders resulting from deficiencies in clotting factors VIII (haemophilia A) and IX (haemophilia B). Patients with severe deficiency, defined as having less than 1% of normal plasma factor activivity, often have spontaneous bleeding within the first few years of life. Those with moderate and mild deficiencies typically present with post-traumatic or post-surgical bleeding later in life. A high index of suspicion and measurement of factor activity in plasma facilitates early diagnosis. In the 21st century, therapeutic advances and comprehensive care have substantially improved both mortality and morbidity associated with these conditions. Management strategies for haemophilia include on-demand treatment for bleeding episodes and all surgeries and regular treatment (ie, prophylaxis) aimed at reducing bleeds, morbidity, and mortality, thereby enhancing quality of life. Treatment options include factor replacement therapy, non-replacement therapies that increase thrombin generation, and gene therapies that facilitate in vivo clotting factor synthesis. The therapies differ in their use for prophylaxis and on-demand treatment, the mode and frequency of administration, duration of treatment effect, degree of haemostatic protection, and side-effects. Monitoring the effectiveness of these prophylactic therapies involves assessing annual bleeding rates and joint damage. Personalised management strategies, which align treatment with individual goals (eg, playing competitive sports), initiated at diagnosis and maintained throughout the lifespan, are crucial for optimal outcomes. These strategies are facilitated by a multidisciplinary team and supported by clinician-led education for both clinicians and patients.

Schistosomiasis is a neglected tropical disease caused by infection with blood flukes of the genus Schistosoma. Widely distributed in the Middle East, southeast Asia, Latin America, and (mostly) sub-Saharan Africa, schistosomiasis is acquired upon skin penetration of infective larvae released by freshwater snails. Acute infection might present with self-limiting hypersensitivity reactions (known as Katayama fever). Chronic infection typically leads to two main clinical patterns: intestinal or urogenital schistosomiasis, depending on the infecting species. Impairment of other body sites (eg, the CNS or respiratory tract) can occur. The intestinal form is characterised by abdominal pain and diarrhoea, with or without blood; complications are hepatic fibrosis, portal hypertension, splenomegaly, and variceal bleeding. The urogenital form is characterised by dysuria and haematuria; complications are renal failure and squamous-cell carcinoma of the bladder. Conventional diagnosis is based on egg detection in faeces or urine, although sensitivity might be low. Praziquantel is the first-line treatment, and it is also provided in preventive chemotherapy campaigns by mass drug administration to afflicted communities.

Atopic dermatitis is the most common chronic inflammatory skin disease globally. Key features include an eczematous eruption accompanied by intense itch, which can have an enormous negative effect on patients' quality of life, especially in those with moderate-to-severe disease. Atopic dermatitis is part of a spectrum of atopic conditions that can also include several non-cutaneous organs such as respiratory (eg, allergic rhinitis and asthma) and gastrointestinal (eg, food allergy) systems. For decades, long-term disease control and maintenance were particularly challenging given that treatment options were limited to broad topical and systemic immunosuppressive agents. However, better insights into the pathophysiology of this condition over the past decade have led to the development and approval of safe and efficacious novel targeted treatment approaches. The updated pathophysiological understanding and the evolving therapeutic landscape of atopic dermatitis are discussed in this Seminar.

Some of the physiological changes that occur in pregnancy manifest in the liver. These alterations might exacerbate or improve some pre-existent liver diseases, while many conditions remain unaffected. Some hepatic manifestations during pregnancy are secondary to disorders unique to pregnancy. Due to improved management of chronic conditions and assisted conception methods, pregnancies in people with cirrhosis or after liver transplantation are increasingly common. With pregnancy also becoming more common in older people and with the rising prevalence of comorbidities, such as obesity, diabetes, and metabolic syndrome, hypertensive disorders of pregnancy and gestational diabetes are increasing in prevalance. Thus, a broad range of specialists might encounter liver abnormalities in pregnancy, necessitating an understanding of how the liver changes during pregnancy and the importance of multi-disciplinary input to mitigate maternal-fetal risks. From a global health perspective, pregnancy also offers a unique opportunity to influence disease management and initiate interventions that might influence the life course of pregnant people and their families. In this Review, we describe the challenges of diagnosing, risk stratifying, and managing liver disease in pregnancy, and explore factors that might affect future maternal health.

Hidradenitis suppurativa is a chronic inflammatory disease characterised by painful, deep-seated nodules, abscesses, and draining tunnels in the skin of axillary, inguinal, genitoanal, or inframammary areas. In recent years, the body of knowledge in hidradenitis suppurativa has advanced greatly. This disorder typically starts in the second or third decade of life. The average worldwide prevalence is 1% but varies geographically. Hidradenitis suppurativa has a profound negative effect on patients' quality of life and on the gross value added to society. Comorbidities (eg, metabolic syndrome, inflammatory arthritis, and inflammatory bowel disease) frequently accompany skin alterations, because of systemic inflammation. Pathogenesis of hidradenitis suppurativa is complex and includes innate immune mechanisms (eg, macrophages, neutrophils, IL-1β, tumour necrosis factor [TNF], and granulocyte colony-stimulating factor), T-cell mechanisms (eg, IL-17 and IFN-γ), and B-cell mechanisms (eg, associated with dermal tertiary lymphatic structures and autoantibodies). Chronic inflammation leads to irreversible skin damage with tunnel formation and morbid scarring. Current treatment includes drug therapy (for the initial, purely inflammatory phase), combined drug and surgical therapy (for the destructive phase), or surgery alone (for the burnout phase). The first systemic therapies approved for hidradenitis suppurativa targeting TNF (adalimumab) and IL-17 (secukinumab and bimekizumab) have expanded drug therapy options for moderate-to-severe disease, which were previously mainly restricted to oral antibiotics. Moreover, there is a robust pipeline of immunomodulatory drugs in various stages of development for hidradenitis suppurativa. Aims of management should include early intervention to prevent irreversible skin damage, adequate control of symptoms including pain, and mitigation of extra-cutaneous comorbidities, all requiring early diagnosis and an interdisciplinary, holistic and personalised approach.

For over a century, radiotherapy has revolutionised cancer treatment. Technological advancements aim to deliver high doses to tumours with increased precision while minimising off-target effects to organs at risk. Despite advancements such as image-guided, high-precision radiotherapy delivery, long-term toxic effects on healthy tissues remain a great clinical challenge. In this Review, we summarise common mechanisms driving acute and long-term side-effects and discuss monitoring strategies for radiotherapy survivors. We explore ways to mitigate toxic effects through novel technologies and proper patient selection and counselling. Additionally, we address policies and management strategies to minimise the severity and impact of toxicity during and after treatment. Finally, we examine the potential advantages of emerging technologies and innovative approaches to improve conformity, accuracy, and minimise off-target effects.

Multidrug-resistant Gram-negative bacterial infections cause significant morbidity and mortality globally. These pathogens easily acquire antimicrobial resistance (AMR), further highlighting their clinical significance. Third-generation cephalosporin-resistant and carbapenem-resistant Enterobacterales (eg, Escherichia coli and Klebsiella spp), multidrug-resistant Pseudomonas aeruginosa, and carbapenem-resistant Acinetobacter baumannii are the most problematic and have been identified as priority pathogens. In response, several new diagnostic technologies aimed at rapidly detecting AMR have been developed, including biochemical, molecular, genomic, and proteomic techniques. The last decade has also seen the licensing of multiple antibiotics that have changed the treatment landscape for these challenging infections.

Acute kidney injury (AKI) is a common, heterogeneous, multifactorial condition, which is part of the overarching syndrome of acute kidney diseases and disorders. This condition's incidence highest in low-income and middle-income countries. In the short term, AKI is associated with increased mortality, an increased risk of complications, extended stays in hospital, and high health-care costs. Long-term complications include chronic kidney disease, kidney failure, cardiovascular morbidity, and an increased risk of death. Several strategies are available to prevent and treat AKI in specific clinical contexts. Otherwise, AKI care is primarily supportive, focused on treatment of the underlying cause, prevention of further injury, management of complications, and short-term renal replacement therapy in case of refractory complications. Evidence confirming that AKI subphenotyping is necessary to identify precision-oriented interventions is growing. Long-term follow-up of individuals recovered from AKI is recommended but the most effective models of care remain unclear.

Axial spondyloarthritis manifests as a chronic inflammatory disease primarily affecting the sacroiliac joints and spine. Although chronic back pain and spinal stiffness are typical initial symptoms, peripheral (ie, enthesitis, arthritis, and dactylitis) and extra-musculoskeletal (ie, uveitis, inflammatory bowel disease, and psoriasis) manifestations are also common. Timely and accurate diagnosis is challenging and relies on identifying a clinical pattern with a combination of clinical, laboratory (HLA-B27 positivity), and imaging findings (eg, structural damage on pelvic radiographs and bone marrow oedema on MRI of the sacroiliac joints). The Assessment in SpondyloArthritis international Society classification criteria for axial spondyloarthritis are widely used for research and have contributed to a better understanding of the gestalt of axial spondyloarthritis. Persistent disease activity, assessed mainly by the Axial Spondyloarthritis Disease Activity Score, leads to irreversible structural damage and functional impairment. Management involves non-pharmacological (eg, education, smoking cessation, exercise, physiotherapy) and pharmacological therapy. Non-steroidal anti-inflammatory drugs remain first line pharmacotherapy, while tumour necrosis factor, IL-17, and Janus kinase inhibitors are considered second-line therapies. Future advances are expected to increase disease awareness, facilitate early and accurate diagnosis, optimise disease management, and enhance overall quality of life in patients with axial spondyloarthritis.

Osteoarthritis is a heterogeneous disorder that is increasingly prevalent largely due to aging and obesity, resulting in a major disease burden worldwide. Knowledge about the underlying aetiology has improved, with increased understanding of the role of genetic factors, the microbiome, and existence of different pain mechanisms. However, this knowledge has not yet been translated into new treatment options. New evidence has questioned the efficacy of recommended treatments, such as therapeutic exercise programmes and the focus on weight loss, but managing obesity and maintaining activity remain important for the prevention and management of osteoarthritis. Approaches should consider individual and cultural preferences and resource availability to increase patient and community engagement, and optimise outcomes worldwide. Most of the focus has been on established osteoarthritis where management is primarily directed at relieving symptoms. The search for the much needed effective treatments that improve both symptoms and structure, often referred to as disease-modifying osteoarthritic drugs, is ongoing. Promising data indicate that targeting inflammation is effective in hand osteoarthritis.

Trials of endovascular therapy for basilar artery occlusion, including vertebral occlusion extending into the basilar artery, have shown inconsistent results. We aimed to pool data to estimate safety and efficacy and to explore the benefit across pre-specified subgroups through individual patient data meta-analysis.

In this Review, we examine the concurrent outbreaks of mpox in Africa, focusing on clade 1a, the newly emerged clade 1b, and clade 2b lineage A, and how they differ from the 2022 global outbreak caused by clade 2b lineage B.1. Historically, clades 1a and 2a have caused sporadic, small outbreaks in central and west Africa, respectively, primarily through zoonotic transmission. Clade 2b first caused an outbreak in Nigeria in 2017, and later spread globally via sexual contact in 2022. In August, 2024, WHO declared a global health emergency due to the newly identified clade 1b outbreak in eastern Democratic Republic of the Congo. This outbreak has now expanded to several other countries and is spreading through direct and sexual contact in urban centres and refugee camps. Clades, route of exposure, infectious dose, and host immune response are the main factors influencing clinical presentation of mpox. For clades 1a and 2a, zoonotic transmission plays an important role, whereas for clades 1b and 2b, the spread occurs through sustained human-to-human transmission without zoonotic exposure. For both clades 1a and 2a, lesions have a generalised centrifugal distribution, whereas for clade 2b they are mainly localised to the anogenital area. For clade 1b, data are still emerging, but current cases show a mix of localised lesions and centrifugal distribution. The severity of the disease is higher for clade 1a (case fatality rate up to 12%) compared with other clades (case fatality rates 0-3·6%). Diagnostic challenges include false negative results for clade 1b with existing PCR assays and poor testing access in remote areas. Tecovirimat, the primary antiviral during the 2022 outbreak, has shown reduced effectiveness against clade 1a in preliminary study results, whereas its efficacy against other clades is still under investigation. The modified vaccinia Ankara-Bavarian Nordic vaccine has been shown to be up to 90% effective against clade 2b after two doses and is safe for children, although its effectiveness drops to 20% when used as post-exposure prophylaxis. Given the evolving nature of the monkeypox virus, ongoing research and strong public health responses are key to managing potential future outbreaks.

Chronic pancreatitis is a progressive fibroinflammatory disease primarily caused by a complex interplay of environmental and genetic risk factors. It might result in pancreatic exocrine and endocrine insufficiency, chronic pain, reduced quality of life, and increased mortality. The diagnosis is based on the presence of typical symptoms and multiple morphological manifestations of the pancreas, including pancreatic duct stones and strictures, parenchymal calcifications, and pseudocysts. Management of chronic pancreatitis consists of prevention and treatment of complications, requiring a multidisciplinary approach focusing on lifestyle modifications, exocrine insufficiency, nutritional status, bone health, endocrine insufficiency, pain management, and psychological care. To optimise clinical outcomes, screening for complications and evaluation of treatment efficacy are indicated in all patients with chronic pancreatitis.

This Health Policy examines the relationship between child cash benefits and child health, with the goal of informing future policy development in the USA. As of 2024, more than 140 countries have adopted large-scale, government-funded child cash transfer programmes. High-income countries more often adopt universal or near universal programmes, while lower-income countries often impose means tests or condition benefits on specific behaviours. Evidence on the adoption of child cash benefits from a broad set of nations finds that they can improve a range of child health outcomes, with the most robust evidence of health benefits occurring when delivered to children younger than 5 years and during the prenatal period. During the 2021 expanded Child Tax Credit (CTC), the USA briefly joined other high-income countries by introducing a near universal, unconditional child cash benefit, which led to a historic decline in child poverty. Although the expanded CTC expired, state and local governments and communities have continued to advocate for and implement policies like it. On the basis of this success and building on global evidence, the USA should adopt a permanent child cash benefit consistent with other high-income countries and the 2021 expanded CTC. Nations further developing their cash benefits should also give special attention to the prenatal and infant period.

As the beginning of the next US presidential administration approaches, the USA faces a series of complex challenges that threaten the health of the American people and the effectiveness and sustainability of their health and health-care systems. Taking office in January, 2025, the next administration will need to address myriad systems-level and public health challenges, including the long-term health impacts of COVID-19 and threat of future pandemics, negative effects of climate change on health, unaffordability and inefficiencies in health care, and resulting and long-standing disparities in health-care access and health outcomes. Without decisive policy action, population health is likely to stagnate or even deteriorate. We present five priority areas to guide US federal strategy in 2025 and beyond: improve public health and address health and social inequities; catalyse transformation towards a more effective, equitable health system; address crucial health issues such as climate change; advance artificial intelligence for health and health care; and strengthen responsible science and innovation. To achieve these goals, we suggest policy action items for federal stakeholders and emphasise the importance of social determinants of health, cross-sector collaboration, population health perspectives, and transformative partnerships. By prioritising these strategic imperatives, the incoming administration can set a plan towards a healthier, more resilient future for all Americans.

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.