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.

Support for the treatment of uncomplicated appendicitis with non-operative management rather than surgery has been increasing in the literature. We aimed to investigate whether treatment of uncomplicated appendicitis with antibiotics in children is inferior to appendicectomy by comparing failure rates for the two treatments.

Accurate mortality estimates help quantify and memorialise the impact of war. We used multiple data sources to estimate deaths due to traumatic injury in the Gaza Strip between Oct 7, 2023, and June 30, 2024.

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.

Dermatomyositis is a chronic autoimmune disease with distinctive cutaneous eruptions and muscle weakness, and the pathophysiology is characterised by type I interferon (IFN) dysregulation. This study aims to assess the efficacy, safety, and target engagement of dazukibart, a potent, selective, humanised IgG1 neutralising monoclonal antibody directed against IFNβ, in adults with moderate-to-severe dermatomyositis.

FT596 is an induced pluripotent stem-cell (iPSC)-derived chimeric antigen receptor (CAR) natural killer (NK) cell therapy with three antitumour modalities: a CD19 CAR; a high-affinity, non-cleavable CD16 Fc receptor; and interleukin-15-interleukin-15 receptor fusion. In this study, we aimed to determine the recommended phase 2 dose (RP2D) and evaluate the safety and tolerability of FT596 as monotherapy and in combination with rituximab. We also aimed to evaluate the antitumour activity and characterise the pharmacokinetics of FT596 as monotherapy and in combination with rituximab.

Transarterial chemoembolisation (TACE) is standard of care for patients with unresectable hepatocellular carcinoma that is amenable to embolisation; however, median progression-free survival is still approximately 7 months. We aimed to assess whether adding durvalumab, with or without bevacizumab, might improve progression-free survival.

Transarterial chemoembolisation (TACE) is standard care for unresectable, non-metastatic hepatocellular carcinoma. We aimed to evaluate the addition of lenvatinib and pembrolizumab to TACE versus dual placebo plus TACE in patients with unresectable, non-metastatic hepatocellular carcinoma.

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.

Spatial repellent products are used for prevention of insect bites, and a body of evidence exists on spatial repellent entomological efficacy. A new option for vector control, spatial repellent products are designed to release active ingredient into the air for disruption of human-vector contact thereby reducing human exposure to mosquito-borne pathogens. Clinical trials have shown spatial repellent epidemiological efficacy against Aedes-borne viruses but inconclusive outcomes against malaria. We aimed to show and quantify the protective efficacy of spatial repellents in reducing malaria infection incidence in Busia County, Kenya.

Interleukin-23 inhibition is effective in treating ulcerative colitis. Guselkumab is a dual-acting, human IgG1, interleukin-23p19 subunit inhibitor that potently neutralises interleukin-23 and can bind to CD64. We aimed to evaluate the efficacy and safety of guselkumab as induction and maintenance therapy in patients with ulcerative colitis.

Health systems experience difficult trade-offs when paying for new drugs. In England, funding recommendations by the National Institute for Health and Care Excellence (NICE) for new drugs might generate health gains, but inevitably result in forgone health as the funds cannot be used for alternative treatments and services. We aimed to evaluate the population-health impact of NICE recommendations for new drugs during 2000-20.

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.

The six global nutrition targets (GNTs) related to low birthweight, exclusive breastfeeding, child growth (ie, wasting, stunting, and overweight), and anaemia among females of reproductive age were chosen by the World Health Assembly in 2012 as key indicators of maternal and child health, but there has yet to be a comprehensive report on progress for the period 2012 to 2021. We aimed to evaluate levels, trends, and observed-to-expected progress in prevalence and attributable burden from 2012 to 2021, with prevalence projections to 2050, in 204 countries and territories.

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.

The capacity to anticipate future health issues is important for both policy makers and practitioners in the USA, as such insights can facilitate effective planning, investment, and implementation strategies. Forecasting trends in disease and injury burden is not only crucial for policy makers but also garners substantial interest from the general populace and leads to a better-informed public. Through the integration of new data sources, the refinement of methodologies, and the inclusion of additional causes, we have improved our previous forecasting efforts within the scope of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) to produce forecasts at the state and national levels for the USA under various possible scenarios.