First discovered in 1999 in Malaysia, Nipah virus (NiV) causes yearly outbreaks throughout south and southeast Asia with associated mortality rates of 40-75%. Due to the structural and sequence similarities between the NiV and Hendra virus (HeV) attachment G glycoproteins, and the extensive extant evidence of the ability of a recombinant soluble glycoprotein G (HeV-sG) to provide heterologous cross-protective immunity when used as vaccine (HeV-sG-V), this study aimed to evaluate HeV-sG-V for safety, tolerability, and immunogenicity against NiV.

Acute kidney injury (AKI) is a common and important complication of major surgery, yet recommended preventive care is rarely administered. We used urinary biomarkers to identify patients at high risk of AKI and implemented a preventive care strategy to reduce AKI within 72 h after major surgery.

Hyperemesis gravidarum describes nausea and vomiting in pregnancy severe enough to cause weight loss, dehydration, electrolyte imbalance, and nutritional deficiencies. The condition can render women so physically and mentally unwell that they are at increased risk of terminating a wanted pregnancy and experiencing suicidal ideation. Concerns regarding prescribing in pregnancy and inaccurate assumptions that the condition is self-limiting result in women being dismissed and having difficulty accessing appropriate care. Over the past decade, a wealth of literature has been published that gives new insights into the causes of hyperemesis gravidarum, the safety of antiemetic therapy, and short-term and long-term consequences for women with the condition and their children. This Review summarises the findings of this literature with the aim of informing decisions about the care of these women and future research priorities.

Lately, autologous CD19-targeting chimeric antigen receptor (CAR) T cells have shown excellent efficacy in treatment of autoimmune diseases, but with great safety concerns, such as infections. In this study, we aimed to evaluate the safety, tolerability, and efficacy of allogeneic CD19 CAR natural killer (NK)-cell therapy in patients with relapsed or refractory systemic lupus erythematosus (SLE).

GLP-1-glucagon dual receptor agonists such as pemvidutide have shown promise in treating metabolic dysfunction-associated steatohepatitis (MASH). The aim of this trial was to assess the effects of pemvidutide on MASH resolution and fibrosis improvement in patients with liver fibrosis stage F2 or F3 MASH at 24 weeks of treatment.

Type 1 diabetes begins with autoimmunity against pancreatic islet antigens, including insulin. The aim of the Primary Oral Insulin Trial (POInT) was to evaluate the efficacy and safety of daily high-dose oral insulin to prevent the development of islet autoantibodies and diabetes.

Poverty is strongly associated with numerous adverse health outcomes. Government-led cash transfer programmes are crucial to poverty reduction strategies in many low-income and middle-income countries (LMICs). Although extensive research from individual programmes exists on the effects of cash transfers on beneficiaries, evidence of these programmes' population-wide health effects remains scarce. Previously, we showed that cash transfer programmes are associated with substantially reduced mortality rates among women and young children at the population level in LMICs. In this study, we aimed to explore the mechanisms underlying these reductions.

In patients presenting with acute coronary syndromes and multivessel coronary artery disease, the question of whether to undertake a strategy of complete revascularisation in cases in which percutaneous coronary intervention (PCI) is performed routinely on non-culprit lesions (in addition to the culprit lesion) or whether to restrict PCI only to the culprit lesion is a common dilemma. The Complete Revascularisation Trialists' Collaboration aimed to determine, based on the totality of data from randomised trials, the effect of a complete revascularisation strategy on major cardiovascular events and whether it reduces cardiovascular death.

Sodium glucose co-transporter 2 (SGLT2) inhibitors reduce albuminuria and risk of progression of chronic kidney disease. Non-steroidal mineralocorticoid receptor antagonists (MRA) have similar effects in patients with type 2 diabetes with chronic kidney disease. We aimed to assess efficacy and safety of the novel MRA balcinrenone combined with the SGLT2 inhibitor dapagliflozin in a randomised controlled trial.

Coagulation factor XI (FXI) inhibitors can reduce the incidence of thrombosis without increasing bleeding risk. FXI is activated by factor XIIa (FXIIa) or thrombin. REGN7508Cat is an antibody that binds to the FXI catalytic domain, blocking both its activity and activation by FXIIa and thrombin. REGN9933A2 binds to the FXI apple 2 domain and blocks FXI activation by FXIIa. We aimed to compare the efficacy and safety of REGN9933A2 and enoxaparin, with apixaban as an exploratory comparator, and REGN7508Cat and enoxaparin for venous thromboembolism prevention.

Chronic kidney disease (CKD) is common and ranks among the leading causes of mortality and morbidity. This analysis aimed to present global CKD estimates using the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 to inform evidence-based policies for CKD identification and treatment.

Amylin-based therapies are emerging as promising obesity medications. Eloralintide is a novel, selective amylin receptor agonist in development for weight management. We performed a phase 2, double blind, randomised, placebo-controlled trial with the aim of evaluating the efficacy and safety of a range of doses and dose escalation schemes of once-per-week eloralintide versus placebo in adults with obesity or overweight and had at least one weight-related comorbidity.

We hypothesise that amylin receptor agonists (eg, pramlintide) and dual amylin and calcitonin-receptor agonists (eg, cagrilintide), which are emerging treatments for obesity and type 2 diabetes, can activate the renin-angiotensin system (RAS) and potentially undermine the cardiorenal benefits of these therapies. Paradoxically, new-generation amylin-based therapies, such as CagriSema, showed substantial blood pressure reductions in phase 3 trials. Beyond amylin's weight loss-mediated effects, we hypothesise that concurrent use of RAS inhibitors (angiotensin-converting enzyme [ACE] inhibitors or angiotensin-receptor blockers) redirects amylin-induced RAS activation towards the protective alternative RAS pathway, which is characterised by vasodilatory, anti-inflammatory, and antiproliferative effects via Mas receptors, potentially explaining part of their therapeutic benefit and cardioprotective and renoprotective potential. To test this, we propose: (1) preclinical studies investigating amylin-RAS interactions with or without RAS blockade; (2) post-hoc analyses of phase 2/3 trials stratified by RAS inhibitor use; (3) biomarker studies monitoring renin, aldosterone, angiotensin-(1-7), and ACE2; and (4) mechanistic human studies prospectively assessing cardiovascular-kidney metabolic effects by RAS inhibitor status. These suggestions aim to determine whether RAS inhibition enhances the overall efficacy of amylin-based therapies, and whether RAS blockers should be strongly recommended in patients receiving them.

Sexual and reproductive health and rights are fundamental to both human and societal wellbeing and sustainable development, and encompass a broad array of sociocultural and clinical issues that affect all people across the life course. In 2018, the Guttmacher-Lancet Commission described sexual and reproductive health as a state of physical, emotional, mental, and social wellbeing in relation to all aspects of sexuality and reproduction, not merely the absence of disease, dysfunction, or infirmity. The Commission advocated for a positive approach to sexuality and reproduction that recognises the role of pleasurable sexual relationships, trust, and communication in promoting self-esteem and overall wellbeing. The Commission also stipulated that people have a right to make decisions governing their bodies and to access services that support that right. In light of recent sociocultural changes, biomedical advances that have impacted sexual and reproductive health and rights, and the key findings of the Guttmacher-Lancet Commission, we bring together themes from this Lancet Series to discuss the new scientific developments and sociopolitical changes that affect the programmatic integration of sexual and reproductive health services. As people who present for one sexual and reproductive health service frequently have other unmet sexual and reproductive health-related needs, there are often benefits to interventions and services that address multiple connected sexual and reproductive health issues during one clinical encounter (eg, family planning visits, including testing for HIV and other sexually transmitted infections), which supports the rationale for an integrated approach. Historically, key components of sexual and reproductive health have been managed separately, partly because of siloed and inadequate funding streams and structural limitations (eg, separate location of service delivery or insufficient staff cross-training). Vertical methods have also evolved from the need for different approaches to reach key populations, who might be reluctant to seek care from primary health care clinics. We build on the findings of the papers in this Series to discuss the rationale for sexual and reproductive health programmatic integration, which has the potential to better engage patients in care by meeting their preferences, simplify the user experience, and save resources when implemented in a thoughtful, culturally tailored manner. However, wide-scale sexual and reproductive health programmatic integration faces multiple challenges, requiring broadly trained health-care providers, a range of clinical and outreach channels, and well-resourced health systems. Programmatic integration might be further constrained by societal norms and regulations (eg, punitive laws, institutional homophobia, legal restrictions on access to safe abortion, and opposition to sexual and reproductive rights). Notably, the Trump Administration's withdrawal of support from various sexual and reproductive health programmes in January, 2025, is a major threat to continued progress. This Series paper provides a call to action based on the key findings from this Series that delineates the steps needed to better integrate programmes to optimise sexual and reproductive health outcomes.

This Series paper provides a summary of what is known about the funding, cost, and cost-effectiveness of sexual and reproductive health and rights interventions, interrogates the likely impacts of increasing or reducing future sexual and reproductive health and rights funding, and provides recommendations for policy and regulatory changes from an economic perspective. Interventions that target HIV and sexually transmitted infections, contraceptive interventions, and abortion care are among the most cost-effective health interventions worldwide, but their funding is under severe duress. In 2023, approximately US$35 billion was spent on these intervention areas across low-income and middle-income countries-only two-thirds of the $52 billion needed per year. HIV treatment and prevention, as well as contraceptive commodities, rely heavily on donor funding, which has decreased since 2017. The discontinuation of the US Agency for International Development funding in early 2025, in particular, requires that the most impacted countries will have to do more with much less going forward.

The interconnectedness of the global HIV and sexually transmitted infection (STI) epidemics necessitates integrated strategies to address both. This Series paper highlights the biological link between HIV and STIs, and describes the successful progress in HIV response versus STI response over the past decades. The concept of undetectable=untransmissible (U=U) in HIV treatment has revolutionised HIV prevention by reducing stigma and promoting early treatment. In line with this approach, we discuss the role of chronic suppressive therapy for herpes simplex virus type 2 and the importance of the accurate diagnosis and treatment of curable STIs to prevent transmission between sexual partners. This Series paper explores the potential of pre-exposure prophylaxis (PrEP) for HIV in different forms (eg, daily oral PrEP, event-driven PrEP, and long-acting injectable PrEP), and highlights the challenges of adherence to daily regimens and the promise of longer-acting agents, such as cabotegravir and lenacapavir. The potential of doxycycline post-exposure prophylaxis for the prevention of bacterial STIs is also discussed, with concerns about antimicrobial resistance. Although vaccine development for HIV and STIs is a key biomedical advance, we discuss the challenges and possibilities of developing effective vaccines, including lessons learnt from previous HIV vaccine trials, the potential of mRNA-based vaccines for herpes simplex virus, ongoing trials for gonorrhoea and chlamydia vaccines, and the impact of existing human papillomavirus and mpox vaccines. Diagnostic innovations emphasise the importance of point-of-care tests for HIV and STIs. This Series paper discusses the benefits, landscape, and pipeline of rapid diagnostic tests (eg, lateral flow tests and molecular assays) and the challenges of implementing these tests in low-resource settings, particularly the need for rapid results to inform clinical decisions, promote convenience, and reduce cost. This Series paper also addresses innovations in service delivery and advocates for integrated and person-centred approaches (eg, differentiated services) that combine HIV and STI services, and highlights the potential of community-based and home-based models to improve access and reduce stigma.

Contraception and family planning are vital aspects of sexual and reproductive health and rights. Despite major advances in modern contraception over the past 60 years many gaps remain, and the rate of unplanned pregnancies and abortions remains high. These issues have given rise to a new era in contraception research with great opportunities and many challenges. These opportunities include new innovations, particularly in the areas of male contraception, non-hormonal female contraception, and multipurpose prevention methods that provide contraception in combination with protection against leading sexually transmitted pathogens; fast tracking new inventions currently in the pipeline by intensifying support from government, non-profit, and industry entities; the provision of new methods, services, and messaging for underserved populations including men, marginalised women, and transgender individuals; and better understanding the needs of diverse populations. Major challenges in contraception research include inertia, especially in industry involvement; a new wave of conservatism and government interventions that threaten to impede contraception development, services, and education; and understanding what people want and how to provide solutions. The best way to improve family planning and promote women's health is to offer better contraception options to those who wish to avoid unplanned pregnancy. This can be done by renewed commitment from scientists, private foundations, and government institutions, and from industry partners who are needed to bring promising developments to market.

The concept of sexual and reproductive health and rights has evolved in the 21st century from previous narrower conceptualisations. In 2018, the Guttmacher-Lancet Commission proposed a broader and integrated defining framework, together with a package of essential health service elements. Despite this, progress on the sexual and reproductive health agenda has been inconsistent, with progress in some areas and considerable gaps in others. Even in areas that have seen breakthroughs in biomedicine and technology, progress has been partial owing to inadequacies in funding, policy, and implementation. Additionally, initial executive orders of the Trump administration in early 2025 presented a major challenge to sexual and reproductive health and rights in the USA, and orders on US foreign aid threaten devastating impacts on sexual and reproductive health and rights in recipient low-income and middle-income countries. As discussions of sexual and reproductive health and rights are often seen to be sensitive or controversial, even when had at a senior government level, any consideration of time trends in sexual and reproductive health outcomes need to consider the complex interplay between trends in social and cultural factors, politics and legal frameworks, and technology and biomedicine. The perceived sensitivity of sexual and reproductive health means that providing adequate education on sex, sexuality, and relationships is crucial, and this education is often resisted by religion or traditionalist sentiments. Furthermore, technological change means that many young people receive this education online, which has both positive and negative effects. A thorough understanding of the driving factors behind global epidemiological trends in sexual and reproductive health-such as fluidity in gender and sexual identity, biomedical innovations in contraception and the treatment and prevention of HIV and other sexually transmitted infections, gender-based violence, access to safe abortion, fertility needs, and comprehensive sexuality education-is crucial in assessing progress on the sexual and reproductive health and rights agenda. To this end, this Series paper provides an overview of trends in sexual and reproductive health and rights outcomes since 2018.

Peripartum cardiomyopathy is increasingly recognised and diagnosed in clinical practice. Over the past two decades, a substantial amount of new knowledge on this condition has been accrued, including a better understanding of the pathophysiology, genetic predisposition for a proportion of patients, diagnostic tools, management with a disease-specific therapy, and predictors of outcome. Peripartum cardiomyopathy occurs globally in all ethnic groups and should be suspected in any women who are peripartum presenting with symptoms and signs indicative of heart failure towards the end of pregnancy or in the months following delivery. Verification of left ventricular systolic dysfunction (ejection fraction <45%) is crucial for the diagnosis of peripartum cardiomyopathy and the exclusion of other causes of heart failure, such as pre-existing cardiomyopathy, valvular heart disease, or congenital heart disease. Peripartum cardiomyopathy is a disease with considerable maternal and neonatal morbidity and mortality, with only half of women experiencing complete myocardial recovery within 6 months of the onset of symptoms. This Seminar summarises current knowledge of peripartum cardiomyopathy genetics, pathophysiology, diagnostic approaches, medical management, and outcome. Furthermore, we provide guidance on both risk stratification by use of a novel score to predict recovery and on the outcomes of a subsequent pregnancy.

Patients with severe mitral regurgitation are frequently not candidates for surgery or transcatheter edge-to-edge repair (TEER). We aimed to evaluate 1-year outcomes of a novel percutaneous transseptal transcatheter mitral valve replacement (TMVR) system in patients unsuitable for surgery or TEER.