Direct-acting oral anticoagulant use for stroke prevention in atrial fibrillation is limited by bleeding concerns. Asundexian, a novel, oral small molecule activated coagulation factor XIa (FXIa) inhibitor, might reduce thrombosis with minimal effect on haemostasis. We aimed to determine the optimal dose of asundexian and to compare the incidence of bleeding with that of apixaban in patients with atrial fibrillation.

Dietary restriction of sodium has been suggested to prevent fluid overload and adverse outcomes for patients with heart failure. We designed the Study of Dietary Intervention under 100 mmol in Heart Failure (SODIUM-HF) to test whether or not a reduction in dietary sodium reduces the incidence of future clinical events.

Oral pre-exposure prophylaxis has been introduced in more than 70 countries, including many in sub-Saharan Africa, but women experience considerable barriers to daily pill-taking, such as stigma, judgement, and the fear of violence. Safe and effective long-acting agents for HIV prevention are needed for women. We aimed to evaluate the safety and efficacy of injectable cabotegravir compared with daily oral tenofovir diphosphate plus emtricitabine (TDF-FTC) for HIV prevention in HIV-uninfected women.

Pembrolizumab prolongs progression-free and overall survival among patients with advanced melanoma and recurrence-free survival in resected stage III disease. KEYNOTE-716 assessed pembrolizumab as adjuvant therapy in patients with completely resected, high-risk, stage II melanoma. We report results from the planned first and second interim analyses for recurrence-free survival.

Although substantial progress has been made in the diagnosis and treatment of acute coronary syndromes, cardiovascular disease remains the leading cause of death globally, with nearly half of these deaths due to ischaemic heart disease. The broadening availability of high-sensitivity troponin assays has allowed for rapid rule-out algorithms in patients with suspected non-ST-segment elevated myocardial infarction (NSTEMI). Dual antiplatelet therapy is recommended for 12 months following an acute coronary syndrome in most patients, and additional secondary prevention measures including intensive lipid-lowering therapy (LDL-C <1·4 mmol/L), neurohormonal agents, and lifestyle modification, are crucial. The scientific evidence for diagnosis and management of acute coronary syndromes continues to evolve rapidly, including adapting to the COVID-19 pandemic, which has impacted all aspects of care. This Seminar provides a clinically relevant overview of the pathobiology, diagnosis, and management of acute coronary syndromes, and describes key scientific advances.

Rubella is an acute illness caused by rubella virus and characterised by fever and rash. Although rubella is a clinically mild illness, primary rubella virus infection in early pregnancy can result in congenital rubella syndrome, which has serious medical and public health consequences. WHO estimates that approximately 100 000 congenital rubella syndrome cases occur per year. Rubella virus is transmitted through respiratory droplets and direct contact. 25-50% of people infected with rubella virus are asymptomatic. Clinical disease often results in mild, self-limited illness characterised by fever, a generalised erythematous maculopapular rash, and lymphadenopathy. Complications include arthralgia, arthritis, thrombocytopenic purpura, and encephalitis. Common presenting signs and symptoms of congenital rubella syndrome include cataracts, sensorineural hearing impairment, congenital heart disease, jaundice, purpura, hepatosplenomegaly, and microcephaly. Rubella and congenital rubella syndrome can be prevented by rubella-containing vaccines, which are commonly administered in combination with measles vaccine. Although global rubella vaccine coverage reached only 70% in 2020 global rubella eradiation remains an ambitious but achievable goal.

ZyCoV-D, a DNA-based vaccine, showed promising safety and immunogenicity in a phase 1/2 trial. We now report the interim efficacy results of phase 3 clinical trial with ZyCoV-D vaccine in India.