Non-segmental vitiligo is an autoimmune inflammatory disease characterised by loss of melanocytes leading to skin depigmentation. No systemic therapies have been approved, and additional therapeutic options are needed. Here, we report the efficacy and safety of upadacitinib, a selective once-daily Janus kinase inhibitor, in adults and adolescents with non-segmental vitiligo.

The identification of a clear standard of care for patients with advanced clear-cell renal cell carcinoma following anti-PD-1 or anti-PD-L1 therapy warrants study as an unmet need. We aimed to investigate belzutifan plus lenvatinib versus cabozantinib in participants with clear-cell renal cell carcinoma previously treated with immune checkpoint inhibitors.

Antiretroviral therapies with long dosing intervals have the potential to improve virological outcomes and treatment satisfaction for people with HIV-1. We report the primary endpoint results from week 48 of ISLEND-2, a phase 3 trial evaluating the efficacy and safety of switching to once-weekly oral islatravir-lenacapavir from daily oral standard of care in virologically suppressed adults with HIV-1.

A contemporary standard of care for patients with metastatic androgen pathway modulator-naive/sensitive (APMN/S) prostate cancer (also known as metastatic hormone-sensitive prostate cancer) is androgen deprivation therapy (ADT) plus an androgen receptor pathway inhibitor (ARPI) until progression. PSMAddition aimed to evaluate the efficacy and safety of [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) combined with ADT plus ARPI in prostate-specific membrane antigen (PSMA)-positive metastatic APMN/S prostate cancer.

Coronary artery bypass grafting (CABG) is a common but invasive operation traditionally performed through a median sternotomy. Minimally invasive cardiac surgery (MICS) CABG via small thoracotomy might improve postoperative recovery, but randomised evidence has been scarce. We aimed to compare patient-reported recovery after MICS CABG versus sternotomy CABG in patients with multivessel coronary artery disease and to describe clinical and safety outcomes.

Zenagamtide (formerly amycretin) is a unimolecular agonist of GLP-1, amylin, and calcitonin receptors. We aimed to investigate the dose-response relationship with respect to the efficacy and safety of once-weekly subcutaneous zenagamtide compared with placebo in adults with type 2 diabetes.

Zenagamtide (formerly amycretin) is a unimolecular peptide agonist of GLP-1, amylin, and calcitonin receptors. We aimed to investigate the dose-response relationship with respect to the efficacy and safety of once-daily oral zenagamtide compared with placebo in adults with type 2 diabetes.

Psoriasis is a common, chronic, immune-mediated skin disease affecting more than 40 million individuals worldwide. Psoriasis, along with psoriatic arthritis, are part of a broader psoriatic disease spectrum, and present with inflammatory skin and musculoskeletal manifestations driven by shared genetic, environmental, and immunological mechanisms. Skin psoriasis presents with diverse clinical phenotypes, including chronic plaque psoriasis, guttate, palmoplantar, erythrodermic, and pustular forms. Beyond cutaneous manifestations, psoriasis is associated with a substantial psychosocial burden and a wide range of comorbidities, including mental health disorders and cardio-metabolic diseases. Key psoriasis risk factors include genetic polymorphisms (most notably HLA-C*06:02), obesity, and environmental factors such as trauma, infections, and specific medications. Advances in understanding the key role of the IL-23-IL-17 inflammatory axis and related immunogenetic pathways have redefined psoriasis as a complex immune disorder, leading to the development of highly effective targeted biologic and small-molecule therapies that modulate cytokine signalling and intracellular pathways, offering improved disease control across cutaneous and musculoskeletal domains.

Duchenne muscular dystrophy (DMD) is an X-linked genetic disease of skeletal and cardiac muscle that leads to loss of ambulation and premature death due to progressive myopathy and cardiomyopathy. Deramiocel, a heart-derived cellular therapy consisting of human allogeneic cardiosphere-derived cells, improved cardiac and skeletal muscle function in phase 1-2 studies of DMD. Our aim was to assess the efficacy and safety of deramiocel in advanced DMD and support the findings of HOPE-2.

Pulmonary arterial hypertension (PAH) is a rare, progressive disease characterised by elevated pulmonary vascular resistance that can lead to right ventricular failure and premature death. Ralinepag is an oral, once-daily, selective prostacyclin IP receptor agonist developed to treat PAH. We aimed to evaluate the efficacy and safety of ralinepag in patients with PAH.

WHO recommends 5 days of intravenous antibiotics for children hospitalised with severe community-acquired pneumonia (CAP). We aimed to investigate the safety of a step-down to different oral antibiotics and the shortest effective duration.

Consolidation therapy for primary CNS lymphoma (PCNSL) includes high-dose chemotherapy with autologous stem-cell transplantation (HCT-ASCT), yet its efficacy compared with non-myeloablative chemoimmunotherapy remains uncertain. This study aimed to provide randomised comparative evidence on the efficacy and safety of thiotepa-based HCT-ASCT versus non-myeloablative R-DeVIC consolidation after uniform MATRix induction in newly diagnosed PCNSL.

Mortality among infants with severe HIV-associated pneumonia remains high. This trial (EMPIRICAL) tested whether empirical valganciclovir treatment for cytomegalovirus improves survival in infants in Africa.

The optimal duration of dual antithrombotic therapy after percutaneous coronary intervention (PCI) in patients with atrial fibrillation remains uncertain. We aimed to compare the efficacy and safety of 1-month versus 12-month dual antithrombotic therapy in this population.

Latin America faces a high dementia burden, with increased prevalence of factors associated with cognitive decline. Multidomain lifestyle interventions might delay cognitive decline, but populations from Latin America remain under-represented in dementia prevention trials. We aimed to investigate the feasibility of a culturally adapted, multidomain, systematic lifestyle intervention and investigate its effects on global cognitive function in at-risk older adults (aged 60-77 years).

Older patients represent the fastest growing patient group in clinical care. They are a heterogeneous group, for whom evidence for making treatment decisions is often scarce. Important domains for advancing the relevance of clinical trials for older patients are selection and inclusion of representative patients, choosing appropriate therapeutic interventions, and studying relevant outcomes. In the last decade, a myriad of publications has recommended multiple solutions that improve the relevance of trials for older people. Although uptake of these recommendations has been slow, there are now some excellent and successful implementation approaches that show that it is possible to design and execute trials that are inclusive of older patients, address relevant outcomes, and allow for real-world comparisons of intervention effectiveness. Observational studies based on different data sources add useful complementary information. This narrative review aims to synthesise best practices and successful strategies to improve the relevance of clinical trials for older patients.

Alternatives to carbapenems for the treatment of third-generation cephalosporin-resistant Enterobacterales (3GCR-E) are urgently needed to reduce the selection pressure posed by these drugs. Temocillin is a neglected narrow-spectrum β-lactam. The aim of the trial was to investigate if temocillin is non-inferior to carbapenems for the targeted treatment of bacteraemia due to 3GCR-E.

Venetoclax-rituximab (VR) following covalent Bruton tyrosine kinase (BTK) inhibitor therapy is the fixed-duration standard of care for patients with chronic lymphocytic leukaemia (including small lymphocytic lymphoma). Pirtobrutinib, a non-covalent BTK inhibitor, is approved for use after treatment with a covalent BTK inhibitor as a continuous therapy option. We aimed to evaluate the addition of pirtobrutinib to VR as a fixed-duration regimen in patients with relapsed or refractory chronic lymphocytic leukaemia.

Currently children's needs, perspectives, and rights are not adequately included in public policies, with negative consequences for the health and wellbeing of children and future generations. The 2020 WHO-UNICEF-Lancet Commission reviewed threats to children's health and concluded that children's needs and voices should be centred in all policies for a sustainable future. Since 2021, Children in All Policies 2030, a global collaboration of policy makers, scientists, and advocates, has implemented the Commission's recommendations by fostering new approaches to participatory, intersectoral policy making across diverse countries. Efforts to implement the Commission's recommendations encountered challenges including flawed assumptions in prevailing policy-making models, failure to fulfil children's right to participate, and an ongoing scarcity of intersectoral policy integration. Eight lessons on what works for improving policy making and implementation emerged: use creative means to involve children, patiently assemble coalitions, prepare to seize political opportunities, harmonise global data to bridge UN partnerships, create national political and technical platforms, use media to change cultural perceptions, use strategic framing to overcome sectoral barriers, and embrace joint learning. Harnessing people's consideration and concern for children and future generations and engaging children's voices represents a powerful political opportunity to reach current development goals and ensure a healthier, more sustainable future.

Once rapidly fatal, neglected, and orphan diseases without approved therapeutic options, systemic amyloidoses are now highly treatable. Basic scientific discoveries regarding the molecular mechanisms of transthyretin misfolding and aggregation have driven the development of drugs for the treatment of transthyretin (ATTR) amyloidosis, with six novel therapies approved since 2018. The combination of daratumumab, cyclophosphamide, bortezomib, and dexamethasone was approved for the treatment of light chain (AL) amyloidosis in 2021. Since then, highly effective immunotherapies, such as bispecific T-cell engagers, have been tested in clinical trials in patients with relapsed AL amyloidosis, with unprecedented efficacy. Thus, suspicion of systemic amyloidosis should be raised early in individuals with a suggestive clinical presentation, followed by rapid tissue diagnosis, with appropriate protein typing and prompt commencement of active therapy. These rapid and exciting therapeutic advancements set the stage for this Review on the epidemiology, pathophysiology, and diagnosis of systemic amyloidosis. Through the lens of the molecular mechanisms underlying amyloidosis pathogenesis, we will focus on approved and investigational therapies. We also discuss future directions and challenges concerning a cure for patients with AL or ATTR amyloidosis.