Insulin efsitora alfa (efsitora), a once-weekly basal insulin, has the potential to reduce the treatment burden of people with type 2 diabetes who require insulin. We aimed to assess the efficacy and safety of once-weekly efsitora compared with insulin glargine U100 in adults with type 2 diabetes treated with basal and prandial insulin.

Once-weekly insulin efsitora alfa (efsitora) is in development for the treatment of people with diabetes. The aim of the current study was to assess the efficacy and safety of once-weekly efsitora compared with daily insulin degludec (degludec) in adults with type 2 diabetes using basal insulin.

Sierra Leone has very high maternal and neonatal mortality rates, and a large proportion of these deaths occur in adolescents, a particularly vulnerable group, and is usually driven by poverty, lack of education, and sparse employment opportunities. We evaluated the feasibility and potential effects of a community-based mentoring intervention from pregnancy up to 1 year after birth to inform a subsequent larger trial aiming to reduce mortality among adolescent girls and their newborns (2YoungLives).

Surgery and corticosteroid injections are established treatments for carpal tunnel syndrome, but the optimal treatment strategy remains unclear. This study aimed to compare starting treatment with surgery versus starting with a corticosteroid injection.

Retifanlimab has activity in programmed death ligand 1-positive advanced squamous cell anal carcinoma (SCAC) that has progressed on platinum chemotherapy. We aimed to prospectively assess the benefit of adding retifanlimab to initial carboplatin-paclitaxel for this disease.

Currently, no worldwide approved therapies exist for adults with neurofibromatosis type 1 (NF1) and symptomatic, inoperable plexiform neurofibromas. The KOMET study aimed to evaluate selumetinib (ARRY-142886, AZD6244) efficacy and safety in this population.

Despite improved efficacy with first-line immune checkpoint inhibitors plus platinum-based chemotherapy for extensive-stage small-cell lung cancer (ES-SCLC), survival remains poor. In this study, we aimed to compare lurbinectedin plus atezolizumab and atezolizumab alone as maintenance therapies in patients with ES-SCLC without progression after induction therapy with atezolizumab, carboplatin, and etoposide.

Relacorilant, a first-in-class selective glucocorticoid receptor antagonist, increases a tumour's sensitivity to chemotherapy by reducing cortisol signalling. This study aimed to show whether the addition of relacorilant to nab-paclitaxel improves progression-free and overall survival in females with platinum-resistant ovarian cancer.

Claudin-18 isoform 2 (CLDN18.2) has emerged as a promising therapeutic target in gastric or gastro-oesophageal junction cancer. Satricabtagene autoleucel (satri-cel; also known as CT041), an autologous CLDN18.2-specific chimeric antigen receptor (CAR) T-cell therapy, showed encouraging activity in previously treated patients with advanced gastric or gastro-oesophageal junction cancer in phase 1 clinical trials. In this Article, we report the primary results from the phase 2 pivotal trial (CT041-ST-01) investigating the efficacy and safety of satri-cel for gastric or gastro-oesophageal junction cancer.

The universally accepted best practice protocol for monitoring patients who receive intravenous thrombolysis for acute ischaemic stroke was established in the 1990s. However, the protocol is burdensome for nurses, disrupts the sleep of patients, and is potentially less relevant in patients at low risk of symptomatic intracerebral haemorrhage. We aimed to assess whether implementing a low-intensity monitoring protocol would be as safe and effective as standard high-intensity monitoring for patients with acute ischaemic stroke at low risk.

It is not known which supplemental imaging technique is most beneficial for women with dense breasts attending breast screening. This study compares abbreviated MRI, automated whole breast ultrasound (ABUS), and contrast-enhanced mammography versus standard of care in women with dense breasts and a negative mammogram. We report on interim results from the first round of supplemental imaging.

ACURATE neo2 is an open-cell, supra-annular, self-expanding transcatheter heart valve that is commercially available in over 50 countries but has not previously been evaluated in a randomised trial. ACURATE-IDE aimed to prospectively evaluate the safety and efficacy of transcatheter aortic valve replacement (TAVR) with the ACURATE neo2 valve compared with commercially available valves for the treatment of severe symptomatic aortic stenosis.

Genetic studies have established angiopoietin-related protein 4 (ANGPTL4) as a key regulator of triglyceride metabolism and a promising target to reduce atherosclerotic cardiovascular disease (ASCVD) risk beyond traditional risk factors. Human ANGPTL4 loss-of-function shows no adverse consequences and is associated with reduced triglycerides and remnant cholesterol, and a reduced risk of type 2 diabetes and ASCVD. Nonetheless, development of ANGPTL4 inhibitors has been delayed due to adverse findings in ANGPTL4-knockout mice fed a high saturated fat diet, including lipid accumulation in mesenteric lymph nodes, systemic inflammation, adverse clinical signs, and reduced survival. We previously reported the development and preclinical characterisation of MAR001, an ANGPTL4 inhibitory antibody. Here, we report a comprehensive safety assessment of ANGPTL4 inhibition, including novel analysis of genetic ANGPTL4 loss on mesenteric lymph node architecture in humans and two early-phase clinical trials.

Amyotrophic lateral sclerosis (ALS) is a life-threatening disease characterised by progressive loss of motor neurons with few therapeutic options. The MIROCALS study tested the hypothesis that low-dose interleukin-2 (IL-2LD) improves survival and function in ALS.

Patients with unresectable hepatocellular carcinoma have a poor prognosis, and treatments with long-term benefits are needed. We report results from the preplanned interim analysis of the CheckMate 9DW trial assessing nivolumab plus ipilimumab versus lenvatinib or sorafenib for unresectable hepatocellular carcinoma in the first-line setting.

Reducing LDL cholesterol prevents atherosclerotic cardiovascular disease (ASCVD) events. The aim of this study was to evaluate the LDL cholesterol-lowering efficacy of a fixed-dose combination (FDC) of obicetrapib, a CETP inhibitor, and ezetimibe.

WHO recommends treating hepatitis C infection with one of three antiviral combinations for 8-12 weeks. No randomised trials have compared these regimens, and high cure rates might be achievable with shorter durations of therapy. We aimed to compare sofosbuvir-daclatasvir with sofosbuvir-velpatasvir, and to evaluate potential novel treatment strategies.

The benefits and harms of early induction of labour to reduce shoulder dystocia in fetuses suspected to be large for gestational age (LGA) are uncertain. We aimed to investigate whether early induction of labour is associated with a reduced risk of shoulder dystocia compared with standard care.

Chronic hand eczema is a heterogeneous, fluctuating, and long-lasting disease affecting the hands and wrists that substantially affects quality of life. For severe chronic hand eczema, topical corticosteroids are often unsatisfactory and systemic treatment can be required. The aim of the head-to-head, phase 3 DELTA FORCE trial was to evaluate the efficacy and safety of topical delgocitinib cream versus oral alitretinoin, the only currently approved systemic drug for severe chronic hand eczema.

Surgical wound healing by secondary intention (SWHSI) presents a substantial management and financial challenge. Negative pressure wound therapy (NPWT) has increasingly been used as a treatment despite an absence of comparative evidence of effectiveness. We evaluated the effectiveness of NPWT compared with usual care for improving time to wound healing in patients with an SWHSI.