Non-coeliac gluten sensitivity (NCGS) refers to individuals who report intestinal and extraintestinal symptoms related to the ingestion of gluten-based or wheat-based foods, in the absence of coeliac disease or wheat allergy. Gluten is found in multiple cereals, including wheat, rye, and barley, although the precise trigger of symptoms in NCGS remains unclear. Although approximately 10% of adults worldwide self-report gluten or wheat sensitivity, meta-analyses suggest that, during controlled challenge studies, 16-30% of these individuals have symptoms specifically triggered by gluten. However, methodological variability-including the presence of fermentable carbohydrates in challenge preparations-limits interpretation. Current evidence suggests that fermentable carbohydrates and nocebo effects contribute considerably to symptom generation in many cases. The substantial size of the gluten-free market raises questions about commercial and media influences on how NCGS is portrayed, and on the direction of related research. Definitive diagnosis of NCGS remains elusive due to the absence of biomarkers, significant overlap with disorders of gut-brain interaction, and methodological challenges in dietary evaluation. Until causative agents are identified and diagnostic tests developed, NCGS remains a diagnosis of exclusion, requiring careful systematic evaluation. Management approaches should balance dietary modification with recognition of psychological factors while ensuring nutritional adequacy. This Review critically examines current evidence regarding NCGS as a distinct entity, explores potential mechanisms, and provides practical guidance for assessment and management, while acknowledging major uncertainties in the field.

The SELECT trial found semaglutide reduced major adverse cardiovascular events (MACE) in patients with overweight or obesity with cardiovascular disease but without diabetes. We report a prespecified analysis of the SELECT trial on the relationships between baseline adiposity measures, treatment-induced adiposity changes, and subsequent MACE risk.

Cancers of the breast, cervix, and ovary are a major public health problem worldwide. Evaluating the consistency with clinical guidelines for treatment by use of individual high-resolution data from population-based cancer registries is a powerful tool to help interpretation of global inequalities in cancer survival. The VENUSCANCER project aims to assess the worldwide variation in patterns of care and time to initial treatment for women diagnosed with one of these three common cancers.

Despite extraordinary scientific and medical resources, the US health-care system underperforms. In this Review we consider the damage wrought by decades of market-based policies that have stimulated profit-seeking by insurers and health-care providers. Policy makers have subcontracted coverage under the public Medicaid and Medicare programmes for people with low incomes and those older than 64 years to private insurance firms-which now derive most of their revenues from those programmes-raising taxpayers' costs and constricting patients' care. Despite worrisome evidence of misbehaviour, firms obligated to prioritise shareholders' interests-and, more recently, private equity firms with a single-minded focus on short-term profit-have gained control of vital clinical resources. President Biden rescinded some of Donald Trump's most egregious first-term policies, expanded coverage for lower-income Americans, and initiated modest drug price controls. Since regaining office, President Trump has laid siege to science and public health, cut US$990 billion from Medicaid to offset tax reductions for the wealthy, and is accelerating Medicare's privatisation. State governments can tighten regulation of profit-driven abuses, and the medical community should resist Trump's health-harming agenda. But neither restoring the pre-Trump status quo, nor further attempts to reconcile the human rights of patients with the property claims of investors will suffice. Reforms must, instead, decommercialise insurance and care provision.

Antidepressants induce physiological alterations; however, the degree to which these occur in treatment with various antidepressants is unclear. We aimed to compare and rank antidepressants based on physiological side-effects by synthesising data from randomised controlled trials (RCTs).

Zanzalintinib is a multitargeted tyrosine-kinase inhibitor that, when combined with atezolizumab, showed promising antitumour activity and manageable toxicity in a phase 1 study. We aimed to compare the efficacy and safety of zanzalintinib-atezolizumab versus regorafenib in patients with previously treated metastatic colorectal cancer.

Surgical resection is the preferred curative approach for patients with early-stage hepatocellular carcinoma, but recurrence remains a major challenge. Consequently, neoadjuvant and adjuvant therapies have been proposed to reduce tumour burden and mitigate the risk of recurrence. The CARES-009 trial aimed to evaluate perioperative camrelizumab plus rivoceranib in patients with resectable hepatocellular carcinoma at intermediate or high risk of recurrence.