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.

People with recurrent or metastatic nasopharyngeal carcinoma that progressed after chemotherapy and programmed cell death protein 1 (PD-1) and its ligand (PD-L1) inhibitors have few treatment options and a poor prognosis. We therefore aimed to investigate the efficacy and safety of the bispecific antibody-drug conjugate izalontamab brengitecan (iza-bren) in heavily pretreated individuals with recurrent or metastatic nasopharyngeal carcinoma.

Squamous non-small-cell lung cancer (NSCLC) is associated with worse clinical outcomes than non-squamous NSCLC, but treatment options are scarce. We aimed to evaluate the efficacy and safety of ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy as a first-line therapy for patients with advanced squamous NSCLC.

Although widely used, cefazolin efficacy for the treatment of meticillin-susceptible Staphylococcus aureus (MSSA) bacteraemia has not thus far been investigated in a clinical trial. In this study, we aimed to compare the efficacy and safety of cefazolin with that of cloxacillin in patients with MSSA bacteraemia.

Two large-scale trials comparing high-dose inactivated influenza vaccine (HD-IIV) versus standard-dose inactivated influenza vaccine (SD-IIV) against hospitalisation outcomes have been conducted in Denmark and Spain. We aimed to analyse the pooled data from these trials to enhance generalisability and assess the relative vaccine effectiveness (rVE) of HD-IIV versus SD-IIV against severe clinical outcomes in older adults.

Patients with high-risk non-muscle-invasive bladder cancer (NMIBC) often have recurrence or progression after transurethral resection of bladder tumour (TURBT) and subsequent BCG therapy. We aimed to evaluate whether 1 year of durvalumab with BCG could improve outcomes versus BCG alone for these patients.

Community-acquired pneumonia is a major global health challenge that disproportionately affects vulnerable populations, including older people, immunocompromised people, those with chronic conditions, and young children. Once considered solely an acute illness, community-acquired pneumonia is now recognised as a disease with long-term complications, including cardiovascular events, respiratory impairment, and cognitive decline. Advances, such as nucleic acid amplification tests (NAATs) and the broader availability of point-of-care lung ultrasound, allow for rapid pathogen detection and personalised treatment. However, substantial uncertainties remain regarding the role of NAATs, lung ultrasounds, and serum biomarkers in clinical practice. Antibiotics are the cornerstone of community-acquired pneumonia treatment, but the roles of adjunctive therapies, including corticosteroids and immunomodulators, remain incompletely defined. Comprehensive community-acquired pneumonia management emphasises personalised treatment, rehabilitation after the acute episode, routine cardiovascular screening, and strengthening preventive measures, such as vaccination. As precision medicine advances, integrating diagnostics and tailored therapies will improve outcomes and reduce the global burden of community-acquired pneumonia.

Timely and comprehensive analyses of causes of death stratified by age, sex, and location are essential for shaping effective health policies aimed at reducing global mortality. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 provides cause-specific mortality estimates measured in counts, rates, and years of life lost (YLLs). GBD 2023 aimed to enhance our understanding of the relationship between age and cause of death by quantifying the probability of dying before age 70 years (70q0) and the mean age at death by cause and sex. This study enables comparisons of the impact of causes of death over time, offering a deeper understanding of how these causes affect global populations.

Comprehensive, comparable, and timely estimates of demographic metrics-including life expectancy and age-specific mortality-are essential for evaluating, understanding, and addressing trends in population health. The COVID-19 pandemic highlighted the importance of timely and all-cause mortality estimates for being able to respond to changing trends in health outcomes, showing a strong need for demographic analysis tools that can produce all-cause mortality estimates more rapidly with more readily available all-age vital registration (VR) data. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) is an ongoing research effort that quantifies human health by estimating a range of epidemiological quantities of interest across time, age, sex, location, cause, and risk. This study-part of the latest GBD release, GBD 2023-aims to provide new and updated estimates of all-cause mortality and life expectancy for 1950 to 2023 using a novel statistical model that accounts for complex correlation structures in demographic data across age and time.

For more than three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has provided a framework to quantify health loss due to diseases, injuries, and associated risk factors. This paper presents GBD 2023 findings on disease and injury burden and risk-attributable health loss, offering a global audit of the state of world health to inform public health priorities. This work captures the evolving landscape of health metrics across age groups, sexes, and locations, while reflecting on the remaining post-COVID-19 challenges to achieving our collective global health ambitions.

Alcohol use disorders consist of conditions characterised by compulsive heavy alcohol use and loss of control over alcohol intake. Alcohol use disorders are some of the most prevalent mental disorders globally, with higher prevalence in high-income countries and lower prevalence in low-income countries. The recent COVID-19 pandemic was associated with an increase in fully alcohol-attributable mortality, in part triggered by alcohol-specific interactions with stress. Despite their high prevalence, alcohol use disorders remain undertreated, even though there are scientifically established and cost-effective psychosocial, community, and pharmacological interventions available. In addition, promising new treatment modalities have been developed and are currently being tested. The two main barriers to better access to evidence-based alcohol use disorder treatment are low availability, due to the absence of government or public funding for such treatment, and stigma. The first barrier could be overcome by increasing alcohol excise taxation, which currently falls considerably short of covering the social costs of alcohol use. In addition to generating revenues, increasing excise taxation could reduce health-care costs by reducing hospitalisations for all alcohol-attributable conditions, including alcohol use disorders. Overall, integrated alcohol control policies could improve the prevention of alcohol use disorders, improve access to treatment, and reduce stigma.

Obstructive sleep apnoea (OSA) is highly prevalent but approved pharmacological treatment options are missing. Sultiame improves the ventilatory response and upper airway muscle activity by inhibiting carbonic anhydrase. This study aimed to prospectively assess the efficacy and safety of three dosages of sultiame in OSA.

Since October, 2023, Palestinian children in the Gaza Strip have suffered war-induced displacement, food insecurity, malnutrition, and elevated risks of famine and mortality. In this study, we aimed to document the extent of, and patterns in, wasting malnutrition in children aged 6-59 months across the Gaza Strip between January, 2024, and August, 2025.

Postpartum haemorrhage (excessive bleeding after birth) is a leading cause of maternal mortality and morbidity worldwide. However, there is no global consensus on which clinical markers best define excessive bleeding or reliably predict adverse maternal outcomes. The aim of this study was to assess the prognostic accuracy of clinical markers of postpartum bleeding in predicting maternal mortality or severe morbidity.