The Lancet

[Articles] Sex inequality in disease burden attributable to smoking, secondhand smoke and chewing tobacco: A systematic analysis for the Global Burden of Disease Study 2023 https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(26)00402-5/fulltext?rss=yes While smoking- and SHS-attributable ASDRs have declined and chewing tobacco-attributable ASDR has remained stable, sex disparities have varied by time, region, and life stage. These findings may inform the integration of sex-specific perspectives into tobacco control strategies, which could strengthen the implementation of the Framework Convention on Tobacco Control and help mitigate the future burden of tobacco use.

[Articles] Intergenerational contact and depressive symptoms in midlife and older adults: an analysis of six cohort studies across 33 countries https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(26)00401-3/fulltext?rss=yes The association between intergenerational contact and depressive symptoms among midlife and older adults is context dependent. Residential separation combined with infrequent contact may reflect reduced emotional support and is linked to an increased burden of depressive symptoms across various settings. Conversely, frequent intergenerational contact can help mitigate this risk in certain cultural contexts. Future research is needed to clarify causal pathways across diverse settings.

[Articles] Longitudinal patterns of fentanyl utilisation (medical versus illicit sources) in the United States 2015–2023: a retrospective cohort study https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(26)00394-9/fulltext?rss=yes Illicit-source fentanyl exposure is associated with a markedly higher risk of opioid-related harmful outcomes than medical-source exposure, providing evidence that illicit fentanyl is a driver of adverse patient outcomes. Whilst acknowledging the limitations of this analysis, these findings underscore the substantial contribution of illicit fentanyl to the ongoing opioid epidemic and highlight the need for deeper investigation of how medical and illicit fentanyl use interact over time. Further research is warranted.

[Correspondence] The 2026 Kumamoto earthquake: rescue alone is not enough https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(26)01590-4/fulltext?rss=yes On July 28, 2026, a magnitude 7·1 earthquake struck Kumamoto Prefecture in southern Japan.1 By the next morning, at least 13 people were confirmed dead; more than 30 000 households remained without power, more than 80 000 without water, and damage or utility outages were reported at 46 health-care facilities.1 In 2016, the same region was struck by successive magnitude 6·5 and 7·3 earthquakes.2 A large shopping mall, which was damaged in 2016 and reopened in June 2026, partly collapsed before an explosion, exposing the fragility of rebuilt infrastructure.

[Articles] Belzutifan plus lenvatinib versus cabozantinib in patients with previously treated advanced renal cell carcinoma (LITESPARK-011): an open-label, randomised, controlled, phase 3 trial https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(26)01089-5/fulltext?rss=yes Belzutifan–lenvatinib represents a novel and efficacious treatment option. Although overall survival was not significantly different between the groups, belzutifan–lenvatinib might be a new standard of care for patients with advanced clear-cell renal cell carcinoma with disease progression after previous anti-PD-1 or anti-PD-L1 therapy. The safety profile of belzutifan–lenvatinib was consistent with those of the individual drugs.

[Comment] Redefining therapy for previously treated renal cell carcinoma https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(26)01246-8/fulltext?rss=yes For more than a decade, the question of what to offer patients with metastatic clear-cell renal cell carcinoma after front-line therapy was familiar. Treatment consisted of a VEGFR-tyrosine-kinase inhibitor, frequently sequenced after another. The framework began with the TARGET trial1 in patients with cytokine-refractory disease, and matured in the post-VEGFR-tyrosine-kinase inhibitor population through the AXIS trial,2 which showed superiority of axitinib over sorafenib, and the pivotal METEOR trial,3 which established cabozantinib as a second-line standard of care.

[Articles] Switch to once-weekly, single-tablet islatravir–lenacapavir from daily standard of care for HIV-1 (ISLEND-2): a multicentre, randomised, open-label, active-controlled, phase 3 non-inferiority trial https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(26)01442-X/fulltext?rss=yes Once-weekly islatravir–lenacapavir showed non-inferior efficacy to the standard of care and was generally well tolerated. Longer-term safety data will provide further valuable insights beyond the week 48 data presented here. Islatravir–lenacapavir has potential to be the first once-weekly complete oral single-tablet regimen for HIV-1 treatment.

[Comment] Once-weekly oral antiretroviral therapy for HIV https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(26)01557-6/fulltext?rss=yes For the past four decades, oral antiretroviral therapy for HIV has required daily doses. Long-acting injectable cabotegravir and rilpivirine has ended that obligation,1 requiring an injection every month or every 2 months. In The Lancet, Amy E Colson and colleagues2 report ISLEND-2, a randomised, open-label trial in which 626 virologically suppressed adults with HIV-1 either switched to a once-weekly, single oral tablet containing islatravir, a nucleoside reverse transcriptase translocation inhibitor, and lenacapavir, a capsid inhibitor, or continued daily standard-of-care therapy.

[Comment] Towards a joint classification of neurological and psychiatric disorders https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(26)01498-4/fulltext?rss=yes Psychiatry has been called the other half of medicine,1 reflecting the separation of mental health services from the rest of health care. Patients with a mental illness are treated in different clinics and hospitals to those with physical illnesses. Advances in neuroscience and medicine have gradually eroded the justification for this divide, but the compelling evidence for the interdependence of brain and mind is easily neglected within our siloed specialties and services. We believe this separation causes harm to patients with disorders on either side of the line and propose that a joint classification of neurological and psychiatric disorders is theoretically justified, practically feasible, and would benefit psychiatry, neurology, and medicine more broadly.

[Articles] Intensive versus standard blood pressure control and overall brain small vessel disease burden: a post-hoc analysis of the SPRINT randomized clinical trial https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(26)00396-2/fulltext?rss=yes Among hypertensive adults, targeting an SBP of <120 mmHg, compared with <140 mmHg, was associated with less progression of SVD burden. Even modest SBP reductions of ≤10 mmHg conferred measurable brain benefits, with larger reductions providing incrementally greater protection against SVD progression.

[Articles] RAS/MAPK pathway modulation with simvastatin in children with Noonan syndrome: a multicentre, randomised, double-blind, placebo-controlled phase 3 trial https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(26)00367-6/fulltext?rss=yes In children with NS, 12 months of simvastatin did not result in significant improvements in the primary endpoint or in major outcomes of clinical relevance under the conditions tested. Changes in DKK1 concentrations and the Ea/Aa ratio should be interpreted cautiously as exploratory secondary findings requiring confirmation in adequately powered studies. Further research is needed to explore alternative treatment strategies and more direct approaches to RAS/MAPK pathway modulation.

[Review] Hepatitis A vaccination and its public-health impact in routine prevention and outbreak control: a systematic review and meta-analysis https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(26)00397-4/fulltext?rss=yes Hepatitis A vaccination provides very high protection in pre-exposure settings. Post-exposure vaccination may also be effective, but confidence in this estimate is limited by very low-certainty evidence and substantial heterogeneity. Population-level findings support the public health value of routine immunisation and suggest potential benefit in outbreak response.

[Articles] Efficacy and safety of sublingual cilostazol and dexborneol for the treatment of acute ischaemic stroke: a randomised phase 2 trial in China https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(26)00368-8/fulltext?rss=yes Our findings indicate that, for patients with ischaemic stroke undergoing endovascular treatment for large vessel occlusion, Y-6 sublingual tablets (cilostazol and dexborneol) were safe with tolerance. Although the trial did not demonstrate statistically significant efficacy on the primary outcome, the signal toward improved functional outcomes without haemorrhage risk supports the biological plausibility of the intervention and justifies further investigation. Large-scale phase 3 clinical trials are warranted to further this research.

[Health Policy] Building a genomics-capable cancer workforce: a competency-based framework for education and training in precision oncology https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(26)00395-0/fulltext?rss=yes This framework provides an implementation-oriented structure to support workforce development, curriculum design, continuing professional education, role mapping, competency assessment, and service planning in precision oncology. Its application may support scalable, equitable, and sustainable integration of genomics into routine cancer care.

[Review] The silent zone of paediatric asthma: integrating small airway dysfunction assessment into clinical practice https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(26)00385-8/fulltext?rss=yes Small airway dysfunction (SAD) is increasingly recognised as a clinically relevant component of paediatric asthma because peripheral airway abnormalities may precede spirometric impairment and contribute to poor disease control despite preserved FEV1. This narrative review summarises current evidence on the assessment and clinical implications of SAD in children, based on studies identified through PubMed/MEDLINE and the Cochrane Library. Spirometry remains the cornerstone of asthma evaluation but has limited sensitivity for early peripheral airway disease.

[Articles] Machine learning to predict adverse perinatal outcomes: a systematic review and meta-analysis https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(26)00391-3/fulltext?rss=yes ML prediction models showed moderate performance, were at high risk of bias and did not always outperform traditional statistical methods. To improve perinatal outcome prediction, methodological improvements and better predictors are needed.

[Articles] [177Lu]Lu-DOTA-TATE plus long-acting octreotide in patients with newly diagnosed, advanced, grade 2–3, gastroenteropancreatic neuroendocrine tumours: preplanned and post-hoc efficacy analyses from the randomised, phase 3 NETTER-2 trial https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(26)00362-7/fulltext?rss=yes These findings support the use of first-line 177Lu-DOTATATE for patients with advanced, well-differentiated, higher grade 2–3 (Ki67 ≥10% and ≤55%), somatostatin receptor-positive GEP-NETs, and for whom chemotherapy is not considered the most appropriate treatment option, regardless of NET grade (2/3) or origin (pancreas/gastrointestinal).

[Articles] Chronic obstructive pulmonary disease and risk of incident cardiovascular disease, chronic kidney disease, and death: a systematic review and meta-analysis https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(26)00384-6/fulltext?rss=yes COPD is associated with an increased risk for a range of incident cardiovascular diseases, chronic kidney disease and mortality. The impact of current and novel treatments on a broader range of cardiovascular and kidney outcomes in patients with COPD requires prospective randomised assessment.