61. Stopping of adalimumab in juvenile idiopathic arthritis-associated uveitis (ADJUST): a multicentre, double-masked, randomised controlled trial.
作者: Nisha R Acharya.;Athimalaipet V Ramanan.;Alison B Coyne.;Kathryn L Dudum.;Elia M Rubio.;Sydney M Woods.;Catherine M Guly.;Elena Moraitis.;Harry J D Petrushkin.;Kate Armon.;Narman Puvanachandra.;Jessy T Choi.;Daniel P Hawley.;Benjamin F Arnold.; .
来源: Lancet. 2025年405卷10475期303-313页
Adalimumab is an effective treatment for juvenile idiopathic arthritis-associated uveitis. Data are scarce on the effects of discontinuing adalimumab after control of the disease had been reached. We aimed to assess efficacy and safety of discontinuing treatment in patients with juvenile idiopathic arthritis-associated uveitis.
62. Hidradenitis suppurativa.
作者: Robert Sabat.;Afsaneh Alavi.;Kerstin Wolk.;Ximena Wortsman.;Barry McGrath.;Amit Garg.;Jacek C Szepietowski.
来源: Lancet. 2025年405卷10476期420-438页
Hidradenitis suppurativa is a chronic inflammatory disease characterised by painful, deep-seated nodules, abscesses, and draining tunnels in the skin of axillary, inguinal, genitoanal, or inframammary areas. In recent years, the body of knowledge in hidradenitis suppurativa has advanced greatly. This disorder typically starts in the second or third decade of life. The average worldwide prevalence is 1% but varies geographically. Hidradenitis suppurativa has a profound negative effect on patients' quality of life and on the gross value added to society. Comorbidities (eg, metabolic syndrome, inflammatory arthritis, and inflammatory bowel disease) frequently accompany skin alterations, because of systemic inflammation. Pathogenesis of hidradenitis suppurativa is complex and includes innate immune mechanisms (eg, macrophages, neutrophils, IL-1β, tumour necrosis factor [TNF], and granulocyte colony-stimulating factor), T-cell mechanisms (eg, IL-17 and IFN-γ), and B-cell mechanisms (eg, associated with dermal tertiary lymphatic structures and autoantibodies). Chronic inflammation leads to irreversible skin damage with tunnel formation and morbid scarring. Current treatment includes drug therapy (for the initial, purely inflammatory phase), combined drug and surgical therapy (for the destructive phase), or surgery alone (for the burnout phase). The first systemic therapies approved for hidradenitis suppurativa targeting TNF (adalimumab) and IL-17 (secukinumab and bimekizumab) have expanded drug therapy options for moderate-to-severe disease, which were previously mainly restricted to oral antibiotics. Moreover, there is a robust pipeline of immunomodulatory drugs in various stages of development for hidradenitis suppurativa. Aims of management should include early intervention to prevent irreversible skin damage, adequate control of symptoms including pain, and mitigation of extra-cutaneous comorbidities, all requiring early diagnosis and an interdisciplinary, holistic and personalised approach.
63. Radiotherapy toxicities: mechanisms, management, and future directions.
作者: Ioannis I Verginadis.;Deborah E Citrin.;Bonnie Ky.;Steven J Feigenberg.;Alexandros G Georgakilas.;Christine E Hill-Kayser.;Constantinos Koumenis.;Amit Maity.;Jeffrey D Bradley.;Alexander Lin.
来源: Lancet. 2025年405卷10475期338-352页
For over a century, radiotherapy has revolutionised cancer treatment. Technological advancements aim to deliver high doses to tumours with increased precision while minimising off-target effects to organs at risk. Despite advancements such as image-guided, high-precision radiotherapy delivery, long-term toxic effects on healthy tissues remain a great clinical challenge. In this Review, we summarise common mechanisms driving acute and long-term side-effects and discuss monitoring strategies for radiotherapy survivors. We explore ways to mitigate toxic effects through novel technologies and proper patient selection and counselling. Additionally, we address policies and management strategies to minimise the severity and impact of toxicity during and after treatment. Finally, we examine the potential advantages of emerging technologies and innovative approaches to improve conformity, accuracy, and minimise off-target effects.
64. Multidrug-resistant Gram-negative bacterial infections.
Multidrug-resistant Gram-negative bacterial infections cause significant morbidity and mortality globally. These pathogens easily acquire antimicrobial resistance (AMR), further highlighting their clinical significance. Third-generation cephalosporin-resistant and carbapenem-resistant Enterobacterales (eg, Escherichia coli and Klebsiella spp), multidrug-resistant Pseudomonas aeruginosa, and carbapenem-resistant Acinetobacter baumannii are the most problematic and have been identified as priority pathogens. In response, several new diagnostic technologies aimed at rapidly detecting AMR have been developed, including biochemical, molecular, genomic, and proteomic techniques. The last decade has also seen the licensing of multiple antibiotics that have changed the treatment landscape for these challenging infections.
65. Acute kidney injury.
作者: Marlies Ostermann.;Nuttha Lumlertgul.;Rachel Jeong.;Emily See.;Michael Joannidis.;Matthew James.
来源: Lancet. 2025年405卷10474期241-256页
Acute kidney injury (AKI) is a common, heterogeneous, multifactorial condition, which is part of the overarching syndrome of acute kidney diseases and disorders. This condition's incidence highest in low-income and middle-income countries. In the short term, AKI is associated with increased mortality, an increased risk of complications, extended stays in hospital, and high health-care costs. Long-term complications include chronic kidney disease, kidney failure, cardiovascular morbidity, and an increased risk of death. Several strategies are available to prevent and treat AKI in specific clinical contexts. Otherwise, AKI care is primarily supportive, focused on treatment of the underlying cause, prevention of further injury, management of complications, and short-term renal replacement therapy in case of refractory complications. Evidence confirming that AKI subphenotyping is necessary to identify precision-oriented interventions is growing. Long-term follow-up of individuals recovered from AKI is recommended but the most effective models of care remain unclear.
66. Appendicectomy versus antibiotics for acute uncomplicated appendicitis in children: an open-label, international, multicentre, randomised, non-inferiority trial.
作者: Shawn D St Peter.;Janelle R Noel-MacDonnell.;Nigel J Hall.;Simon Eaton.;Janne S Suominen.;Tomas Wester.;Jan F Svensson.;Markus Almström.;E Pete Muenks.;Marianne Beaudin.;Nelson Piché.;Mary Brindle.;Ali MacRobie.;Richard Keijzer.;Helene Engstrand Lilja.;Ann-Marie Kassa.;Tim Jancelewicz.;Andreana Butter.;Jacob Davidson.;Erik Skarsgard.;Yap Te-Lu.;Shireen Nah.;Andrew R Willan.;Agostino Pierro.
来源: Lancet. 2025年405卷10474期233-240页
Support for the treatment of uncomplicated appendicitis with non-operative management rather than surgery has been increasing in the literature. We aimed to investigate whether treatment of uncomplicated appendicitis with antibiotics in children is inferior to appendicectomy by comparing failure rates for the two treatments.
67. Traumatic injury mortality in the Gaza Strip from Oct 7, 2023, to June 30, 2024: a capture-recapture analysis.
作者: Zeina Jamaluddine.;Hanan Abukmail.;Sarah Aly.;Oona M R Campbell.;Francesco Checchi.
来源: Lancet. 2025年405卷10477期469-477页
Accurate mortality estimates help quantify and memorialise the impact of war. We used multiple data sources to estimate deaths due to traumatic injury in the Gaza Strip between Oct 7, 2023, and June 30, 2024.
68. Axial spondyloarthritis.
作者: Victoria Navarro-Compán.;Alexandre Sepriano.;Dafne Capelusnik.;Xenofon Baraliakos.
来源: Lancet. 2025年405卷10473期159-172页
Axial spondyloarthritis manifests as a chronic inflammatory disease primarily affecting the sacroiliac joints and spine. Although chronic back pain and spinal stiffness are typical initial symptoms, peripheral (ie, enthesitis, arthritis, and dactylitis) and extra-musculoskeletal (ie, uveitis, inflammatory bowel disease, and psoriasis) manifestations are also common. Timely and accurate diagnosis is challenging and relies on identifying a clinical pattern with a combination of clinical, laboratory (HLA-B27 positivity), and imaging findings (eg, structural damage on pelvic radiographs and bone marrow oedema on MRI of the sacroiliac joints). The Assessment in SpondyloArthritis international Society classification criteria for axial spondyloarthritis are widely used for research and have contributed to a better understanding of the gestalt of axial spondyloarthritis. Persistent disease activity, assessed mainly by the Axial Spondyloarthritis Disease Activity Score, leads to irreversible structural damage and functional impairment. Management involves non-pharmacological (eg, education, smoking cessation, exercise, physiotherapy) and pharmacological therapy. Non-steroidal anti-inflammatory drugs remain first line pharmacotherapy, while tumour necrosis factor, IL-17, and Janus kinase inhibitors are considered second-line therapies. Future advances are expected to increase disease awareness, facilitate early and accurate diagnosis, optimise disease management, and enhance overall quality of life in patients with axial spondyloarthritis.
69. Efficacy, safety, and target engagement of dazukibart, an IFNβ specific monoclonal antibody, in adults with dermatomyositis: a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial.
作者: David Fiorentino.;Aaron R Mangold.;Victoria P Werth.;Lisa Christopher-Stine.;Alisa Femia.;Myron Chu.;Amy C M Musiek.;Jason C Sluzevich.;Lauren V Graham.;Anthony P Fernandez.;Rohit Aggarwal.;Kerri Rieger.;Karen M Page.;Xingpeng Li.;Craig Hyde.;Natalie Rath.;Abigail Sloan.;Barry Oemar.;Anindita Banerjee.;Mikhail Salganik.;Christopher Banfield.;Srividya Neelakantan.;Jean S Beebe.;Michael S Vincent.;Elena Peeva.;Ruth Ann Vleugels.
来源: Lancet. 2025年405卷10473期137-146页
Dermatomyositis is a chronic autoimmune disease with distinctive cutaneous eruptions and muscle weakness, and the pathophysiology is characterised by type I interferon (IFN) dysregulation. This study aims to assess the efficacy, safety, and target engagement of dazukibart, a potent, selective, humanised IgG1 neutralising monoclonal antibody directed against IFNβ, in adults with moderate-to-severe dermatomyositis.
70. Induced pluripotent stem-cell-derived CD19-directed chimeric antigen receptor natural killer cells in B-cell lymphoma: a phase 1, first-in-human trial.
作者: Armin Ghobadi.;Veronika Bachanova.;Krish Patel.;Jae H Park.;Ian Flinn.;Peter A Riedell.;Carlos Bachier.;Catherine S Diefenbach.;Carol Wong.;Cara Bickers.;Lilly Wong.;Deepa Patel.;Jode Goodridge.;Matthew Denholt.;Bahram Valamehr.;Rebecca L Elstrom.;Paolo Strati.
来源: Lancet. 2025年405卷10473期127-136页
FT596 is an induced pluripotent stem-cell (iPSC)-derived chimeric antigen receptor (CAR) natural killer (NK) cell therapy with three antitumour modalities: a CD19 CAR; a high-affinity, non-cleavable CD16 Fc receptor; and interleukin-15-interleukin-15 receptor fusion. In this study, we aimed to determine the recommended phase 2 dose (RP2D) and evaluate the safety and tolerability of FT596 as monotherapy and in combination with rituximab. We also aimed to evaluate the antitumour activity and characterise the pharmacokinetics of FT596 as monotherapy and in combination with rituximab.
71. Durvalumab with or without bevacizumab with transarterial chemoembolisation in hepatocellular carcinoma (EMERALD-1): a multiregional, randomised, double-blind, placebo-controlled, phase 3 study.
作者: Bruno Sangro.;Masatoshi Kudo.;Joseph P Erinjeri.;Shukui Qin.;Zhenggang Ren.;Stephen L Chan.;Yasuaki Arai.;Jeong Heo.;Anh Mai.;Jose Escobar.;Yamil Alonso Lopez Chuken.;Jung-Hwan Yoon.;Won Young Tak.;Valeriy V Breder.;Tanita Suttichaimongkol.;Mohamed Bouattour.;Shi-Ming Lin.;Jean-Marie Peron.;Quang T Nguyen.;Lunan Yan.;Chang-Fang Chiu.;Florinda A Santos.;Anil Veluvolu.;Satheesh Chiradoni Thungappa.;Marco Matos.;Magdalena Żotkiewicz.;Stephanie I Udoye.;John F Kurland.;Gordon J Cohen.;Riccardo Lencioni.; .
来源: Lancet. 2025年405卷10474期216-232页
Transarterial chemoembolisation (TACE) is standard of care for patients with unresectable hepatocellular carcinoma that is amenable to embolisation; however, median progression-free survival is still approximately 7 months. We aimed to assess whether adding durvalumab, with or without bevacizumab, might improve progression-free survival.
72. Transarterial chemoembolisation combined with lenvatinib plus pembrolizumab versus dual placebo for unresectable, non-metastatic hepatocellular carcinoma (LEAP-012): a multicentre, randomised, double-blind, phase 3 study.
作者: Masatoshi Kudo.;Zhenggang Ren.;Yabing Guo.;Guohong Han.;Hailan Lin.;Jinfang Zheng.;Sadahisa Ogasawara.;Ji Hoon Kim.;Haitao Zhao.;Chuan Li.;David C Madoff.;R Mark Ghobrial.;Tomokazu Kawaoka.;René Gerolami.;Masafumi Ikeda.;Hiromitsu Kumada.;Anthony B El-Khoueiry.;Arndt Vogel.;Xiang Peng.;Kalgi Mody.;Corina Dutcus.;Leonid Dubrovsky.;Abby B Siegel.;Richard S Finn.;Josep M Llovet.; .
来源: Lancet. 2025年405卷10474期203-215页
Transarterial chemoembolisation (TACE) is standard care for unresectable, non-metastatic hepatocellular carcinoma. We aimed to evaluate the addition of lenvatinib and pembrolizumab to TACE versus dual placebo plus TACE in patients with unresectable, non-metastatic hepatocellular carcinoma.
73. Osteoarthritis.
Osteoarthritis is a heterogeneous disorder that is increasingly prevalent largely due to aging and obesity, resulting in a major disease burden worldwide. Knowledge about the underlying aetiology has improved, with increased understanding of the role of genetic factors, the microbiome, and existence of different pain mechanisms. However, this knowledge has not yet been translated into new treatment options. New evidence has questioned the efficacy of recommended treatments, such as therapeutic exercise programmes and the focus on weight loss, but managing obesity and maintaining activity remain important for the prevention and management of osteoarthritis. Approaches should consider individual and cultural preferences and resource availability to increase patient and community engagement, and optimise outcomes worldwide. Most of the focus has been on established osteoarthritis where management is primarily directed at relieving symptoms. The search for the much needed effective treatments that improve both symptoms and structure, often referred to as disease-modifying osteoarthritic drugs, is ongoing. Promising data indicate that targeting inflammation is effective in hand osteoarthritis.
74. Effect of a spatial repellent on malaria incidence in an area of western Kenya characterised by high malaria transmission, insecticide resistance, and universal coverage of insecticide treated nets (part of the AEGIS Consortium): a cluster-randomised, controlled trial.
作者: Eric O Ochomo.;John E Gimnig.;Quentin Awori.;Bernard Abong'o.;Prisca Oria.;Nickline K Ashitiba.;Brian Polo.;Vincent Moshi.;Hilda Otanga.;Ferdinard Adung'o.;Eunice A Ouma.;Susan Outa.;Edith Ramaita.;Rebecca Levine.;Wycliffe Odongo.;Steven A Harvey.;April Monroe.;Ashley Hudson.;Bradley Sandberg.;Jared Hendrickson.;Xingyuan Zhao.;Ruyu Zhou.;Fang Liu.;Nicole L Achee.;John P Grieco.
来源: Lancet. 2025年405卷10473期147-156页
Spatial repellent products are used for prevention of insect bites, and a body of evidence exists on spatial repellent entomological efficacy. A new option for vector control, spatial repellent products are designed to release active ingredient into the air for disruption of human-vector contact thereby reducing human exposure to mosquito-borne pathogens. Clinical trials have shown spatial repellent epidemiological efficacy against Aedes-borne viruses but inconclusive outcomes against malaria. We aimed to show and quantify the protective efficacy of spatial repellents in reducing malaria infection incidence in Busia County, Kenya.
75. Guselkumab in patients with moderately to severely active ulcerative colitis (QUASAR): phase 3 double-blind, randomised, placebo-controlled induction and maintenance studies.
作者: David T Rubin.;Jessica R Allegretti.;Julián Panés.;Nicole Shipitofsky.;Shadi S Yarandi.;Kuan-Hsiang Gary Huang.;Matthew Germinaro.;Rebbecca Wilson.;Hongyan Zhang.;Jewel Johanns.;Brian G Feagan.;Tadakazu Hisamatsu.;Gary R Lichtenstein.;Brian Bressler.;Laurent Peyrin-Biroulet.;Bruce E Sands.;Axel Dignass.; .
来源: Lancet. 2025年405卷10472期33-49页
Interleukin-23 inhibition is effective in treating ulcerative colitis. Guselkumab is a dual-acting, human IgG1, interleukin-23p19 subunit inhibitor that potently neutralises interleukin-23 and can bind to CD64. We aimed to evaluate the efficacy and safety of guselkumab as induction and maintenance therapy in patients with ulcerative colitis.
76. Population-health impact of new drugs recommended by the National Institute for Health and Care Excellence in England during 2000-20: a retrospective analysis.
作者: Huseyin Naci.;Peter Murphy.;Beth Woods.;James Lomas.;Jinru Wei.;Irene Papanicolas.
来源: Lancet. 2025年405卷10472期50-60页
Health systems experience difficult trade-offs when paying for new drugs. In England, funding recommendations by the National Institute for Health and Care Excellence (NICE) for new drugs might generate health gains, but inevitably result in forgone health as the funds cannot be used for alternative treatments and services. We aimed to evaluate the population-health impact of NICE recommendations for new drugs during 2000-20.
77. Endovascular therapy for acute vertebrobasilar occlusion (VERITAS): a systematic review and individual patient data meta-analysis.
作者: Raul G Nogueira.;Tudor G Jovin.;Xinfeng Liu.;Wei Hu.;Lucianne C M Langezaal.;Chuanhui Li.;Qiliang Dai.;Chunrong Tao.;Francisco J A Mont'Alverne.;Xunming Ji.;Rui Liu.;Rui Li.;Diederik W J Dippel.;Chuanjie Wu.;Wusheng Zhu.;Pengfei Xu.;Wim H van Zwam.;Longfei Wu.;Chao Zhang.;Patrik Michel.;Jian Chen.;Li Wang.;Volker Puetz.;Wenbo Zhao.;Tianlong Liu.;Heinrich J Audebert.;Zhongjun Chen.;Octavio M Pontes-Neto.;Tingyu Yi.;Timothy P Moran.;Mohamed F Doheim.;Wouter J Schonewille.; .
来源: Lancet. 2025年405卷10472期61-69页
Trials of endovascular therapy for basilar artery occlusion, including vertebral occlusion extending into the basilar artery, have shown inconsistent results. We aimed to pool data to estimate safety and efficacy and to explore the benefit across pre-specified subgroups through individual patient data meta-analysis.
78. Concurrent outbreaks of mpox in Africa-an update.
作者: Camila G Beiras.;Emile Malembi.;Roser Escrig-Sarreta.;Steve Ahuka.;Placide Mbala.;Hypolite M Mavoko.;Lorenzo Subissi.;Ana B Abecasis.;Michael Marks.;Oriol Mitjà.
来源: Lancet. 2025年405卷10472期86-96页
In this Review, we examine the concurrent outbreaks of mpox in Africa, focusing on clade 1a, the newly emerged clade 1b, and clade 2b lineage A, and how they differ from the 2022 global outbreak caused by clade 2b lineage B.1. Historically, clades 1a and 2a have caused sporadic, small outbreaks in central and west Africa, respectively, primarily through zoonotic transmission. Clade 2b first caused an outbreak in Nigeria in 2017, and later spread globally via sexual contact in 2022. In August, 2024, WHO declared a global health emergency due to the newly identified clade 1b outbreak in eastern Democratic Republic of the Congo. This outbreak has now expanded to several other countries and is spreading through direct and sexual contact in urban centres and refugee camps. Clades, route of exposure, infectious dose, and host immune response are the main factors influencing clinical presentation of mpox. For clades 1a and 2a, zoonotic transmission plays an important role, whereas for clades 1b and 2b, the spread occurs through sustained human-to-human transmission without zoonotic exposure. For both clades 1a and 2a, lesions have a generalised centrifugal distribution, whereas for clade 2b they are mainly localised to the anogenital area. For clade 1b, data are still emerging, but current cases show a mix of localised lesions and centrifugal distribution. The severity of the disease is higher for clade 1a (case fatality rate up to 12%) compared with other clades (case fatality rates 0-3·6%). Diagnostic challenges include false negative results for clade 1b with existing PCR assays and poor testing access in remote areas. Tecovirimat, the primary antiviral during the 2022 outbreak, has shown reduced effectiveness against clade 1a in preliminary study results, whereas its efficacy against other clades is still under investigation. The modified vaccinia Ankara-Bavarian Nordic vaccine has been shown to be up to 90% effective against clade 2b after two doses and is safe for children, although its effectiveness drops to 20% when used as post-exposure prophylaxis. Given the evolving nature of the monkeypox virus, ongoing research and strong public health responses are key to managing potential future outbreaks.
79. Global, regional, and national progress towards the 2030 global nutrition targets and forecasts to 2050: a systematic analysis for the Global Burden of Disease Study 2021.
The six global nutrition targets (GNTs) related to low birthweight, exclusive breastfeeding, child growth (ie, wasting, stunting, and overweight), and anaemia among females of reproductive age were chosen by the World Health Assembly in 2012 as key indicators of maternal and child health, but there has yet to be a comprehensive report on progress for the period 2012 to 2021. We aimed to evaluate levels, trends, and observed-to-expected progress in prevalence and attributable burden from 2012 to 2021, with prevalence projections to 2050, in 204 countries and territories.
80. Chronic pancreatitis.
作者: Naomi DE Thierens.;Robert C Verdonk.;J Matthias Löhr.;Hjalmar C van Santvoort.;Stefan Aw Bouwense.;Jeanin E van Hooft.
来源: Lancet. 2025年404卷10471期2605-2618页
Chronic pancreatitis is a progressive fibroinflammatory disease primarily caused by a complex interplay of environmental and genetic risk factors. It might result in pancreatic exocrine and endocrine insufficiency, chronic pain, reduced quality of life, and increased mortality. The diagnosis is based on the presence of typical symptoms and multiple morphological manifestations of the pancreas, including pancreatic duct stones and strictures, parenchymal calcifications, and pseudocysts. Management of chronic pancreatitis consists of prevention and treatment of complications, requiring a multidisciplinary approach focusing on lifestyle modifications, exocrine insufficiency, nutritional status, bone health, endocrine insufficiency, pain management, and psychological care. To optimise clinical outcomes, screening for complications and evaluation of treatment efficacy are indicated in all patients with chronic pancreatitis.
|