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221. Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis.
作者: Arun J Sanyal.;Philip N Newsome.;Iris Kliers.;Laura Harms Østergaard.;Michelle T Long.;Mette Skalshøi Kjær.;Anna M G Cali.;Elisabetta Bugianesi.;Mary E Rinella.;Michael Roden.;Vlad Ratziu.; .
来源: N Engl J Med. 2025年392卷21期2089-2099页
Semaglutide, a glucagon-like peptide-1 receptor agonist, is a candidate for the treatment of metabolic dysfunction-associated steatohepatitis (MASH).
222. Zongertinib in Previously Treated HER2-Mutant Non-Small-Cell Lung Cancer.
作者: John V Heymach.;Gerrina Ruiter.;Myung-Ju Ahn.;Nicolas Girard.;Egbert F Smit.;David Planchard.;Yi-Long Wu.;Byoung Chul Cho.;Noboru Yamamoto.;Joshua K Sabari.;Yanqiu Zhao.;Hai-Yan Tu.;Kiyotaka Yoh.;Ernest Nadal.;Behbood Sadrolhefazi.;Maren Rohrbacher.;Ute von Wangenheim.;Sabina Eigenbrod-Giese.;Jon Zugazagoitia.; .
来源: N Engl J Med. 2025年392卷23期2321-2333页
Innovative oral targeted therapies are warranted for patients with human epidermal growth factor receptor 2 (HER2)-mutant non-small-cell lung cancer (NSCLC). Zongertinib is an oral, irreversible, HER2-selective tyrosine kinase inhibitor that has been shown to have efficacy in persons with advanced or metastatic solid tumors with HER2 alterations in a phase 1 study.
223. Nonoperative Management of Mismatch Repair-Deficient Tumors.
作者: Andrea Cercek.;Michael B Foote.;Benoit Rousseau.;J Joshua Smith.;Jinru Shia.;Jenna Sinopoli.;Jill Weiss.;Melissa Lumish.;Lindsay Temple.;Miteshkumar Patel.;Callahan Wilde.;Leonard B Saltz.;Guillem Argiles.;Zsofia Stadler.;Oliver Artz.;Steven Maron.;Geoffrey Ku.;Ping Gu.;Yelena Y Janjigian.;Daniela Molena.;Gopa Iyer.;Jonathan Coleman.;Wassim Abida.;Seth Cohen.;Kevin Soares.;Mark Schattner.;Vivian E Strong.;Rona Yaeger.;Philip Paty.;Marina Shcherba.;Ryan Sugarman.;Paul B Romesser.;Alice Zervoudakis.;Avni Desai.;Neil H Segal.;Imane El Dika.;Maria Widmar.;Iris Wei.;Emmanouil Pappou.;Gerard Fumo.;Santiago Aparo.;Mithat Gonen.;Marc Gollub.;Vetri S Jayaprakasam.;Tae-Hyung Kim.;Julio Garcia Aguilar.;Martin Weiser.;Luis A Diaz.
来源: N Engl J Med. 2025年392卷23期2297-2308页
Among patients with mismatch repair-deficient (dMMR), locally advanced rectal cancer, neoadjuvant checkpoint blockade eliminated the need for surgery in a high proportion of patients. Whether this approach can be extended to all early-stage dMMR solid tumors, regardless of tumor site, is unknown.
224. Long-Term Effects of Atidarsagene Autotemcel for Metachromatic Leukodystrophy.
作者: Francesca Fumagalli.;Valeria Calbi.;Vera Gallo.;Alberto Andrea Zambon.;Salvatore Recupero.;Francesca Ciotti.;Marina Sarzana.;Maddalena Fraschini.;Stefano Scarparo.;Fabiola De Mattia.;Simona Miglietta.;Clelia Pierini.;Matias Soncini.;Francesco Morena.;Eugenio Montini.;Federica Barzaghi.;Giulia Consiglieri.;Francesca Ferrua.;Maddalena Migliavacca.;Francesca Tucci.;Elena Sophia Fratini.;Alessia Ippolito.;Paolo Silvani.;Maria Rosa Calvi.;Alessandra Clerici.;Ambra Corti.;Marcella Facchini.;Sara Locatelli.;Mara Sangalli.;Stefano Zancan.;Federica Miotto.;Maria Grazia Natali Sora.;Cristina Baldoli.;Sabata Martino.;Angélica Córdoba-Claros.;Sean L Moro.;Nicholas D Gollop.;Jeff Abate.;Muska N Yarzi.;Philippa Nutkins.;Andrew Shenker.;Mattia Calissano.;Jean Brooks.;Alan Richardson.;Laura Campbell.;Massimo Filippi.;Luigi Naldini.;Maria Pia Cicalese.;Fabio Ciceri.;Maria Ester Bernardo.;Alessandro Aiuti.
来源: N Engl J Med. 2025年392卷16期1609-1620页
Metachromatic leukodystrophy (MLD) is an ultrarare, severe lysosomal storage disorder caused by a deficiency of arylsulfatase A (ARSA).
225. Tumor-Infiltrating Clonal Hematopoiesis.
作者: Oriol Pich.;Elsa Bernard.;Maria Zagorulya.;Andrew Rowan.;Constandina Pospori.;Ramy Slama.;Hector Huerga Encabo.;Jennifer O'Sullivan.;Despoina Papazoglou.;Panayiotis Anastasiou.;Chrysante S Iliakis.;Sally-Ann Clark.;Krijn K Dijkstra.;Vittorio Barbè.;Chris Bailey.;Aaron J Stonestrom.;Katey S S Enfield.;Mary Green.;Charlotte K Brierley.;Alastair Magness.;David R Pearce.;Robert E Hynds.;Rija Zaidi.;Jayant K Rane.;Ángel F Álvarez-Prado.;Kerstin Thol.;Rachel Scott.;Supreet Kaur Bola.;Elena Hoxha.;Steve K Harris.;Karl S Peggs.;Sergio A Quezada.;Allan Hackshaw.;Simone Zaccaria.;Johanna A Joyce.;Ilaria Malanchi.;Michael F Berger.;Mariam Jamal-Hanjani.;Andreas Wack.;Julian Downward.;William Grey.;Cristina Lo Celso.;Eva Grönroos.;Charles M Rudin.;Adam J Mead.;Dominique Bonnet.;Elli Papaemmanuil.;Charles Swanton.
来源: N Engl J Med. 2025年392卷16期1594-1608页
Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition associated with increased mortality among patients with cancer. CHIP mutations with high variant-allele frequencies can be detected in tumors, a phenomenon we term tumor-infiltrating clonal hematopoiesis (TI-CH). The frequency of TI-CH and its effect on tumor evolution are unclear.
226. Efficacy of Baloxavir Treatment in Preventing Transmission of Influenza.
作者: Arnold S Monto.;Klaus Kuhlbusch.;Corrado Bernasconi.;Bin Cao.;Herman Avner Cohen.;Emily Graham.;Aeron C Hurt.;Laurie Katugampola.;Takashi Kamezawa.;Adam S Lauring.;Barry McLean.;Takahiro Takazono.;Andreas Widmer.;Steffen Wildum.;Benjamin J Cowling.
来源: N Engl J Med. 2025年392卷16期1582-1593页
Baloxavir marboxil (baloxavir) rapidly reduces influenza virus shedding, which suggests that it may reduce transmission. Studies of treatment with neuraminidase inhibitors have not shown sufficient evidence that they prevent transmission to contacts.
227. Phase 3 Trial of the DPP-1 Inhibitor Brensocatib in Bronchiectasis.
作者: James D Chalmers.;Pierre-Régis Burgel.;Charles L Daley.;Anthony De Soyza.;Charles S Haworth.;David Mauger.;Michael R Loebinger.;Pamela J McShane.;Felix C Ringshausen.;Francesco Blasi.;Michal Shteinberg.;Kevin Mange.;Ariel Teper.;Carlos Fernandez.;Migdalia Zambrano.;Chunpeng Fan.;Xiangmin Zhang.;Mark L Metersky.; .
来源: N Engl J Med. 2025年392卷16期1569-1581页
In bronchiectasis, neutrophilic inflammation is associated with an increased risk of exacerbations and disease progression. Brensocatib, an oral, reversible inhibitor of dipeptidyl peptidase 1 (DPP-1), targets neutrophil serine proteases, key mediators of neutrophilic inflammation.
228. Lorundrostat Efficacy and Safety in Patients with Uncontrolled Hypertension.
作者: Luke J Laffin.;Branko Kopjar.;Carrie Melgaard.;Kathy Wolski.;Jessica Ibbitson.;Shivani Bhikam.;Matthew R Weir.;Elizabeth O Ofili.;Reena Mehra.;James M Luther.;Debbie L Cohen.;Ashish Sarraju.;Michael J Wilkinson.;John M Flack.;David Rodman.;Steven E Nissen.; .
来源: N Engl J Med. 2025年392卷18期1813-1823页
Aldosterone dysregulation contributes to hypertension. Lorundrostat is an aldosterone synthase inhibitor, but data on its efficacy and safety in patients with hypertension are limited.
229. Fidanacogene Elaparvovec for Hemophilia B - A Multiyear Follow-up Study.
作者: John E J Rasko.;Benjamin J Samelson-Jones.;Lindsey A George.;Adam Giermasz.;Jonathan M Ducore.;Jerome M Teitel.;Catherine E McGuinn.;Katherine A High.;Ype P de Jong.;Amit Chhabra.;Amanda O'Brien.;Lynne M Smith.;Ian Winburn.;Jeremy Rupon.
来源: N Engl J Med. 2025年392卷15期1508-1517页
Treatment with fidanacogene elaparvovec, a recombinant adeno-associated virus (AAV) vector developed for the treatment of hemophilia B, led to sustained expression of the high-activity factor IX variant (FIX-R338L, or FIX-Padua) in a phase 1-2a study. The long-term safety and efficacy of this treatment are not known.
230. Tecovirimat for Clade I MPXV Infection in the Democratic Republic of Congo.
作者: .;Rosine Ali.;Jules Alonga.;Jean-Luc Biampata.;Michael Kombozi Basika.;Irina Maljkovic Berry.;Nella Bisento.;Emily Blum.;Tyler Bonnett.;Katherine Cone.;Ian Crozier.;Richard Davey.;Ali Dilu.;Lori E Dodd.;Iman Gulati.;Dennis Hruby.;Augustin Ibanda.;Francis Isse.;Sylva Sivasingana Kasareka.;Gaby Kayembe.;Richard Kojan.;Esaie Kindombe Luzolo.;H Clifford Lane.;Leader Lawanga.;Laurens Liesenborghs.;Claude Shosongo Lunghe.;Yves Lula.;Mariano Lusakibanza.;Gaston Tona Lutete.;Placide Mbala-Kingebeni.;Alejandra Miranda.;Daniel Mukadi-Bamuleka.;Gael Mukendi.;Patrick Mutombo Lupola.;Jean-Jacques Muyembe-Tamfum.;Robin Ndungunu.;Bruce Nganga.;Nsengi Ntamabyaliro.;Veronique Nussenblatt.;Imoite Omulepu.;John Omalokoho Onosomba.;Michael Proschan.;Kevin Rubenstein.;Inga Saknite.;Adam Schechner.;Kathryn Shaw-Saliba.;Billy Sivahera.;Mary Smolskis.;Amy Tillman.;Eric Tkaczyk.;Celestin Tshimanga.;Olivier Tshiani Mbaya.;Antoine Tshomba.;Freddy Yemba Unda Tshomba.;David Vallee.;Susan Vogel.;Shera Weyers.
来源: N Engl J Med. 2025年392卷15期1484-1496页
Tecovirimat is available for the treatment of mpox (formerly known as monkeypox) in Europe and the United States, on the basis of findings from efficacy studies in animals and safety evaluations in healthy humans. Evidence from randomized, controlled trials of safety and efficacy in patients with mpox is lacking.
231. Assessment of a Polygenic Risk Score in Screening for Prostate Cancer.
作者: Jana K McHugh.;Elizabeth K Bancroft.;Edward Saunders.;Mark N Brook.;Eva McGrowder.;Sarah Wakerell.;Denzil James.;Reshma Rageevakumar.;Barbara Benton.;Natalie Taylor.;Kathryn Myhill.;Matthew Hogben.;Netty Kinsella.;Aslam A Sohaib.;Declan Cahill.;Stephen Hazell.;Samuel J Withey.;Naami Mcaddy.;Elizabeth C Page.;Andrea Osborne.;Sarah Benafif.;Ann-Britt Jones.;Dhruv Patel.;Dean Y Huang.;Kaljit Kaur.;Bradley Russell.;Ray Nicholson.;Fionnuala Croft.;Justyna Sobczak.;Claire McNally.;Fiona Mutch.;Samantha Bennett.;Lenita Kingston.;Questa Karlsson.;Tokhir Dadaev.;Sibel Saya.;Susan Merson.;Angela Wood.;Nening Dennis.;Nafisa Hussain.;Alison Thwaites.;Syed Hussain.;Imran Rafi.;Michelle Ferris.;Pardeep Kumar.;Nicholas D James.;Nora Pashayan.;Zsofia Kote-Jarai.;Rosalind A Eeles.; .
来源: N Engl J Med. 2025年392卷14期1406-1417页
The incidence of prostate cancer is increasing. Screening with an assay of prostate-specific antigen (PSA) has a high rate for false positive results. Genomewide association studies have identified common germline variants in persons with prostate cancer, which can be used to calculate a polygenic risk score associated with risk of prostate cancer.
232. Tolebrutinib in Nonrelapsing Secondary Progressive Multiple Sclerosis.
作者: Robert J Fox.;Amit Bar-Or.;Anthony Traboulsee.;Celia Oreja-Guevara.;Gavin Giovannoni.;Patrick Vermersch.;Sana Syed.;Ye Li.;Wendy S Vargas.;Timothy J Turner.;Erik Wallstroem.;Daniel S Reich.; .
来源: N Engl J Med. 2025年392卷19期1883-1892页
Throughout the course of multiple sclerosis, gradually progressive neurologic impairment can occur, which has been called disability accrual. Current disease-modifying therapies for multiple sclerosis have limited effects on disability accrual unrelated to relapses, which is thought to be partially caused by chronic, nonresolving neuroinflammation within the central nervous system. Tolebrutinib is an oral, brain-penetrant Bruton's tyrosine kinase inhibitor that targets myeloid cells (including microglia) and B cells in both the periphery and central nervous system. There are no approved treatments for nonrelapsing secondary progressive multiple sclerosis.
233. Tolebrutinib versus Teriflunomide in Relapsing Multiple Sclerosis.
作者: Jiwon Oh.;Douglas L Arnold.;Bruce A C Cree.;Carolina Ionete.;Ho Jin Kim.;Maria Pia Sormani.;Sana Syed.;Yixin Chen.;Christina R Maxwell.;Patrick Benoit.;Timothy J Turner.;Erik Wallstroem.;Heinz Wiendl.; .
来源: N Engl J Med. 2025年392卷19期1893-1904页
Tolebrutinib is an oral, brain-penetrant, and bioactive Bruton's tyrosine kinase inhibitor that modulates peripheral inflammation and persistent immune activation within the central nervous system, including disease-associated microglia and B cells. More data are needed on its efficacy and safety in treating relapsing multiple sclerosis.
234. A Phase 3 Trial of Inebilizumab in Generalized Myasthenia Gravis.
作者: Richard J Nowak.;Michael Benatar.;Emma Ciafaloni.;James F Howard.;M Isabel Leite.;Kimiaki Utsugisawa.;John Vissing.;Mikhail Rojavin.;Qing Li.;Fengming Tang.;Yanping Wu.;Nishi Rampal.;Sue Cheng.; .
来源: N Engl J Med. 2025年392卷23期2309-2320页
Autoimmune generalized myasthenia gravis is a disease that manifests with fluctuating muscle weakness. Inebilizumab is a monoclonal antibody that depletes CD19+ B cells, which are central to disease pathogenesis.
235. A Phase 3 Trial of Upadacitinib for Giant-Cell Arteritis.
作者: Daniel Blockmans.;Sara K Penn.;Arathi R Setty.;Wolfgang A Schmidt.;Andrea Rubbert-Roth.;Ellen M Hauge.;Helen I Keen.;Tomonori Ishii.;Nader Khalidi.;Christian Dejaco.;Maria C Cid.;Bernhard Hellmich.;Meng Liu.;Weihan Zhao.;Ivan Lagunes.;Ana B Romero.;Peter K Wung.;Peter A Merkel.; .
来源: N Engl J Med. 2025年392卷20期2013-2024页
Giant-cell arteritis is a systemic vasculitis with limited treatment options. The efficacy and safety of upadacitinib - a selective Janus kinase (JAK) inhibitor that blocks the signaling of several cytokines, including interleukin-6 and interferon-γ - are unknown in patients with giant-cell arteritis.
236. Association between Wealth and Mortality in the United States and Europe.
作者: Sara Machado.;Ilias Kyriopoulos.;E John Orav.;Irene Papanicolas.
来源: N Engl J Med. 2025年392卷13期1310-1319页
Amid growing wealth disparity, we have little information on how health among older Americans compares with that among older Europeans across the distribution of wealth.
237. The Genetic Architecture of Congenital Diarrhea and Enteropathy.
作者: Zeenat Gaibee.;Neil Warner.;Katlynn Bugda Gwilt.;Wenjuan Li.;Rei Guan.;Michael Yourshaw.;Ryder Whittaker Hawkins.;Christiane Zorbas.;Jonathan St-Germain.;Mahdi Tabatabaie.;Suli Mao.;Vered Pinsk.;Baruch Yerushalmi.;Lee-Kai Wang.;Stanley F Nelson.;Laura Wozniak.;Dror S Shouval.;Manar Matar.;Amit Assa.;Nathaniel Frost.;Lissette Jimenez.;Sari Acra.;Thomas Walters.;Stephen Mouat.;Michael Li.;Denis L J Lafontaine.;Matthew Tyska.;Brian Raught.;Yaron Avitzur.;Wayne I Lencer.;James R Goldenring.;Martín G Martín.;Jay R Thiagarajah.;Aleixo M Muise.
来源: N Engl J Med. 2025年392卷13期1297-1309页
Next-generation sequencing has enabled precision therapeutic approaches that have improved the lives of children with rare diseases. Congenital diarrhea and enteropathies (CODEs) are associated with high morbidity and mortality. Although treatment of these disorders is largely supportive, emerging targeted therapies based on genetic diagnoses include specific diets, pharmacologic treatments, and surgical interventions.
238. Alteplase for Posterior Circulation Ischemic Stroke at 4.5 to 24 Hours.
作者: Shenqiang Yan.;Ying Zhou.;Maarten G Lansberg.;David S Liebeskind.;Changzheng Yuan.;Han Yu.;Fujian Chen.;Hongfang Chen.;Bing Zhang.;Lingqun Mao.;Xiaoling Zhang.;Xiaona Wang.;Xuting Zhang.;Yi Chen.;Huan Zhou.;Wansi Zhong.;Yaode He.;Kun Chen.;Jianbing Wang.;Hui Chen.;Yuhui Huang.;Bruce C V Campbell.;Min Lou.; .
来源: N Engl J Med. 2025年392卷13期1288-1296页
The effects and risks of the use of intravenous thrombolysis between 4.5 and 24 hours after the onset of a posterior circulation ischemic stroke are not well studied.
239. Sotatercept in Patients with Pulmonary Arterial Hypertension at High Risk for Death.
作者: Marc Humbert.;Vallerie V McLaughlin.;David B Badesch.;H Ardeschir Ghofrani.;J Simon R Gibbs.;Mardi Gomberg-Maitland.;Ioana R Preston.;Rogerio Souza.;Aaron B Waxman.;Victor M Moles.;Laurent Savale.;Carmine Dario Vizza.;Stephan Rosenkranz.;Yaru Shi.;Barry Miller.;Harald S Mackenzie.;Samuel S Kim.;Maria José Loureiro.;Mahesh J Patel.;Joerg Koglin.;Alexandra G Cornell.;Marius M Hoeper.; .
来源: N Engl J Med. 2025年392卷20期1987-2000页
Sotatercept improves exercise capacity and delays the time to clinical worsening in patients with World Health Organization (WHO) functional class II or III pulmonary arterial hypertension. The effects of add-on sotatercept in patients with advanced pulmonary arterial hypertension and a high risk of death are unclear.
240. Pulsed Field or Cryoballoon Ablation for Paroxysmal Atrial Fibrillation.
作者: Tobias Reichlin.;Thomas Kueffer.;Patrick Badertscher.;Peter Jüni.;Sven Knecht.;Gregor Thalmann.;Nikola Kozhuharov.;Philipp Krisai.;Corinne Jufer.;Jens Maurhofer.;Dik Heg.;Tiago V Pereira.;Felix Mahfoud.;Helge Servatius.;Hildegard Tanner.;Michael Kühne.;Laurent Roten.;Christian Sticherling.; .
来源: N Engl J Med. 2025年392卷15期1497-1507页
Pulmonary-vein isolation is an effective treatment for paroxysmal atrial fibrillation. Pulsed field ablation (PFA) is a nonthermal ablation method with few adverse effects beyond the myocardium. Data are lacking on outcomes after PFA as compared with cryoballoon ablation as assessed with continuous rhythm monitoring.
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