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41. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity.
作者: Louis J Aronne.;Deborah Bade Horn.;Carel W le Roux.;Wayne Ho.;Beverly L Falcon.;Elisa Gomez Valderas.;Sagar Das.;Clare J Lee.;Leonard C Glass.;Cagri Senyucel.;Julia P Dunn.; .
来源: N Engl J Med. 2025年
Tirzepatide and semaglutide are highly effective medications for obesity management. The efficacy and safety of tirzepatide as compared with semaglutide in adults with obesity but without type 2 diabetes is unknown.
42. Efruxifermin in Compensated Liver Cirrhosis Caused by MASH.
作者: Mazen Noureddin.;Mary E Rinella.;Naga P Chalasani.;Guy W Neff.;K Jean Lucas.;Manuel E Rodriguez.;Madhavi Rudraraju.;Rashmee Patil.;Cynthia Behling.;Mark Burch.;Doreen C Chan.;Erik J Tillman.;Arian Zari.;Brittany de Temple.;Reshma Shringarpure.;Meena Jain.;Timothy Rolph.;Andrew Cheng.;Kitty Yale.
来源: N Engl J Med. 2025年
In phase 2 trials involving patients with stage 2 or 3 fibrosis caused by metabolic dysfunction-associated steatohepatitis (MASH), efruxifermin, a bivalent fibroblast growth factor 21 (FGF21) analogue, reduced fibrosis and resolved MASH. Data are needed on the efficacy and safety of efruxifermin in patients with compensated cirrhosis (stage 4 fibrosis) caused by MASH.
43. Safety and Efficacy of Obicetrapib in Patients at High Cardiovascular Risk.
作者: Stephen J Nicholls.;Adam J Nelson.;Marc Ditmarsch.;John J P Kastelein.;Christie M Ballantyne.;Kausik K Ray.;Ann Marie Navar.;Steven E Nissen.;Mariko Harada-Shiba.;Danielle L Curcio.;Annie Neild.;Douglas Kling.;Andrew Hsieh.;Julie Butters.;Brian A Ference.;Ulrich Laufs.;Maciej Banach.;Roxana Mehran.;Alberico L Catapano.;Yong Huo.;Michael Szarek.;Violeta Balinskaite.;Michael H Davidson.; .
来源: N Engl J Med. 2025年
Obicetrapib is a highly selective cholesteryl ester transfer protein inhibitor that reduces low-density lipoprotein (LDL) cholesterol levels. The efficacy and safety of obicetrapib have not been fully characterized among patients at high risk for cardiovascular events.
44. Enhanced CAR T-Cell Therapy for Lymphoma after Previous Failure.
作者: Jakub Svoboda.;Daniel J Landsburg.;James Gerson.;Sunita D Nasta.;Stefan K Barta.;Elise A Chong.;Michael Cook.;Noelle V Frey.;Joanne Shea.;Amanda Cervini.;Amy Marshall.;Megan Four.;Megan M Davis.;Julie K Jadlowsky.;Anne Chew.;Edward Pequignot.;Vanessa Gonzalez.;Julia Han Noll.;Luca Paruzzo.;Juliana Rojas-Levine.;Gabriela Plesa.;John Scholler.;Donald L Siegel.;Bruce L Levine.;David L Porter.;Saba Ghassemi.;Marco Ruella.;Andrew Rech.;Rachel M Leskowitz.;Joseph A Fraietta.;Wei-Ting Hwang.;Elizabeth Hexner.;Stephen J Schuster.;Carl H June.
来源: N Engl J Med. 2025年392卷18期1824-1835页
Chimeric antigen receptor (CAR) T cells targeting CD19 have transformed the treatment of B-cell cancers, but many patients do not have long-term remission. We designed an anti-CD19 enhanced (armored) CAR T-cell product (huCART19-IL18) that secretes interleukin-18 to enhance antitumor activity.
45. BCG Revaccination for the Prevention of Mycobacterium tuberculosis Infection.
作者: Alexander C Schmidt.;Lee Fairlie.;Elizabeth Hellström.;Angelique Luabeya Kany Kany.;Keren Middelkoop.;Kogieleum Naidoo.;Gonasagrie Nair.;Anele Gela.;Elisa Nemes.;Thomas J Scriba.;Amy Cinar.;Nicole Frahm.;Robin Mogg.;David Kaufman.;Michael W Dunne.;Mark Hatherill.; .
来源: N Engl J Med. 2025年392卷18期1789-1800页
In a previous phase 2 trial, bacille Calmette-Guérin (BCG) revaccination was not shown to provide protection from primary Mycobacterium tuberculosis infection but prevented sustained M. tuberculosis infection, defined by an initial conversion on a QuantiFERON-TB (QFT) test (an interferon-γ release assay) from negative to positive, followed by two additional positive QFT tests at 3 and 6 months after the initial conversion (a secondary end point). A vaccine efficacy of 45% (95% confidence interval [CI], 6 to 68) was observed.
46. Mepolizumab to Prevent Exacerbations of COPD with an Eosinophilic Phenotype.
作者: Frank C Sciurba.;Gerard J Criner.;Stephanie A Christenson.;Fernando J Martinez.;Alberto Papi.;Nicolas Roche.;Jean Bourbeau.;Stephanie Korn.;Mona Bafadhel.;MeiLan K Han.;Stefanie Kolterer.;Karen Miller.;Dalal Mouneimne.;Joanne Fletcher.;Bhabita Mayer.;Jeff Min.;Ian D Pavord.; .
来源: N Engl J Med. 2025年392卷17期1710-1720页
Mepolizumab is a humanized monoclonal antibody that targets interleukin-5, a cytokine that plays a central role in eosinophilic inflammation, which is present in 20 to 40% of patients with chronic obstructive pulmonary disease (COPD).
47. Lentiviral Gene Therapy for Severe Leukocyte Adhesion Deficiency Type 1.
作者: Claire Booth.;Julián Sevilla.;Elena Almarza.;Caroline Y Kuo.;Josune Zubicaray.;Dayna Terrazas.;Gráinne O'Toole.;Maria Chitty-Lopez.;Grace Choi.;Eileen Nicoletti.;Janel Long-Boyle.;Augustine Fernandes.;Kritika Chetty.;Satiro De Oliveira.;Crystal Banuelos.;Jinhua Xu-Bayford.;Antonella Lucía Bastone.;Philipp John-Neek.;Connie Jackson.;Theodore B Moore.;Kimberly Gilmour.;Axel Schambach.;Michael Rothe.;Sanchali Kasbekar.;Gayatri R Rao.;Kinnari Patel.;Gaurav Shah.;Adrian J Thrasher.;Juan A Bueren.;Jonathan D Schwartz.;Donald B Kohn.
来源: N Engl J Med. 2025年392卷17期1698-1709页
The β2 common integrin subunit CD18 is essential for leukocyte-endothelial adhesion and extravasation to inflamed or infected tissue. Damaging variants in ITGB2, which encodes CD18, cause leukocyte adhesion deficiency type I (LAD-I), an inborn error of immunity that leads to frequent life-threatening infections and a high risk of death among affected children. Allogeneic hematopoietic stem-cell transplantation (HSCT) represents a curative treatment but is limited by donor availability, a high incidence of graft-versus-host disease, and graft failure.
48. Identification of Hepatic-like EPO as a Cause of Polycythemia.
作者: Laurent Martin.;Darko Maric.;Salam Idriss.;Marine Delamare.;Amandine Le Roy.;Nada Maaziz.;Amandine Caillaud.;Karim Si-Tayeb.;Florence Robriquet.;Marion Lenglet.;Lucie Erceau.;Christine Bellanné-Chantelot.;Isabelle Plo.;Bernard Aral.;Céline Garrec.;Fabrice Airaud.;Clara Gianfermi.;Vincent Antunes.;Anna Keppner.;Sarah Mathilda Vincent.;Alexis Desfontaine.;Nina Modé.;Fabien Laporte.;Anne Gaignerie.;Caroline Chariau.;Isabelle Leray.;Coline Rogue.;Laurent David.;Richard Redon.;Stéphane Bézieau.;Lamisse Mansour-Hendili.;Frédéric Galactéros.;Thibault Maillet.;Marlène Pasquet.;Pierre Cougoul.;Anne-Marie Nloga.;Claude Gardin.;Corinne Guitton.;Viviane Dubruille.;Vannina Giacobbi-Milet.;Thierry Leblanc.;Zuhre Kaya.;Denis Semama.;Chloé James.;Serge Carillo.;Marlène Ochmann.;Anders Waage.;Erwan Mortier.;Mike Maillasson.;Agnès Quéméner.;Holger Cario.;Radek C Skoda.;Yaël Zermati.;David Hoogewijs.;Alexandre Marchand.;François Girodon.;Betty Gardie.
来源: N Engl J Med. 2025年392卷17期1684-1697页
Secondary erythrocytosis often results from conditions that cause tissue hypoxia or an improper increase in erythropoietin (EPO) production. EPO, the major regulator of erythropoiesis, has a complex and tightly regulated expression during development, with a liver-to-kidney switch shortly after birth.
49. 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).
50. 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.
51. 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.
52. 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).
53. 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.
54. 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.
55. 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.
56. 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.
57. 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.
58. 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.
59. 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.
60. 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.
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