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1. Phase 3 Trial of Inhaled Molgramostim in Autoimmune Pulmonary Alveolar Proteinosis.
作者: Bruce C Trapnell.;Yoshikazu Inoue.;Francesco Bonella.;Tisha Wang.;Cormac McCarthy.;Toru Arai.;Keiichi Akasaka.;Francesca Mariani.;Nesrin Mogulkoc.;Jin Woo Song.;Tomohisa Baba.;Stephane Jouneau.;Tadahisa Numakura.;Nesrin Öcal.;Florin Mihaltan.;Ali Ataya.;Elisabeth Bendstrup.;Ilaria Campo.;Brenna Carey.;Ross Arena.;Brian Robinson.;Rosanna Fleming.;Yasmine Wasfi.;Raymond Pratt.; .
来源: N Engl J Med. 2025年393卷8期764-773页
Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease characterized by progressive surfactant accumulation and hypoxemia caused by autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF), which alveolar macrophages require to clear surfactant. Molgramostim is a formulation of inhaled recombinant human GM-CSF, but its efficacy and safety in patients with aPAP have not been studied sufficiently.
2. Risdiplam in Presymptomatic Spinal Muscular Atrophy.
作者: Richard S Finkel.;Laurent Servais.;Dmitry Vlodavets.;Edmar Zanoteli.;Maria Mazurkiewicz-Bełdzińska.;Yuh-Jyh Jong.;Aledie Navas-Nazario.;Mohammad Al-Muhaizea.;Alexandra P Q C Araujo.;Leslie Nelson.;Yi Wang.;Birgit Jaber.;Ksenija Gorni.;Heidemarie Kletzl.;Laura Palfreeman.;Michael Rabbia.;Dave Summers.;Eleni Gaki.;Kathryn R Wagner.;Paulo Fontoura.;Michelle A Farrar.;Enrico Bertini.; .
来源: N Engl J Med. 2025年393卷7期671-682页
Risdiplam, an oral pre-messenger RNA splicing modifier, is an efficacious treatment for persons with symptomatic spinal muscular atrophy (SMA). The safety and efficacy of risdiplam in presymptomatic disease are unclear.
3. Ciprofloxacin versus Aminoglycoside-Ciprofloxacin for Bubonic Plague.
作者: Rindra Vatosoa Randremanana.;Mihaja Raberahona.;Josephine Bourner.;Minoarisoa Rajerison.;Tansy Edwards.;Ravaka Randriamparany.;Tsinjo Fehizoro Razafindratsinana.;Lisy Hanitra Razananaivo.;Gabriella Zadonirina.;Théodora Mayouya-Gamana.;Alex Paddy Abdel Salam.;Reziky Tiandraza Mangahasimbola.;Voahangy Andrianaivoarimanana.;Elise Pesonel.;Rivonirina Andry Rakotoarivelo.;Mamy Jean de Dieu Randria.;Peter Horby.;Piero Olliaro.; .
来源: N Engl J Med. 2025年393卷6期544-555页
Plague is a high-consequence infectious disease with epidemic potential. Current treatment guidelines are based on weak evidence.
4. Survival of Transplanted Allogeneic Beta Cells with No Immunosuppression.
作者: Per-Ola Carlsson.;Xiaomeng Hu.;Hanne Scholz.;Sofie Ingvast.;Torbjörn Lundgren.;Tim Scholz.;Olof Eriksson.;Per Liss.;Di Yu.;Tobias Deuse.;Olle Korsgren.;Sonja Schrepfer.
来源: N Engl J Med. 2025年
The need to suppress a patient's immune system after the transplantation of allogeneic cells is associated with wide-ranging side effects. We report the outcomes of transplantation of genetically modified allogeneic donor islet cells into a man with long-standing type 1 diabetes. We used clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 12b (Cas12b) editing and lentiviral transduction to genetically edit the cells to avoid rejection; the cells were then transplanted into the participant's forearm muscle. He did not receive any immunosuppressive drugs and, at 12 weeks after transplantation, showed no immune response against the gene-edited cells. C-peptide measurements showed stable and glucose-responsive insulin secretion. A total of four adverse events occurred, none of which were serious or related to the study drug. (Funded by the Leona M. and Harry B. Helmsley Charitable Trust; EudraCT number, 2023-507988-19-00; ClinicalTrials.gov number, NCT06239636.).
5. Resolution of Squamous-Cell Carcinoma by Restoring T-Cell Receptor Signaling.
作者: Peiying Ye.;Jenna R E Bergerson.;Isaac Brownell.;Gabriel J Starrett.;Roshini S Abraham.;Megan V Anderson.;Triscia Martin.;Derek MacMath.;Hye Sun Kuehn.;Jyothi Padiadpu.;Siqi Zhao.;Sergio D Rosenzweig.;Roxane Tussiwand.;Warren J Leonard.;Stefania Pittaluga.;Mark Raffeld.;Danielle E Arnold.;Andrea Lisco.
来源: N Engl J Med. 2025年393卷5期469-478页
Cutaneous squamous-cell carcinoma (SCC) is primarily caused by oncogenesis mediated by ultraviolet radiation, and β-human papillomavirus (β-HPV) is believed to be a mere facilitator that is dispensable for the maintenance of cutaneous SCC. Here, we describe a woman with benign and malignant HPV-related diseases that include a recurrent, unresectable, invasive cutaneous SCC with β-HPV19 genomic integration in the context of germline pathogenic mutations in ZAP70, an adapter required for T-cell receptor (TCR) signal transduction. Restoration of the integrity of TCR signaling by allogeneic hematopoietic-cell transplantation led to the resolution of all HPV-related diseases, thereby revealing a direct role of β-HPV in skin carcinogenesis in hosts with defective adaptive T-cell responses. (Funded by the National Institutes of Health.).
6. Ivermectin to Control Malaria - A Cluster-Randomized Trial.
作者: Carlos Chaccour.;Marta Maia.;Mercy Kariuki.;Paula Ruiz-Castillo.;Caroline Wanjiku.;Lydia Kasiwa.;Aurelia Brazeal.;Aina Casellas.;Mwanajuma Ngama.;Truphena Onyango.;Eldo Elobolobo.;Karisa Kazungu.;Mary Mael.;Winnie Wangari.;Khadija Nuru.;Rachel Otuko.;Almudena Sanz.;Isaac Ringera.;Allan Matano.;Starford Mitora.;Marta Ribes.;Joe Brew.;Nika Gorski.;Patricia Nicolas.;Sara Stanulovic.;Isaiah Omondi.;Joanna Furnival-Adams.;Laura Túnez.;Jamal Mbarak.;Vegovito Vegove.;Esther Yaa.;Shadrack Mramba.;Yegon Kibet.;Naomi Nyambura.;Charles Rotich.;Scholastica Wanjiru.;Musa Vura.;Faith Wanjiku.;Leslie Sam.;Lisa Collins.;Kang Xia.;Felix Hammann.;Francisco Saúte.;Matthew Rudd.;Cassidy Rist.;Caroline Jones.;Joseph Mwangangi.;N Regina Rabinovich.
来源: N Engl J Med. 2025年393卷4期362-375页
Malaria control and elimination is threatened by the spread of insecticide resistance and behavioral adaptation of vectors. Whether mass administration of ivermectin, a broad-spectrum antiparasitic drug that also kills mosquitoes feeding on treated persons, can reduce malaria transmission is unclear.
7. Mitochondrial Donation in a Reproductive Care Pathway for mtDNA Disease.
作者: Robert McFarland.;Louise A Hyslop.;Catherine Feeney.;Rekha N Pillai.;Emma L Blakely.;Eilis Moody.;Matthew Prior.;Anita Devlin.;Robert W Taylor.;Mary Herbert.;Meenakshi Choudhary.;Jane A Stewart.;Douglass M Turnbull.
来源: N Engl J Med. 2025年393卷5期461-468页
Pathogenic variants in mitochondrial DNA (mtDNA) are a common cause of severe, often fatal, inherited metabolic disease. A reproductive care pathway was implemented to provide women carrying pathogenic mtDNA variants with reproductive options. A total of 22 women with pathogenic mtDNA variants have commenced or completed pronuclear transfer (and thus receipt of a mitochondrial donation), and there have been 8 live births. All 8 children were healthy at birth, with no or low levels of mtDNA heteroplasmy in blood. Hyperlipidemia and cardiac arrhythmia developed in a child whose mother had hyperlipidemia during pregnancy; both of the child's conditions responded to treatment. Infant myoclonic epilepsy developed in another child, with spontaneous remission. At the time of this report, all the children have made normal developmental progress. (Funded by the U.K. National Health Service and others.).
8. Mitochondrial Donation and Preimplantation Genetic Testing for mtDNA Disease.
作者: Louise A Hyslop.;Emma L Blakely.;Magomet Aushev.;Jordan Marley.;Yuko Takeda.;Angela Pyle.;Eilis Moody.;Catherine Feeney.;Jan Dutton.;Carol Shaw.;Sarah J Smith.;Kate Craig.;Charlotte L Alston.;Lisa Lister.;Karina Endacott.;Samantha Byerley.;Helen McDermott.;Kathryn Wilson.;Lynne Botham.;Beth Matthew.;Nilendran Prathalingam.;Matthew Prior.;Alison Murdoch.;Douglass M Turnbull.;Gavin Hudson.;Meenakshi Choudhary.;Robert W Taylor.;Rekha N Pillai.;Jane A Stewart.;Robert McFarland.;Mary Herbert.
来源: N Engl J Med. 2025年393卷5期438-449页
Children born to women who carry pathogenic variants in mitochondrial DNA (mtDNA) are at risk for a range of clinical syndromes collectively known as mtDNA disease. Mitochondrial donation by pronuclear transfer involves transplantation of nuclear genome from a fertilized egg from the affected woman to an enucleated fertilized egg donated by an unaffected woman. Thus, pronuclear transfer offers affected women the potential to have a genetically related child with a reduced risk of mtDNA disease.
9. On-Table Reanimation of a Pediatric Heart from Donation after Circulatory Death.
Cardiac allotransplantation is warranted in children with end-stage heart failure or irreparable congenital heart disease. A dearth of organs for transplantation has contributed to long wait-list times and resultant deaths in this population. Donation after circulatory death (DCD) with normothermic regional perfusion has the potential to increase the donor pool by up to 30%. Ethical concerns have limited adoption of this technique in the United States and abroad. Consequently, a method facilitating ex vivo resuscitation of hearts from deceased donors after circulatory death (i.e., DCD hearts) is needed. We describe an on-table reanimation of a pediatric DCD heart transplanted into a 3-month-old recipient. Adverse events are reported.
10. Rapid Recovery of Donor Hearts for Transplantation after Circulatory Death.
作者: Aaron M Williams.;John M Trahanas.;Swaroop Bommareddi.;Brian Lima.;Stephen A DeVries.;Joshua Lowman.;Awab Ahmad.;Eric Quintana.;Shelley R Scholl.;Stacy Tsai.;Dawn Pedrotty.;Matthew Warhoover.;Harry Moneypenny.;Stephen Tapia-Ruano.;Matthew Bacchetta.;Kelly Schlendorf.;Ashish S Shah.
来源: N Engl J Med. 2025年393卷3期267-274页
We report a method for the recovery of hearts for transplantation from deceased donors after circulatory death that obviates the need for thoracoabdominal normothermic regional perfusion or ex situ perfusion systems. After death, the aorta is clamped and a flush circuit is established to perform a controlled, extended, ultraoxygenated flush of the donor heart at a mean aortic-root pressure of 80 mm Hg. In the first three reported cases in which this method was used, the hearts were transplanted successfully with normal biventricular function, no evidence of acute cellular or antibody-mediated rejection, and excellent early postoperative outcomes. No adverse events were reported during the perioperative period. By avoiding the limitations of ex situ perfusion platforms as well as the controversial aspects of thoracoabdominal normothermic regional perfusion, this method of heart recovery offers the possibility of broad application.
11. Multidose Ondansetron after Emergency Visits in Children with Gastroenteritis.
作者: Stephen B Freedman.;Sarah Williamson-Urquhart.;Amy C Plint.;Andrew Dixon.;Darcy Beer.;Gary Joubert.;Petros Pechlivanoglou.;Yaron Finkelstein.;Anna Heath.;Jasper Zhongyuan Zhang.;Angela Wallace.;Martin Offringa.;Terry P Klassen.; .
来源: N Engl J Med. 2025年393卷3期255-266页
Ondansetron improves outcomes when administered in emergency departments to children with acute gastroenteritis-associated vomiting. It is commonly prescribed at discharge to reduce symptoms, but evidence to support this practice is limited.
12. Early Tirofiban Infusion after Intravenous Thrombolysis for Stroke.
作者: Chunrong Tao.;Tianlong Liu.;Tao Cui.;Jie Liu.;Zongliang Li.;Youquan Ren.;Xingli Zhao.;Fuyou Xie.;Jianqiao Li.;Hao Wang.;Ling Huang.;Jianjun Li.;Jianshang Wen.;Jianzhong Zeng.;Junyong Zhu.;Zhide Li.;Dajun Li.;Xuefeng Hu.;Biao Huang.;Jing Wang.;Chi Zhang.;Bin Ye.;Yubao Hou.;Yanlin Gan.;Hong Sun.;Fei Guan.;Ya Shao.;Zongtao Liu.;Zehu Ou.;Shikai Fan.;Yao Wang.;Hongjiang Zhai.;Chunhua Ni.;Hao Wang.;Chenggang Zhang.;Yan Zhao.;Guoping Wang.;Yuyou Zhu.;Rui Li.;Jun Sun.;Haiying Hu.;Jiangping Cui.;Li Wang.;Chao Zhang.;Jianlong Song.;Xiaozhong Jing.;Anmo Wang.;Jinjing Wang.;Pengfei Xu.;Adnan I Qureshi.;Thanh N Nguyen.;Raul G Nogueira.;Jeffrey L Saver.;Wei Hu.; .
来源: N Engl J Med. 2025年
Intravenous thrombolysis remains a standard treatment for acute ischemic stroke within 4.5 hours after onset. Vascular reocclusion may occur after intravenous thrombolysis and may be preventable with an antiplatelet agent within the first 24 hours after thrombolysis. Tirofiban, a platelet glycoprotein IIb-IIIa receptor antagonist, has reduced macrovascular reocclusion in experimental models.
13. AAV9-Mediated Gene Therapy for Infantile-Onset Pompe's Disease.
作者: Xiuwei Ma.;Lu Zhuang.;Wenhao Ma.;Jun Li.;Yingying Mao.;Jianhua Wang.;Xiaodong Wang.;Juan Xu.;Shuangqing Yu.;Ruijie Gu.;Yongxia Wang.;Zhongqiu Li.;Xinyang Jiang.;Sheng Zhang.;Fang He.;Xiao Yang.;Lina Zhu.;Shan Zhang.;Yanping Zhang.;Ting Li.;Qiuping Li.;Zhijie Wu.;Cengceng Zhang.;Yiying Zhang.;Xiaoyan Dong.;Hui Xiong.;Xiaobing Wu.;Zhichun Feng.
来源: N Engl J Med. 2025年392卷24期2438-2446页
Four patients with infantile-onset Pompe's disease received a single intravenous injection of an adeno-associated virus serotype 9 vector carrying codon-optimized complementary DNA encoding human acid α-glucosidase (GAA) (dose, 1.2 × 1014 vector genomes per kilogram of body weight). One patient was withdrawn from the study and subsequently died. The other patients had improvement in cardiac outcomes and motor function over a 52-week observation period. Anti-GAA antibodies were not detected in any of the patients during the observation period. Respiratory tract infections were the most common adverse events. (Funded by the National Natural Science Foundation of China and National High Level Hospital Clinical Research Funding; Chinese Clinical Trial Registry number, ChiCTR2200063229.).
14. Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity - A Phase 2 Trial.
作者: Ania M Jastreboff.;Donna H Ryan.;Harold E Bays.;Peter R Ebeling.;Mia G Mackowski.;Nisha Philipose.;Leorah Ross.;Yimeng Liu.;Cassandra E Burns.;Siddique A Abbasi.;Nicola Pannacciulli.; .
来源: N Engl J Med. 2025年
Maridebart cafraglutide (known as MariTide) is a long-acting peptide-antibody conjugate that combines glucagon-like peptide-1 receptor agonism and glucose-dependent insulinotropic polypeptide receptor antagonism and that is intended for the treatment of obesity.
15. Weekly Fixed-Dose Insulin Efsitora in Type 2 Diabetes without Previous Insulin Therapy.
作者: Julio Rosenstock.;Timothy Bailey.;Lisa Connery.;Eden Miller.;Cyrus Desouza.;Qianqian Wang.;Jennifer Leohr.;Alastair Knights.;Molly C Carr.;Christopher J Child.; .
来源: N Engl J Med. 2025年393卷4期325-335页
In previous treat-to-target trials, adjustments to the dose of basal insulin have been made at least weekly, according to fasting blood glucose levels. A fixed-dose regimen of insulin efsitora alfa (efsitora), a once-weekly basal insulin, may provide a benefit in adults with type 2 diabetes who have not received previous insulin therapy.
16. Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist, in Early Type 2 Diabetes.
作者: Julio Rosenstock.;Stanley Hsia.;Luis Nevarez Ruiz.;Sarah Eyde.;David Cox.;Wen-Shuo Wu.;Rong Liu.;Jianghao Li.;Laura Fernández Landó.;Max Denning.;Lisa Ludwig.;Yanyun Chen.; .
来源: N Engl J Med. 2025年
Orforglipron is a small-molecule, nonpeptide glucagon-like peptide-1 (GLP-1) receptor agonist in clinical development for type 2 diabetes and weight management. Additional data on the efficacy and safety of orforglipron are needed.
17. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity.
作者: W Timothy Garvey.;Matthias Blüher.;Cynthia Karenina Osorto Contreras.;Melanie J Davies.;Eva Winning Lehmann.;Kirsi H Pietiläinen.;Domenica Rubino.;Paolo Sbraccia.;Thomas Wadden.;Niels Zeuthen.;John P H Wilding.; .
来源: N Engl J Med. 2025年393卷7期635-647页
Semaglutide at a dose of 2.4 mg has established weight-loss and cardiovascular benefits, and cagrilintide at a dose of 2.4 mg has shown promising results in early-phase trials; the efficacy of the combination (known as CagriSema) on weight loss in persons with either overweight and coexisting conditions or obesity is unknown.
18. Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes.
作者: Melanie J Davies.;Harpreet S Bajaj.;Christa Broholm.;Astrid Eliasen.;W Timothy Garvey.;Carel W le Roux.;Ildiko Lingvay.;Christian Bøge Lyndgaard.;Julio Rosenstock.;Sue D Pedersen.; .
来源: N Engl J Med. 2025年393卷7期648-659页
Cagrilintide and semaglutide have each been shown to induce weight loss as monotherapies. Data are needed on the coadministration of cagrilintide and semaglutide (called CagriSema) for weight management in adults with type 2 diabetes, including those in a subgroup who are undergoing continuous glucose monitoring.
19. Stem Cell-Derived, Fully Differentiated Islets for Type 1 Diabetes.
作者: Trevor W Reichman.;James F Markmann.;Jon Odorico.;Piotr Witkowski.;John J Fung.;Martin Wijkstrom.;Fouad Kandeel.;Eelco J P de Koning.;Anne L Peters.;Chantal Mathieu.;Leslie S Kean.;Bote G Bruinsma.;Chenkun Wang.;Molly Mascia.;Bastiano Sanna.;Gautham Marigowda.;Felicia Pagliuca.;Doug Melton.;Camillo Ricordi.;Michael R Rickels.; .
来源: N Engl J Med. 2025年
Zimislecel is an allogeneic stem cell-derived islet-cell therapy. Data on the safety and efficacy of zimislecel in persons with type 1 diabetes are needed.
20. Neoadjuvant and Adjuvant Pembrolizumab in Locally Advanced Head and Neck Cancer.
作者: Ravindra Uppaluri.;Robert I Haddad.;Yungan Tao.;Christophe Le Tourneau.;Nancy Y Lee.;William Westra.;Rebecca Chernock.;Makoto Tahara.;Kevin J Harrington.;Arkadiy L Klochikhin.;Irene Braña.;Gustavo Vasconcelos Alves.;Brett G M Hughes.;Marc Oliva.;Iane Pinto Figueiredo Lima.;Tsutomu Ueda.;Tomasz Rutkowski.;Ursula Schroeder.;Paul-Stefan Mauz.;Thorsten Fuereder.;Simon Laban.;Nobuhiko Oridate.;Aron Popovtzer.;Nicolas Mach.;Yevhen Korobko.;Diogo Alpuim Costa.;Anupama Hooda-Nehra.;Cristina P Rodriguez.;R Bryan Bell.;Cole Manschot.;Kimberly Benjamin.;Burak Gumuscu.;Douglas Adkins.; .
来源: N Engl J Med. 2025年393卷1期37-50页
The benefit of the addition of perioperative pembrolizumab to standard care with surgery and adjuvant therapy for patients with locally advanced head and neck squamous-cell carcinoma (HNSCC) is unclear.
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