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209. 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).
210. 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.
211. 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.
212. 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).
216. 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.
217. 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.
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