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4441. Adagrasib with or without Cetuximab in Colorectal Cancer with Mutated KRAS G12C.
作者: Rona Yaeger.;Jared Weiss.;Meredith S Pelster.;Alexander I Spira.;Minal Barve.;Sai-Hong I Ou.;Ticiana A Leal.;Tanios S Bekaii-Saab.;Cloud P Paweletz.;Grace A Heavey.;James G Christensen.;Karen Velastegui.;Thian Kheoh.;Hirak Der-Torossian.;Samuel J Klempner.
来源: N Engl J Med. 2023年388卷1期44-54页
Adagrasib, an oral small-molecule inhibitor of mutant KRAS G12C protein, has shown clinical activity in pretreated patients with several tumor types, including colorectal cancer. Preclinical studies suggest that combining a KRAS G12C inhibitor with an epidermal growth factor receptor antibody could be an effective clinical strategy.
4442. Sotorasib in KRAS p.G12C-Mutated Advanced Pancreatic Cancer.
作者: John H Strickler.;Hironaga Satake.;Thomas J George.;Rona Yaeger.;Antoine Hollebecque.;Ignacio Garrido-Laguna.;Martin Schuler.;Timothy F Burns.;Andrew L Coveler.;Gerald S Falchook.;Mark Vincent.;Yu Sunakawa.;Laetitia Dahan.;David Bajor.;Sun-Young Rha.;Charlotte Lemech.;Dejan Juric.;Marko Rehn.;Gataree Ngarmchamnanrith.;Pegah Jafarinasabian.;Qui Tran.;David S Hong.
来源: N Engl J Med. 2023年388卷1期33-43页
KRAS p.G12C mutation occurs in approximately 1 to 2% of pancreatic cancers. The safety and efficacy of sotorasib, a KRAS G12C inhibitor, in previously treated patients with KRAS p.G12C-mutated pancreatic cancer are unknown.
4446. Deep Intronic FGF14 GAA Repeat Expansion in Late-Onset Cerebellar Ataxia.
作者: David Pellerin.;Matt C Danzi.;Carlo Wilke.;Mathilde Renaud.;Sarah Fazal.;Marie-Josée Dicaire.;Carolin K Scriba.;Catherine Ashton.;Christopher Yanick.;Danique Beijer.;Adriana Rebelo.;Clarissa Rocca.;Zane Jaunmuktane.;Joshua A Sonnen.;Roxanne Larivière.;David Genís.;Laura Molina Porcel.;Karine Choquet.;Rawan Sakalla.;Sylvie Provost.;Rebecca Robertson.;Xavier Allard-Chamard.;Martine Tétreault.;Sarah J Reiling.;Sara Nagy.;Vikas Nishadham.;Meera Purushottam.;Seena Vengalil.;Mainak Bardhan.;Atchayaram Nalini.;Zhongbo Chen.;Jean Mathieu.;Rami Massie.;Colin H Chalk.;Anne-Louise Lafontaine.;François Evoy.;Marie-France Rioux.;Jiannis Ragoussis.;Kym M Boycott.;Marie-Pierre Dubé.;Antoine Duquette.;Henry Houlden.;Gianina Ravenscroft.;Nigel G Laing.;Phillipa J Lamont.;Mario A Saporta.;Rebecca Schüle.;Ludger Schöls.;Roberta La Piana.;Matthis Synofzik.;Stephan Zuchner.;Bernard Brais.
来源: N Engl J Med. 2023年388卷2期128-141页
The late-onset cerebellar ataxias (LOCAs) have largely resisted molecular diagnosis.
4447. Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia.
作者: Jennifer R Brown.;Barbara Eichhorst.;Peter Hillmen.;Wojciech Jurczak.;Maciej Kaźmierczak.;Nicole Lamanna.;Susan M O'Brien.;Constantine S Tam.;Lugui Qiu.;Keshu Zhou.;Martin Simkovic.;Jiri Mayer.;Amanda Gillespie-Twardy.;Alessandra Ferrajoli.;Peter S Ganly.;Robert Weinkove.;Sebastian Grosicki.;Andrzej Mital.;Tadeusz Robak.;Anders Osterborg.;Habte A Yimer.;Tommi Salmi.;Megan-Der-Yu Wang.;Lina Fu.;Jessica Li.;Kenneth Wu.;Aileen Cohen.;Mazyar Shadman.
来源: N Engl J Med. 2023年388卷4期319-332页
In a multinational, phase 3, head-to-head trial, ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, was compared with zanubrutinib, a BTK inhibitor with greater specificity, as treatment for relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). In prespecified interim analyses, zanubrutinib was superior to ibrutinib with respect to overall response (the primary end point). Data from the final analysis of progression-free survival are now available.
4448. Expectant Management or Early Ibuprofen for Patent Ductus Arteriosus.
作者: Tim Hundscheid.;Wes Onland.;Elisabeth M W Kooi.;Daniel C Vijlbrief.;Willem B de Vries.;Koen P Dijkman.;Anton H van Kaam.;Eduardo Villamor.;André A Kroon.;Remco Visser.;Susanne M Mulder-de Tollenaer.;Barbara De Bisschop.;Peter H Dijk.;Daniela Avino.;Catheline Hocq.;Alexandra Zecic.;Marisse Meeus.;Tessa de Baat.;Frank Derriks.;Tine B Henriksen.;Kasper J Kyng.;Rogier Donders.;Debbie H G M Nuytemans.;Bart Van Overmeire.;Antonius L Mulder.;Willem P de Boode.; .
来源: N Engl J Med. 2023年388卷11期980-990页
Cyclooxygenase inhibitors are commonly used in infants with patent ductus arteriosus (PDA), but the benefit of these drugs is uncertain.
4451. Efficacy of Antiviral Agents against Omicron Subvariants BQ.1.1 and XBB.
作者: Masaki Imai.;Mutsumi Ito.;Maki Kiso.;Seiya Yamayoshi.;Ryuta Uraki.;Shuetsu Fukushi.;Shinji Watanabe.;Tadaki Suzuki.;Ken Maeda.;Yuko Sakai-Tagawa.;Kiyoko Iwatsuki-Horimoto.;Peter J Halfmann.;Yoshihiro Kawaoka.
来源: N Engl J Med. 2023年388卷1期89-91页 4453. Lecanemab in Early Alzheimer's Disease.
作者: Christopher H van Dyck.;Chad J Swanson.;Paul Aisen.;Randall J Bateman.;Christopher Chen.;Michelle Gee.;Michio Kanekiyo.;David Li.;Larisa Reyderman.;Sharon Cohen.;Lutz Froelich.;Sadao Katayama.;Marwan Sabbagh.;Bruno Vellas.;David Watson.;Shobha Dhadda.;Michael Irizarry.;Lynn D Kramer.;Takeshi Iwatsubo.
来源: N Engl J Med. 2023年388卷1期9-21页
The accumulation of soluble and insoluble aggregated amyloid-beta (Aβ) may initiate or potentiate pathologic processes in Alzheimer's disease. Lecanemab, a humanized IgG1 monoclonal antibody that binds with high affinity to Aβ soluble protofibrils, is being tested in persons with early Alzheimer's disease.
4454. Progression of Atrial Fibrillation after Cryoablation or Drug Therapy.
作者: Jason G Andrade.;Marc W Deyell.;Laurent Macle.;George A Wells.;Matthew Bennett.;Vidal Essebag.;Jean Champagne.;Jean-Francois Roux.;Derek Yung.;Allan Skanes.;Yaariv Khaykin.;Carlos Morillo.;Umjeet Jolly.;Paul Novak.;Evan Lockwood.;Guy Amit.;Paul Angaran.;John Sapp.;Stephan Wardell.;Sandra Lauck.;Julia Cadrin-Tourigny.;Simon Kochhäuser.;Atul Verma.; .
来源: N Engl J Med. 2023年388卷2期105-116页
Atrial fibrillation is a chronic, progressive disorder, and persistent forms of atrial fibrillation are associated with increased risks of thromboembolism and heart failure. Catheter ablation as initial therapy may modify the pathogenic mechanism of atrial fibrillation and alter progression to persistent atrial fibrillation.
4455. Phase 2 Trial of Baxdrostat for Treatment-Resistant Hypertension.
作者: Mason W Freeman.;Yuan-Di Halvorsen.;William Marshall.;Mackenzie Pater.;Jon Isaacsohn.;Catherine Pearce.;Brian Murphy.;Nicholas Alp.;Ajay Srivastava.;Deepak L Bhatt.;Morris J Brown.; .
来源: N Engl J Med. 2023年388卷5期395-405页
Aldosterone synthase controls the synthesis of aldosterone and has been a pharmacologic target for the treatment of hypertension for several decades. Selective inhibition of aldosterone synthase is essential but difficult to achieve because cortisol synthesis is catalyzed by another enzyme that shares 93% sequence similarity with aldosterone synthase. In preclinical and phase 1 studies, baxdrostat had 100:1 selectivity for enzyme inhibition, and baxdrostat at several dose levels reduced plasma aldosterone levels but not cortisol levels.
4456. Duration of Device-Based Fever Prevention after Cardiac Arrest.
作者: Christian Hassager.;Henrik Schmidt.;Jacob E Møller.;Johannes Grand.;Simon Mølstrøm.;Rasmus P Beske.;Søren Boesgaard.;Britt Borregaard.;Ditte Bekker-Jensen.;Jordi S Dahl.;Martin S Frydland.;Dan E Høfsten.;Yusuf A Isse.;Jakob Josiassen.;Vibeke R Lind Jørgensen.;Daniel Kondziella.;Matias G Lindholm.;Emil Moser.;Benjamin C Nyholm.;Laust E R Obling.;Laura Sarkisian.;Frederik T Søndergaard.;Jakob H Thomsen.;Jens J Thune.;Søren Venø.;Sebastian C Wiberg.;Matilde Winther-Jensen.;Martin A S Meyer.;Jesper Kjaergaard.
来源: N Engl J Med. 2023年388卷10期888-897页
Guidelines recommend active fever prevention for 72 hours after cardiac arrest. Data from randomized clinical trials of this intervention have been lacking.
4457. Trial of an Intervention to Improve Acute Heart Failure Outcomes.
作者: Douglas S Lee.;Sharon E Straus.;Michael E Farkouh.;Peter C Austin.;Monica Taljaard.;Alice Chong.;Christine Fahim.;Stephanie Poon.;Peter Cram.;Stuart Smith.;Robert S McKelvie.;Liane Porepa.;Michael Hartleib.;Peter Mitoff.;Robert M Iwanochko.;Andrea MacDougall.;Steven Shadowitz.;Howard Abrams.;Esam Elbarasi.;Jiming Fang.;Jacob A Udell.;Michael J Schull.;Susanna Mak.;Heather J Ross.; .
来源: N Engl J Med. 2023年388卷1期22-32页
Patients with acute heart failure are frequently or systematically hospitalized, often because the risk of adverse events is uncertain and the options for rapid follow-up are inadequate. Whether the use of a strategy to support clinicians in making decisions about discharging or admitting patients, coupled with rapid follow-up in an outpatient clinic, would affect outcomes remains uncertain.
4458. Empagliflozin in Patients with Chronic Kidney Disease.
作者: .;William G Herrington.;Natalie Staplin.;Christoph Wanner.;Jennifer B Green.;Sibylle J Hauske.;Jonathan R Emberson.;David Preiss.;Parminder Judge.;Kaitlin J Mayne.;Sarah Y A Ng.;Emily Sammons.;Doreen Zhu.;Michael Hill.;Will Stevens.;Karl Wallendszus.;Susanne Brenner.;Alfred K Cheung.;Zhi-Hong Liu.;Jing Li.;Lai Seong Hooi.;Wen Liu.;Takashi Kadowaki.;Masaomi Nangaku.;Adeera Levin.;David Cherney.;Aldo P Maggioni.;Roberto Pontremoli.;Rajat Deo.;Shinya Goto.;Xavier Rossello.;Katherine R Tuttle.;Dominik Steubl.;Michaela Petrini.;Dan Massey.;Jens Eilbracht.;Martina Brueckmann.;Martin J Landray.;Colin Baigent.;Richard Haynes.
来源: N Engl J Med. 2023年388卷2期117-127页
The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients.
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