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  • Timing of Endoscopy for Acute Upper Gastrointestinal Bleeding
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-04-02
    James Y.W. Lau; Yuanyuan Yu; Raymond S.Y. Tang; Heyson C.H. Chan; Hon-Chi Yip; Shannon M. Chan; Sally W.Y. Luk; Sunny H. Wong; Louis H.S. Lau; Rashid N. Lui; Ting T. Chan; Joyce W.Y. Mak; Francis K.L. Chan; Joseph J.Y. Sung

    Background It is recommended that patients with acute upper gastrointestinal bleeding undergo endoscopy within 24 hours after gastroenterologic consultation. The role of endoscopy performed within time frames shorter than 24 hours has not been adequately defined. Methods To evaluate whether urgent endoscopy improves outcomes in patients predicted to be at high risk for further bleeding or death, we

    更新日期:2020-04-03
  • Multidrug-Resistant Bacterial Infections in U.S. Hospitalized Patients, 2012–2017
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-04-02
    John A. Jernigan; Kelly M. Hatfield; Hannah Wolford; Richard E. Nelson; Babatunde Olubajo; Sujan C. Reddy; Natalie McCarthy; Prabasaj Paul; L. Clifford McDonald; Alex Kallen; Anthony Fiore; Michael Craig; James Baggs

    Background Multidrug-resistant (MDR) bacteria that are commonly associated with health care cause a substantial health burden. Updated national estimates for this group of pathogens are needed to inform public health action. Methods Using data from patients hospitalized in a cohort of 890 U.S. hospitals during the period 2012–2017, we generated national case counts for both hospital-onset and community-onset

    更新日期:2020-04-03
  • Trends in U.S. Burden of Clostridioides difficile Infection and Outcomes
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-04-02
    Alice Y. Guh; Yi Mu; Lisa G. Winston; Helen Johnston; Danyel Olson; Monica M. Farley; Lucy E. Wilson; Stacy M. Holzbauer; Erin C. Phipps; Ghinwa K. Dumyati; Zintars G. Beldavs; Marion A. Kainer; Maria Karlsson; Dale N. Gerding; L. Clifford McDonald

    Background Efforts to prevent Clostridioides difficile infection continue to expand across the health care spectrum in the United States. Whether these efforts are reducing the national burden of C. difficile infection is unclear. Methods The Emerging Infections Program identified cases of C. difficile infection (stool specimens positive for C. difficile in a person ≥1 year of age with no positive

    更新日期:2020-04-03
  • KTE-X19 CAR T-Cell Therapy in Relapsed or Refractory Mantle-Cell Lymphoma
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-04-02
    Michael Wang; Javier Munoz; Andre Goy; Frederick L. Locke; Caron A. Jacobson; Brian T. Hill; John M. Timmerman; Houston Holmes; Samantha Jaglowski; Ian W. Flinn; Peter A. McSweeney; David B. Miklos; John M. Pagel; Marie-Jose Kersten; Noel Milpied; Henry Fung; Max S. Topp; Roch Houot; Amer Beitinjaneh; Weimin Peng; Lianqing Zheng; John M. Rossi; Rajul K. Jain; Arati V. Rao; Patrick M. Reagan

    Background Patients with relapsed or refractory mantle-cell lymphoma who have disease progression during or after the receipt of Bruton’s tyrosine kinase (BTK) inhibitor therapy have a poor prognosis. KTE-X19, an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, may have benefit in patients with relapsed or refractory mantle-cell lymphoma. Methods In a multicenter, phase 2 trial, we evaluated

    更新日期:2020-04-03
  • A Phase 3 Trial of Luspatercept in Patients with Transfusion-Dependent β-Thalassemia
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-03-26
    M. Domenica Cappellini; Vip Viprakasit; Ali T. Taher; Pencho Georgiev; Kevin H.M. Kuo; Thomas Coates; Ersi Voskaridou; Hong-Keng Liew; Idit Pazgal-Kobrowski; G.L. Forni; Silverio Perrotta; Abderrahim Khelif; Ashutosh Lal; Antonis Kattamis; Efthymia Vlachaki; Raffaella Origa; Yesim Aydinok; Mohamed Bejaoui; P. Joy Ho; Lee-Ping Chew; Ping-Chong Bee; Soo-Min Lim; Meng-Yao Lu; Adisak Tantiworawit; Penka

    Background Patients with transfusion-dependent β-thalassemia need regular red-cell transfusions. Luspatercept, a recombinant fusion protein that binds to select transforming growth factor β superfamily ligands, may enhance erythroid maturation and reduce the transfusion burden (the total number of red-cell units transfused) in such patients. Methods In this randomized, double-blind, phase 3 trial,

    更新日期:2020-03-26
  • Fostemsavir in Adults with Multidrug-Resistant HIV-1 Infection
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-03-26
    Michael Kozal; Judith Aberg; Gilles Pialoux; Pedro Cahn; Melanie Thompson; Jean-Michel Molina; Beatriz Grinsztejn; Ricardo Diaz; Antonella Castagna; Princy Kumar; Gulam Latiff; Edwin DeJesus; Mark Gummel; Margaret Gartland; Amy Pierce; Peter Ackerman; Cyril Llamoso; Max Lataillade

    Background Among some patients with human immunodeficiency virus type 1 (HIV-1) infection who have undergone multiple antiretroviral therapies and have limited options for treatment, new classes of antiretroviral drugs with novel mechanisms of action are needed. Fostemsavir is the prodrug of temsavir, a first-in-class investigational HIV-1 attachment inhibitor. Methods In this ongoing phase 3 trial

    更新日期:2020-03-26
  • Surgery versus Conservative Care for Persistent Sciatica Lasting 4 to 12 Months
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-03-19
    Chris S. Bailey; Parham Rasoulinejad; David Taylor; Keith Sequeira; Thomas Miller; Jim Watson; Richard Rosedale; Stewart I. Bailey; Kevin R. Gurr; Fawaz Siddiqi; Andrew Glennie; Jennifer C. Urquhart

    Background The treatment of chronic sciatica caused by herniation of a lumbar disk has not been well studied in comparison with acute disk herniation. Data are needed on whether diskectomy or a conservative approach is better for sciatica that has persisted for several months. Methods In a single-center trial, we randomly assigned patients with sciatica that had lasted for 4 to 12 months and lumbar

    更新日期:2020-03-19
  • Long-Acting Cabotegravir and Rilpivirine for Maintenance of HIV-1 Suppression
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-03-19
    Susan Swindells; Jaime-Federico Andrade-Villanueva; Gary J. Richmond; Giuliano Rizzardini; Axel Baumgarten; Mar Masiá; Gulam Latiff; Vadim Pokrovsky; Fritz Bredeek; Graham Smith; Pedro Cahn; Yeon-Sook Kim; Susan L. Ford; Christine L. Talarico; Parul Patel; Vasiliki Chounta; Herta Crauwels; Wim Parys; Simon Vanveggel; Joseph Mrus; Jenny Huang; Conn M. Harrington; Krischan J. Hudson; David A. Margolis;

    Background Simplified regimens for the treatment of human immunodeficiency virus type 1 (HIV-1) infection may increase patient satisfaction and facilitate adherence. Methods In this phase 3, open-label, multicenter, noninferiority trial involving patients who had had plasma HIV-1 RNA levels of less than 50 copies per milliliter for at least 6 months while taking standard oral antiretroviral therapy

    更新日期:2020-03-19
  • Long-Acting Cabotegravir and Rilpivirine after Oral Induction for HIV-1 Infection
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-03-19
    Chloe Orkin; Keikawus Arasteh; Miguel Górgolas Hernández-Mora; Vadim Pokrovsky; Edgar T. Overton; Pierre-Marie Girard; Shinichi Oka; Sharon Walmsley; Chris Bettacchi; Cynthia Brinson; Patrick Philibert; Johan Lombaard; Marty St. Clair; Herta Crauwels; Susan L. Ford; Parul Patel; Vasiliki Chounta; Ronald D’Amico; Simon Vanveggel; David Dorey; Amy Cutrell; Sandy Griffith; David A. Margolis; Peter E.

    Background Long-acting injectable regimens may simplify therapy for patients with human immunodeficiency virus type 1 (HIV-1) infection. Methods We conducted a phase 3, randomized, open-label trial in which adults with HIV-1 infection who had not previously received antiretroviral therapy were given 20 weeks of daily oral induction therapy with dolutegravir–abacavir–lamivudine. Participants who had

    更新日期:2020-03-19
  • Liberal or Conservative Oxygen Therapy for Acute Respiratory Distress Syndrome
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-03-12
    Loic Barrot; Pierre Asfar; Frederic Mauny; Hadrien Winiszewski; Florent Montini; Julio Badie; Jean-Pierre Quenot; Sebastien Pili-Floury; Belaid Bouhemad; Guillaume Louis; Bertrand Souweine; Olivier Collange; Julien Pottecher; Bruno Levy; Marc Puyraveau; Lucie Vettoretti; Jean-Michel Constantin; Gilles Capellier

    Background In patients with acute respiratory distress syndrome (ARDS), the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network recommends a target partial pressure of arterial oxygen (Pao2) between 55 and 80 mm Hg. Prospective validation of this range in patients with ARDS is lacking. We hypothesized that targeting the lower limit of this range would improve outcomes in patients

    更新日期:2020-03-12
  • Consequences of Undervaccination — Measles Outbreak, New York City, 2018–2019
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-03-12
    Jane R. Zucker; Jennifer B. Rosen; Martha Iwamoto; Robert J. Arciuolo; Marisa Langdon-Embry; Neil M. Vora; Jennifer L. Rakeman; Beth M. Isaac; Antonine Jean; Mekete Asfaw; Simone C. Hawkins; Thomas G. Merrill; Maura O. Kennelly; Beth Maldin Morgenthau; Demetre C. Daskalakis; Oxiris Barbot

    Background Measles was declared eliminated in the United States in 2000, but the risk of outbreaks owing to international importations remains. An outbreak of measles in New York City began when one unvaccinated child returned home from Israel with measles; onset of rash occurred on September 30, 2018, 9 days after the child returned home. Methods We investigated suspected cases of measles by conducting

    更新日期:2020-03-12
  • Association of Aspirin with Hepatocellular Carcinoma and Liver-Related Mortality
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-03-12
    Tracey G. Simon; Ann-Sofi Duberg; Soo Aleman; Raymond T. Chung; Andrew T. Chan; Jonas F. Ludvigsson

    Background More information is needed about the long-term effects of low-dose aspirin (≤160 mg) on incident hepatocellular carcinoma, liver-related mortality, and gastrointestinal bleeding in persons with chronic hepatitis B or hepatitis C virus infection. Methods Using nationwide Swedish registries, we identified all adults who received a diagnosis of chronic hepatitis B or hepatitis C from 2005 through

    更新日期:2020-03-12
  • Treatment of Highly Drug-Resistant Pulmonary Tuberculosis
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-03-05
    Francesca Conradie; Andreas H. Diacon; Nosipho Ngubane; Pauline Howell; Daniel Everitt; Angela M. Crook; Carl M. Mendel; Erica Egizi; Joanna Moreira; Juliano Timm; Timothy D. McHugh; Genevieve H. Wills; Anna Bateson; Robert Hunt; Christo Van Niekerk; Mengchun Li; Morounfolu Olugbosi; Melvin Spigelman

    Patients with highly drug-resistant forms of tuberculosis have limited treatment options and historically have had poor outcomes.

    更新日期:2020-03-05
  • MRI-Targeted, Systematic, and Combined Biopsy for Prostate Cancer Diagnosis
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-03-05
    Michael Ahdoot; Andrew R. Wilbur; Sarah E. Reese; Amir H. Lebastchi; Sherif Mehralivand; Patrick T. Gomella; Jonathan Bloom; Sandeep Gurram; Minhaj Siddiqui; Paul Pinsky; Howard Parnes; W. Marston Linehan; Maria Merino; Peter L. Choyke; Joanna H. Shih; Baris Turkbey; Bradford J. Wood; Peter A. Pinto

    Background The use of 12-core systematic prostate biopsy is associated with diagnostic inaccuracy that contributes to both overdiagnosis and underdiagnosis of prostate cancer. Biopsies performed with magnetic resonance imaging (MRI) targeting may reduce the misclassification of prostate cancer in men with MRI-visible lesions. Methods Men with MRI-visible prostate lesions underwent both MRI-targeted

    更新日期:2020-03-05
  • Five-Year Outcomes of Transcatheter or Surgical Aortic-Valve Replacement.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-01-29
    Raj R Makkar,Vinod H Thourani,Michael J Mack,Susheel K Kodali,Samir Kapadia,John G Webb,Sung-Han Yoon,Alfredo Trento,Lars G Svensson,Howard C Herrmann,Wilson Y Szeto,D Craig Miller,Lowell Satler,David J Cohen,Todd M Dewey,Vasilis Babaliaros,Mathew R Williams,Dean J Kereiakes,Alan Zajarias,Kevin L Greason,Brian K Whisenant,Robert W Hodson,David L Brown,William F Fearon,Mark J Russo,Philippe Pibarot

    BACKGROUND There are scant data on long-term clinical outcomes and bioprosthetic-valve function after transcatheter aortic-valve replacement (TAVR) as compared with surgical aortic-valve replacement in patients with severe aortic stenosis and intermediate surgical risk. METHODS We enrolled 2032 intermediate-risk patients with severe, symptomatic aortic stenosis at 57 centers. Patients were stratified

    更新日期:2020-02-27
  • Pembrolizumab for Early Triple-Negative Breast Cancer.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-02-27
    Peter Schmid,Javier Cortes,Lajos Pusztai,Heather McArthur,Sherko Kümmel,Jonas Bergh,Carsten Denkert,Yeon Hee Park,Rina Hui,Nadia Harbeck,Masato Takahashi,Theodoros Foukakis,Peter A Fasching,Fatima Cardoso,Michael Untch,Liyi Jia,Vassiliki Karantza,Jing Zhao,Gursel Aktan,Rebecca Dent,Joyce O'Shaughnessy,

    BACKGROUND Previous trials showed promising antitumor activity and an acceptable safety profile associated with pembrolizumab in patients with early triple-negative breast cancer. Whether the addition of pembrolizumab to neoadjuvant chemotherapy would significantly increase the percentage of patients with early triple-negative breast cancer who have a pathological complete response (defined as no invasive

    更新日期:2020-02-27
  • Microbiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-02-27
    Jonathan U Peled,Antonio L C Gomes,Sean M Devlin,Eric R Littmann,Ying Taur,Anthony D Sung,Daniela Weber,Daigo Hashimoto,Ann E Slingerland,John B Slingerland,Molly Maloy,Annelie G Clurman,Christoph K Stein-Thoeringer,Kate A Markey,Melissa D Docampo,Marina Burgos da Silva,Niloufer Khan,André Gessner,Julia A Messina,Kristi Romero,Meagan V Lew,Amy Bush,Lauren Bohannon,Daniel G Brereton,Emily Fontana,Luigi

    BACKGROUND Relationships between microbiota composition and clinical outcomes after allogeneic hematopoietic-cell transplantation have been described in single-center studies. Geographic variations in the composition of human microbial communities and differences in clinical practices across institutions raise the question of whether these associations are generalizable. METHODS The microbiota composition

    更新日期:2020-02-27
  • Effects of Germline VHL Deficiency on Growth, Metabolism, and Mitochondria.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-02-27
    Silverio Perrotta,Domenico Roberti,Debora Bencivenga,Paola Corsetto,Katie A O'Brien,Martina Caiazza,Emanuela Stampone,Leanne Allison,Roland A Fleck,Saverio Scianguetta,Immacolata Tartaglione,Peter A Robbins,Maddalena Casale,James A West,Clara Franzini-Armstrong,Julian L Griffin,Angela M Rizzo,Antonio A Sinisi,Andrew J Murray,Adriana Borriello,Federico Formenti,Fulvio Della Ragione

    Mutations in VHL, which encodes von Hippel-Lindau tumor suppressor (VHL), are associated with divergent diseases. We describe a patient with marked erythrocytosis and prominent mitochondrial alterations associated with a severe germline VHL deficiency due to homozygosity for a novel synonymous mutation (c.222C→A, p.V74V). The condition is characterized by early systemic onset and differs from Chuvash

    更新日期:2020-02-27
  • Trial of Nemolizumab in Moderate-to-Severe Prurigo Nodularis.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-02-20
    Sonja Ständer,Gil Yosipovitch,Franz J Legat,Jean-Philippe Lacour,Carle Paul,Joanna Narbutt,Thomas Bieber,Laurent Misery,Andreas Wollenberg,Adam Reich,Faiz Ahmad,Christophe Piketty

    BACKGROUND Prurigo nodularis is a chronic pruritic skin disease with multiple nodular skin lesions. Nemolizumab is a monoclonal antibody targeting the interleukin-31 receptor, which is involved in the pathogenesis of prurigo nodularis. METHODS We conducted a 12-week, randomized, double-blind, phase 2 trial of nemolizumab (at a dose of 0.5 mg per kilogram of body weight) administered subcutaneously

    更新日期:2020-02-20
  • A Community-Based Intervention for Managing Hypertension in Rural South Asia.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-02-20
    Tazeen H Jafar,Mihir Gandhi,H Asita de Silva,Imtiaz Jehan,Aliya Naheed,Eric A Finkelstein,Elizabeth L Turner,Donald Morisky,Anuradhani Kasturiratne,Aamir H Khan,John D Clemens,Shah Ebrahim,Pryseley N Assam,Liang Feng,

    BACKGROUND The burden of hypertension is escalating, and control rates are poor in low- and middle-income countries. Cardiovascular mortality is high in rural areas. METHODS We conducted a cluster-randomized, controlled trial in rural districts in Bangladesh, Pakistan, and Sri Lanka. A total of 30 communities were randomly assigned to either a multicomponent intervention (intervention group) or usual

    更新日期:2020-02-20
  • A Novel Coronavirus from Patients with Pneumonia in China, 2019.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-01-24
    Na Zhu,Dingyu Zhang,Wenling Wang,Xingwang Li,Bo Yang,Jingdong Song,Xiang Zhao,Baoying Huang,Weifeng Shi,Roujian Lu,Peihua Niu,Faxian Zhan,Xuejun Ma,Dayan Wang,Wenbo Xu,Guizhen Wu,George F Gao,Wenjie Tan,

    In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus

    更新日期:2020-02-20
  • Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-02-13
    Michael Walsh,Peter A Merkel,Chen-Au Peh,Wladimir M Szpirt,Xavier Puéchal,Shouichi Fujimoto,Carmel M Hawley,Nader Khalidi,Oliver Floßmann,Ron Wald,Louis P Girard,Adeera Levin,Gina Gregorini,Lorraine Harper,William F Clark,Christian Pagnoux,Ulrich Specks,Lucy Smyth,Vladimir Tesar,Toshiko Ito-Ihara,Janak Rashme de Zoysa,Wojciech Szczeklik,Luis Felipe Flores-Suárez,Simon Carette,Loïc Guillevin,Charles

    BACKGROUND More effective and safer treatments are needed for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. METHODS We conducted a randomized trial with a 2-by-2 factorial design to evaluate the use of plasma exchange and two regimens of oral glucocorticoids in patients with severe ANCA-associated vasculitis (defined by an estimated glomerular filtration rate of <50 ml per minute

    更新日期:2020-02-13
  • Outbreak of Listeriosis in South Africa Associated with Processed Meat.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-02-13
    Juno Thomas,Nevashan Govender,Kerrigan M McCarthy,Linda K Erasmus,Timothy J Doyle,Mushal Allam,Arshad Ismail,Ntsieni Ramalwa,Phuti Sekwadi,Genevie Ntshoe,Andronica Shonhiwa,Vivien Essel,Nomsa Tau,Shannon Smouse,Hlengiwe M Ngomane,Bolele Disenyeng,Nicola A Page,Nelesh P Govender,Adriano G Duse,Rob Stewart,Teena Thomas,Deon Mahoney,Mathieu Tourdjman,Olivier Disson,Pierre Thouvenot,Mylène M Maury,Alexandre

    BACKGROUND An outbreak of listeriosis was identified in South Africa in 2017. The source was unknown. METHODS We conducted epidemiologic, trace-back, and environmental investigations and used whole-genome sequencing to type Listeria monocytogenes isolates. A case was defined as laboratory-confirmed L. monocytogenes infection during the period from June 11, 2017, to April 7, 2018. RESULTS A total of

    更新日期:2020-02-13
  • Reduced Lung-Cancer Mortality with Volume CT Screening in a Randomized Trial.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-01-29
    Harry J de Koning,Carlijn M van der Aalst,Pim A de Jong,Ernst T Scholten,Kristiaan Nackaerts,Marjolein A Heuvelmans,Jan-Willem J Lammers,Carla Weenink,Uraujh Yousaf-Khan,Nanda Horeweg,Susan van 't Westeinde,Mathias Prokop,Willem P Mali,Firdaus A A Mohamed Hoesein,Peter M A van Ooijen,Joachim G J V Aerts,Michael A den Bakker,Erik Thunnissen,Johny Verschakelen,Rozemarijn Vliegenthart,Joan E Walter,Kevin

    BACKGROUND There are limited data from randomized trials regarding whether volume-based, low-dose computed tomographic (CT) screening can reduce lung-cancer mortality among male former and current smokers. METHODS A total of 13,195 men (primary analysis) and 2594 women (subgroup analyses) between the ages of 50 and 74 were randomly assigned to undergo CT screening at T0 (baseline), year 1, year 3,

    更新日期:2020-02-06
  • Six-Year Follow-up of a Trial of Antenatal Vitamin D for Asthma Reduction
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-02-06
    Augusto A. Litonjua; Vincent J. Carey; Nancy Laranjo; Benjamin J. Stubbs; Hooman Mirzakhani; George T. O’Connor; Megan Sandel; Avraham Beigelman; Leonard B. Bacharier; Robert S. Zeiger; Michael Schatz; Bruce W. Hollis; Scott T. Weiss

    Background We previously reported the results of a trial of prenatal vitamin D supplementation to prevent asthma and recurrent wheeze in young children, which suggested that supplementation provided a protective effect at the age of 3 years. We followed the children through the age of 6 years to determine the course of asthma and recurrent wheeze. Methods In this follow-up study, investigators and

    更新日期:2020-02-06
  • Lower versus Traditional Treatment Threshold for Neonatal Hypoglycemia.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-02-06
    Anne A M W van Kempen,P Frank Eskes,Debbie H G M Nuytemans,Johanna H van der Lee,Lea M Dijksman,Nicole R van Veenendaal,Flip J P C M van der Hulst,Rob M J Moonen,Luc J I Zimmermann,Ellen P van 't Verlaat,Minouche van Dongen-van Baal,Ben A Semmekrot,Hélène G Stas,Ron H T van Beek,José J Vlietman,Peter H Dijk,Jacqueline U M Termote,Rogier C J de Jonge,Amerik C de Mol,Marianne W A Huysman,Joke H Kok,Martin

    BACKGROUND Worldwide, many newborns who are preterm, small or large for gestational age, or born to mothers with diabetes are screened for hypoglycemia, with a goal of preventing brain injury. However, there is no consensus on a treatment threshold that is safe but also avoids overtreatment. METHODS In a multicenter, randomized, noninferiority trial involving 689 otherwise healthy newborns born at

    更新日期:2020-02-06
  • Use of CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-02-06
    Enli Liu,David Marin,Pinaki Banerjee,Homer A Macapinlac,Philip Thompson,Rafet Basar,Lucila Nassif Kerbauy,Bethany Overman,Peter Thall,Mecit Kaplan,Vandana Nandivada,Indresh Kaur,Ana Nunez Cortes,Kai Cao,May Daher,Chitra Hosing,Evan N Cohen,Partow Kebriaei,Rohtesh Mehta,Sattva Neelapu,Yago Nieto,Michael Wang,William Wierda,Michael Keating,Richard Champlin,Elizabeth J Shpall,Katayoun Rezvani

    BACKGROUND Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has shown remarkable clinical efficacy in B-cell cancers. However, CAR T cells can induce substantial toxic effects, and the manufacture of the cells is complex. Natural killer (NK) cells that have been modified to express an anti-CD19 CAR have the potential to overcome these limitations. METHODS In this phase 1 and 2 trial, we administered

    更新日期:2020-02-06
  • Conservative versus Interventional Treatment for Spontaneous Pneumothorax.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-01-30
    Simon G A Brown,Emma L Ball,Kyle Perrin,Stephen E Asha,Irene Braithwaite,Diana Egerton-Warburton,Peter G Jones,Gerben Keijzers,Frances B Kinnear,Ben C H Kwan,K V Lam,Y C Gary Lee,Mike Nowitz,Catherine A Read,Graham Simpson,Julian A Smith,Quentin A Summers,Mark Weatherall,Richard Beasley,

    BACKGROUND Whether conservative management is an acceptable alternative to interventional management for uncomplicated, moderate-to-large primary spontaneous pneumothorax is unknown. METHODS In this open-label, multicenter, noninferiority trial, we recruited patients 14 to 50 years of age with a first-known, unilateral, moderate-to-large primary spontaneous pneumothorax. Patients were randomly assigned

    更新日期:2020-01-29
  • Soluble Urokinase Receptor and Acute Kidney Injury.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-01-30
    Salim S Hayek,David E Leaf,Ayman Samman Tahhan,Mohamad Raad,Shreyak Sharma,Sushrut S Waikar,Sanja Sever,Alex Camacho,Xuexiang Wang,Ranadheer R Dande,Nasrien E Ibrahim,Rebecca M Baron,Mehmet M Altintas,Changli Wei,David Sheikh-Hamad,Jenny S-C Pan,Michael W Holliday,James L Januzzi,Steven D Weisbord,Arshed A Quyyumi,Jochen Reiser

    BACKGROUND Acute kidney injury is common, with a major effect on morbidity and health care utilization. Soluble urokinase plasminogen activator receptor (suPAR) is a signaling glycoprotein thought to be involved in the pathogenesis of kidney disease. We investigated whether a high level of suPAR predisposed patients to acute kidney injury in multiple clinical contexts, and we used experimental models

    更新日期:2020-01-29
  • Family History of Gastric Cancer and Helicobacter pylori Treatment.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-01-30
    Il Ju Choi,Chan Gyoo Kim,Jong Yeul Lee,Young-Il Kim,Myeong-Cherl Kook,Boram Park,Jungnam Joo

    BACKGROUND Helicobacter pylori infection and a family history of gastric cancer are the main risk factors for gastric cancer. Whether treatment to eradicate H. pylori can reduce the risk of gastric cancer in persons with a family history of gastric cancer in first-degree relatives is unknown. METHODS In this single-center, double-blind, placebo-controlled trial, we screened 3100 first-degree relatives

    更新日期:2020-01-29
  • Fatal Cytomegalovirus Infection in an Adult with Inherited NOS2 Deficiency.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-01-30
    Scott B Drutman,Davood Mansouri,Seyed Alireza Mahdaviani,Anna-Lena Neehus,David Hum,Ruslana Bryk,Nicholas Hernandez,Serkan Belkaya,Franck Rapaport,Benedetta Bigio,Robert Fisch,Mahbuba Rahman,Taushif Khan,Fatima Al Ali,Majid Marjani,Nahal Mansouri,Lazaro Lorenzo-Diaz,Jean-François Emile,Nico Marr,Emmanuelle Jouanguy,Jacinta Bustamante,Laurent Abel,Stéphanie Boisson-Dupuis,Vivien Béziat,Carl Nathan,Jean-Laurent

    BACKGROUND Cytomegalovirus (CMV) can cause severe disease in children and adults with a variety of inherited or acquired T-cell immunodeficiencies, who are prone to multiple infections. It can also rarely cause disease in otherwise healthy persons. The pathogenesis of idiopathic CMV disease is unknown. Inbred mice that lack the gene encoding nitric oxide synthase 2 (Nos2) are susceptible to the related

    更新日期:2020-01-29
  • Vaccination of Infants with Meningococcal Group B Vaccine (4CMenB) in England.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-01-23
    Shamez N Ladhani,Nick Andrews,Sydel R Parikh,Helen Campbell,Joanne White,Michael Edelstein,Xilian Bai,Jay Lucidarme,Ray Borrow,Mary E Ramsay

    BACKGROUND In September 2015, the United Kingdom introduced the multicomponent meningococcal group B vaccine (4CMenB, Bexsero) into its publicly funded national immunization program at a reduced two-dose priming schedule for infants, with a 12-month booster. METHODS Using data from enhanced national surveillance of invasive meningococcal disease in England, we evaluated the effect of vaccination on

    更新日期:2020-01-23
  • Meningococcal B Vaccine and Meningococcal Carriage in Adolescents in Australia.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-01-23
    Helen S Marshall,Mark McMillan,Ann P Koehler,Andrew Lawrence,Thomas R Sullivan,Jenny M MacLennan,Martin C J Maiden,Shamez N Ladhani,Mary E Ramsay,Caroline Trotter,Ray Borrow,Adam Finn,Charlene M Kahler,Jane Whelan,Kumaran Vadivelu,Peter Richmond

    BACKGROUND The meningococcal group B vaccine 4CMenB is a new, recombinant protein-based vaccine that is licensed to protect against invasive group B meningococcal disease. However, its role in preventing transmission and, therefore, inducing population (herd) protection is uncertain. METHODS We used cluster randomization to assign, according to school, students in years 10 to 12 (age, 15 to 18 years)

    更新日期:2020-01-23
  • Elagolix for Heavy Menstrual Bleeding in Women with Uterine Fibroids.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-01-23
    William D Schlaff,Ronald T Ackerman,Ayman Al-Hendy,David F Archer,Kurt T Barnhart,Linda D Bradley,Bruce R Carr,Eve C Feinberg,Sandra M Hurtado,JinHee Kim,Ran Liu,R Garn Mabey,Charlotte D Owens,Alfred Poindexter,Elizabeth E Puscheck,Henry Rodriguez-Ginorio,James A Simon,Ahmed M Soliman,Elizabeth A Stewart,Nelson B Watts,Ozgul Muneyyirci-Delale

    BACKGROUND Uterine fibroids are hormone-responsive neoplasms that are associated with heavy menstrual bleeding. Elagolix, an oral gonadotropin-releasing hormone antagonist resulting in rapid, reversible suppression of ovarian sex hormones, may reduce fibroid-associated bleeding. METHODS We conducted two identical, double-blind, randomized, placebo-controlled, 6-month phase 3 trials (Elaris Uterine

    更新日期:2020-01-23
  • Teprotumumab for the Treatment of Active Thyroid Eye Disease.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-01-23
    Raymond S Douglas,George J Kahaly,Amy Patel,Saba Sile,Elizabeth H Z Thompson,Renee Perdok,James C Fleming,Brian T Fowler,Claudio Marcocci,Michele Marinò,Alessandro Antonelli,Roger Dailey,Gerald J Harris,Anja Eckstein,Jade Schiffman,Rosa Tang,Christine Nelson,Mario Salvi,Sara Wester,Jeffrey W Sherman,Thomas Vescio,Robert J Holt,Terry J Smith

    BACKGROUND Thyroid eye disease is a debilitating, disfiguring, and potentially blinding periocular condition for which no Food and Drug Administration-approved medical therapy is available. Strong evidence has implicated the insulin-like growth factor I receptor (IGF-IR) in the pathogenesis of this disease. METHODS In a randomized, double-masked, placebo-controlled, phase 3 multicenter trial, we assigned

    更新日期:2020-01-23
  • Trial of Anifrolumab in Active Systemic Lupus Erythematosus.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2019-12-18
    Eric F Morand,Richard Furie,Yoshiya Tanaka,Ian N Bruce,Anca D Askanase,Christophe Richez,Sang-Cheol Bae,Philip Z Brohawn,Lilia Pineda,Anna Berglind,Raj Tummala,

    BACKGROUND Anifrolumab, a human monoclonal antibody to type I interferon receptor subunit 1 investigated for the treatment of systemic lupus erythematosus (SLE), did not have a significant effect on the primary end point in a previous phase 3 trial. The current phase 3 trial used a secondary end point from that trial as the primary end point. METHODS We randomly assigned patients in a 1:1 ratio to

    更新日期:2020-01-16
  • A Randomized Trial of Erythropoietin for Neuroprotection in Preterm Infants.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-01-16
    Sandra E Juul,Bryan A Comstock,Rajan Wadhawan,Dennis E Mayock,Sherry E Courtney,Tonya Robinson,Kaashif A Ahmad,Ellen Bendel-Stenzel,Mariana Baserga,Edmund F LaGamma,L Corbin Downey,Raghavendra Rao,Nancy Fahim,Andrea Lampland,Ivan D Frantz Iii,Janine Y Khan,Michael Weiss,Maureen M Gilmore,Robin K Ohls,Nishant Srinivasan,Jorge E Perez,Victor McKay,Phuong T Vu,Jean Lowe,Karl Kuban,T Michael O'Shea,Adam

    BACKGROUND High-dose erythropoietin has been shown to have a neuroprotective effect in preclinical models of neonatal brain injury, and phase 2 trials have suggested possible efficacy; however, the benefits and safety of this therapy in extremely preterm infants have not been established. METHODS In this multicenter, randomized, double-blind trial of high-dose erythropoietin, we assigned 941 infants

    更新日期:2020-01-16
  • Lipoprotein(a) Reduction in Persons with Cardiovascular Disease.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-01-01
    Sotirios Tsimikas,Ewa Karwatowska-Prokopczuk,Ioanna Gouni-Berthold,Jean-Claude Tardif,Seth J Baum,Elizabeth Steinhagen-Thiessen,Michael D Shapiro,Erik S Stroes,Patrick M Moriarty,Børge G Nordestgaard,Shuting Xia,Jonathan Guerriero,Nicholas J Viney,Louis O'Dea,Joseph L Witztum,

    BACKGROUND Lipoprotein(a) levels are genetically determined and, when elevated, are a risk factor for cardiovascular disease and aortic stenosis. There are no approved pharmacologic therapies to lower lipoprotein(a) levels. METHODS We conducted a randomized, double-blind, placebo-controlled, dose-ranging trial involving 286 patients with established cardiovascular disease and screening lipoprotein(a)

    更新日期:2020-01-16
  • JAK Inhibitor Therapy in a Child with Inherited USP18 Deficiency.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-01-16
    Fahad Alsohime,Marta Martin-Fernandez,Mohamad-Hani Temsah,Majed Alabdulhafid,Tom Le Voyer,Malak Alghamdi,Xueer Qiu,Najla Alotaibi,Areej Alkahtani,Sofija Buta,Emmanuelle Jouanguy,Ayman Al-Eyadhy,Conor Gruber,Gamal M Hasan,Fahad A Bashiri,Rabih Halwani,Hamdy H Hassan,Saleh Al-Muhsen,Nouf Alkhamis,Zobaida Alsum,Jean-Laurent Casanova,Jacinta Bustamante,Dusan Bogunovic,Abdullah A Alangari

    Deficiency of ubiquitin-specific peptidase 18 (USP18) is a severe type I interferonopathy. USP18 down-regulates type I interferon signaling by blocking the access of Janus-associated kinase 1 (JAK1) to the type I interferon receptor. The absence of USP18 results in unmitigated interferon-mediated inflammation and is lethal during the perinatal period. We describe a neonate who presented with hydrocephalus

    更新日期:2020-01-16
  • Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-01-09
    Pierre Fenaux,Uwe Platzbecker,Ghulam J Mufti,Guillermo Garcia-Manero,Rena Buckstein,Valeria Santini,María Díez-Campelo,Carlo Finelli,Mario Cazzola,Osman Ilhan,Mikkael A Sekeres,José F Falantes,Beatriz Arrizabalaga,Flavia Salvi,Valentina Giai,Paresh Vyas,David Bowen,Dominik Selleslag,Amy E DeZern,Joseph G Jurcic,Ulrich Germing,Katharina S Götze,Bruno Quesnel,Odile Beyne-Rauzy,Thomas Cluzeau,Maria-Teresa

    BACKGROUND Patients with anemia and lower-risk myelodysplastic syndromes in whom erythropoiesis-stimulating agent therapy is not effective generally become dependent on red-cell transfusions. Luspatercept, a recombinant fusion protein that binds transforming growth factor β superfamily ligands to reduce SMAD2 and SMAD3 signaling, showed promising results in a phase 2 study. METHODS In a double-blind

    更新日期:2020-01-09
  • A Comparison of Two LDL Cholesterol Targets after Ischemic Stroke.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2019-11-18
    Pierre Amarenco,Jong S Kim,Julien Labreuche,Hugo Charles,Jérémie Abtan,Yannick Béjot,Lucie Cabrejo,Jae-Kwan Cha,Grégory Ducrocq,Maurice Giroud,Celine Guidoux,Cristina Hobeanu,Yong-Jae Kim,Bertrand Lapergue,Philippa C Lavallée,Byung-Chul Lee,Kyung-Bok Lee,Didier Leys,Marie-Hélène Mahagne,Elena Meseguer,Norbert Nighoghossian,Fernando Pico,Yves Samson,Igor Sibon,P Gabriel Steg,Sang-Min Sung,Pierre-Jean

    BACKGROUND The use of intensive lipid-lowering therapy by means of statin medications is recommended after transient ischemic attack (TIA) and ischemic stroke of atherosclerotic origin. The target level for low-density lipoprotein (LDL) cholesterol to reduce cardiovascular events after stroke has not been well studied. METHODS In this parallel-group trial conducted in France and South Korea, we randomly

    更新日期:2020-01-02
  • Alcohol Abstinence in Drinkers with Atrial Fibrillation.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-01-02
    Aleksandr Voskoboinik,Jonathan M Kalman,Anurika De Silva,Thomas Nicholls,Benedict Costello,Shane Nanayakkara,Sandeep Prabhu,Dion Stub,Sonia Azzopardi,Donna Vizi,Geoffrey Wong,Chrishan Nalliah,Hariharan Sugumar,Michael Wong,Emily Kotschet,David Kaye,Andrew J Taylor,Peter M Kistler

    BACKGROUND Excessive alcohol consumption is associated with incident atrial fibrillation and adverse atrial remodeling; however, the effect of abstinence from alcohol on secondary prevention of atrial fibrillation is unclear. METHODS We conducted a multicenter, prospective, open-label, randomized, controlled trial at six hospitals in Australia. Adults who consumed 10 or more standard drinks (with 1

    更新日期:2020-01-02
  • Multiyear Follow-up of AAV5-hFVIII-SQ Gene Therapy for Hemophilia A.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2020-01-02
    K John Pasi,Savita Rangarajan,Nina Mitchell,Will Lester,Emily Symington,Bella Madan,Michael Laffan,Chris B Russell,Mingjin Li,Glenn F Pierce,Wing Y Wong

    BACKGROUND Adeno-associated virus (AAV)-mediated gene therapy is under investigation as a therapeutic option for persons with hemophilia A. Efficacy and safety data include 3 years of follow-up after a single administration of AAV5-hFVIII-SQ. METHODS We report durable efficacy, long-term safety, and clinical and biologic results in 15 adults with severe hemophilia A (factor VIII level, ≤1 IU per deciliter)

    更新日期:2020-01-02
  • Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2019-11-21
    Suresh S Ramalingam,Johan Vansteenkiste,David Planchard,Byoung Chul Cho,Jhanelle E Gray,Yuichiro Ohe,Caicun Zhou,Thanyanan Reungwetwattana,Ying Cheng,Busyamas Chewaskulyong,Riyaz Shah,Manuel Cobo,Ki Hyeong Lee,Parneet Cheema,Marcello Tiseo,Thomas John,Meng-Chih Lin,Fumio Imamura,Takayasu Kurata,Alexander Todd,Rachel Hodge,Matilde Saggese,Yuri Rukazenkov,Jean-Charles Soria,

    BACKGROUND Osimertinib is a third-generation, irreversible tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR-TKI) that selectively inhibits both EGFR-TKI-sensitizing and EGFR T790M resistance mutations. A phase 3 trial compared first-line osimertinib with other EGFR-TKIs in patients with EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC). The trial showed longer

    更新日期:2020-01-02
  • Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2019-11-16
    Jean-Claude Tardif,Simon Kouz,David D Waters,Olivier F Bertrand,Rafael Diaz,Aldo P Maggioni,Fausto J Pinto,Reda Ibrahim,Habib Gamra,Ghassan S Kiwan,Colin Berry,José López-Sendón,Petr Ostadal,Wolfgang Koenig,Denis Angoulvant,Jean C Grégoire,Marc-André Lavoie,Marie-Pierre Dubé,David Rhainds,Mylène Provencher,Lucie Blondeau,Andreas Orfanos,Philippe L L'Allier,Marie-Claude Guertin,François Roubille

    BACKGROUND Experimental and clinical evidence supports the role of inflammation in atherosclerosis and its complications. Colchicine is an orally administered, potent antiinflammatory medication that is indicated for the treatment of gout and pericarditis. METHODS We performed a randomized, double-blind trial involving patients recruited within 30 days after a myocardial infarction. The patients were

    更新日期:2019-12-26
  • Cabazitaxel versus Abiraterone or Enzalutamide in Metastatic Prostate Cancer.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2019-09-30
    Ronald de Wit,Johann de Bono,Cora N Sternberg,Karim Fizazi,Bertrand Tombal,Christian Wülfing,Gero Kramer,Jean-Christophe Eymard,Aristotelis Bamias,Joan Carles,Roberto Iacovelli,Bohuslav Melichar,Ásgerður Sverrisdóttir,Christine Theodore,Susan Feyerabend,Carole Helissey,Ayse Ozatilgan,Christine Geffriaud-Ricouard,Daniel Castellano,

    BACKGROUND The efficacy and safety of cabazitaxel, as compared with an androgen-signaling-targeted inhibitor (abiraterone or enzalutamide), in patients with metastatic castration-resistant prostate cancer who were previously treated with docetaxel and had progression within 12 months while receiving the alternative inhibitor (abiraterone or enzalutamide) are unclear. METHODS We randomly assigned, in

    更新日期:2019-12-26
  • Schistosomiasis - Assessing Progress toward the 2020 and 2025 Global Goals.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2019-12-26
    Arminder K Deol,Fiona M Fleming,Beatriz Calvo-Urbano,Martin Walker,Victor Bucumi,Issah Gnandou,Edridah M Tukahebwa,Samuel Jemu,Upendo J Mwingira,Abdulhakeem Alkohlani,Mahamadou Traoré,Eugene Ruberanziza,Seydou Touré,Maria-Gloria Basáñez,Michael D French,Joanne P Webster

    BACKGROUND With the vision of "a world free of schistosomiasis," the World Health Organization (WHO) set ambitious goals of control of this debilitating disease and its elimination as a public health problem by 2020 and 2025, respectively. As these milestones become imminent, and if programs are to succeed, it is important to evaluate the WHO programmatic guidelines empirically. METHODS We collated

    更新日期:2019-12-26
  • Early High-Dose Vitamin D3 for Critically Ill, Vitamin D-Deficient Patients.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2019-12-11
    ,Adit A Ginde,Roy G Brower,Jeffrey M Caterino,Lani Finck,Valerie M Banner-Goodspeed,Colin K Grissom,Douglas Hayden,Catherine L Hough,Robert C Hyzy,Akram Khan,Joseph E Levitt,Pauline K Park,Nancy Ringwood,Emanuel P Rivers,Wesley H Self,Nathan I Shapiro,B Taylor Thompson,Donald M Yealy,Daniel Talmor

    BACKGROUND Vitamin D deficiency is a common, potentially reversible contributor to morbidity and mortality among critically ill patients. The potential benefits of vitamin D supplementation in acute critical illness require further study. METHODS We conducted a randomized, double-blind, placebo-controlled, phase 3 trial of early vitamin D3 supplementation in critically ill, vitamin D-deficient patients

    更新日期:2019-12-26
  • Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2019-09-28
    Antonio González-Martín,Bhavana Pothuri,Ignace Vergote,René DePont Christensen,Whitney Graybill,Mansoor R Mirza,Colleen McCormick,Domenica Lorusso,Paul Hoskins,Gilles Freyer,Klaus Baumann,Kris Jardon,Andrés Redondo,Richard G Moore,Christof Vulsteke,Roisin E O'Cearbhaill,Bente Lund,Floor Backes,Pilar Barretina-Ginesta,Ashley F Haggerty,Maria J Rubio-Pérez,Mark S Shahin,Giorgia Mangili,William H Bradley

    BACKGROUND Niraparib, an inhibitor of poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP), has been associated with significantly increased progression-free survival among patients with recurrent ovarian cancer after platinum-based chemotherapy, regardless of the presence or absence of BRCA mutations. The efficacy of niraparib in patients with newly diagnosed advanced ovarian cancer after a

    更新日期:2019-12-19
  • Veliparib with First-Line Chemotherapy and as Maintenance Therapy in Ovarian Cancer.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2019-09-28
    Robert L Coleman,Gini F Fleming,Mark F Brady,Elizabeth M Swisher,Karina D Steffensen,Michael Friedlander,Aikou Okamoto,Kathleen N Moore,Noa Efrat Ben-Baruch,Theresa L Werner,Noelle G Cloven,Ana Oaknin,Paul A DiSilvestro,Mark A Morgan,Joo-Hyun Nam,Charles A Leath,Shibani Nicum,Andrea R Hagemann,Ramey D Littell,David Cella,Sally Baron-Hay,Jesus Garcia-Donas,Mika Mizuno,Katherine Bell-McGuinn,Danielle

    BACKGROUND Data are limited regarding the use of poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors, such as veliparib, in combination with chemotherapy followed by maintenance as initial treatment in patients with high-grade serous ovarian carcinoma. METHODS In an international, phase 3, placebo-controlled trial, we assessed the efficacy of veliparib added to first-line induction chemotherapy

    更新日期:2019-12-19
  • Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2019-12-19
    Isabelle Ray-Coquard,Patricia Pautier,Sandro Pignata,David Pérol,Antonio González-Martín,Regina Berger,Keiichi Fujiwara,Ignace Vergote,Nicoletta Colombo,Johanna Mäenpää,Frédéric Selle,Jalid Sehouli,Domenica Lorusso,Eva M Guerra Alía,Alexander Reinthaller,Shoji Nagao,Claudia Lefeuvre-Plesse,Ulrich Canzler,Giovanni Scambia,Alain Lortholary,Frederik Marmé,Pierre Combe,Nikolaus de Gregorio,Manuel Rodrigues

    BACKGROUND Olaparib has shown significant clinical benefit as maintenance therapy in women with newly diagnosed advanced ovarian cancer with a BRCA mutation. The effect of combining maintenance olaparib and bevacizumab in patients regardless of BRCA mutation status is unknown. METHODS We conducted a randomized, double-blind, international phase 3 trial. Eligible patients had newly diagnosed, advanced

    更新日期:2019-12-19
  • Final Analysis of a Trial of M72/AS01E Vaccine to Prevent Tuberculosis.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2019-10-29
    Dereck R Tait,Mark Hatherill,Olivier Van Der Meeren,Ann M Ginsberg,Elana Van Brakel,Bruno Salaun,Thomas J Scriba,Elaine J Akite,Helen M Ayles,Anne Bollaerts,Marie-Ange Demoitié,Andreas Diacon,Thomas G Evans,Paul Gillard,Elizabeth Hellström,James C Innes,Maria Lempicki,Mookho Malahleha,Neil Martinson,Doris Mesia Vela,Monde Muyoyeta,Videlis Nduba,Thierry G Pascal,Michele Tameris,Friedrich Thienemann

    BACKGROUND Results of an earlier analysis of a trial of the M72/AS01E candidate vaccine against Mycobacterium tuberculosis showed that in infected adults, the vaccine provided 54.0% protection against active pulmonary tuberculosis disease, without evident safety concerns. We now report the results of the 3-year final analysis of efficacy, safety, and immunogenicity. METHODS From August 2014 through

    更新日期:2019-12-19
  • A Randomized, Controlled Trial of Ebola Virus Disease Therapeutics.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2019-11-27
    Sabue Mulangu,Lori E Dodd,Richard T Davey,Olivier Tshiani Mbaya,Michael Proschan,Daniel Mukadi,Mariano Lusakibanza Manzo,Didier Nzolo,Antoine Tshomba Oloma,Augustin Ibanda,Rosine Ali,Sinaré Coulibaly,Adam C Levine,Rebecca Grais,Janet Diaz,H Clifford Lane,Jean-Jacques Muyembe-Tamfum,,Billy Sivahera,Modet Camara,Richard Kojan,Robert Walker,Bonnie Dighero-Kemp,Huyen Cao,Philippe Mukumbayi,Placide Mbala-Kingebeni

    BACKGROUND Although several experimental therapeutics for Ebola virus disease (EVD) have been developed, the safety and efficacy of the most promising therapies need to be assessed in the context of a randomized, controlled trial. METHODS We conducted a trial of four investigational therapies for EVD in the Democratic Republic of Congo, where an outbreak began in August 2018. Patients of any age who

    更新日期:2019-12-13
  • Metoprolol for the Prevention of Acute Exacerbations of COPD.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2019-10-20
    Mark T Dransfield,Helen Voelker,Surya P Bhatt,Keith Brenner,Richard Casaburi,Carolyn E Come,J Allen D Cooper,Gerard J Criner,Jeffrey L Curtis,MeiLan K Han,Umur Hatipoğlu,Erika S Helgeson,Vipul V Jain,Ravi Kalhan,David Kaminsky,Robert Kaner,Ken M Kunisaki,Allison A Lambert,Matthew R Lammi,Sarah Lindberg,Barry J Make,Fernando J Martinez,Charlene McEvoy,Ralph J Panos,Robert M Reed,Paul D Scanlon,Frank

    BACKGROUND Observational studies suggest that beta-blockers may reduce the risk of exacerbations and death in patients with moderate or severe chronic obstructive pulmonary disease (COPD), but these findings have not been confirmed in randomized trials. METHODS In this prospective, randomized trial, we assigned patients between the ages of 40 and 85 years who had COPD to receive either a beta-blocker

    更新日期:2019-12-13
  • Asciminib in Chronic Myeloid Leukemia after ABL Kinase Inhibitor Failure.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2019-12-12
    Timothy P Hughes,Michael J Mauro,Jorge E Cortes,Hironobu Minami,Delphine Rea,Daniel J DeAngelo,Massimo Breccia,Yeow-Tee Goh,Moshe Talpaz,Andreas Hochhaus,Philipp le Coutre,Oliver Ottmann,Michael C Heinrich,Juan L Steegmann,Michael W N Deininger,Jeroen J W M Janssen,Francois-Xavier Mahon,Yosuke Minami,David Yeung,David M Ross,Martin S Tallman,Jae H Park,Brian J Druker,David Hynds,Yuyan Duan,Christophe

    BACKGROUND Asciminib is an allosteric inhibitor that binds a myristoyl site of the BCR-ABL1 protein, locking BCR-ABL1 into an inactive conformation through a mechanism distinct from those for all other ABL kinase inhibitors. Asciminib targets both native and mutated BCR-ABL1, including the gatekeeper T315I mutant. The safety and antileukemic activity of asciminib in patients with Philadelphia chromosome-positive

    更新日期:2019-12-13
  • Targeted Temperature Management for Cardiac Arrest with Nonshockable Rhythm.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2019-10-02
    Jean-Baptiste Lascarrou,Hamid Merdji,Amélie Le Gouge,Gwenhael Colin,Guillaume Grillet,Patrick Girardie,Elisabeth Coupez,Pierre-François Dequin,Alain Cariou,Thierry Boulain,Noelle Brule,Jean-Pierre Frat,Pierre Asfar,Nicolas Pichon,Mickael Landais,Gaëtan Plantefeve,Jean-Pierre Quenot,Jean-Charles Chakarian,Michel Sirodot,Stéphane Legriel,Julien Letheulle,Didier Thevenin,Arnaud Desachy,Arnaud Delahaye

    BACKGROUND Moderate therapeutic hypothermia is currently recommended to improve neurologic outcomes in adults with persistent coma after resuscitated out-of-hospital cardiac arrest. However, the effectiveness of moderate therapeutic hypothermia in patients with nonshockable rhythms (asystole or pulseless electrical activity) is debated. METHODS We performed an open-label, randomized, controlled trial

    更新日期:2019-12-13
  • Total Hip Arthroplasty or Hemiarthroplasty for Hip Fracture.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2019-09-26
    ,Mohit Bhandari,Thomas A Einhorn,Gordon Guyatt,Emil H Schemitsch,Robert D Zura,Sheila Sprague,Frede Frihagen,Ernesto Guerra-Farfán,Ydo V Kleinlugtenbelt,Rudolf W Poolman,Amar Rangan,Sofia Bzovsky,Diane Heels-Ansdell,Lehana Thabane,Stephen D Walter,P J Devereaux

    BACKGROUND Globally, hip fractures are among the top 10 causes of disability in adults. For displaced femoral neck fractures, there remains uncertainty regarding the effect of a total hip arthroplasty as compared with hemiarthroplasty. METHODS We randomly assigned 1495 patients who were 50 years of age or older and had a displaced femoral neck fracture to undergo either total hip arthroplasty or hemiarthroplasty

    更新日期:2019-12-05
  • Phase 3 Efficacy Analysis of a Typhoid Conjugate Vaccine Trial in Nepal.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2019-12-05
    Mila Shakya,Rachel Colin-Jones,Katherine Theiss-Nyland,Merryn Voysey,Dikshya Pant,Nicola Smith,Xinxue Liu,Susan Tonks,Olga Mazur,Yama G Farooq,Jenny Clarke,Jennifer Hill,Anup Adhikari,Sabina Dongol,Abhilasha Karkey,Binod Bajracharya,Sarah Kelly,Meeru Gurung,Stephen Baker,Kathleen M Neuzil,Shrijana Shrestha,Buddha Basnyat,Andrew J Pollard,

    BACKGROUND Salmonella Typhi is a major cause of fever in children in low- and middle-income countries. A typhoid conjugate vaccine (TCV) that was recently prequalified by the World Health Organization was shown to be efficacious in a human challenge model, but data from efficacy trials in areas where typhoid is endemic are lacking. METHODS In this phase 3, randomized, controlled trial in Lalitpur,

    更新日期:2019-12-05
  • Endoscopic or Surgical Myotomy in Patients with Idiopathic Achalasia.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2019-12-05
    Yuki B Werner,Bengt Hakanson,Jan Martinek,Alessandro Repici,Burkhard H A von Rahden,Albert J Bredenoord,Raf Bisschops,Helmut Messmann,Marius C Vollberg,Tania Noder,Jan F Kersten,Oliver Mann,Jakob Izbicki,Alexander Pazdro,Uberto Fumagalli,Riccardo Rosati,Christoph-Thomas Germer,Marlies P Schijven,Alice Emmermann,Daniel von Renteln,Paul Fockens,Guy Boeckxstaens,Thomas Rösch

    BACKGROUND Pneumatic dilation and laparoscopic Heller's myotomy (LHM) are established treatments for idiopathic achalasia. Peroral endoscopic myotomy (POEM) is a less invasive therapy with promising early study results. METHODS In a multicenter, randomized trial, we compared POEM with LHM plus Dor's fundoplication in patients with symptomatic achalasia. The primary end point was clinical success, defined

    更新日期:2019-12-05
  • Ubrogepant for the Treatment of Migraine.
    N. Engl. J. Med. (IF 70.67) Pub Date : 2019-12-05
    David W Dodick,Richard B Lipton,Jessica Ailani,Kaifeng Lu,Michelle Finnegan,Joel M Trugman,Armin Szegedi

    BACKGROUND Ubrogepant is an oral, small-molecule calcitonin gene-related peptide receptor antagonist for acute migraine treatment. METHODS We conducted a randomized trial to evaluate the efficacy, safety, and side-effect profile of ubrogepant. We assigned adults with migraine, with or without aura, in a 1:1:1 ratio to receive an initial dose of placebo, ubrogepant at a dose of 50 mg, or ubrogepant

    更新日期:2019-12-05
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