{"title":"Clonal Hematopoiesis as a Driver of Solid Tumors.","authors":"Lachelle D Weeks,Benjamin L Ebert","doi":"10.1056/nejme2504775","DOIUrl":"https://doi.org/10.1056/nejme2504775","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"7 1","pages":"1654-1656"},"PeriodicalIF":158.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143871969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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
BACKGROUNDBaloxavir 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.METHODSWe conducted a multicountry, phase 3b trial to assess the efficacy of single-dose baloxavir treatment to reduce influenza transmission from index patients to household contacts. Influenza-positive index patients 5 to 64 years of age were randomly assigned in a 1:1 ratio to receive baloxavir or placebo within 48 hours after symptom onset. The primary end point was transmission of influenza virus from an index patient to a household contact by day 5. The first secondary end point was transmission of influenza virus by day 5 that resulted in symptoms.RESULTSOverall, 1457 index patients and 2681 household contacts were enrolled across the 2019-2024 influenza seasons; 726 index patients were assigned to the baloxavir group, and 731 to the placebo group. By day 5, transmission of laboratory-confirmed influenza was significantly lower with baloxavir than with placebo (adjusted incidence, 9.5% vs. 13.4%; adjusted odds ratio, 0.68; 95.38% confidence interval [CI], 0.50 to 0.93; P = 0.01), with an adjusted relative risk reduction of 29% (95.38% CI, 12 to 45). The adjusted incidence of transmission of influenza virus by day 5 that resulted in symptoms was 5.8% with baloxavir and 7.6% with placebo; however, the difference was not significant (adjusted odds ratio, 0.75; 95.38% CI, 0.50 to 1.12; P = 0.16). Emergence of drug-resistant viruses during the follow-up period occurred in 7.2% (95% CI, 4.1 to 11.6) of the index patients in the baloxavir group; no resistant viruses were detected in household contacts. No new safety signals were identified.CONCLUSIONSTreatment with a single oral dose of baloxavir led to a lower incidence of transmission of influenza virus to close contacts than placebo. (Funded by F. Hoffmann-La Roche and others; CENTERSTONE ClinicalTrials.gov number, NCT03969212.).
{"title":"Efficacy of Baloxavir Treatment in Preventing Transmission of Influenza.","authors":"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","doi":"10.1056/nejmoa2413156","DOIUrl":"https://doi.org/10.1056/nejmoa2413156","url":null,"abstract":"BACKGROUNDBaloxavir 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.METHODSWe conducted a multicountry, phase 3b trial to assess the efficacy of single-dose baloxavir treatment to reduce influenza transmission from index patients to household contacts. Influenza-positive index patients 5 to 64 years of age were randomly assigned in a 1:1 ratio to receive baloxavir or placebo within 48 hours after symptom onset. The primary end point was transmission of influenza virus from an index patient to a household contact by day 5. The first secondary end point was transmission of influenza virus by day 5 that resulted in symptoms.RESULTSOverall, 1457 index patients and 2681 household contacts were enrolled across the 2019-2024 influenza seasons; 726 index patients were assigned to the baloxavir group, and 731 to the placebo group. By day 5, transmission of laboratory-confirmed influenza was significantly lower with baloxavir than with placebo (adjusted incidence, 9.5% vs. 13.4%; adjusted odds ratio, 0.68; 95.38% confidence interval [CI], 0.50 to 0.93; P = 0.01), with an adjusted relative risk reduction of 29% (95.38% CI, 12 to 45). The adjusted incidence of transmission of influenza virus by day 5 that resulted in symptoms was 5.8% with baloxavir and 7.6% with placebo; however, the difference was not significant (adjusted odds ratio, 0.75; 95.38% CI, 0.50 to 1.12; P = 0.16). Emergence of drug-resistant viruses during the follow-up period occurred in 7.2% (95% CI, 4.1 to 11.6) of the index patients in the baloxavir group; no resistant viruses were detected in household contacts. No new safety signals were identified.CONCLUSIONSTreatment with a single oral dose of baloxavir led to a lower incidence of transmission of influenza virus to close contacts than placebo. (Funded by F. Hoffmann-La Roche and others; CENTERSTONE ClinicalTrials.gov number, NCT03969212.).","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"24 1","pages":"1582-1593"},"PeriodicalIF":158.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Tirzepatide for Heart Failure and Obesity.","authors":"Joseph E Marine,John Mandrola,Vinay Prasad","doi":"10.1056/nejmc2502743","DOIUrl":"https://doi.org/10.1056/nejmc2502743","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"14 1","pages":"1660"},"PeriodicalIF":158.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143871970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Case 12-2025: A 56-Year-Old Woman with Sore Throat and Rash.","authors":"John Trinidad,Kimon C Zachary,Ting Zhao","doi":"10.1056/nejmcpc2412522","DOIUrl":"https://doi.org/10.1056/nejmcpc2412522","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"5 1","pages":"1637-1645"},"PeriodicalIF":158.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143871991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kalli G Koukounas,Meehir N Dixit,Rebecca Thorsness,Rachel E Patzer,Adam S Wilk,Kelsey M Drewry,Rajnish Mehrotra,Maricruz Rivera-Hernandez,David J Meyers,Daeho Kim,Ankur D Shah,Christopher H Schmid,Amal N Trivedi
{"title":"Performance of Dialysis Facilities after Health-Equity Scoring Incentive.","authors":"Kalli G Koukounas,Meehir N Dixit,Rebecca Thorsness,Rachel E Patzer,Adam S Wilk,Kelsey M Drewry,Rajnish Mehrotra,Maricruz Rivera-Hernandez,David J Meyers,Daeho Kim,Ankur D Shah,Christopher H Schmid,Amal N Trivedi","doi":"10.1056/nejmc2413208","DOIUrl":"https://doi.org/10.1056/nejmc2413208","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"69 1","pages":"1657-1659"},"PeriodicalIF":158.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Timothy M Uyeki,Vivien G Dugan,Demetre C Daskalakis
{"title":"Baloxavir Treatment to Reduce Influenza Virus Transmission.","authors":"Timothy M Uyeki,Vivien G Dugan,Demetre C Daskalakis","doi":"10.1056/nejme2503242","DOIUrl":"https://doi.org/10.1056/nejme2503242","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"258 1","pages":"1652-1654"},"PeriodicalIF":158.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Brensocatib in Bronchiectasis - A New Sheriff in Town?","authors":"Scott C Bell,Keith Grimwood","doi":"10.1056/nejme2502618","DOIUrl":"https://doi.org/10.1056/nejme2502618","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"69 1","pages":"1647-1648"},"PeriodicalIF":158.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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
BACKGROUNDMetachromatic leukodystrophy (MLD) is an ultrarare, severe lysosomal storage disorder caused by a deficiency of arylsulfatase A (ARSA).METHODSWe treated patients who had MLD with atidarsagene autotemcel (arsa-cel), a hematopoietic stem-cell-based gene therapy, in two prospective open-label clinical studies and expanded-access programs. We compared their outcomes with those of untreated patients (natural history cohort). The primary end point was survival free from severe motor impairment (the time from birth to the first occurrence of loss of locomotion and of sitting without support or death from any cause).RESULTSA total of 39 treated patients and 49 untreated patients were included. The median follow-up was 6.76 years (range, 0.64 to 12.19). Arsa-cel resulted in a significantly lower risk of severe motor impairment or death than no treatment among patients with presymptomatic late-infantile MLD (P<0.001), those with presymptomatic early-juvenile MLD (P = 0.04), and those with early-symptomatic early-juvenile MLD (P<0.001). The estimated percentage of patients surviving without severe motor impairment at 6 years of age was 0% (95% confidence interval [CI], not evaluable) among untreated patients with late-infantile MLD and 100% (95% CI, 100 to 100) among treated patients with presymptomatic late-infantile MLD. The estimated percentage of patients surviving without severe motor impairment at 10 years of age was 11.2% (95% CI, 0.9 to 36.4) among untreated patients with early-juvenile MLD and 87.5% (95% CI, 38.7 to 98.1) and 80.0% (95% CI, 40.9 to 94.6) among treated patients with presymptomatic and early-symptomatic early-juvenile MLD, respectively. No evidence of insertional oncogenesis was found. The most common grade 3 or higher adverse event was febrile neutropenia. Anti-ARSA antibodies were detected transiently in 6 of 39 patients (15%). Three deaths occurred, all of which were considered by the investigators to be unrelated to arsa-cel.CONCLUSIONSAmong patients with presymptomatic late-infantile or early-juvenile MLD and those with early-symptomatic early-juvenile MLD, the risk of severe motor impairment or death was significantly lower among those who received treatment with arsa-cel than in a natural history cohort that did not receive treatment. (Funded by Orchard Therapeutics and others; ClinicalTrials.gov numbers, NCT01560182 and NCT03392987.).
{"title":"Long-Term Effects of Atidarsagene Autotemcel for Metachromatic Leukodystrophy.","authors":"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","doi":"10.1056/nejmoa2405727","DOIUrl":"https://doi.org/10.1056/nejmoa2405727","url":null,"abstract":"BACKGROUNDMetachromatic leukodystrophy (MLD) is an ultrarare, severe lysosomal storage disorder caused by a deficiency of arylsulfatase A (ARSA).METHODSWe treated patients who had MLD with atidarsagene autotemcel (arsa-cel), a hematopoietic stem-cell-based gene therapy, in two prospective open-label clinical studies and expanded-access programs. We compared their outcomes with those of untreated patients (natural history cohort). The primary end point was survival free from severe motor impairment (the time from birth to the first occurrence of loss of locomotion and of sitting without support or death from any cause).RESULTSA total of 39 treated patients and 49 untreated patients were included. The median follow-up was 6.76 years (range, 0.64 to 12.19). Arsa-cel resulted in a significantly lower risk of severe motor impairment or death than no treatment among patients with presymptomatic late-infantile MLD (P<0.001), those with presymptomatic early-juvenile MLD (P = 0.04), and those with early-symptomatic early-juvenile MLD (P<0.001). The estimated percentage of patients surviving without severe motor impairment at 6 years of age was 0% (95% confidence interval [CI], not evaluable) among untreated patients with late-infantile MLD and 100% (95% CI, 100 to 100) among treated patients with presymptomatic late-infantile MLD. The estimated percentage of patients surviving without severe motor impairment at 10 years of age was 11.2% (95% CI, 0.9 to 36.4) among untreated patients with early-juvenile MLD and 87.5% (95% CI, 38.7 to 98.1) and 80.0% (95% CI, 40.9 to 94.6) among treated patients with presymptomatic and early-symptomatic early-juvenile MLD, respectively. No evidence of insertional oncogenesis was found. The most common grade 3 or higher adverse event was febrile neutropenia. Anti-ARSA antibodies were detected transiently in 6 of 39 patients (15%). Three deaths occurred, all of which were considered by the investigators to be unrelated to arsa-cel.CONCLUSIONSAmong patients with presymptomatic late-infantile or early-juvenile MLD and those with early-symptomatic early-juvenile MLD, the risk of severe motor impairment or death was significantly lower among those who received treatment with arsa-cel than in a natural history cohort that did not receive treatment. (Funded by Orchard Therapeutics and others; ClinicalTrials.gov numbers, NCT01560182 and NCT03392987.).","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"7 1","pages":"1609-1620"},"PeriodicalIF":158.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Defanging the Neutrophil to Treat Bronchiectasis.","authors":"Adam T Hill","doi":"10.1056/nejme2500787","DOIUrl":"https://doi.org/10.1056/nejme2500787","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"26 1","pages":"1649-1652"},"PeriodicalIF":158.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Neonatal Fc Receptor - Biology and Therapeutics.","authors":"James B Bussel,Douglas B Cines,Richard S Blumberg","doi":"10.1056/nejmra2312718","DOIUrl":"https://doi.org/10.1056/nejmra2312718","url":null,"abstract":"","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"53 1","pages":"1621-1635"},"PeriodicalIF":158.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143871992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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