The Lancet最新文献

{"title":"Evaluating the benefits of the early use of GLP-1 receptor agonists","authors":"Peter-James H Zushin, Joseph C Wu","doi":"10.1016/s0140-6736(24)02255-4","DOIUrl":"https://doi.org/10.1016/s0140-6736(24)02255-4","url":null,"abstract":"No Abstract","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and efficacy of pembrolizumab, radiation therapy, and surgery versus radiation therapy and surgery for stage III soft tissue sarcoma of the extremity (SU2C-SARC032): an open-label, randomised clinical trial","authors":"Yvonne M Mowery, Karla V Ballman, Angela M Hong, Scott M Schuetze, Andrew J Wagner, Varun Monga, Rachel S Heise, Steven Attia, Edwin Choy, Melissa A Burgess, Susie Bae, David I Pryor, Brian A Van Tine, Gabriel Tinoco, Bartosz Chmielowski, Carolyn Freeman, Alessandro Gronchi, Christian F Meyer, Mark A Dickson, Lee Hartner, David G Kirsch","doi":"10.1016/s0140-6736(24)01812-9","DOIUrl":"https://doi.org/10.1016/s0140-6736(24)01812-9","url":null,"abstract":"<h3>Background</h3>Approximately half of patients with localised, high-risk soft tissue sarcoma of the extremity develop metastases. We aimed to assess whether the addition of pembrolizumab to preoperative radiotherapy and surgery would improve disease-free survival.<h3>Methods</h3>We completed an open-label, randomised clinical trial in patients with grade 2 or 3, stage III undifferentiated pleomorphic sarcoma or dedifferentiated or pleomorphic liposarcoma of the extremity and limb girdle. Patients were enrolled at 20 academic institutions in Australia, Canada, Italy, and the USA. Patients were randomly assigned to preoperative radiotherapy then surgery (control group) or preoperative pembrolizumab with radiotherapy (initiated 1–14 days after the first dose of pembrolizumab) then surgery and postoperative pembrolizumab (experimental group). Pembrolizumab (200 mg intravenously every 3 weeks) was administered as three neoadjuvant cycles (before, during, and after radiotherapy) and 14 or less adjuvant cycles. Primary endpoint was disease-free survival. This study is registered with <span><span>ClincialTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span> (<span><span>NCT03092323</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>).<h3>Findings</h3>Between Nov 18, 2017, and Nov 14, 2023, 143 participants were randomly assigned to treatment. A modified intention-to-treat analysis of 127 patients with median follow-up of 43 months showed that the experimental group (n=64) had significantly longer disease-free survival than the control group (n=63; log-rank one-sided p=0·035; hazard ratio [HR] 0·61; 90% CI 0·39–0·96). The 2-year disease-free survival increased by 15% with addition of pembrolizumab: 52% (90% CI 42–64) and 67% (90% CI 58–78) for the control and experimental groups, respectively. Disease-free survival was similarly improved with pembrolizumab for the intention-to-treat patient population (HR 0·61 [90% CI 0·39–0·95]). Grade 3 or higher adverse events occurred more frequently in the experimental group (56%) than the control group (31%).<h3>Interpretation</h3>Addition of pembrolizumab to preoperative radiotherapy and surgery improves disease-free survival for patients with stage III undifferentiated pleomorphic sarcoma and pleomorphic or dedifferentiated liposarcoma of the extremity, which establishes a promising new treatment option for these patients.<h3>Funding</h3>Stand Up to Cancer and Merck Sharp &amp; Dohme.","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative medicine for the treatment of stroke","authors":"Simiao Wu","doi":"10.1016/s0140-6736(24)02257-8","DOIUrl":"https://doi.org/10.1016/s0140-6736(24)02257-8","url":null,"abstract":"No Abstract","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scientific consideration of sex and gender is the responsibility of the many, not the few","authors":"Alice Witt, Robyn Norton, Mark Woodward, Kate Womersley","doi":"10.1016/s0140-6736(24)02469-3","DOIUrl":"https://doi.org/10.1016/s0140-6736(24)02469-3","url":null,"abstract":"No Abstract","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"71 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142598520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mobilising the health community to protect health care from attack","authors":"Martin Chalfie, Leonard Rubenstein, Lujain Alqodmani, Georges C Benjamin, Pamela F Cipriano, Carlos del Rio, Victor J Dzau, Timothy Johnson, Robert S Lawrence, Michele Heisler","doi":"10.1016/s0140-6736(24)02421-8","DOIUrl":"https://doi.org/10.1016/s0140-6736(24)02421-8","url":null,"abstract":"No Abstract","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142598518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mexico Summit 20 years on—gains and challenges","authors":"Tikki Pang, Ulysses Panisset, Francisco Becerra-Posada, Julio Frenk","doi":"10.1016/s0140-6736(24)02354-7","DOIUrl":"https://doi.org/10.1016/s0140-6736(24)02354-7","url":null,"abstract":"No Abstract","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Betibeglogene autotemcel gene therapy in patients with transfusion-dependent, severe genotype β-thalassaemia (HGB-212): a non-randomised, multicentre, single-arm, open-label, single-dose, phase 3 trial","authors":"Janet L Kwiatkowski, Mark C Walters, Suradej Hongeng, Evangelia Yannaki, Andreas E Kulozik, Joachim B Kunz, Martin G Sauer, Adrian J Thrasher, Isabelle Thuret, Ashutosh Lal, Ge Tao, Shamshad Ali, Himal L Thakar, Heidi Elliot, Ankit Lodaya, Ji Lee, Richard A Colvin, Franco Locatelli, Alexis A Thompson","doi":"10.1016/s0140-6736(24)01884-1","DOIUrl":"https://doi.org/10.1016/s0140-6736(24)01884-1","url":null,"abstract":"&lt;h3&gt;Background&lt;/h3&gt;Transfusion-dependent β-thalassaemia (TDT) is a severe disease, resulting in lifelong blood transfusions, iron overload, and associated complications. Betibeglogene autotemcel (beti-cel) gene therapy uses autologous haematopoietic stem and progenitor cells (HSPCs) transduced with BB305 lentiviral vector to enable transfusion independence.&lt;h3&gt;Methods&lt;/h3&gt;HGB-212 was a non-randomised, multicentre, single-arm, open-label, phase 3 study of beti-cel in patients with TDT conducted at eight centres in France, Germany, Greece, Italy, the UK, and the USA. Patients with β&lt;sup&gt;0&lt;/sup&gt;/β&lt;sup&gt;0&lt;/sup&gt;, β&lt;sup&gt;0&lt;/sup&gt;/β&lt;sup&gt;+IVS-I-110&lt;/sup&gt;, or β&lt;sup&gt;+IVS-I-110&lt;/sup&gt;/β&lt;sup&gt;+IVS-I-110&lt;/sup&gt; genotypes, clinically stable TDT, and a transfusion history of at least 100 mL/kg per year of packed red blood cells (pRBCs) or at least eight transfusions of pRBCs per year in the 2 years before enrolment were eligible for participation. After undergoing HSPC mobilisation and busulfan-based, pharmacokinetic-adjusted myeloablative conditioning, patients were infused with beti-cel and followed up for 24 months. The primary efficacy outcome was transfusion independence, defined as weighted average haemoglobin level of 9 g/dL or above without pRBC transfusions for 12 or more months. The primary outcome was measured in all patients who received an infusion of beti-cel (transplant population); safety was evaluated in all patients who initiated study treatment (intention-to-treat population). Patients were eligible to enrol in the ongoing 13-year long-term follow-up study (for a total of 15 years), LTF-303 (registered at &lt;span&gt;&lt;span&gt;ClinicalTrials.gov&lt;/span&gt;&lt;svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"&gt;&lt;path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;NCT02633943&lt;/span&gt;&lt;svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"&gt;&lt;path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt;). This trial, HGB-212, was registered at &lt;span&gt;&lt;span&gt;ClinicalTrials.gov&lt;/span&gt;&lt;svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"&gt;&lt;path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt; (&lt;span&gt;&lt;span&gt;NCT03207009&lt;/span&gt;&lt;svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"&gt;&lt;path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt;), and is complete.&lt;h3&gt;Findings&lt;/h3&gt;From June 8, 2017, to March 12, 2020, 20 patients were screened for eligibility. One patient was ineligible and one withdrew consent before HSPC mobilisation and myeloablative conditioning. Of the 18 patients who received beti-cel, ten (56%) were male and eight (44%) were female; 13 (72%) were younger than 18 years at the time of i","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Japan's lonely deaths: a social epidemic","authors":"Megan Tatum","doi":"10.1016/s0140-6736(24)02470-x","DOIUrl":"https://doi.org/10.1016/s0140-6736(24)02470-x","url":null,"abstract":"No Abstract","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"65 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142598093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Marina Romanello: tracking climate change and health","authors":"Aarathi Prasad","doi":"10.1016/s0140-6736(24)02425-5","DOIUrl":"https://doi.org/10.1016/s0140-6736(24)02425-5","url":null,"abstract":"No Abstract","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Induced pluripotent stem-cell-derived corneal epithelium for transplant surgery: a single-arm, open-label, first-in-human interventional study in Japan","authors":"Takeshi Soma, Yoshinori Oie, Hiroshi Takayanagi, Shoko Matsubara, Tomomi Yamada, Masaki Nomura, Yu Yoshinaga, Kazuichi Maruyama, Atsushi Watanabe, Kayo Takashima, Zaixing Mao, Andrew J Quantock, Ryuhei Hayashi, Kohji Nishida","doi":"10.1016/s0140-6736(24)01764-1","DOIUrl":"https://doi.org/10.1016/s0140-6736(24)01764-1","url":null,"abstract":"<h3>Background</h3>The loss of corneal epithelial stem cells from the limbus at the edge of the cornea has severe consequences for vision, with the pathological manifestations of a limbal stem-cell deficiency (LSCD) difficult to treat. Here, to the best of our knowledge, we report the world's first use of corneal epithelial cell sheets derived from human induced pluripotent stem cells (iPSCs) to treat LSCD.<h3>Methods</h3>This non-randomised, single-arm, clinical study involved four eyes of four patients with LSCD at the Department of Ophthalmology, Osaka University Hospital. They comprised a woman aged 44 years with idiopathic LSCD (patient 1), a man aged 66 years with ocular mucous membrane pemphigoid (patient 2), a man aged 72 years with idiopathic LSCD (patient 3), and a woman aged 39 years with toxic epidermal necrosis (patient 4). Allogeneic human iPSC-derived corneal epithelial cell sheets (iCEPSs) were transplanted onto affected eyes. This was done sequentially in two sets of HLA-mismatched surgeries, with patients 1 and 2 receiving low-dose cyclosporin and patients 3 and 4 not. The primary outcome measure was safety, ascertained by adverse events. These were monitored continuously throughout the 52-week follow-up period, and during an additional 1-year safety monitoring period. Secondary outcomes, reflective of efficacy, were also recorded. This study is registered with UMIN, UMIN000036539 and is complete.<h3>Findings</h3>Patients were enrolled between June 17, 2019 and Nov 16, 2020. We had 26 adverse events during the 52-week follow-up period (consisting of 18 mild and one moderate event in treated eyes, and seven mild non-ocular events), with nine recorded in the additional 1-year safety monitoring period. No serious adverse events, such as tumourigenesis or clinical rejection, occurred during the whole 2-year observational period. At 52 weeks, secondary measures of efficacy showed that the disease stage had improved, corrected distance visual acuity was enhanced, and corneal opacification had diminished in all treated eyes. Corneal epithelial defects, subjective symptoms, quality-of-life questionnaire scores and corneal neovascularisation mostly improved or were unchanged. Overall, the beneficial efficacy outcomes achieved for patients 1 and 2 were better than those achieved for patients 3 and 4.<h3>Interpretation</h3>iCEPS transplantation for LSCD was found to be safe throughout the study period. A larger clinical trial is planned to further investigate the efficacy of the procedure.<h3>Funding</h3>The Japan Agency for Medical Research and Development, the Ministry of Education, Culture, Sports, Science, and Technology—Japan, and the UK Biotechnology and Biological Sciences Research Council.","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}