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Antimicrobial resistance: now is the time to revisit global commitments. 抗菌药耐药性:现在是重新审视全球承诺的时候了。
IF 98.4 3区 化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-12 Epub Date: 2024-09-27 DOI: 10.1016/S0140-6736(24)02140-8
Jakob Forssmed
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引用次数: 0
Health and humanitarian toll of Sudan's forgotten war. 苏丹被遗忘的战争造成的健康和人道主义损失。
IF 98.4 3区 化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-12 Epub Date: 2024-09-24 DOI: 10.1016/S0140-6736(24)01939-1
Ezzeldin Saleh, Khalid M Dousa, Ahmed Babiker, Nour Elhouda At Alla Rahma, Hamad Abdel Hadi, Mustafa Elsayed, Suleima Ishag Elkhalifa, Sami Mahmoud Abdelkhair Momin, Ahmed Abubaker, Omer Mergani Nemery, Luai Mohmmed Bashir, Shahinaz Bedri, Nada Fadul, Yasir Hamad, Zahir Osman Eltahir Babiker
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引用次数: 0
The time to address the antibiotic pipeline and access crisis is now. 现在是解决抗生素管道和获取危机的时候了。
IF 98.4 3区 化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-12 Epub Date: 2024-09-20 DOI: 10.1016/S0140-6736(24)01940-8
Manica Balasegaram, Kevin Outterson, John-Arne Røttingen
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引用次数: 0
Reflections on The Lancet menopause Series. 对《柳叶刀》更年期系列的思考。
IF 98.4 3区 化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-05 Epub Date: 2024-09-25 DOI: 10.1016/S0140-6736(24)01710-0
Gemma Sharp, Alisha Randhawa, Anne Nileshni Fernando
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引用次数: 0
Rechallenging with anti-PD-1 therapy in advanced renal cell carcinoma. 晚期肾细胞癌患者再次接受抗 PD-1 治疗。
IF 98.4 3区 化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-05 Epub Date: 2024-09-13 DOI: 10.1016/S0140-6736(24)01866-X
Zachary A Yochum, David A Braun
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引用次数: 0
Tivozanib plus nivolumab versus tivozanib monotherapy in patients with renal cell carcinoma following an immune checkpoint inhibitor: results of the phase 3 TiNivo-2 Study. 对使用免疫检查点抑制剂的肾细胞癌患者进行替沃扎尼加尼沃单抗治疗与替沃扎尼单药治疗的比较:TiNivo-2 3 期研究结果。
IF 98.4 3区 化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-05 Epub Date: 2024-09-13 DOI: 10.1016/S0140-6736(24)01758-6
Toni K Choueiri, Laurence Albiges, Philippe Barthélémy, Roberto Iacovelli, Sheik Emambux, Javier Molina-Cerrillo, Benjamin Garmezy, Pedro Barata, Arnab Basu, Maria T Bourlon, Helen Moon, Raffaele Ratta, Rana R McKay, Alexander Chehrazi-Raffle, Hans Hammers, Daniel Y C Heng, Edgar Braendle, Kathryn E Beckermann, Bradley A McGregor, Robert J Motzer

Background: Immune checkpoint inhibitors (ICIs) and vascular endothelial growth factor receptor tyrosine kinase inhibitors are cornerstones of first-line treatment for advanced renal cell carcinoma; however, optimal treatment sequencing after progression is unknown. This study aimed to assess clinical outcomes of tivozanib-nivolumab versus tivozanib monotherapy in patients with metastatic renal cell carcinoma who have progressed following one or two lines of therapy in the post-ICI setting.

Methods: TiNivo-2 is a multicentre, randomised, open-label, phase 3 trial at 190 sites across 16 countries, in Australia, Europe, North America, and South America. Patients with advanced renal cell carcinoma and progression during or after one to two previous lines of therapy (including one ICI) were randomised 1:1 to tivozanib (0·89 mg per day, orally) plus nivolumab (480 mg every 4 weeks, intravenously) or tivozanib (1·34 mg per day, orally). Randomisation was stratified by immediate previous therapy (ICI or non-ICI) and International Metastatic Renal Cell Carcinoma Database Consortium risk category. The primary endpoint was progression-free survival (PFS), defined as the time from randomisation to first documentation of objective progressive disease according to RECIST 1·1 or death from any cause, whichever came first, by independent radiology review. Efficacy was evaluated in the intention-to-treat population, and safety was assessed in patients who received one or more doses of the study drug. This trial was registered on ClinicalTrials.gov (NCT04987203) and is active and not recruiting.

Findings: From Nov 4, 2021, to June 16, 2023, 343 patients were randomly assigned to tivozanib-nivolumab (n=171) or tivozanib monotherapy (n=172). Median follow-up was 12·0 months. Median PFS was 5·7 months (95% CI 4·0-7·4) with tivozanib-nivolumab and 7·4 months (5·6-9·2) with tivozanib monotherapy (hazard ratio 1·10, 95% CI 0·84-1·43; p=0·49). Among those with an ICI as their immediate previous therapy (n=244), median PFS was 7·4 months (95% CI 5·6-9·6) with tivozanib-nivolumab and 9·2 months (7·4-10·0) with tivozanib monotherapy. With non-ICIs as the most recent therapy, lower median PFS was observed, with no difference between groups (tivozanib-nivolumab 3·7 months [95% CI 2·7-5·4] and with tivozanib monotherapy 3·7 months [1·9-7·2]). Serious adverse events occurred in 54 (32%) of 168 patients receiving tivozanib-nivolumab and 64 (37%) of 171 patients receiving tivozanib monotherapy. One (<1%) treatment-related death occurred (tivozanib group).

Interpretation: These data further support that ICI rechallenge should be discouraged in patients with advanced renal cell carcinoma. Furthermore, these data suggest that tivozanib monotherapy has efficacy in the post-ICI setting.

Funding: Aveo Pharmaceuticals.

背景:免疫检查点抑制剂(ICIs)和血管内皮生长因子受体酪氨酸激酶抑制剂是晚期肾细胞癌一线治疗的基石;然而,进展后的最佳治疗顺序尚不清楚。本研究旨在评估在ICI治疗后,经过一线或二线治疗后病情进展的转移性肾细胞癌患者接受tivozanib-nivolumab与tivozanib单药治疗的临床疗效:TiNivo-2 是一项多中心、随机、开放标签的 3 期试验,在澳大利亚、欧洲、北美和南美 16 个国家的 190 个地点进行。晚期肾细胞癌患者在接受一到两种治疗(包括一种 ICI)期间或之后病情出现进展,按 1:1 随机分配到 tivozanib(每天 0-89 毫克,口服)加 nivolumab(每 4 周 480 毫克,静脉注射)或 tivozanib(每天 1-34 毫克,口服)。随机分组按照既往治疗(ICI或非ICI)和国际转移性肾细胞癌数据库联盟风险类别进行。主要终点是无进展生存期(PFS),即从随机化到根据RECIST 1-1标准首次记录客观进展性疾病或因任何原因死亡(以先到者为准)的时间。疗效评估在意向治疗人群中进行,安全性评估在接受过一次或多次治疗的患者中进行。该试验已在ClinicalTrials.gov(NCT04987203)上注册,目前正在进行中,没有招募结果:从2021年11月4日到2023年6月16日,343名患者被随机分配到tivozanib-nivolumab(n=171)或tivozanib单药治疗(n=172)。中位随访时间为12-0个月。tivozanib-nivolumab的中位PFS为5-7个月(95% CI 4-0-7-4),tivozanib单药治疗的中位PFS为7-4个月(5-6-9-2)(危险比1-10,95% CI 0-84-1-43;P=0-49)。在既往接受过ICI治疗的患者中(n=244),tivozanib-nivolumab的中位PFS为7-4个月(95% CI 5-6-9-6),tivozanib单药治疗的中位PFS为9-2个月(7-4-10-0)。如果最近接受的治疗不是ICIs,则中位PFS较低,组间无差异(tivozanib-nivolumab为3-7个月[95% CI 2-7-5-4],tivozanib单药为3-7个月[1-9-7-2])。在接受tivozanib-nivolumab治疗的168例患者中,有54例(32%)发生了严重不良事件;在接受tivozanib单药治疗的171例患者中,有64例(37%)发生了严重不良事件。一个(解释:这些数据进一步证明,晚期肾细胞癌患者不应再进行 ICI 重试。此外,这些数据还表明,tivozanib单药治疗在ICI治疗后具有疗效:Aveo Pharmaceuticals.
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引用次数: 0
Renaming mpox in Spanish, French, and Portuguese: using language to address stigma and racism. 用西班牙语、法语和葡萄牙语重新命名 mpox:用语言消除耻辱感和种族主义。
IF 98.4 3区 化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-05 Epub Date: 2024-09-24 DOI: 10.1016/S0140-6736(24)02079-8
Jaime García-Iglesias, Angélica Cabezas-Pino, Francisco Javier Membrillo de Novales, Axel Rodrigo Bautista Pérez, Jorge Garrido Fuentes, Fernando Villaamil Pérez, Alfonso J Rodríguez-Morales, Diego Zamora Estay, Edith Guajardo Zuñiga, Lucas J Núñez Saavedra, Emilio de Benito Cañizares
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引用次数: 0
Mpox global emergency: strengthening African leadership. Mpox 全球紧急状况:加强非洲的领导力。
IF 98.4 3区 化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-05 Epub Date: 2024-09-20 DOI: 10.1016/S0140-6736(24)02068-3
Ibrahim Abubakar, Julius Lutwama, Catherine Kyobutungi, Osman Sankoh
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引用次数: 0
An urgent case for measles vaccination in Gaza. 在加沙紧急接种麻疹疫苗。
IF 98.4 3区 化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-05 Epub Date: 2024-09-20 DOI: 10.1016/S0140-6736(24)02076-2
Ronald Waldman, Robert Steinglass, Phillip Nieburg
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引用次数: 0
Reflections on The Lancet menopause Series - Authors' reply. 对《柳叶刀》绝经系列的思考--作者的回复。
IF 98.4 3区 化学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-05 Epub Date: 2024-09-25 DOI: 10.1016/S0140-6736(24)01712-4
Lydia Brown, Myra S Hunter, Carolyn J Crandall, Hadine Joffe Connors, Martha Hickey, Jennifer Doust, Andrea La Croix, Gita D Mishra, Muthusamy Sivakami
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引用次数: 0
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Photochemical & Photobiological Sciences
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