原创 倪恬 华西医院耳鼻喉科
华西耳鼻喉前沿学术速递——文献导读（第70期）
【The New England Journal of Medicine】
2025年1-2月刊论文导读
期刊介绍：
《新英格兰医学杂志》（The New England Journal of Medicine，简称NEJM），是由美国麻州医学协会所出版的世界一流的综合性医学期刊。发表与各医学专业相关的研究，以及关于医学伦理、公共卫生和医疗政策的文章。文章类型主要是临床研究、综述、病例报告和社论等。这一期刊对生物医学科学与临床实践具有重要意义。该刊创刊于1812年，为周刊，最新影响因子为96.2。
本期文献导读将呈现1-2月的主要刊物内容。
January 23；Volume 392（4）：313-416
在2025年1月23日，共发表19篇文章，其中包括4篇Perspective，4篇Original Articles，1篇Review Article，2篇Images in Clinical Medicine，1篇Interactive Medical Case，1篇Case Records of the Massachusetts General Hospital，3篇Editorials，1篇Medicine and Society，2篇Correspondence。
1.Perioperative Chemotherapy or Preoperative Chemoradiotherapy in Esophageal Cancer
食管癌围手术期化疗或术前放化疗
德国比勒费尔德大学
奥地利格拉茨医科大学
Abstract
BACKGROUND
The best multimodal approach for resectable locally advanced esophageal adenocarcinoma is unclear. An important question is whether perioperative chemotherapy is preferable to preoperative chemoradiotherapy.
METHODS
In this phase 3, multicenter, randomized trial, we assigned in a 1:1 ratio patients with resectable esophageal adenocarcinoma to receive perioperative chemotherapy with FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) plus surgery or preoperative chemoradiotherapy (radiotherapy at a dose of 41.4 Gy and carboplatin and paclitaxel) plus surgery. Eligibility criteria included a primary tumor with a clinical stage of cT1 cN+, cT2–4a cN+, or cT2–4a cN0 disease, in which T indicates the size and extent of the tumor (higher numbers indicate a more advanced tumor), and N indicates the presence (N+) or absence (N0) of cancer spread to the lymph nodes, without evidence of metastatic spread. The primary end point was overall survival.
RESULTS
From February 2016 through April 2020, we assigned 221 patients to the FLOT group and 217 patients to the preoperative-chemoradiotherapy group. With a median follow-up of 55 months, overall survival at 3 years was 57.4% (95% confidence interval [CI], 50.1 to 64.0) in the FLOT group and 50.7% (95% CI, 43.5 to 57.5) in the preoperative-chemoradiotherapy group (hazard ratio for death, 0.70; 95% CI, 0.53 to 0.92; P=0.01). Progression-free survival at 3 years was 51.6% (95% CI, 44.3 to 58.4) in the FLOT group and 35.0% (95% CI, 28.4 to 41.7) in the preoperative-chemoradiotherapy group (hazard ratio for disease progression or death, 0.66; 95% CI, 0.51 to 0.85). Among the patients who started the assigned treatment, grade 3 or higher adverse events were observed in 120 of 207 patients (58.0%) in the FLOT group and in 98 of 196 patients (50.0%) in the preoperative-chemoradiotherapy group. Serious adverse events were observed in 98 of 207 patients (47.3%) in the FLOT group and in 82 of 196 patients (41.8%) in the preoperative-chemoradiotherapy group. Mortality at 90 days after surgery was 3.1% in the FLOT group and 5.6% in the preoperative-chemoradiotherapy group.
CONCLUSIONS
Perioperative chemotherapy with FLOT led to improved survival among patients with resectable esophageal adenocarcinoma as compared with preoperative chemoradiotherapy.
摘要背景
对于可切除的局部晚期食管腺癌，最佳的多模式治疗策略尚未确定。其中，围手术期化疗是否优于术前放化疗仍存在争议。
方法
本研究为一项III期、多中心、随机对照试验，旨在比较FLOT（氟尿嘧啶、亚叶酸、奥沙利铂和多西他赛）围手术期化疗与术前放化疗（放疗剂量41.4 Gy，联合卡铂和紫杉醇）在可切除食管腺癌患者中的疗效。符合纳入标准的患者按1:1比例随机分组，分别接受FLOT围手术期化疗+手术，或术前放化疗+手术。纳入标准包括临床分期为cT1 cN+、cT2–4a cN+或cT2–4a cN0的原发性肿瘤（T表示肿瘤大小和范围，数字越大代表晚期程度越高；N表示是否存在淋巴结转移，N+为有转移，N0为无转移），且无远处转移证据。主要研究终点为总生存期（OS）。
结果
自2016年2月至2020年4月，共纳入438例患者，其中FLOT组221例，术前放化疗组217例。中位随访时间为55个月，FLOT组3年总生存率（OS）为57.4%（95% CI，50.1-64.0），术前放化疗组为50.7%（95% CI，43.5-57.5）（死亡风险比 [HR] = 0.70；95% CI，0.53-0.92；P = 0.01）。FLOT组3年无进展生存率（PFS）为51.6%（95% CI，44.3-58.4），术前放化疗组为35.0%（95% CI，28.4-41.7）（疾病进展或死亡风险比 [HR] = 0.66；95% CI，0.51-0.85）。
在接受指定治疗的患者中，FLOT组207例中有120例（58.0%）发生3级及以上不良事件，术前放化疗组196例中有98例（50.0%）发生3级及以上不良事件。FLOT组207例中，98例（47.3%）报告严重不良事件，而术前放化疗组196例中则有82例（41.8%）。术后90天内死亡率在FLOT组为3.1%，术前放化疗组为5.6%。
结论
与术前放化疗相比，FLOT围手术期化疗可显著提高可切除食管腺癌患者的生存率，支持其作为一种有效的治疗选择。
2.A Randomized Trial of Drug Route in Out-of-Hospital Cardiac Arrest
院外心脏骤停患者给药途径的随机试验
英国华威大学医学院
德文郡空中救护车
Abstract
BACKGROUND
In patients with out-of-hospital cardiac arrest, the effectiveness of drugs such as epinephrine is highly time-dependent. An intraosseous route of drug administration may enable more rapid drug administration than an intravenous route; however, its effect on clinical outcomes is uncertain.
METHODS
We conducted a multicenter, open-label, randomized trial across 11 emergency medical systems in the United Kingdom that involved adults in cardiac arrest for whom vascular access for drug administration was needed. Patients were randomly assigned to receive treatment from paramedics by means of an intraosseous-first or intravenous-first vascular access strategy. The primary outcome was survival at 30 days. Key secondary outcomes included any return of spontaneous circulation and favorable neurologic function at hospital discharge (defined by a score of 3 or less on the modified Rankin scale, on which scores range from 0 to 6, with higher scores indicating greater disability). No adjustment for multiplicity was made.
RESULTS
A total of 6082 patients were assigned to a trial group: 3040 to the intraosseous group and 3042 to the intravenous group. At 30 days, 137 of 3030 patients (4.5%) in the intraosseous group and 155 of 3034 (5.1%) in the intravenous group were alive (adjusted odds ratio, 0.94; 95% confidence interval [CI], 0.68 to 1.32; P=0.74). At the time of hospital discharge, a favorable neurologic outcome was observed in 80 of 2994 patients (2.7%) in the intraosseous group and in 85 of 2986 (2.8%) in the intravenous group (adjusted odds ratio, 0.91; 95% CI, 0.57 to 1.47); a return of spontaneous circulation at any time occurred in 1092 of 3031 patients (36.0%) and in 1186 of 3035 patients (39.1%), respectively (adjusted odds ratio, 0.86; 95% CI, 0.76 to 0.97). During the trial, one adverse event, which occurred in the intraosseous group, was reported.
CONCLUSIONS
Among adults with out-of-hospital cardiac arrest requiring drug therapy, the use of an intraosseous-first vascular access strategy did not result in higher 30-day survival than an intravenous-first strategy.
摘要
背景
在院外心脏骤停患者中，肾上腺素等药物的疗效高度依赖于给药时机。相比于静脉途径，骨髓腔内给药可能实现更快速的药物输注，然而其对患者临床结局的影响尚不明确。
方法
本研究为一项多中心、开放标签、随机对照试验，在英国11个急救医疗系统中开展，纳入需血管通路给药的成人心脏骤停患者。患者被随机分配至骨髓腔内优先或静脉优先的血管通路策略组。主要研究终点为30天生存率。关键次要结局包括自主循环的恢复（任意时段）及出院时的良好神经功能（定义为改良 Rankin 量表评分 ≤3，评分范围 0-6，分数越高代表残疾程度越重）。本研究未进行多重假设校正。本试验未进行多重校正。
结果
共有6082名患者接受了随机分配：3040名分配到骨髓腔内组，3042名分配到静脉组。在30天时，骨髓腔内组3030名患者中有137名（4.5%）存活，静脉组3034名患者中有155名（5.1%）存活（校正后比值比，0.94；95% CI，0.68-1.32；P=0.74）。在出院时，骨髓腔组2994名患者中有80名（2.7%）观察到良好的神经功能结局，静脉组2986名患者中有85名（2.8%）观察到良好的神经功能结局（校正后比值比，0.91；95% CI，0.57-1.47）；骨髓腔组3031名患者中有1092名（36.0%），静脉组3035名患者中有1186名（39.1%）在任何时间点恢复自主循环（校正后比值比，0.86；95% CI，0.76-0.97）。试验期间，骨髓腔内组报告了一起不良事件。
结论
在需要药物治疗的院外心脏骤停成年患者中，骨髓腔内优先血管通路策略并未改善30天生存率，相较于静脉优先策略并无显著临床优势。
3.Intraosseous or Intravenous Vascular Access for Out-of-Hospital Cardiac Arrest
院外心脏骤停患者的骨髓腔内通路或静脉血管通路比较
丹麦中部大区院前急救医疗服务
奥胡斯大学临床医学系
Abstract
Background
Out-of-hospital cardiac arrest is a leading cause of death worldwide. Establishing vascular access is critical for administering guideline-recommended drugs during cardiopulmonary resuscitation. Both the intraosseous route and the intravenous route are used routinely, but their comparative effectiveness remains unclear.
Methods
We conducted a randomized clinical trial to compare the effectiveness of initial attempts at intraosseous or intravenous vascular access in adults who had nontraumatic out-of-hospital cardiac arrest. The primary outcome was a sustained return of spontaneous circulation. Key secondary outcomes were survival at 30 days and survival at 30 days with a favorable neurologic outcome, defined by a score of 0 to 3 on the modified Rankin scale (scores range from 0 to 6, with higher scores indicating greater disability).
Results
Among 1506 patients who underwent randomization, 1479 were included in the primary analysis (731 in the intraosseous-access group and 748 in the intravenous-access group). The successful establishment of vascular access within two attempts occurred in 669 patients (92%) assigned to the intraosseous-access group and in 595 patients (80%) assigned to the intravenous-access group. Sustained return of spontaneous circulation occurred in 221 patients (30%) in the intraosseous-access group and in 214 patients (29%) in the intravenous-access group (risk ratio, 1.06; 95% confidence interval [CI], 0.90 to 1.24; P=0.49). At 30 days, 85 patients (12%) in the intraosseous-access group and 75 patients (10%) in the intravenous-access group were alive (risk ratio, 1.16; 95% CI, 0.87 to 1.56); a favorable neurologic outcome at 30 days occurred in 67 patients (9%) and 59 patients (8%), respectively (risk ratio, 1.16; 95% CI, 0.83 to 1.62). Prespecified adverse events were uncommon.
Conclusions
There was no significant difference in sustained return of spontaneous circulation between initial intraosseous and intravenous vascular access in adults who had out-of-hospital cardiac arrest.
摘要
背景
院外心脏骤停是全球范围内导致死亡的主要原因。在心肺复苏过程中，建立血管通路对于施用指南推荐的药物至关重要。骨髓腔内给药途径和静脉给药途径都是常规使用的方法，但两者的效果仍不明确。
方法
研究者开展了一项随机临床试验，旨在比较在发生非创伤性院外心脏骤停的成人中，首次尝试骨髓腔内或静脉血管通路的效果。主要结局是自主循环持续恢复。关键的次要结局包括30天生存率以及30天时具有良好神经功能结局的生存率，良好神经功能结局通过改良Rankin量表评分0-3分来定义（评分范围为0-6分，分数越高表示失能程度越重）。
结果
在接受随机分配的1506名患者中，有1479名患者被纳入主要分析（骨髓腔内通路组731人，静脉通路组748人）。在两次尝试内成功建立血管通路的情况发生在骨髓腔内通路组的669名患者（92%）和静脉通路组的595名患者（80%）。骨髓腔内通路组有221名患者（30%）出现了持续的自主循环恢复，静脉通路组有214名患者（29%）出现了持续的自主循环恢复（危险比，1.06；95% CI，0.90-1.24；P=0.49）。在30天时，骨髓腔内通路组和静脉通路组分别有85名（12%）和75名（10%）患者存活（危险比，1.16；95% CI，0.87-1.56）；在30天时骨髓腔内通路组和静脉通路组具有良好神经功能结局的患者分别为67名（9%）和59名（8%），（危险比，1.16；95% CI，0.83-1.62）。预设的不良事件较为少见。
结论
在发生院外心脏骤停的成人中，首次尝试骨髓腔内通路与静脉通路在持续恢复自主循环方面没有显著差异。
4.Abelacimab versus Rivaroxaban in Patients with Atrial Fibrillation
阿贝拉西单抗与利伐沙班用于房颤患者的比较
哈佛医学院布里格姆妇女医院TIMI研究小组
台北荣民总医院
Abstract
Background
Abelacimab is a fully human monoclonal antibody that binds to the inactive form of factor XI and blocks its activation. The safety of abelacimab as compared with a direct oral anticoagulant in patients with atrial fibrillation is unknown.
Methods
Patients with atrial fibrillation and a moderate-to-high risk of stroke were randomly assigned, in a 1:1:1 ratio, to receive subcutaneous injection of abelacimab (150 mg or 90 mg once monthly) administered in a blinded fashion or oral rivaroxaban (20 mg once daily) administered in an open-label fashion. The primary end point was major or clinically relevant nonmajor bleeding.
Results
A total of 1287 patients underwent randomization; the median age was 74 years, and 44% were women. At 3 months, the median reduction in free factor XI levels with abelacimab at a dose of 150 mg was 99% (interquartile range, 98 to 99) and with abelacimab at a dose of 90 mg was 97% (interquartile range, 51 to 99). The trial was stopped early on the recommendation of the independent data monitoring committee because of a greater-than-anticipated reduction in bleeding events with abelacimab. The incidence rate of major or clinically relevant nonmajor bleeding was 3.2 events per 100 person-years with 150-mg abelacimab and 2.6 events per 100 person-years with 90-mg abelacimab, as compared with 8.4 events per 100 person-years with rivaroxaban (hazard ratio for 150-mg abelacimab vs. rivaroxaban, 0.38 [95% confidence interval {CI}, 0.24 to 0.60]; hazard ratio for 90-mg abelacimab vs. rivaroxaban, 0.31 [95% CI, 0.19 to 0.51]; P<0.001 for both comparisons). The incidence and severity of adverse events appeared to be similar in the three groups.
Conclusions
Among patients with atrial fibrillation who were at moderate-to-high risk for stroke, treatment with abelacimab resulted in markedly lower levels of free factor XI and fewer bleeding events than treatment with rivaroxaban.
摘要
背景
阿贝拉西单抗是一种全人源单克隆抗体，可与凝血因子XI的非活性形式结合并阻断其活化。与直接口服抗凝剂相比，阿贝拉西单抗在房颤患者中的安全性尚不清楚。
方法
将有中高度卒中风险的房颤患者以1:1:1的比例随机分配，分别接受以下治疗：每月一次皮下注射阿贝拉西单抗（150 mg或90 mg，盲法给药）或每日一次口服利伐沙班（20 mg，开放标签给药）。主要终点是大出血或临床相关非大出血事件的发生。
结果
共有1287名患者接受了随机分组；中位年龄为74岁，其中44%为女性。在3个月时，阿贝拉西单抗150 mg剂量组的游离凝血因子XI水平中位降低99%（四分位间距，98-99），90 mg剂量组降低97%（四分位间距为51-99）。由于阿贝拉西单抗组出血事件的减少幅度显著超过预期，根据独立数据监测委员会的建议，试验提前终止。150 mg阿贝拉西单抗组大出血或临床相关非大出血事件的发生率为3.2例/100人/年，90 mg阿贝拉西单抗组为2.6例/100人/年，而利伐沙班组为8.4例/100人/年（150 mg阿贝拉西单抗组与利伐沙班组的风险比HR为0.38 [95% CI，0.24-0.60]；90 mg阿贝拉西单抗与利伐沙班的风险比HR为0.31 [95% CI，0.19-0.51]；P值均<0.001）。三组中不良事件的发生率和严重程度相似。
结论
在有中高度卒中风险的房颤患者中，与利伐沙班治疗相比，阿贝拉西单抗治疗显著降低了游离凝血因子XI水平，并减少了出血事件的发生，相较于利伐沙班治疗具有显著的安全性优势。
January 30；Volume 392（5）：417-520
在2025年1月30日，共发表22篇文章，其中包括4篇Perspective，5篇Original Articles，1篇Clinical Practice，2篇Images in Clinical Medicine，1篇Case Records of the Massachusetts General Hospital，5篇Editorials，1篇Clinical Decisions，3篇Correspondence。
5.Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity
替尔泊肽用于治疗伴有肥胖的射血分数保留型心力衰竭
美国贝勒大学医学中心
英国帝国理工学院
Abstract
Background
Obesity increases the risk of heart failure with preserved ejection fraction. Tirzepatide, a long-acting agonist of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, causes considerable weight loss, but data are lacking with respect to its effects on cardiovascular outcomes.
Methods
In this international, double-blind, randomized, placebo-controlled trial, we randomly assigned, in a 1:1 ratio, 731 patients with heart failure, an ejection fraction of at least 50%, and a body-mass index (the weight in kilograms divided by the square of the height in meters) of at least 30 to receive tirzepatide (up to 15 mg subcutaneously once per week) or placebo for at least 52 weeks. The two primary end points were a composite of adjudicated death from cardiovascular causes or a worsening heart-failure event (assessed in a time-to-first-event analysis) and the change from baseline to 52 weeks in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; scores range from 0 to 100, with higher scores indicating better quality of life).
Results
A total of 364 patients were assigned to the tirzepatide group and 367 to the placebo group; the median duration of follow-up was 104 weeks. Adjudicated death from cardiovascular causes or a worsening heart-failure event occurred in 36 patients (9.9%) in the tirzepatide group and in 56 patients (15.3%) in the placebo group (hazard ratio, 0.62; 95% confidence interval [CI], 0.41 to 0.95; P=0.026). Worsening heart-failure events occurred in 29 patients (8.0%) in the tirzepatide group and in 52 patients (14.2%) in the placebo group (hazard ratio, 0.54; 95% CI, 0.34 to 0.85), and adjudicated death from cardiovascular causes occurred in 8 patients (2.2%) and 5 patients (1.4%), respectively (hazard ratio, 1.58; 95% CI, 0.52 to 4.83). At 52 weeks, the mean (±SD) change in the KCCQ-CSS was 19.5±1.2 in the tirzepatide group as compared with 12.7±1.3 in the placebo group (between-group difference, 6.9; 95% CI, 3.3 to 10.6; P<0.001). Adverse events (mainly gastrointestinal) leading to discontinuation of the trial drug occurred in 23 patients (6.3%) in the tirzepatide group and in 5 patients (1.4%) in the placebo group.
Conclusions
Treatment with tirzepatide led to a lower risk of a composite of death from cardiovascular causes or worsening heart failure than placebo and improved health status in patients with heart failure with preserved ejection fraction and obesity.
摘要
背景
肥胖会增加射血分数保留型心力衰竭的风险。替尔泊肽是一种长效的葡萄糖依赖性促胰岛素多肽（GIP）受体和胰高血糖素样肽-1（GLP-1）受体双重激动剂，能显著减轻体重，但其对心血管结局的影响尚缺乏相关数据。
方法
在这项国际性、双盲、随机、安慰剂对照试验中，研究者将731名射血分数≥50%且体重指数（体重（千克）/身高（米）的平方）≥30的心衰患者，按照1:1的比例随机分配，接受每周一次皮下注射最高15毫克的替尔泊肽或安慰剂治疗，疗程持续至少52周。研究的两个主要终点是：经判定的心血管原因死亡或心衰加重事件的复合终点（通过首次事件发生时间分析评估），以及从基线到52周时堪萨斯城心肌病问卷临床总结评分（KCCQ-CSS；评分范围为0-100，分数越高表示生活质量越好）的变化。
结果
共有364名患者被分配至替尔泊肽组，367名患者被分配至安慰剂组，中位随访时间为104周。替尔泊肽组有36例患者（9.9%）发生经判定的心血管原因死亡或心力衰竭恶化事件，而安慰剂组为56例（15.3%）（风险比0.62；95% CI 0.41-0.95；P=0.026）。其中，心力衰竭恶化事件在替尔泊肽组发生29例（8.0%），安慰剂组为52例（14.2%）（风险比0.54；95% CI 0.34-0.85），而经裁定的心血管原因死亡分别为8例（2.2%）和5例（1.4%）（风险比1.58；95% CI 0.52-4.83）。在随访52周时，替尔泊肽组的堪萨斯城心肌病问卷临床总结评分（KCCQ-CSS）平均提高19.5±1.2分，安慰剂组为12.7±1.3分，组间差异为6.9分（95% CI，3.3-10.6；P<0.001）。导致试验药物停用的不良事件主要为胃肠道反应，发生率在替尔泊肽组为23例（6.3%），安慰剂组为5例（1.4%）。
结论
在射血分数保留的心力衰竭合并肥胖症患者中，与安慰剂相比，替尔泊肽治疗可降低心血管原因死亡或心力衰竭恶化的复合终点风险，并改善患者的健康状态。
6.Continuation versus Interruption of Oral Anticoagulation during TAVI
经导管主动脉瓣置入术（TAVI）期间持续与中断口服抗凝治疗的对比
荷兰圣安东尼斯医院
阿姆斯特丹大学医学中心
Abstract
Background
One third of patients undergoing transcatheter aortic-valve implantation (TAVI) have an indication for oral anticoagulation owing to concomitant diseases. Interruption of oral anticoagulation during TAVI may decrease the risk of bleeding, whereas continuation may decrease the risk of thromboembolism.
Methods
We conducted an international, open-label, randomized, noninferiority trial involving patients who were receiving oral anticoagulants and were planning to undergo TAVI. Patients were randomly assigned in a 1:1 ratio to periprocedural continuation or interruption of oral anticoagulation. The primary outcome was a composite of death from cardiovascular causes, stroke from any cause, myocardial infarction, major vascular complications, or major bleeding within 30 days after TAVI.
Results
A total of 858 patients were included in the modified intention-to-treat population: 431 were assigned to continuation and 427 to interruption of oral anticoagulation. A primary-outcome event occurred in 71 patients (16.5%) in the continuation group and in 63 (14.8%) in the interruption group (risk difference, 1.7 percentage points; 95% confidence interval [CI], −3.1 to 6.6; P=0.18 for noninferiority). Thromboembolic events occurred in 38 patients (8.8%) in the continuation group and in 35 (8.2%) in the interruption group (risk difference, 0.6 percentage points; 95% CI, −3.1 to 4.4). Bleeding occurred in 134 patients (31.1%) in the continuation group and in 91 (21.3%) in the interruption group (risk difference, 9.8 percentage points; 95% CI, 3.9 to 15.6).
Conclusions
In patients undergoing TAVI with a concomitant indication for oral anticoagulation, periprocedural continuation was not noninferior to interruption of oral anticoagulation during TAVI with respect to the incidence of a composite of death from cardiovascular causes, stroke, myocardial infarction, major vascular complications, or major bleeding at 30 days.
摘要：
背景：
在接受经导管主动脉瓣置入术（TAVI）的患者中，约三分之一因合并其他疾病需要口服抗凝药物。在TAVI期间中断口服抗凝药物可能会减少出血风险，而继续使用则可降低血栓栓塞的风险。
方法：
研究者开展了一项国际性、开放标签、随机、非劣效性试验，研究对象为正在接受口服抗凝药物且计划进行经导管主动脉瓣置入术（TAVI）的患者。患者以1:1的比例随机分配，分别在围手术期继续使用或中断口服抗凝药物。主要终点是TAVI后30天内因心血管原因导致的死亡、任何原因引起的卒中、心肌梗死、主要血管并发症或大出血的复合终点。
结果：
共有858名患者被纳入改良意向性治疗人群：431名患者被分配到继续使用口服抗凝药物组，427名患者被分配到中断口服抗凝药物组。在继续使用口服抗凝药物组中，有71名患者（16.5%）发生了主要终点事件；而在中断口服抗凝药物组中，有63名患者（14.8%）发生了主要终点事件（风险差异，1.7%；95% CI，-3.1至6.6；非劣效性检验P值，0.18）。继续使用口服抗凝药物组的38名患者（8.8%）和中断口服抗凝药物组的35名患者（8.2%）发生了血栓栓塞事件（风险差异，0.6%；95% CI，-3.1至4.4）。继续使用口服抗凝药物组134名患者（31.1%）和中断口服抗凝药物组的91名患者（21.3%）发生出血事件（风险差异，9.8%；95% CI，3.9-15.6）。
结论：
在接受TAVI治疗且需口服抗凝治疗的患者中，围手术期继续使用口服抗凝药物，在30天内心血管原因死亡、中风、心肌梗死、主要血管并发症或大出血的复合结局发生率方面，并不劣于TAVI期间暂停抗凝治疗。
February 6；Volume 392（6）：521-624
在2025年2月6日，共发表21篇文章，其中包括4篇Perspective，5篇Original Articles，1篇Review Article，2篇Images in Clinical Medicine，1篇Clinical Problem-Solving，2篇Editorials，1篇Clinical Implications of Basic Research，5篇Correspondence。
7.Alternative Complement Pathway Inhibition with Iptacopan in IgA Nephropathy
用盐酸伊普可泮抑制IgA肾病中的替代补体途径
澳大利亚新南威尔士大学
英国莱斯特大学
Abstract
Background
The alternative complement pathway plays a key role in the pathogenesis of IgA nephropathy. Iptacopan specifically binds to factor B and inhibits the alternative pathway.
Methods
In this phase 3, double-blind, randomized, placebo-controlled trial, we enrolled adults with biopsy-confirmed IgA nephropathy and proteinuria with a 24-hour urinary protein-to-creatinine ratio of 1 or higher (with protein and creatinine both measured in grams) despite optimized supportive therapy. Patients were randomly assigned, in a 1:1 ratio, to receive oral iptacopan (200 mg) or placebo twice daily for 24 months while continuing to receive supportive therapy. The primary objective of this prespecified interim analysis was to assess the efficacy of iptacopan as compared with that of placebo in reducing proteinuria at month 9; the primary end point was the change from baseline in the 24-hour urinary protein-to-creatinine ratio at month 9. The proportion of patients who had a 24-hour urinary protein-to-creatinine ratio of less than 1 at month 9 without receiving rescue or alternative medication or undergoing kidney-replacement therapy (dialysis or transplantation) was a secondary end point. Safety was also assessed. The effect of iptacopan on kidney function will be assessed at the end of the 2-year double-blind treatment period.
Results
The main trial population included 222 patients in the iptacopan group and 221 in the placebo group. The interim efficacy analysis included the first 250 patients who underwent randomization in the main trial population (125 patients in each group) and who remained in the trial until month 9 or discontinued the trial by month 9. Safety was assessed in all the patients in the main trial population. At month 9, the adjusted geometric mean 24-hour urinary protein-to-creatinine ratio was 38.3% (95% confidence interval, 26.0 to 48.6; two-sided P<0.001) lower with iptacopan than with placebo. The reduction in proteinuria was supported by consistent results in secondary end point analyses. There were no unexpected safety findings with iptacopan. The incidence of adverse events that occurred during the treatment period was similar in the two groups; most events were mild to moderate in severity and reversible. No increased risk of infection was observed.
Conclusions
Among patients with IgA nephropathy, treatment with iptacopan resulted in a significant and clinically meaningful reduction in proteinuria as compared with placebo.
摘要：
背景：
替代补体途径在IgA肾病的发病机制中起着关键作用。盐酸伊普可泮能够特异性结合因子B，从而抑制替代补体途径的激活。
方法：
在这项 3 期、双盲、随机、安慰剂对照试验中，研究者纳入了经活检确诊的 IgA 肾病患者，这些患者在优化支持治疗后仍存在蛋白尿且24小时尿蛋白与肌酐比值≥1（蛋白和肌酐均以克为单位）。患者按1:1比例随机分配，在继续接受支持治疗的同时，每日两次口服盐酸伊普可泮（200 mg）或安慰剂，持续24个月。本次预设中期分析的主要目的是评估第9个月时盐酸伊普可泮与安慰剂相比降低蛋白尿的疗效；主要终点为第9个月时24小时尿蛋白与肌酐比值较基线的变化。次要终点包括第9个月时24小时尿蛋白与肌酐比值<1且未接受挽救/替代药物或肾脏替代治疗（透析或移植）的患者比例。同时评估了安全性。盐酸伊普可泮对肾功能的影响将在2年双盲治疗期结束时进行评估。
结果：
主要试验人群包括盐酸伊普可泮组222例患者和安慰剂组221例患者。中期疗效分析纳入了主要试验人群中前250例参与了随机分组的患者（每组各125例），这些患者在持续至第9个月时仍在参与试验或到第9个月时已退出试验。所有主要试验人群患者均接受了安全性评估。第9个月时，盐酸伊普可泮组的校正几何平均24小时尿蛋白/肌酐比值较安慰剂组降低了38.3%（95%CI，26.0-48.6；双侧P<0.001）。次要终点分析结果同样支持蛋白尿的减少。盐酸伊普可泮未发现新的安全性问题。两组患者在治疗期间的不良事件发生率相似，且大多数不良事件为轻度至中度，并且可逆。未观察到感染风险增加的情况。
结论：
在 IgA 肾病患者中，与安慰剂相比，使用盐酸伊普可泮治疗可显著减少蛋白尿，且具有临床意义。
8.Atrasentan in Patients with IgA Nephropathy
阿曲生坦在IgA肾病患者中的应用
荷兰格罗宁根大学医学中心临床药学与药理学系
澳大利亚悉尼大学
Abstract
Background
Patients with IgA nephropathy and severe proteinuria have a high lifetime risk of kidney failure. The efficacy and safety of the selective endothelin type A receptor antagonist atrasentan in reducing proteinuria in patients with IgA nephropathy are incompletely understood.
Methods
We are conducting a phase 3, multinational, double-blind, randomized, controlled trial involving adults with biopsy-proven IgA nephropathy, a total urinary protein excretion of at least 1 g per day, and an estimated glomerular filtration rate of at least 30 ml per minute per 1.73 m2 of body-surface area. Patients were randomly assigned to receive atrasentan (0.75 mg per day) or matched placebo for 132 weeks. The primary outcome, assessed at a prespecified interim analysis of data from the first 270 patients in the main stratum, was the change in the 24-hour urinary protein-to-creatinine ratio from baseline to week 36; the change was estimated with the use of a repeated-measures model. (An exploratory stratum of patients who were receiving a sodium–glucose cotransporter 2 inhibitor were included in a separate analysis.) Safety analyses were based on adverse events across the entire main stratum.
Results
A total of 340 patients were recruited into the main stratum. Among the first 270 patients in the main stratum (135 per trial group) who completed the week 36 visit, the geometric mean percentage change in the urinary protein-to-creatinine ratio relative to baseline was significantly greater with atrasentan (−38.1%) than with placebo (−3.1%), with a geometric mean between-group difference of −36.1 percentage points (95% confidence interval, −44.6 to −26.4; P<0.001). The percentage of patients with adverse events did not differ substantially between the two groups. Fluid retention was reported by 19 of 169 patients (11.2%) in the atrasentan group and in 14 of 170 (8.2%) in the placebo group but did not lead to discontinuation of the trial regimen. No apparent cases of cardiac failure or severe edema occurred.
Conclusions
In this prespecified interim analysis, atrasentan resulted in a significant and clinically meaningful reduction in proteinuria as compared with placebo in patients with IgA nephropathy.
摘要：
背景：
IgA肾病伴严重蛋白尿的患者面临较高的肾衰竭风险。阿曲生坦，作为选择性内皮素A型受体拮抗剂，其在降低IgA肾病患者蛋白尿方面的疗效和安全性尚未完全明确。
方法;
研究者正在开展一项3期、多国、双盲、随机对照试验，旨在评估阿曲生坦在经活检确诊的IgA肾病成人患者中的疗效与安全性。纳入标准为尿蛋白总排泄量≥1克/天，且估算肾小球滤过率（eGFR）≥30毫升/分钟/1.73平方米体表面积的患者。患者被随机分配到每日服用 0.75 毫克阿曲生坦组或匹配的安慰剂组，为期 132 周。主要结局指标是在预先设定的对主要分析层中前 270 例患者的数据进行中期分析时，评估从基线到第 36 周 24 小时尿蛋白 / 肌酐比值的变化；该变化是通过重复测量模型估计的。（还纳入了一个单独分析的探索性分层，即接受钠-葡萄糖协同转运蛋白 2（SGLT2）抑制剂治疗的患者。）安全性分析基于整个主要分析层中的不良事件。
结果：
在主要分析层中共纳入340例患者。其中前270例完成第36周随访的患者（每组135例）中，阿曲生坦组的尿蛋白与肌酐比值相对于基线的几何平均百分比变化（−38.1%）显著优于安慰剂组（−3.1%），组间几何平均差异为−36.1%（95%CI，−44.6至−26.4；P<0.001）。两组患者的不良事件发生率无显著差异。阿曲生坦组169例患者中有19例（11.2%）报告体液潴留，安慰剂组170例中有14例（8.2%），但均未导致试验用药终止。未观察到明显的心力衰竭或严重水肿病例。
结论：
在这项预先设定的中期分析中，与安慰剂相比，阿曲生坦可显著减少 IgA 肾病患者的蛋白尿，且具有临床意义。
Liraglutide for Children 6 to<12 Years of Age with Obesity — A Randomized Trial
利拉鲁肽用于6至<12岁肥胖儿童——一项随机试验
明尼苏达大学医学院儿科系
墨西哥普埃布拉安吉利斯医院
Abstract
Background
No medications are currently approved for the treatment of nonmonogenic, nonsyndromic obesity in children younger than 12 years of age. Although the use of liraglutide has been shown to induce weight loss in adults and adolescents with obesity, its safety and efficacy have not been established in children.
Methods
In this phase 3a trial, which consisted of a 56-week treatment period and a 26-week follow-up period, we randomly assigned children (6 to<12 years of age) with obesity, in a 2:1 ratio, to receive either once-daily subcutaneous liraglutide at a dose of 3.0 mg (or the maximum tolerated dose) or placebo, plus lifestyle interventions. The primary end point was the percentage change in the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters). The confirmatory secondary end points were the percentage change in body weight and a reduction in BMI of at least 5%.
Results
A total of 82 participants underwent randomization; 56 were assigned to the liraglutide group and 26 to the placebo group. At week 56, the mean percentage change from baseline in BMI was −5.8% with liraglutide and 1.6% with placebo, representing an estimated difference of −7.4 percentage points (95% confidence interval [CI], −11.6 to −3.2; P<0.001). The mean percentage change in body weight was 1.6% with liraglutide and 10.0% with placebo, representing an estimated difference of −8.4 percentage points (95% CI, −13.4 to −3.3; P=0.001), and a reduction in BMI of at least 5% occurred in 46% of participants in the liraglutide group and in 9% of participants in the placebo group (adjusted odds ratio, 6.3 [95% CI, 1.4 to 28.8]; P=0.02). Adverse events occurred in 89% and 88% of participants in the liraglutide and placebo groups, respectively. Gastrointestinal adverse events were more common in the liraglutide group (80% vs. 54%); serious adverse events were reported in 12% and 8% of participants in the liraglutide and placebo groups, respectively.
Conclusions
Among children (6 to<12 years of age) with obesity, treatment with liraglutide for 56 weeks plus lifestyle interventions resulted in a greater reduction in BMI than placebo plus lifestyle interventions.
摘要：
背景：
目前尚无任何获批药物可用于治疗12岁以下儿童的非单基因性、非综合征性肥胖。虽然利拉鲁肽已被证明可帮助成人和青少年肥胖患者减轻体重，但其在儿童中的安全性和有效性尚未得到证实。
方法：
在这项包括56周治疗期和26周随访期的Ⅲa期试验中，研究者以2:1的比例随机分配6至12岁的肥胖儿童接受每日一次皮下注射3.0 mg（或最大耐受剂量）的利拉鲁肽或安慰剂，并对两组均进行生活方式干预。主要终点是体重指数（BMI）的百分比变化。确认性次要终点是体重百分比变化和BMI下降至少5%。
结果：
共计82名受试者接受了随机分组，其中56人被分配到利拉鲁肽组，26人被分配到安慰剂组。第56周时，利拉鲁肽组BMI与基线相比的平均变化百分比为－5.8%，安慰剂组为1.6%，估计差异为－7.4%（95% CI，－11.6至－3.2；P<0.001）。利拉鲁肽组体重的平均变化百分比为1.6%，安慰剂组为10.0%，估计差异为－8.4%（95% CI，－13.4至－3.3；P=0.001），利拉鲁肽组46%受试者和安慰剂组9%受试者的BMI下降了至少5%（校正后比值比，6.3[95% CI，1.4-28.8]；P=0.02）。不良事件发生率在两组相近（利拉鲁肽组89%，安慰剂组88%），但消化道不良事件在利拉鲁肽组更常见（80% vs. 54%）。严重不良事件的发生率分别为12%（利拉鲁肽组）和8%（安慰剂组）。
结论：
在6至12岁以下的肥胖儿童中，利拉鲁肽治疗56周联合生活方式干预，与安慰剂联合生活方式干预相比，可更显著降低BMI。
February 13；Volume 392（7）：625-728
在2025年2月13日，共发表24篇文章，其中包括3篇Perspective，5篇Original Articles，1篇Review Article，2篇Images in Clinical Medicine，1篇Case Records of the Massachusetts General Hospital，5篇Editorials，6篇Correspondence，1篇Correction。
10.Colchicine in Acute Myocardial Infarction
秋水仙碱治疗急性心肌梗死试验
加拿大麦克马斯特大学人口健康研究所
汉密尔顿健康科学研究所
Abstract
Background
Inflammation is associated with adverse cardiovascular events. Data from recent trials suggest that colchicine reduces the risk of cardiovascular events.
Methods
In this multicenter trial with a 2-by-2 factorial design, we randomly assigned patients who had myocardial infarction to receive either colchicine or placebo and either spironolactone or placebo. The results of the colchicine trial are reported here. The primary efficacy outcome was a composite of death from cardiovascular causes, recurrent myocardial infarction, stroke, or unplanned ischemia-driven coronary revascularization, evaluated in a time-to-event analysis. C-reactive protein was measured at 3 months in a subgroup of patients, and safety was also assessed.
Results
A total of 7062 patients at 104 centers in 14 countries underwent randomization; at the time of analysis, the vital status was unknown for 45 patients (0.6%), and this information was most likely missing at random. A primary-outcome event occurred in 322 of 3528 patients (9.1%) in the colchicine group and 327 of 3534 patients (9.3%) in the placebo group over a median follow-up period of 3 years (hazard ratio, 0.99; 95% confidence interval [CI], 0.85 to 1.16; P=0.93). The incidence of individual components of the primary outcome appeared to be similar in the two groups. The least-squares mean difference in C-reactive protein levels between the colchicine group and the placebo group at 3 months, adjusted according to the baseline values, was −1.28 mg per liter (95% CI, −1.81 to −0.75). Diarrhea occurred in a higher percentage of patients with colchicine than with placebo (10.2% vs. 6.6%; P<0.001), but the incidence of serious infections did not differ between groups.
Conclusions
Among patients who had myocardial infarction, treatment with colchicine, when started soon after myocardial infarction and continued for a median of 3 years, did not reduce the incidence of the composite primary outcome (death from cardiovascular causes, recurrent myocardial infarction, stroke, or unplanned ischemia-driven coronary revascularization).
摘要：
背景：
炎症与不良心血管事件有关。近期的试验数据表明，秋水仙碱可降低心血管事件风险。
方法：
在这项采用2x2析因设计的多中心试验中，研究者将心肌梗死患者随机分配接受秋水仙碱或安慰剂，以及螺内酯或安慰剂。本研究报告了秋水仙碱试验的结果。主要终点为心血管原因死亡、复发性心肌梗死、中风或因缺血导致的计划外冠状动脉血运重建的复合事件，并采用时间-事件分析进行评估。此外，在一部分患者中测定了3个月时的C反应蛋白（CRP）水平，并对安全性进行了评估。
结果：
在14个国家的104个中心，共计7062例患者接受了随机分组；在分析时，45例患者（0.6%）的生存状态不明，这些信息很可能是随机缺失的。在中位随访3年期内，秋水仙碱组3528例患者中的322例（9.1%）和安慰剂组3534例患者中的327例（9.3%）发生了主要结局事件（风险比，0.99；95%CI，0.85-1.16；P=0.93）。两组之间主要结局的各个构成部分的发生率相似。根据基线值校正后，3个月时秋水仙碱组与安慰剂组之间C反应蛋白水平的最小二乘平均差异为－1.28 mg/L（95% CI，－1.81至－0.75）。安全性方面，秋水仙碱组的腹泻发生率高于安慰剂组（10.2% vs. 6.6%，P<0.001），但两组严重感染的发生率无显著差异。
结论：
在接受心肌梗死治疗的患者中，早期使用秋水仙碱并持续治疗中位3年，并未显著降低心血管原因死亡、复发性心肌梗死、中风或缺血导致的计划外冠状动脉血运重建的复合终点事件发生率。
11.Evolving Epidemiology of Mpox in Africa in 2024
2024年非洲猴痘流行病学演变
非洲疾病预防控制中心
奥巴费米阿沃洛沃大学
Abstract
Background
For decades after the identification of mpox in humans in the Democratic Republic of Congo (DRC) in 1970, the disease was largely confined to the rural areas of Central and West Africa and thus did not garner broad attention. On August 13, 2024, mpox was declared a Public Health Emergency of Continental Security (PHECS) by the Africa Centers for Disease Control and Prevention (Africa CDC), a notice that was followed the next day by a declaration of a Public Health Emergency of International Concern (PHEIC) by the World Health Organization.
Methods
In this study we analyzed all mpox cases and deaths, based on clinical or laboratory diagnosis, that were reported to the Africa CDC from January 1, 2022, to October 30, 2024, to identify temporal variations, geographic distributions, and epidemiologic trends.
Results
From January 1, 2022, to August 18, 2024, a total of 45,652 mpox cases were clinically diagnosed and laboratory-confirmed in 12 African countries. These cases resulted in 1492 deaths (case fatality rate, 3.3%). From 2022 to 2024, weekly laboratory-confirmed mpox cases increased by a factor of 2.8 (from 176 to 489 cases), whereas all weekly reported cases (including those with a clinical diagnosis) increased by a factor of 4.3 (from 669 to 2900 cases). The DRC, which had reported approximately 88% of mpox cases in Africa in 2024, had 19,513 cases before the emergency declaration, with a case fatality rate of 3.1% — a weekly average of 591 cases as compared with 281 in 2023. In 2024, six African countries reported their first imported mpox infections, with Burundi also reporting local transmission.
Conclusions
The high mpox disease burden in Africa, especially in the DRC — with a rising number of cases, high case fatality rate, and high degree of spread to other previously mpox-free African countries — is cause for increased international concern. Case detection, contact tracing, public health measures, and affordable vaccines are needed to implement interventions in the DRC to reduce the risk of global spread of the virus.
摘要：
背景：
自 1970 年在刚果民主共和国（DRC）首次发现人类感染猴痘（mpox）以来，该疾病长期局限于中非和西非的农村地区，未引起足够关注。2024 年 8 月 13 日，非洲疾病预防控制中心（Africa CDC）宣布猴痘为非洲大陆公共卫生紧急事件（PHECS）；次日，世界卫生组织（WHO）亦将其列为国际公共卫生紧急事件（PHEIC）。
方法：
在这项研究中，研究者分析了2022年1月1日至2024年10月30日期间向非洲疾病预防控制中心报告的所有猴痘病例和死亡病例，这些病例和死亡病例基于临床或实验室诊断，以确定时间变化、地理分布和流行病学趋势。
结果：
从2022年1月1日至2024年8月18日，在12个非洲国家中，共有45,652例经临床诊断和实验室确认的猴痘病例，其中 1,492 例死亡（病死率 3.3%）。从2022年到2024年，每周实验室确诊的猴痘病例增加了2.8倍（从176例增加到489例），而每周报告的所有病例（包括临床诊断的病例）增加了4.3倍（从669例增加到2900例）。2024年，刚果民主共和国报告了非洲大约88%的猴痘病例，在宣布紧急状态之前有19,513例病例，病死率为3.1% —— 每周平均为591例，而2023年每周平均281例。在2024年，六个非洲国家报告了他们的首例输入性猴痘感染，布隆迪也报告了本地传播病例。
结论：
猴痘在非洲，尤其是刚果民主共和国，已造成沉重的疾病负担——病例持续增长，病死率较高，并加速向此前无猴痘病例的非洲国家传播，引发国际社会关注。刚果民主共和国亟需加强病例检测、接触者追踪、公共卫生干预，并推广可负担的疫苗接种，以减少病毒全球传播的风险。
February 20；Volume 392（8）： 729-831
在2025年2月20日，共发表20篇文章，其中包括3篇Perspective，5篇Original Articles，1篇Clinical Practice，2篇Images in Clinical Medicine，1篇Case Records of the Massachusetts General Hospital，4篇Editorials，4篇Correspondence。
12.Catheter Ablation or Antiarrhythmic Drugs for Ventricular Tachycardia
导管消融术或抗心律失常药物治疗室性心动过速
加拿大戴尔豪斯大学
加拿大韦仕敦大学
Abstract
Background
Patients with ventricular tachycardia and ischemic cardiomyopathy are at high risk for adverse outcomes. Catheter ablation is commonly used when antiarrhythmic drugs do not suppress ventricular tachycardia. Whether catheter ablation is more effective than antiarrhythmic drugs as a first-line therapy in patients with ventricular tachycardia is uncertain.
Methods
In an international trial, we randomly assigned in a 1:1 ratio patients with previous myocardial infarction and clinically significant ventricular tachycardia (defined as ventricular tachycardia storm, receipt of appropriate implantable cardioverter–defibrillator [ICD] shock or antitachycardia pacing, or sustained ventricular tachycardia terminated by emergency treatment) to receive antiarrhythmic drug therapy or to undergo catheter ablation. All the patients had an ICD. Catheter ablation was performed within 14 days after randomization; sotalol or amiodarone was administered as antiarrhythmic drug therapy according to prespecified criteria. The primary end point was a composite of death from any cause during follow-up or, more than 14 days after randomization, ventricular tachycardia storm, appropriate ICD shock, or sustained ventricular tachycardia treated by medical intervention.
Results
A total of 416 patients were followed for a median of 4.3 years. A primary end-point event occurred in 103 of 203 patients (50.7%) assigned to catheter ablation and in 129 of 213 (60.6%) assigned to drug therapy (hazard ratio, 0.75; 95% confidence interval, 0.58 to 0.97; P=0.03). Among patients in the catheter ablation group, adverse events within 30 days after the procedure included death in 2 patients (1.0%) and nonfatal adverse events in 23 patients (11.3%). Among the patients assigned to drug therapy, adverse events that were attributed to antiarrhythmic drug treatment included death from pulmonary toxic effects in 1 patient (0.5%) and nonfatal adverse events in 46 patients (21.6%).
Conclusions
Among patients with ischemic cardiomyopathy and ventricular tachycardia, an initial strategy of catheter ablation led to a lower risk of a composite primary end-point event than antiarrhythmic drug therapy.
摘要：
背景：
室性心动过速合并缺血性心肌病的患者面临较高的不良结局风险。当抗心律失常药物无法抑制室性心动过速时，通常会采用导管消融术。目前尚不明确在室性心动过速患者中，导管消融作为一线治疗是否比抗心律失常药物更有效。
方法：
在一项国际性试验中，研究者以1:1比例随机分配既往发生过心肌梗死，并且患有临床意义的室性心动过速（定义为室速风暴、接受适当的植入式心律转复除颤器[ICD]电击或抗心动过速起搏，或经紧急治疗终止的持续性室性心动过速）的患者接受抗心律失常药治疗或导管消融术。所有患者均植入了ICD。导管消融术在随机分组后14天内进行；索他洛尔或胺碘酮作为抗心律失常药，按照预设标准进行治疗。主要终点为全因死亡或随机分组后14天内发生室速风暴、适当ICD电击或通过医疗干预治疗的持续性室性心动过速构成的复合终点。
结果：
本试验对共计416例患者进行了中位4.3年的随访。导管消融术组203例患者中的103例（50.7%）和药物治疗组213例患者中的129例（60.6%）发生了主要终点事件（风险比，0.75；95%CI，0.58-0.97；P=0.03）。在导管消融术组患者中，术后30天内的不良事件包括2人（1.0%）死亡，23人（11.3%）发生非致死性不良事件。在药物治疗组患者中，与抗心律失常药物相关的不良事件包括1例患者（0.5%）发生肺部毒性效应导致死亡，以及46例患者（21.6%）发生非致死性不良事件。
结论：
在患有缺血性心肌病和室性心动过速的患者中，与抗心律失常药物治疗相比，导管消融的初始策略可降低发生复合主要终点事件的风险。
13.Microvascular Inflammation of Kidney Allografts and Clinical Outcomes
同种异体移植肾的微血管炎症与临床结局
巴黎西岱大学
巴黎公共医疗救助机构
Abstract
Background
The heterogeneous clinical presentation of graft microvascular inflammation poses a major challenge to successful kidney transplantation. The effect of microvascular inflammation on allograft outcomes is unclear.
Methods
We conducted a cohort study that included kidney-transplant recipients from more than 30 transplantation centers in Europe and North America who had undergone allograft biopsy between 2004 and 2023. We integrated clinical and pathological data to classify biopsy specimens according to the 2022 Banff Classification of Renal Allograft Pathology, which includes two new diagnostic categories: probable antibody-mediated rejection and microvascular inflammation without evidence of an antibody-mediated response. We then assessed the association between the newly recognized microvascular inflammation phenotypes and allograft survival and disease progression.
Results
A total of 16,293 kidney-transplant biopsy specimens from 6798 patients were assessed. We identified the newly recognized microvascular inflammation phenotypes in 788 specimens, of which 641 were previously categorized as specimens with no evidence of rejection. As compared with patients without rejection, the hazard ratio for graft loss was 2.1 (95% confidence interval [CI], 1.5 to 3.1) among patients with microvascular inflammation without evidence of an antibody-mediated response and 2.7 (95% CI, 2.2 to 3.3) among patients with antibody-mediated rejection. Patients with a diagnosis of probable antibody-mediated rejection had a higher risk of graft failure beyond year 5 after biopsy than those without rejection (hazard ratio, 1.7; 95% CI, 0.8 to 3.5). Patients with a diagnosis of either newly recognized microvascular inflammation phenotype had a higher risk of progression of transplant glomerulopathy during follow-up than patients without microvascular inflammation.
Conclusions
Microvascular inflammation in kidney allografts includes distinct phenotypes, with various disease progression and allograft outcomes. Our findings support the clinical use of additional rejection phenotypes to standardize diagnostics for kidney allografts.
摘要：
背景：
移植物微血管炎症的异质性临床表现对肾脏移植的成功实施构成了重大挑战。微血管炎症对异体移植物的结局影响尚不清楚。
方法：
研究者进行了一项队列研究，涵盖了来自欧洲和北美洲30多个移植中心的肾移植受者，这些受者在2004年至2023年期间接受过异体移植物活检。本研究整合了临床和病理数据，并根据2022年Banff肾脏异体移植物病理学分类对活检样本进行分类，该分类包括两个新的诊断类别：可能的抗体介导的排斥反应和没有抗体介导反应证据的微血管炎症。研究者进一步评估了新识别的微血管炎症表型与移植物存活和疾病进展之间的关联。
结果：
研究共评估了6798名患者的16,293份肾移植活检样本。研究者在788份样本中发现了新识别的微血管炎症表型，其中641份样本之前被归类为无排斥反应证据的标本。与没有排斥反应的患者相比，没有抗体介导反应证据的微血管炎症患者的移植物丢失风险比为2.1（95% CI，1.5-3.1），而在抗体介导排斥反应患者中，移植物失功的风险比为2.7（95% CI，2.2-3.3）。在活检后随访超过5年以上的患者中，诊断为可能存在抗体介导的排斥反应的患者，其移植物失功的风险较没有排斥反应的患者显著增加（风险比，1.7；95% CI，0.8-3.5）。此外，在随访期间，诊断出新识别的微血管炎症表型的患者比没有微血管炎症的患者有更高的移植肾小球病进展风险。
结论：
肾脏异体移植中的微血管炎症包括不同的表型，其疾病进展和异体移植结局也各不相同。本研究结果支持临床使用更多的排斥表型来标准化肾脏异体移植的诊断。
14.Low-Dose Yellow Fever Vaccine in Adults in Africa
非洲成人接种低剂量黄热病疫苗
肯尼亚医学研究所
塞内加尔达喀尔巴斯德研究所
Abstract
Background
Yellow fever vaccine is highly effective with a single dose, but vaccine supply is limited. The minimum dose requirements for seroconversion remain unknown.
Methods
In this double-blind, randomized, noninferiority trial in Uganda and Kenya, we assigned adults with no history of yellow fever vaccination or infection to receive vaccination with the Institut Pasteur de Dakar 17D-204 yellow fever vaccine at a standard dose (13,803 IU) or at a fractional dose of 1000 IU, 500 IU, or 250 IU. The primary outcome was seroconversion at 28 days after vaccination with each fractional dose as compared with the standard dose, evaluated in a noninferiority analysis. Seroconversion was defined as an antibody titer at day 28 that was at least four times as high as the antibody titer before vaccination, as measured by a plaque reduction neutralization test. We conducted noninferiority analyses in the per-protocol and intention-to-treat populations. Noninferiority was shown if the lower boundary of the 95% confidence interval for the difference in the incidence of seroconversion between the fractional dose and the standard dose was higher than −10 percentage points.
Results
A total of 480 participants underwent randomization (120 participants in each group). The incidence of seroconversion was 98% (95% confidence interval [CI], 94 to 100) with the standard dose. The difference in the incidence of seroconversion between the 1000-IU dose and the standard dose was 0.01 percentage points (95% CI, −5.0 to 5.1) in the intention-to-treat population and −1.9 percentage points (95% CI, −7.0 to 3.2) in the per-protocol population; the corresponding differences between the 500-IU dose and the standard dose were 0.01 percentage points (95% CI, −5.0 to 5.1) and −1.8 percentage points (95% CI, −6.7 to 3.2), and those between the 250-IU dose and the standard dose were −4.4 percentage points (95% CI, −9.4 to 0.7) and −6.7 percentage points (95% CI, −11.7 to 1.6). A total of 111 vaccine-related adverse events were reported: 103 were mild in severity, 7 were moderate, and 1 was severe. The incidence of adverse events was similar in the four groups.
Conclusions
A yellow fever vaccination dose as low as 500 IU was noninferior to the standard dose of 13,803 IU for producing seroconversion within 28 days.
摘要：
背景：
黄热病疫苗单剂接种即具有高效性，但疫苗供应有限。目前实现血清转换所需的最低剂量尚不清楚。
方法：
在这项于乌干达和肯尼亚开展的双盲、随机、非劣效性试验中，研究者招募了没有黄热病疫苗接种史和感染史的成年人，随机分配他们接受达喀尔巴斯德研究所生产的17D-204黄热病疫苗的标准剂量（13,803 IU）或部分剂量（1000 IU、500 IU或250 IU）。主要结局是在接种疫苗后28天，各个部分剂量组与标准剂量组相比的血清转换率，通过非劣效性分析进行评估。血清转换定义为第28天的抗体滴度至少是接种疫苗前抗体滴度的四倍，通过蚀斑减少中和试验测量。研究者对符合方案人群和意向性治疗人群进行了非劣效性分析。如果部分剂量和标准剂量之间血清转换率差异的95%CI的下限高于-10%，则认为达到了非劣效性。
结果：
共有480名参与者被随机分配（每组120名）。标准剂量组的血清转换率为98%（95% CI，94-100）。在意向治疗人群中，1000 IU剂量与标准剂量之间的血清转换率差异为0.01%（95% CI，-5.0至5.1），在符合方案人群中为-1.9%（95% CI，-7.0至3.2）；500 IU剂量与标准剂量之间的差异分别为0.01%（95% CI，-5.0至5.1）和-1.8%（95% CI，-6.7至3.2）；250 IU与标准剂量之间的差异分别为-4.4%（95% CI，-9.4至0.7）和-6.7%（95% CI，-11.7至-1.6）。共报告111起与疫苗相关的不良事件：103起为轻度，7起为中度，1起为重度。四组的不良事件发生率相似。
结论：
在28天内实现血清转换方面，500 IU以上的黄热病疫苗剂量不劣于13,803 IU的标准剂量。此结果支持低剂量疫苗作为有效的替代方案。
汇报人：倪恬
导师：赵宇
审核：夏晓旭、饶郁芳、任建君
