2023年3月30日 |《新英格兰医学杂志》英文音频和中英文摘要

阿奇霉素预防计划经阴道分娩产妇的脓毒症或死亡

背景

阿奇霉素可以降低计划外剖宫产产妇的感染风险，但对计划经阴道分娩产妇的影响尚不清楚。我们需要了解产程中口服阿奇霉素能否降低产妇和后代的脓毒症或死亡风险。

方法

在这项国际性、安慰剂对照、随机试验中，我们将孕周≥28并计划经阴道分娩的产妇分组，分别口服阿奇霉素2 g或安慰剂。两项主要结局是由产妇脓毒症或死亡构成的复合结局，以及由死产或者新生儿死亡或脓毒症构成的复合结局。在期中分析中，数据和安全监查委员会建议，为了产妇的利益，停止该试验。

结果

共计29,278名产妇接受了随机分组。阿奇霉素组的产妇脓毒症或死亡发生率低于安慰剂组（1.6% vs. 2.4%），相对危险度为0.67（95%置信区间[CI]，0.56~0.79；P<0.001），但死产或者新生儿死亡或脓毒症的发生率相似（10.5% vs. 10.3%），相对危险度为1.02（95% CI，0.95~1.09；P=0.56）。产妇主要结局的差异似乎主要源于脓毒症发生率（阿奇霉素组为1.5%，安慰剂组为2.3%），相对危险度为0.65（95% CI，0.55~0.77）；两组的全因死亡率均为0.1%（相对危险度，1.23；95% CI，0.51~2.97）。新生儿脓毒症发生率分别为9.8% vs. 9.6%（相对危险度，1.03；95% CI，0.96~1.10）。两组死产发生率均为0.4%（相对危险度，1.06；95% CI，0.74~1.53）；两组出生后4周内的新生儿死亡率均为1.5%（相对危险度，1.03；95% CI，0.86~1.24）。阿奇霉素组的不良事件发生率并未高于安慰剂组。

Result

A total of 29,278 women underwent randomization. The incidence of maternal sepsis or death was lower in the azithromycin group than in the placebo group (1.6% vs. 2.4%), with a relative risk of 0.67 (95% confidence interval [CI], 0.56 to 0.79; P<0.001), but the incidence of stillbirth or neonatal death or sepsis was similar (10.5% vs. 10.3%), with a relative risk of 1.02 (95% CI, 0.95 to 1.09; P=0.56). The difference in the maternal primary outcome appeared to be driven mainly by the incidence of sepsis (1.5% in the azithromycin group and 2.3% in the placebo group), with a relative risk of 0.65 (95% CI, 0.55 to 0.77); the incidence of death from any cause was 0.1% in the two groups (relative risk, 1.23; 95% CI, 0.51 to 2.97). Neonatal sepsis occurred in 9.8% and 9.6% of the infants, respectively (relative risk, 1.03; 95% CI, 0.96 to 1.10). The incidence of stillbirth was 0.4% in the two groups (relative risk, 1.06; 95% CI, 0.74 to 1.53); neonatal death within 4 weeks after birth occurred in 1.5% in both groups (relative risk, 1.03; 95% CI, 0.86 to 1.24). Azithromycin was not associated with a higher incidence in adverse events.

结论

在计划经阴道分娩的产妇中，单次口服阿奇霉素使产妇脓毒症或死亡风险显著低于安慰剂，但对新生儿脓毒症或死亡的影响很小。(由尤尼斯·肯尼迪·施莱佛国立儿童健康与人类发展研究所[Eunice Kennedy Shriver National Institute of Child Health and Human Development]等资助；A-PLUS在ClinicalTrials.gov注册号为NCT03871491）。

Conclusions

Among women planning a vaginal delivery, a single oral dose of azithromycin resulted in a significantly lower risk of maternal sepsis or death than placebo but had little effect on newborn sepsis or death. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; A-PLUS ClinicalTrials.gov number, NCT03871491.)

慢性严重肢体缺血的经导管深静脉动脉化治疗

Transcatheter Arterialization of Deep Veins in Chronic Limb-Threatening Ischemia

背景

约20%的慢性严重肢体缺血患者没有可供血运重建的血管，因此需要在脚踝以上水平截肢。经导管深静脉动脉化是一种经皮治疗方法，可以连通动脉与静脉，通过静脉系统向缺血的脚部输送含氧血液，从而避免截肢。

我们开展了一项前瞻性、单组、多中心研究，纳入溃疡不愈合且没有手术或血管内血运重建治疗机会的患者，以评估经导管深静脉动脉化的疗效。复合主要终点是6个月内无截肢生存率（定义为未发生脚踝以上水平截肢或任何原因死亡），操作性目标（performance goal）设为54%。次要终点包括肢体挽救、伤口愈合和手术取得技术成功。

We conducted a prospective, single-group, multicenter study to evaluate the effect of transcatheter arterialization of the deep veins in patients with nonhealing ulcers and no surgical or endovascular revascularization treatment options. The composite primary end point was amputation-free survival (defined as freedom from above-ankle amputation or death from any cause) at 6 months, as compared with a performance goal of 54%. Secondary end points included limb salvage, wound healing, and technical success of the procedure.

我们招募了105名慢性严重肢体缺血患者，中位年龄为70岁（四分位距，38~89）。在纳入的患者中，33人（31.4%）为女性，45人（42.8%）为黑种人、西班牙语裔或拉丁裔。104名患者（99.0%）成功进行了经导管深静脉动脉化手术。6个月时，无截肢生存率为66.1%。根据贝叶斯分析，6个月时无截肢生存率超过54%操作性目标的后验概率为0.993，超过了预先设定的0.977阈值。67名患者实现了肢体挽救（避免了脚踝以上水平的截肢）（Kaplan-Meier分析结果为76.0%）。63名患者中有16名（25%）的伤口完全愈合，63名患者中有32名（51%）的伤口正在愈合中。未报告意料之外的设备相关不良事件。

Result

结论

我们发现，在慢性严重肢体缺血且缺乏常规手术或血管内治疗方案的患者中，经导管深静脉动脉化治疗是安全的，而且可以成功实施。(由LimFlow资助；PROMISE II在ClinicalTrials.gov注册号为NCT03970538。)

Conclusions

幽门螺杆菌、同源重组基因和胃癌的关系

Helicobacter pylori, Homologous-Recombination Genes, and Gastric Cancer

背景

幽门螺杆菌感染是众所周知的胃癌危险因素。然而，癌症易感基因的胚系致病变异体以及它们与幽门螺杆菌感染同时存在时对胃癌风险的影响尚未广泛评估。

结果

9个基因（APC、ATM、BRCA1、BRCA2、CDH1、MLH1、MSH2、MSH6和PALB2）的胚系致病变异体与胃癌风险相关。在HERPACC样本中，我们发现在胃癌风险方面，幽门螺杆菌感染和同源重组基因的致病变异体之间存在交互作用（交互作用导致的相对超额危险度，16.01；95%置信区间[CI]， 2.22~29.81；P=0.02）。在85岁时，有致病变异体的幽门螺杆菌感染者的胃癌累积风险高于感染幽门螺杆菌的非致病变异体携带者（45.5% [95% CI，20.7~62.6] vs. 14.4% [95% CI，12.2~16.6]）。

Result

Germline pathogenic variants in nine genes (APC, ATM, BRCA1, BRCA2, CDH1, MLH1, MSH2, MSH6, and PALB2) were associated with the risk of gastric cancer. We found an interaction between H. pylori infection and pathogenic variants in homologous-recombination genes with respect to the risk of gastric cancer in the sample from HERPACC (relative excess risk due to the interaction, 16.01; 95% confidence interval [CI], 2.22 to 29.81; P=0.02). At 85 years of age, persons with H. pylori infection and a pathogenic variant had a higher cumulative risk of gastric cancer than noncarriers infected with H. pylori (45.5% [95% CI, 20.7 to 62.6] vs. 14.4% [95% CI, 12.2 to 16.6]).

结论

幽门螺杆菌感染改变了与同源重组基因胚系致病变异体相关的胃癌风险。（由日本医学研究与发展机构[Japan Agency for Medical Research and Development]等资助。）

Conclusions