Did they just prove that a diagnosis of "septic shock" is meaningless?
Did they just prove that a diagnosis of "septic shock" is meaningless?
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他们只是证明“感染性休克”的诊断毫无意义吗？
DOI：
10.1164/rccm.201404-0632ed
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发表时间：
2014
影响因子：
24.7
通讯作者：
Govindan,Sushant
中科院分区：
文献类型：
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作者：
Iwashyna,TheodoreJ;Govindan,Sushant
Annane和他的同事在2005年《柳叶刀》杂志上发表的一篇关于感染性休克的综述经常被引用，其中有一组可爱的图表(1)。在他们的图1中，顶部有一个标记为“细菌”的小椭圆形。这种普通感染至少触发了8个单独确定的效应途径，这些效应途径分支出来，显示出“从细菌到疾病”的多个系统。在他们的图2中，展示了数十种细胞内相互作用，但细菌唯一的遗迹是细胞外脂多糖。到2013年，Angus和van der Poll的NEJM综述图1完全是关于“严重败血症中的宿主反应”——病原体几乎是看不见的(2)。在对严重败血症的理解中，故事是关于宿主反应，特别是失调的炎症和凝血障碍级联反应。病原体只有在它们产生生理上有趣的分子模式从而触发宿主反应时才会进入。在这一期的《杂志》（第1204-1213页）中，由Leligdowicz博士领导的败血性休克合作抗菌治疗（CATSS）数据库研究小组试图为这一观点注入一个不一致的音符(3)。重症监护病房的从业人员和研究人员都很熟悉这一群体，我们在感染性休克中使用抗生素的时间至关重要的最佳证据就是来自这一群体(4)。在一个扩展的数据库中，作者现在问道，一旦产生感染性休克，所有感染真的都是一样的吗？Leligdowicz和他的同事认为感染性休克有重要的区别。该小组调查了近8000名被诊断为感染性休克的患者。他们发现，医院死亡率随感染源的变化具有临床意义和统计学意义。调整后的死亡率各部位不同，从约三分之一（憩室炎和梗阻相关性尿路感染）到近四分之三（几种腹部感染）。在调整了许多易感因素和下游因素后，这种差异仍然存在，包括入院年份、人口统计学、12种合并症，甚至急性生理和慢性健康评估II （APACHE II）评分。作者建议我们应该考虑感染源，以便对患者进行适当的风险分层，并评估所有影响死亡率的潜在因素以进行干预。作者已经表明，脓毒性休克患者的感染源在短期预后方面存在关键差异。他们是否因此证明了“宿主反应”共识是错误的？更一般地说，它们是否表明我们目前对“败血症”作为一种有意义的诊断的理解过于严重或过于简单化？这些问题取决于我们到底想从诊断中得到什么。关于急性呼吸窘迫综合征的柏林定义的冲突可以用类似的方式来解释（5,6）。我们想说的是，可能我们想从一个诊断中得到太多的东西——甚至是一个疾病诊断，更不用说公认的“综合征”诊断了（见表1）。对于某些情况，特别是研究中的情况，诊断应该是直截了当的：它是一种独特病理障碍的临床表现。我们想从诊断中得到的是定义一个足够同质的临床实体，以便我们能够确定产生said
Annane and colleagues’ oft-cited 2005 review of septic shock in The Lancet features a lovely set of graphics (1). In their Figure 1, there is a small oval at the top labeled “Bacteria.” This generic infection triggers at least eight separately identified effector pathways, which ramify out to show the multiple systems that lead “from bacteria to disease.” In their Figure 2, dozens of intracellular interactions are laid out, but the only vestige of the bacteria is an extracellular lipopolysaccharide. By 2013, Figure 1 of Angus and van der Poll’s NEJM review is entirely about the “Host Response in Severe Sepsis”—the pathogens are nearly invisible (2). In this understanding of severe sepsis, the story is about the host response, particularly the dysregulated inflammatory and coagulopathic cascades. Pathogens enter only to the extent that they create physiologically interesting molecular patterns that trigger this host response. In this issue of the Journal (pp. 1204–1213), the Co-operative Antimicrobial Therapy of Septic Shock (CATSS) Database Research Group, led by Dr. Leligdowicz, seeks to inject a note of discord into this perspective (3). This is a group well known to intensive care unit practitioners and researchers alike—the group whence our best evidence for the critical importance of time to antibiotics in septic shock came (4). In an expanded database, the authors now ask, are all infections really the same once they produce septic shock? Leligdowicz and colleagues suggest there are important differences within septic shock. The group examined a cohort of nearly 8,000 patients diagnosed with septic shock. They found that there was clinically meaningful and statistically significant variation in hospital mortality as a function of the source of infection. Adjusted mortality varied among sites from about one-third (diverticulitis and obstruction-related urinary tract infection) to nearly three-fourths (several abdominal infections). This variation persisted after adjusting for a multitude of predisposing and downstream factors, including year of admission, demographics, 12 comorbidities, and even Acute Physiology and Chronic Health Evaluation II (APACHE II) score. The authors suggest that we should take into account sources of infection so that patients are appropriately risk stratified and all potential factors impacting mortality are evaluated for interventions. The authors have shown that there are crucial differences in short-term outcomes by source of infection in patients with septic shock. Have they thereby proven the “host response” consensus to be wrong? More generally, have they shown that our current understanding of “sepsis” as a meaningful diagnosis is too severe an oversimplification? These questions hinge on what exactly we want from a diagnosis. The conflict over the Berlin definition of acute respiratory distress syndrome may be interpreted in a similar light (5, 6). It may be, we would like to suggest, that we want too many things from a single diagnosis—even a disease diagnosis, let alone an admittedly “syndromic” diagnosis (see Table 1). For some situations, particularly those of research, a diagnosis should be straightforward: it is a clinical representation of a unique pathological disturbance. What we want from a diagnosis is to define a sufficiently homogenous clinical entity for which we can work to identify the specific mechanism that produces said
启动子：结构和功能
DOI：
--
发表时间：
1982
期刊：
影响因子：
--
作者：
Raymond L. Rodriguez;M. Chamberlin
通讯作者：
M. Chamberlin