{"id":17211,"date":"2019-05-22T04:14:15","date_gmt":"2019-05-21T20:14:15","guid":{"rendered":"http:\/\/csccm.org.cn\/?p=17211"},"modified":"2019-06-02T06:41:14","modified_gmt":"2019-06-01T22:41:14","slug":"jama%e6%9c%80%e6%96%b0%e5%8f%91%e8%a1%a8-%e8%84%93%e6%af%92%e7%97%87%e6%96%b0%e4%b8%b4%e5%ba%8a%e8%a1%a8%e5%9e%8b%e7%9a%84%e7%a1%ae%e5%ae%9a%e3%80%81%e9%aa%8c%e8%af%81%e5%8f%8a%e5%8f%af%e8%83%bd","status":"publish","type":"post","link":"https:\/\/csccm.org.cn\/?p=17211","title":{"rendered":"[JAMA\u6700\u65b0\u53d1\u8868]: \u8113\u6bd2\u75c7\u65b0\u4e34\u5e8a\u8868\u578b\u7684\u786e\u5b9a\u3001\u9a8c\u8bc1\u53ca\u53ef\u80fd\u7684\u6cbb\u7597\u63d0\u793a"},"content":{"rendered":"\n

Original Investigation Caring for the Critically Ill PatientMay 19, 2019<\/p>\n\n\n\n

Derivation, Validation, and Potential Treatment Implications of Novel Clinical Phenotypes for Sepsis<\/h1>\n\n\n\n

Christopher W.\u00a0Seymour,\u00a0Jason N.\u00a0Kennedy,\u00a0Shu\u00a0Wang,\u00a0et al<\/h3>\n\n\n\n

JAMA.\u00a0<\/em>Published online May 19, 2019. doi:10.1001\/jama.2019.5791<\/h3>\n\n\n\n

Abstract \u6458\u8981<\/h2>\n\n\n\n

Importance<\/strong>\u00a0\u80cc\u666f<\/h2>\n\n\n\n

Sepsis is a heterogeneous syndrome. Identification of distinct clinical phenotypes may allow more precise therapy and improve care.<\/p>\n\n\n\n

\u8113\u6bd2\u75c7\u662f\u4e00\u79cd\u5f02\u8d28\u6027\u7efc\u5408\u5f81\u3002\u786e\u5b9a\u4e0d\u540c\u7684\u4e34\u5e8a\u8868\u578b\u53ef\u80fd\u6709\u52a9\u4e8e\u6cbb\u7597\u66f4\u52a0\u7cbe\u51c6\u53ca\u7597\u6548\u6539\u5584\u3002<\/p>\n\n\n\n

Objective<\/strong>\u00a0\u76ee\u7684<\/h2>\n\n\n\n

To derive sepsis phenotypes from clinical data, determine their reproducibility and correlation with host-response biomarkers and clinical outcomes, and assess the potential causal relationship with results from randomized clinical trials (RCTs).<\/p>\n\n\n\n

\u901a\u8fc7\u4e34\u5e8a\u6570\u636e\u786e\u5b9a\u8113\u6bd2\u75c7\u8868\u578b\uff0c\u7814\u7a76\u5176\u53ef\u91cd\u590d\u6027\u4ee5\u53ca\u4e0e\u5bbf\u4e3b\u53cd\u5e94\u751f\u7269\u6807\u5fd7\u7269\u548c\u4e34\u5e8a\u9884\u540e\u7684\u76f8\u5173\u6027\uff0c\u6839\u636eRCT\u7ed3\u679c\u8bc4\u4ef7\u53ef\u80fd\u7684\u56e0\u679c\u5173\u7cfb\u3002<\/p>\n\n\n\n

Design, Settings, and Participants<\/strong>\u00a0\u8bd5\u9a8c\u8bbe\u8ba1\u3001\u573a\u666f\u53ca\u7814\u7a76\u5bf9\u8c61<\/h2>\n\n\n\n

Retrospective analysis of data sets using statistical, machine learning, and simulation tools. Phenotypes were derived among 20\u202f189 total patients (16\u202f552 unique patients) who met Sepsis-3 criteria within 6 hours of hospital presentation at 12 Pennsylvania hospitals (2010-2012) using consensus\u00a0k<\/em>\u00a0means clustering applied to 29 variables. Reproducibility and correlation with biological parameters and clinical outcomes were assessed in a second database (2013-2014; n\u2009=\u200943\u202f086 total patients and n\u2009=\u200931\u202f160 unique patients), in a prospective cohort study of sepsis due to pneumonia (n\u2009=\u2009583), and in 3 sepsis RCTs (n\u2009=\u20094737).<\/p>\n\n\n\n

\u91c7\u7528\u7edf\u8ba1\u3001\u673a\u5668\u5b66\u4e60\u53ca\u6a21\u62df\u5de5\u5177\u56de\u987e\u6027\u5206\u6790\u6570\u636e\u96c6\u3002\u6839\u636e\u5bbe\u5915\u6cd5\u5c3c\u4e9a\u5dde12\u6240\u533b\u9662(2010-2012)\u6536\u6cbb\u7684\u6ee1\u8db3sepsis-3\u8bca\u65ad\u6807\u51c6\u768420189\u4f8b\u6b21\u4f4f\u9662\uff0816552\u540d\u60a3\u8005\uff09\u6570\u636e\uff0c\u9488\u5bf929\u4e2a\u53c2\u6570\u91c7\u7528\u4e00\u81f4\u6027k\u5747\u503c\u805a\u7c7b\u786e\u5b9a\u8868\u578b\u3002\u91c7\u7528\u7b2c\u4e8c\u4e2a\u6570\u636e\u5e93\uff082013-2014; n\u2009=\u200943\u202f086\u603b\u4f4f\u9662\u4f8b\u6b21\uff0c n\u2009=\u200931\u202f160\u540d\u60a3\u8005\uff09\u4ee5\u53ca\u4e00\u4e2a\u80ba\u708e\u5f15\u8d77\u8113\u6bd2\u75c7\u7684\u524d\u77bb\u961f\u5217(n = 583)\u548c3\u4e2a\u8113\u6bd2\u75c7RCT\u6570\u636e(n = 4737)\u8bc4\u4ef7\u53ef\u91cd\u590d\u6027\u4ee5\u53ca\u540c\u751f\u7269\u5b66\u6307\u6807\u53ca\u4e34\u5e8a\u9884\u540e\u7684\u76f8\u5173\u6027\u3002<\/p>\n\n\n\n

Exposures<\/strong>\u00a0\u66b4\u9732\u56e0\u7d20<\/h2>\n\n\n\n

All clinical and laboratory variables in the electronic health record.<\/p>\n\n\n\n

\u7535\u5b50\u75c5\u5386\u8bb0\u5f55\u4e2d\u6240\u6709\u4e34\u5e8a\u53ca\u5b9e\u9a8c\u5ba4\u6570\u636e\u3002<\/p>\n\n\n\n

Main Outcomes and Measures<\/strong>\u00a0\u4e3b\u8981\u9884\u540e\u6307\u6807<\/h2>\n\n\n\n

Derived phenotype (\u03b1, \u03b2, \u03b3,<\/em>\u00a0and \u03b4) frequency, host-response biomarkers, 28-day and 365-day mortality, and RCT simulation outputs.<\/p>\n\n\n\n

\u786e\u5b9a\u8868\u578b(\u03b1, \u03b2, \u03b3 \u548c \u03b4)\u9891\u7387\uff0c\u5bbf\u4e3b\u53cd\u5e94\u751f\u7269\u6807\u5fd7\u7269\uff0c28\u5929\u53ca365\u5929\u75c5\u6b7b\u7387\uff0c\u4ee5\u53caRCT\u6a21\u62df\u7ed3\u679c\u7b49\u3002<\/p>\n\n\n\n

Results<\/strong>\u00a0\u7ed3\u679c<\/h2>\n\n\n\n

The derivation cohort included 20\u202f189 patients with sepsis (mean age, 64 [SD, 17] years; 10\u202f022 [50%] male; mean maximum 24-hour Sequential Organ Failure Assessment [SOFA] score, 3.9 [SD, 2.4]). The validation cohort included 43\u202f086 patients (mean age, 67 [SD, 17] years; 21\u202f993 [51%] male; mean maximum 24-hour SOFA score, 3.6 [SD, 2.0]). Of the 4 derived phenotypes, the \u03b1 phenotype was the most common (n\u2009=\u20096625; 33%) and included patients with the lowest administration of a vasopressor; in the \u03b2 phenotype (n\u2009=\u20095512; 27%), patients were older and had more chronic illness and renal dysfunction; in the \u03b3 phenotype (n\u2009=\u20095385; 27%), patients had more inflammation and pulmonary dysfunction; and in the \u03b4 phenotype (n\u2009=\u20092667; 13%), patients had more liver dysfunction and septic shock. Phenotype distributions were similar in the validation cohort. There were consistent differences in biomarker patterns by phenotype. In the derivation cohort, cumulative 28-day mortality was 287 deaths of 5691 unique patients (5%) for the \u03b1 phenotype; 561 of 4420 (13%) for the \u03b2 phenotype; 1031 of 4318 (24%) for the \u03b3 phenotype; and 897 of 2223 (40%) for the \u03b4 phenotype. Across all cohorts and trials, 28-day and 365-day mortality were highest among the \u03b4 phenotype vs the other 3 phenotypes (P<\/em>\u2009<\u2009.001). In simulation models, the proportion of RCTs reporting benefit, harm, or no effect changed considerably (eg, varying the phenotype frequencies within an RCT of early goal-directed therapy changed the results from >33% chance of benefit to >60% chance of harm).<\/p>\n\n\n\n

\u63a8\u5bfc\u961f\u5217\u5305\u62ec20189\u540d\u8113\u6bd2\u75c7\u60a3\u8005\uff08\u5e73\u5747\u5e74\u9f84 64 [SD, 17] \u5c81\uff1b10\u202f022\u540d [50%]\u7537\u6027\uff1b24\u5c0f\u65f6\u6700\u9ad8SOFA\u8bc4\u5206\u5747\u503c\uff0c3.9 [SD, 2.4]\uff09\u3002\u9a8c\u8bc1\u961f\u5217\u5305\u62ec43086\u540d\u60a3\u8005\uff08\u5e73\u5747\u5e74\u9f84 67 [SD, 17] \u5c81\uff1b21\u202f993\u540d [51%]\u7537\u6027\uff1b24\u5c0f\u65f6\u6700\u9ad8SOFA\u8bc4\u5206\u5747\u503c\uff0c3.6 [SD, 2.0]\uff09\u3002\u5728\u786e\u5b9a\u76844\u79cd\u8868\u578b\u4e2d\uff0c\u03b1 \u8868\u578b\u6700\u4e3a\u5e38\u89c1(n\u2009=\u20096625; 33%)\uff0c\u4f7f\u7528\u5347\u538b\u836f\u7269\u5242\u91cf\u6700\u5c0f\uff1b\u03b2 \u8868\u578b (n\u2009=\u20095512; 27%) \u60a3\u8005\u5e74\u9f84\u8f83\u5927\uff0c\u6709\u5f88\u591a\u7684\u6162\u6027\u75c5\u53ca\u80be\u529f\u80fd\u4e0d\u5168\uff1b\u03b3 \u8868\u578b (n\u2009=\u20095385; 27%) \u60a3\u8005\u708e\u75c7\u53cd\u5e94\u548c\u547c\u5438\u529f\u80fd\u4e0d\u5168\u66f4\u591a\uff1b\u03b4 \u8868\u578b (n\u2009=\u20092667; 13%) \u60a3\u8005\u66f4\u591a\u53d1\u751f\u809d\u810f\u529f\u80fd\u4e0d\u5168\u53ca\u611f\u67d3\u6027\u4f11\u514b\u3002\u9a8c\u8bc1\u961f\u5217\u4e2d\u8868\u578b\u5206\u5e03\u76f8\u4f3c\u3002\u4e0d\u540c\u8868\u578b\u60a3\u8005\u751f\u7269\u6807\u5fd7\u7269\u7684\u5dee\u5f02\u4e00\u81f4\u3002\u63a8\u5bfc\u961f\u5217\u7d2f\u79ef28\u5929\u75c5\u6b7b\u7387\uff0c\u03b1 \u8868\u578b\u4e3a287\/5691 (5%)\uff1b\u03b2 \u8868\u578b\u4e3a561\/4420 (13%)\uff1b\u03b3\u8868\u578b\u4e3a1031\/4318 (24%)\uff1b\u03b4\u8868\u578b\u4e3a897\/2223 (40%)\u3002\u5728\u6240\u6709\u961f\u5217\u53ca\u4e34\u5e8a\u8bd5\u9a8c\u4e2d\uff0c\u03b4 \u8868\u578b\u60a3\u800528\u5929\u53ca365\u5929\u75c5\u6b7b\u7387\u6700\u9ad8(P<\/em>\u2009<\u2009.001)\u3002\u5728\u6a21\u62df\u6a21\u578b\u4e2d\uff0c\u62a5\u544a\u83b7\u76ca\u3001\u6709\u5bb3\u6216\u65e0\u6548\u7684RCT\u6bd4\u4f8b\u53d8\u5316\u663e\u8457\uff08\u4f8b\u5982\uff0c\u65e9\u671f\u76ee\u6807\u6307\u5bfc\u6cbb\u7597\u7684\u4e00\u9879RCT\u4e2d\uff0c\u6539\u53d8\u8868\u578b\u9891\u7387\u80fd\u591f\u663e\u8457\u6539\u53d8\u8bd5\u9a8c\u7ed3\u679c\uff0c\u4ece\u83b7\u76ca\u6982\u7387> 33%\u5230\u6709\u5bb3\u6982\u7387> 60%\uff09\u3002<\/p>\n\n\n\n

\"\"\/<\/figure>\n\n\n\n
\"\"\/<\/figure>\n\n\n\n
\"\"\/<\/figure>\n\n\n\n
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\"\"\/<\/figure>\n\n\n\n
\"\"\/<\/figure>\n\n\n\n
\"\"\/<\/figure>\n\n\n\n

Conclusions and Relevance<\/strong>\u00a0\u7ed3\u8bba\u4e0e\u610f\u4e49<\/h2>\n\n\n\n

In this retrospective analysis of data sets from patients with sepsis, 4 clinical phenotypes were identified that correlated with host-response patterns and clinical outcomes, and simulations suggested these phenotypes may help in understanding heterogeneity of treatment effects. Further research is needed to determine the utility of these phenotypes in clinical care and for informing trial design and interpretation.<\/p>\n\n\n\n

\u5728\u8fd9\u9879\u5bf9\u4e8e\u8113\u6bd2\u75c7\u60a3\u8005\u6570\u636e\u96c6\u7684\u56de\u987e\u6027\u5206\u6790\u4e2d\uff0c\u6211\u4eec\u53d1\u73b0\u4e86\u4e0e\u5bbf\u4e3b\u53cd\u5e94\u79cd\u7c7b\u53ca\u4e34\u5e8a\u9884\u540e\u76f8\u5173\u76844\u79cd\u4e34\u5e8a\u8868\u578b\uff0c\u6a21\u62df\u5206\u6790\u63d0\u793a\uff0c\u8fd9\u4e9b\u8868\u578b\u53ef\u80fd\u6709\u52a9\u4e8e\u4e86\u89e3\u6cbb\u7597\u6548\u679c\u7684\u5f02\u8d28\u6027\u3002\u9700\u8981\u8fdb\u4e00\u6b65\u7814\u7a76\u786e\u5b9a\u8fd9\u4e9b\u8868\u578b\u5728\u4e34\u5e8a\u5de5\u4f5c\u4e2d\u7684\u7528\u9014\uff0c\u4ee5\u53ca\u5bf9\u4e34\u5e8a\u8bd5\u9a8c\u8bbe\u8ba1\u53ca\u7ed3\u679c\u89e3\u8bfb\u7684\u610f\u4e49\u3002<\/p>\n","protected":false},"excerpt":{"rendered":"

Original Investigation Caring for the Critically I […]<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[32,23],"tags":[],"_links":{"self":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/17211"}],"collection":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=17211"}],"version-history":[{"count":2,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/17211\/revisions"}],"predecessor-version":[{"id":17213,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/17211\/revisions\/17213"}],"wp:attachment":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=17211"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=17211"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=17211"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}