Metabolomics in pneumonia and sepsis: an analysis of the GenIMS cohort study.
Metabolomics in pneumonia and sepsis: an analysis of the GenIMS cohort study.
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DOI：
10.1007/s00134-013-2935-7
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发表时间：
2013-08
影响因子：
38.9
通讯作者：
Angus, Derek C.
中科院分区：
文献类型：
--
作者：
Seymour, Christopher W.;Yende, Sachin;Scott, Melanie J.;Pribis, John;Mohney, Robert P.;Bell, Lauren N.;Chen, Yi-Fan;Zuckerbraun, Brian S.;Bigbee, William L.;Yealy, Donald M.;Weissfeld, Lisa;Kellum, John A.;Angus, Derek C.
确定社区获得性肺炎（CAP）和脓毒症存活和非存活患者循环血浆中测定的总体代谢组学特征。随机、结局分层病例对照样本来自一项前瞻性研究，该研究纳入了1，895例因CAP和脓毒症住院的患者。病例组（n = 15）为90天内死亡的成人，对照组（n = 15）为存活的成人，人口统计学、感染类型和降钙素原匹配。我们使用非靶向质谱法确定了第一个急诊科血液样本的总体代谢组学特征。我们推导了基于代谢物的90天死亡率预测模型。我们确定了代谢物是否刺激分化的Thp 1单核细胞在体外产生细胞因子，并验证了盲肠结扎穿孔（CLP）脓毒症小鼠肝脏和肾脏匀浆中8小时的代谢物谱。我们鉴定了423种小分子，其中70种（17%）的相对水平在幸存者和非幸存者之间存在差异（p ≤ 0.05）。在氧化应激、胆汁酸代谢和应激反应的途径上存在广泛的差异。90天生存期的基于代谢物的预后模型表现一般（AUC = 0.67，95% CI 0.48，0.81）。在非存活者中，5种核酸代谢产物更高（p ≤ 0.05）。其中，与对照组相比，假尿苷增加了单核细胞TNFα和IL 1 β的表达（p < 0.05）。与假手术组相比，CLP小鼠的肝和肾匀浆中的假尿苷也增加（两者p < 0.05）。虽然需要复制，但我们发现CAP和脓毒症的幸存者和非幸存者之间血浆中的总体代谢组学谱存在很大差异。代谢物为基础的预后模型有适度的性能，虽然氧化应激代谢物可能作为推定的损伤相关的分子模式。
To determine the global metabolomic profile as measured in circulating plasma from surviving and non-surviving patients with community-acquired pneumonia (CAP) and sepsis. Random, outcome-stratified case–control sample from a prospective study of 1,895 patients hospitalized with CAP and sepsis. Cases (n = 15) were adults who died before 90 days, and controls (n = 15) were adults who survived, matched on demographics, infection type, and procalcitonin. We determined the global metabolomic profile in the first emergency department blood sample using non-targeted mass-spectrometry. We derived metabolite-based prognostic models for 90-day mortality. We determined if metabolites stimulated cytokine production by differentiated Thp1 monocytes in vitro, and validated metabolite profiles in mouse liver and kidney homogenates at 8 h in cecal ligation and puncture (CLP) sepsis. We identified 423 small molecules, of which the relative levels of 70 (17 %) were different between survivors and non-survivors (p ≤ 0.05). Broad differences were present in pathways of oxidative stress, bile acid metabolism, and stress response. Metabolite-based prognostic models for 90-day survival performed modestly (AUC = 0.67, 95 % CI 0.48, 0.81). Five nucleic acid metabolites were greater in non-survivors (p ≤ 0.05). Of these, pseudouridine increased monocyte expression of TNFα and IL1β versus control (p < 0.05). Pseudouridine was also increased in liver and kidney homogenates from CLP mice versus sham (p < 0.05 for both). Although replication is required, we show the global metabolomic profile in plasma broadly differs between survivors and non-survivors of CAP and sepsis. Metabolite-based prognostic models had modest performance, though metabolites of oxidative stress may act as putative damage-associated molecular patterns.
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影响因子：
8.8
作者：
Beier K;Eppanapally S;Bazick HS;Chang D;Mahadevappa K;Gibbons FK;Christopher KB
通讯作者：
Christopher KB
影响因子：
120.7
作者：
Jones, Alan E.;Shapiro, Nathan I.;Trzeciak, Stephen;Arnold, Ryan C.;Claremont, Heather A.;Kline, Jeffrey A.
通讯作者：
Kline, Jeffrey A.
DOI：
10.1186/cc2959
发表时间：
2004-12
期刊：
Critical care (London, England)
影响因子：
--
作者：
Poeze M;Ramsay G;Gerlach H;Rubulotta F;Levy M
通讯作者：
Levy M
影响因子：
5
作者：
AMURO, Y;NAKAOKA, H;HIGASHINO, K
通讯作者：
HIGASHINO, K
影响因子：
2.1
作者：
Hinkelbein, Jochen;Feldmann, Robert E.;Kalenka, Armin
通讯作者：
Kalenka, Armin