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在接受单中心治疗性低温临床试验的婴儿和儿童心脏骤停后,血清冷应激激素 FGF21 和 GDF-15 水平。

Serum levels of the cold stress hormones FGF21 and GDF-15 after cardiac arrest in infants and children enrolled in single center therapeutic hypothermia clinical trials.

机构信息

Departments of Critical Care Medicine, Pittsburgh, PA, USA; Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine and UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.

Departments of Critical Care Medicine, Pittsburgh, PA, USA; Pediatrics, Pittsburgh, PA, USA; Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine and UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.

出版信息

Resuscitation. 2022 Mar;172:173-180. doi: 10.1016/j.resuscitation.2021.11.016. Epub 2021 Nov 22.

Abstract

OBJECTIVE

Fibroblast Growth Factor 21 (FGF21) and Growth Differentiation Factor-15 (GDF-15) are putative neuroprotective cold stress hormones (CSHs) provoked by cold exposure that may be age-dependent. We sought to characterize serum FGF21 and GDF-15 levels in pediatric cardiac arrest (CA) patients and their association with use of therapeutic hypothermia (TH).

METHODS

Secondary analysis of serum samples from clinical trials. We measured FGF21 and GDF-15 levels in pediatric patients post-CA and compared levels to both pediatric intensive care (PICU) and healthy controls. Post-CA, we compared normothermia (NT) vs TH (33 °C for 72 h) treated cohorts at < 24 h, 24 h, 48 h, 72 h, and examined the change in CSHs over 72 h. We also assessed association between hospital mortality and initial levels.

RESULTS

We assessed 144 samples from 68 patients (27 CA [14 TH, 13 NT], 9 PICU and 32 healthy controls). Median initial FGF21 levels were higher post-CA vs. healthy controls (392 vs. 40 pg/mL, respectively, P < 0.001). Median GDF-15 levels were higher post-CA vs. healthy controls (7,089 vs. 396 pg/mL, respectively, P < 0.001). In the CA group, the median change in FGF21 from PICU day 1-3 (after 72 h of temperature control), was higher in TH vs. NT (231 vs. -20 pg/mL, respectively, P < 0.05), with no difference in GDF-15 over time. Serum GDF-15 levels were higher in CA patients that died vs. survived (19,450 vs. 5,337 pg/mL, respectively, P < 0.05), whereas serum FGF21 levels were not associated with mortality.

CONCLUSION

Serum levels of FGF21 and GDF-15 increased after pediatric CA, and FGF21 appears to be augmented by TH.

摘要

目的

成纤维细胞生长因子 21(FGF21)和生长分化因子 15(GDF-15)是推测的神经保护冷应激激素(CSHs),由冷暴露引发,可能具有年龄依赖性。我们试图描述儿科心搏骤停(CA)患者血清中 FGF21 和 GDF-15 的水平,并探讨其与低温治疗(TH)的关系。

方法

对临床试验中的血清样本进行二次分析。我们测量了儿科 CA 患者发病后的 FGF21 和 GDF-15 水平,并将其与儿科重症监护病房(PICU)和健康对照组进行比较。发病后,我们比较了 24 小时内、24 小时、48 小时、72 小时内接受常规体温(NT)和 TH(33°C 持续 72 小时)治疗的两组患者的水平,并观察了 72 小时内 CSH 的变化。我们还评估了初始水平与住院死亡率之间的关系。

结果

我们评估了 68 例患者的 144 个样本(27 例 CA[14 例 TH,13 例 NT],9 例 PICU 和 32 例健康对照组)。与健康对照组相比,CA 患者的初始 FGF21 水平更高(分别为 392pg/ml 和 40pg/ml,P<0.001)。CA 患者的 GDF-15 水平高于健康对照组(分别为 7089pg/ml 和 396pg/ml,P<0.001)。在 CA 组中,TH 组与 NT 组相比,从 PICU 第 1 天到第 3 天(体温控制 72 小时后)FGF21 的中位数变化更大(分别为 231pg/ml 和-20pg/ml,P<0.05),而 GDF-15 在整个时间内无差异。与存活患者相比,死亡患者的血清 GDF-15 水平更高(分别为 19450pg/ml 和 5337pg/ml,P<0.05),而血清 FGF21 水平与死亡率无关。

结论

儿科 CA 后血清 FGF21 和 GDF-15 水平升高,FGF21 似乎由 TH 增强。

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