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新生儿脑膜炎:借助组学技术应对诊断、预后及治疗方面的挑战

Neonatal Meningitis: Overcoming Challenges in Diagnosis, Prognosis, and Treatment with Omics.

作者信息

Gordon Scott M, Srinivasan Lakshmi, Harris Mary Catherine

机构信息

Division of Neonatology, Children's Hospital of Philadelphia, Philadelphia, PA, United States.

Division of Neonatology, Children's Hospital of Philadelphia, Perelman School of Medicine, Philadelphia, PA, United States.

出版信息

Front Pediatr. 2017 Jun 16;5:139. doi: 10.3389/fped.2017.00139. eCollection 2017.

Abstract

Neonatal meningitis is a devastating condition. Prognosis has not improved in decades, despite the advent of improved antimicrobial therapy and heightened index of suspicion among clinicians caring for affected infants. One in ten infants die from meningitis, and up to half of survivors develop significant lifelong complications, including seizures, impaired hearing and vision, and delayed or arrested development of such basic skills as talking and walking. At present, it is not possible to predict which infants will suffer poor outcomes. Early treatment is critical to promote more favorable outcomes, though diagnosis of meningitis in infants is technically challenging, time-intensive, and invasive. Profound neuronal injury has long been described in the setting of neonatal meningitis, as has elevated levels of many pro- and anti-inflammatory cytokines. Mechanisms of the host immune response that drive clearance of the offending organism and underlie brain injury due to meningitis are not well understood, however. In this review, we will discuss challenges in diagnosis, prognosis, and treatment of neonatal meningitis. We will highlight transcriptomic, proteomic, and metabolomic data that contribute to suggested mechanisms of inflammation and brain injury in this setting with a view toward fruitful areas for future investigation.

摘要

新生儿脑膜炎是一种极具破坏性的疾病。尽管抗菌治疗有所改进,且照顾患病婴儿的临床医生的怀疑指数有所提高,但几十年来其预后并未得到改善。十分之一的婴儿死于脑膜炎,多达一半的幸存者会出现严重的终身并发症,包括癫痫、听力和视力受损,以及说话和行走等基本技能发育延迟或停滞。目前,尚无法预测哪些婴儿会出现不良后果。早期治疗对于促进更有利的结果至关重要,不过婴儿脑膜炎的诊断在技术上具有挑战性、耗时且具有侵入性。长期以来,在新生儿脑膜炎的情况下一直有关于严重神经元损伤的描述,许多促炎和抗炎细胞因子水平升高的情况也是如此。然而,驱动清除致病微生物并构成脑膜炎所致脑损伤基础的宿主免疫反应机制尚未得到充分了解。在本综述中,我们将讨论新生儿脑膜炎在诊断、预后和治疗方面的挑战。我们将重点介绍有助于阐明这种情况下炎症和脑损伤机制的转录组学、蛋白质组学和代谢组学数据,以期为未来研究的富有成果的领域提供参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9d4/5472684/3f07daca4b96/fped-05-00139-g001.jpg

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