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Mechanisms of Tertiary Neurodegeneration after Neonatal Hypoxic-Ischemic Brain Damage. 新生儿缺氧缺血性脑损伤后三级神经变性的机制
Pub Date : 2022-08-28 DOI: 10.21037/pm-20-104
Steven W Levison, Eridan Rocha-Ferreira, Brian H Kim, Henrik Hagberg, Bobbi Fleiss, Pierre Gressens, Radek Dobrowolski

Neonatal encephalopathy linked to hypoxia-ischemia (H-I) which is regarded as the most important neurological problem of the newborn, can lead to a spectrum of adverse neurodevelopmental outcomes such as cerebral palsy, epilepsy, hyperactivity, cognitive impairment and learning difficulties. There have been numerous reviews that have focused on the epidemiology, diagnosis and treatment of neonatal H-I; however, a topic that is less often considered is the extent to which the injury might worsen over time, which is the focus of this review. Similarly, there have been numerous reviews that have focused on mechanisms that contribute to the acute or subacute injury; however, there is a tertiary phase of recovery that can be defined by cellular and molecular changes that occur many weeks and months after brain injury and this topic has not been the focus of any review for over a decade. Therefore, in this article we review both the clinical and pre-clinical data that show that tertiary neurodegeneration is a significant contributor to the final outcome, especially after mild to moderate injuries. We discuss the contributing roles of apoptosis, necroptosis, autophagy, protein homeostasis, inflammation, microgliosis and astrogliosis. We also review the limited number of studies that have shown that significant neuroprotection and preservation of neurological function can be achieved administering drugs during the period of tertiary neurodegeneration. As the tertiary phase of neurodegeneration is a stage when interventions are eminently feasible, it is our hope that this review will stimulate a new focus on this stage of recovery towards the goal of producing new treatment options for neonatal hypoxic-ischemic encephalopathy.

新生儿脑病与缺氧缺血(H-I)有关,被认为是新生儿最重要的神经问题,可导致一系列不良的神经发育结果,如脑瘫、癫痫、多动、认知障碍和学习困难。已有许多综述关注新生儿 H-I 的流行病学、诊断和治疗;然而,较少考虑的一个主题是损伤可能随时间推移而恶化的程度,这也是本综述的重点。同样,也有许多综述关注造成急性或亚急性损伤的机制;然而,脑损伤后数周或数月内发生的细胞和分子变化可定义为三级恢复阶段,而这一主题十多年来一直未成为任何综述的重点。因此,在这篇文章中,我们回顾了临床和前临床数据,这些数据表明三级神经变性是影响最终结果的重要因素,尤其是在轻度至中度损伤后。我们讨论了细胞凋亡、坏死、自噬、蛋白质平衡、炎症、小神经胶质细胞和星形胶质细胞的作用。我们还回顾了数量有限的研究,这些研究表明在三级神经退行性变期间使用药物可以实现显著的神经保护和神经功能保存。由于神经退行性变的第三阶段是干预措施非常可行的阶段,我们希望本综述能促使人们重新关注这一恢复阶段,从而为新生儿缺氧缺血性脑病提供新的治疗方案。
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引用次数: 0
A narrative review of Hyporeninemic hypertension-an indicator for monogenic forms of hypertension. 低肾素性高血压的叙述性回顾-单基因高血压的一个指标。
Pub Date : 2022-05-01 Epub Date: 2022-05-28 DOI: 10.21037/pm-21-48
Ahmad Mashmoushi, Matthias T F Wolf

Background and objective: While the role of the renin-angiotensin-aldosterone system (RAAS) in the development of hypertension is well known, the significance and contribution of low renin hypertension is often overlooked. RAAS stimulation results in more tubular absorption of sodium and water along the nephron, contributing to a higher circulating vascular volume. In addition, members of the RAAS system, such as angiotensin II, have direct effects on vascular vasoconstriction, the heart, aldosterone synthesis in the adrenal glands, the sympathetic nervous system, and the central nervous system. This has resulted in a line of antihypertensive therapeutics targeting RAAS with angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and renin inhibitors, which prevent conversion of angiotensinogen to angiotensin. While general practitioners and nephrologists are well aware of the causes and the long-term consequences of elevated renin and aldosterone levels, the opposite situation with low renin and/or low aldosterone levels is frequently underappreciated. The objective of this review is to provide insight to the less common forms of hyporeninemic hypertension.

Methods: We searched the PubMed online library for keywords related to hyporeninemic hypertension and focused on the pediatric population. For pathophysiology we focused on literature of the last 5 years.

Key content and findings: The low renin and aldosterone levels may be indicators of inherited (especially when associated with hypokalemia), monogenic forms of hypertension stimulating excessive tubular sodium and water absorption which subsequently results in plasma volume expansion and hypertension. These forms of hypertension require frequently specific forms of therapy. This underlines the importance of the practitioner to be familiar with these rare diseases.

Conclusions: In this review article, we outline the different forms of hypertension characterized by low renin/low aldosterone and low renin/high aldosterone levels, how to diagnose these forms of hypertension, and how to treat them.

背景与目的:虽然肾素-血管紧张素-醛固酮系统(RAAS)在高血压发生中的作用众所周知,但低肾素高血压的重要性和贡献往往被忽视。RAAS刺激导致更多的钠和水沿着肾元的管状吸收,有助于更高的循环血管体积。此外,RAAS系统的成员,如血管紧张素II,对血管收缩、心脏、肾上腺醛固酮合成、交感神经系统和中枢神经系统有直接影响。这导致了一系列针对RAAS的降压治疗药物,包括血管紧张素转换酶(ACE)抑制剂、血管紧张素受体阻滞剂(ARBs)和肾素抑制剂,这些药物可防止血管紧张素原转化为血管紧张素。虽然全科医生和肾病学家很清楚肾素和醛固酮水平升高的原因和长期后果,但低肾素和/或低醛固酮水平的相反情况经常被低估。本综述的目的是为低肾素血症性高血压的不常见形式提供见解。方法:在PubMed在线图书馆中检索与低肾素血症性高血压相关的关键词,重点关注儿童人群。病理生理学方面,我们关注的是最近5年的文献。主要内容和发现:肾素和醛固酮水平低可能是遗传性(特别是当与低钾血症相关时)的指标,单基因形式的高血压刺激过多的小管钠和水吸收,随后导致血浆容量扩大和高血压。这些形式的高血压通常需要特殊的治疗方式。这强调了医生熟悉这些罕见疾病的重要性。结论:在这篇综述文章中,我们概述了以低肾素/低醛固酮和低肾素/高醛固酮水平为特征的不同形式的高血压,如何诊断这些形式的高血压,以及如何治疗它们。
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引用次数: 2
The home environment and its relation to vocalizations in the first year of life. 家庭环境及其与一岁婴儿发声的关系。
Pub Date : 2022-02-01 DOI: 10.21037/pm-21-53
Morgan Hines, Thomas Carpenito, Alaina Martens, Alicia Iizuka, Billi Aspinwall, Emily Zimmerman

Background: Prior data has shown that the home environment impacts child development; however, there remains a paucity of research on how the home environment relates to child and adult words. Therefore, the aim of this prospective and quantitative study was to examine the relationship between the home environment and the quantity of vocalizations or words, and conversational turns produced by infants and parents at 3 and 12 months of age.

Methods: Seventy-two (56% male) full-term infants were assessed at 3 and 12 months of age. The home environment was assessed in person via interview and observation of the child's home using the Infant-Toddler Home Observation for Measurement of the Environment (IT-HOME) Inventory subscales. Vocalizations were measured using the Language Environment Analysis (LENA) device, which measures the adult word count, child vocalization count and conversational turn count. These measures were then averaged for the most voluble, or vocal hour, in the recording period.

Results: At 3 months, IT-HOME Learning Materials scores were significantly associated with a decrease in adult words. We found a statistically significant difference in LENA outcomes between 3 and 12 months when stratified by sex. Specifically, male infants had significantly fewer vocalizations at 12 months when compared to 3 months, whereas females had more vocalizations. There was also a statistically significant difference in IT-HOME Learning Materials, Organization, Responsivity, and Total scores when comparing 3- and 12-month time points.

Conclusions: These findings reveal that the home environment changes significantly over the first year of life. At 3 months, Learning Materials in the home were related to adult words, while between 3 and 12 months, several aspects of the home significantly changed. Male children had reduced vocalizations between 3 and 12 months; whereas, female children had increased vocalizations during the same time points. Future research should focus on examining these outcomes with multiple measures, time points, and patient populations.

背景:先前的数据表明,家庭环境影响儿童的发展;然而,关于家庭环境如何影响儿童和成人词汇的研究仍然很少。因此,本前瞻性和定量研究的目的是研究家庭环境与婴儿和父母在3个月和12个月时产生的发声或单词数量以及会话回合之间的关系。方法:对72名足月婴儿(56%为男性)在3个月和12个月时进行评估。家庭环境是通过访谈和使用婴幼儿家庭环境观察量表(IT-HOME)对儿童家庭进行观察来亲自评估的。发声使用语言环境分析(LENA)设备进行测量,该设备测量成人单词计数,儿童发声计数和会话次数。然后将这些测量值平均为在录音期间最健谈的一小时。结果:在3个月时,IT-HOME学习材料分数与成人词汇的减少显著相关。我们发现,按性别分层时,3个月和12个月的LENA结果在统计学上有显著差异。具体来说,与3个月大的婴儿相比,12个月大的男婴发声明显减少,而女婴发声更多。比较3个月和12个月的时间点,在IT-HOME学习材料、组织、反应性和总分方面也有统计学上的显著差异。结论:这些发现揭示了家庭环境在生命的第一年发生了显著的变化。在3个月时,家里的学习材料与成人词汇有关,而在3到12个月之间,家里的几个方面发生了显著变化。男孩在3到12个月之间发声减少;然而,在同一时间点,女性儿童的发声能力有所增加。未来的研究应侧重于用多种测量方法、时间点和患者群体来检查这些结果。
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引用次数: 0
Landscape of pediatric neuro-oncology care in China 中国儿科神经肿瘤护理的前景
Pub Date : 2022-01-01 DOI: 10.21037/pm-22-45
A. P. Liu, Chenchen Sun, I. Qaddoumi
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引用次数: 0
The Chinese Neonatal Network: a new platform of national collaboration on quality improvement for preterm infants 中国新生儿网络:早产儿质量改进国家合作的新平台
Pub Date : 2022-01-01 DOI: 10.21037/pm-21-114
M. Hei, Yun Cao, Jianhua Sun, Huayan Zhang, Xiaolu Ma, Hui-yue Wu, Xiaoying Li, Si-yuan Jiang, Huiqing Sun, Wei Zhou, Yuan Shi, L. Du, Chao Chen, Shoo K. Lee, Wenhao Zhou
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引用次数: 1
Imaging investigation after urinary tract infection in childhood: narrative review of current recommendations 儿童尿路感染后的影像学调查:目前建议的叙述性综述
Pub Date : 2022-01-01 DOI: 10.21037/pm-21-86
A. C. Simões e Silva, L. Jabour, B. Vieira, E. A. Oliveira
Background and Objective: Urinary tract infections (UTIs) are one of the most common bacterial infections in children. The imaging exams that take place after the occurrence of UTI have the main goal of detecting congenital anomalies of the kidney and urinary tract (CAKUT). The value of imaging investigation relies on guiding the management of the patient and directing measures to prevent recurrent infections and to avoid possible kidney scars. Currently, there has been a general trend to restrict the number of imaging tests performed in clinical practice as can be seen in the most important guidelines regarding the management of patients with febrile UTI. The guidelines from the American Association of Pediatrics (AAP), the National Institute for Health and Care Excellence (NICE), and the European Association of Urology (EAU)/European Society for All Pediatric Urology (ESPU) made recommendations in this regard. We believe that the critical discussion about the advantages and disadvantages of the different guidelines and protocols proposed is important for pediatricians and nephrologists and helps to define the best approach for patients. In this matter, this review aimed to provide a critical view of imaging investigation methods and guidelines after UTIs in pediatric patients. Methods: The authors performed a non-systematic search in PubMed, Cochrane, Scopus, SciELO and in renowned books from the subjects of pediatric nephrology and pediatric urology published up to August 5th, 2021, and critically selected and independently reviewed articles written mainly in English or Portuguese to produce this narrative review. Key Content and Findings: In this narrative review, shortcomings of different imaging guidelines and examinations after urinary tract infections in children are explored, while the principles and advantages of distinct imaging methods are highlighted. We find that, while an initial renal and bladder ultrasonography is of great value, more invasive exams need to be carefully selected to identify patients at risk for further complications whilst minimizing distress and other consequences to the child. Conclusions: A renal ultrasonography with good quality of images and examined by an expert is generally recommended as initial screening after UTI. Additional imaging exams depend on findings provided by renal ultrasonography. but the exam is of low
背景与目的:尿路感染是儿童最常见的细菌感染之一。在尿路感染发生后进行的影像学检查的主要目的是检测肾脏和尿路的先天性异常(CAKUT)。影像学检查的价值在于指导患者的管理,指导预防复发感染和避免可能的肾瘢痕的措施。目前,总的趋势是限制临床实践中进行的影像学检查的次数,这可以从有关发热性尿路感染患者管理的最重要指南中看出。美国儿科协会(AAP)、国家健康与护理卓越研究所(NICE)和欧洲泌尿外科协会(EAU)/欧洲儿科泌尿外科学会(ESPU)的指南在这方面提出了建议。我们认为,对不同指南和方案的优缺点进行批判性讨论对儿科医生和肾病学家很重要,并有助于为患者确定最佳方法。在这方面,本综述旨在为儿科患者uti后的影像学检查方法和指南提供批判性的观点。方法:作者在PubMed、Cochrane、Scopus、SciELO以及截至2021年8月5日出版的儿科肾脏病学和儿科泌尿学领域的知名书籍中进行了非系统检索,并严格选择和独立审查了主要以英语或葡萄牙语撰写的文章,以产生这一叙述性综述。主要内容和发现:本文综述了儿童尿路感染后不同成像指南和检查方法的不足,并强调了不同成像方法的原理和优势。我们发现,虽然最初的肾脏和膀胱超声检查很有价值,但需要仔细选择更多的侵入性检查,以确定有进一步并发症风险的患者,同时尽量减少对儿童的痛苦和其他后果。结论:尿路感染后,一般建议进行高质量的肾脏超声检查,并由专家检查。其他影像学检查取决于肾脏超声检查的结果。但是考试很低
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引用次数: 0
The Spanish Neonatal Network SEN1500: updated information 西班牙新生儿网络SEN1500:最新信息
Pub Date : 2022-01-01 DOI: 10.21037/pm-21-109
L. San Feliciano, M. Moro, J. Figueras, T. Sánchez Tamayo, C. Zozaya, F. García-Muñoz Rodrigo, M. Vento
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引用次数: 4
A narrative review: an update on primary adrenal insufficiency (PAI) in pediatric population 叙述性回顾:儿科人群原发性肾上腺功能不全(PAI)的最新进展
Pub Date : 2022-01-01 DOI: 10.21037/pm-22-2
Berrin Ergun-Longmire, Dustin C. Rowland, John Dewey, Patricia Vining-Maravolo
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引用次数: 0
The role of systemic therapy in paediatric cutaneous melanoma: a review 全身治疗在儿童皮肤黑色素瘤中的作用:综述
Pub Date : 2022-01-01 DOI: 10.21037/pm-22-5
E. A. Corley, A. Schmitt, A. Furness, J. Chisholm
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引用次数: 0
Risk factors for death among children and young people hospitalized with COVID-19: a literature review COVID-19住院儿童和青少年死亡的危险因素:文献综述
Pub Date : 2022-01-01 DOI: 10.21037/pm-22-19
Bi Ze, Bin Chen, Xiaoshan Ji, Wenhao Zhou
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引用次数: 0
期刊
Pediatric medicine (Hong Kong, China)
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