Minimising neonatal brain injury: how research in the past five years has changed my clinical practice

With improving neonatal survival for extremely premature babies, the challenge for neonatology is to improve outcome of surviving babies. This review concentrates on best evidence emerging in recent years on prevention of brain damage by early administration of drugs as well as avoidance of induced brain damage by hyperventilation and dexamethasone therapy given postnatally for chronic lung disease.     

How has research in the past 5 years changed my clinical practice

This article discusses how research in the past 5 years into management strategies influencing respiratory outcomes has changed (or not changed) the author's clinical practice. Changes include using inhaled nitric oxide but no longer systemic pulmonary vasodilators in term born infants with pulmonary hypertension. Use of postnatal steroids is now restricted to systemic administration in infants with severe respiratory failure and who are ventilator dependent beyond 2 weeks of age. Infants with bronchopulmonary dysplasia, unless they have pulmonary hypertension, are maintained at oxygen saturation levels of 90-92% rather than >/=95%. Supine sleeping is instituted in prematurely born infants without contraindications several weeks prior to neonatal discharge to reinforce to parents the importance of supine sleeping their baby at home. Further research is required to identify the optimal respiratory support strategy, particularly for very immature infants.     

How has research in the last five years changed my clinical practice?

The first instruction to examination candidates is to read and answer the question actually set. Doing so in this case leads to the following CONCLUSIONS: how research has changed my clinical practice includes the act of doing research, as well as reading about the work of others. Thus, this article refers to my own clinical practice (tertiary referral paediatric respiratory medicine in a setting where we do not service an accident and emergency department), rather than that of others. This means excluding important conditions such as acute croup and uncomplicated community acquired pneumonia. I should write about what has changed my practice, not what other people think I ought to have changed. So this will be a personal view, limited to research published in a peer review format at the time of writing. I shall also assume that change is an ongoing process, so I shall include change in progress, provided it is supported by published literature.     

How has research changed my practice in the last 5 years?

You can't teach old dogs new tricks. Teaching middle-aged dogs new tricks is hard enough. They tend to stick to particular styles of attacking the postman that over the years have proved pretty reliable, often choosing to ignore new findings, or simply failing to keep up with progress in current discussions on, say, the old trouser versus postbag debate. Some unsettling papers are even asking whether dogs really need to attack postmen at all.     

How have the past 5 years of research changed clinical practice in paediatric nephrology?

Clinical practice in paediatric nephrology is continuously evolving to mirror the research output of the 21st century. The management of antenatally diagnosed renal anomalies, urinary tract infections, nephrotic syndrome and hypertension is becoming more evidence based. Obesity and related hypertension is being targeted at primary and secondary care. The evolving field of molecular and cytogenetics is discovering genes that are facilitating clinicians and families with prenatal diagnoses and understanding of disease processes. The progression of chronic kidney disease in childhood to end-stage renal failure (ESRF) can be delayed using medical treatment to reduce proteinuria and treat hypertension. Pre-emptive living-related renal transplantation has become the treatment of choice for children with ESRF, thereby reducing the morbidity and mortality associated with peritoneal and haemodialysis. Although peritoneal dialysis, which is performed in the patient's home, is the preferred modality for children for whom there is no living or deceased donor for transplantation, home nocturnal haemodialysis is becoming a feasible option. Imaging modalities with the use of magnetic resonance and computerised tomography are continuously improving. As mortality for renal and vasculitic diseases improves, the gauntlet is now thrown down to reduce morbidity with secondary prevention of longer-term complications such as atherosclerosis and hyperlipidaemia. Clinical and drug trials in the fields of hypertension, nephrotic syndrome, systemic lupus erythematosus, vasculitis and transplantation are producing more effective treatments, thereby reducing the morbidity resulting from the disease processes and the side effects of drugs.     

How have the past 5?years of research changed clinical practice in paediatric nephrology?

Clinical practice in paediatric nephrology is continuously evolving to mirror the research output of the 21st century. The management of antenatally diagnosed renal anomalies, urinary tract infections, nephrotic syndrome and hypertension is becoming more evidence based. Obesity and related hypertension is being targeted at primary and secondary care. The evolving field of molecular and cytogenetics is discovering genes that are facilitating clinicians and families with prenatal diagnoses and understanding of disease processes. The progression of chronic kidney disease in childhood to end‐stage renal failure (ESRF) can be delayed using medical treatment to reduce proteinuria and treat hypertension. Pre‐emptive living‐related renal transplantation has become the treatment of choice for children with ESRF, thereby reducing the morbidity and mortality associated with peritoneal and haemodialysis. Although peritoneal dialysis, which is performed in the patient''s home, is the preferred modality for children for whom there is no living or deceased donor for transplantation, home nocturnal haemodialysis is becoming a feasible option. Imaging modalities with the use of magnetic resonance and computerised tomography are continuously improving. As mortality for renal and vasculitic diseases improves, the gauntlet is now thrown down to reduce morbidity with secondary prevention of longer‐term complications such as atherosclerosis and hyperlipidaemia. Clinical and drug trials in the fields of hypertension, nephrotic syndrome, systemic lupus erythematosus, vasculitis and transplantation are producing more effective treatments, thereby reducing the morbidity resulting from the disease processes and the side effects of drugs.Clinical research influences our clinical practice as paediatricians. Although the practicalities of embarking on research are becoming more bureaucratic, the foundation of the Medicines for Children Research Network with local infrastructure will continue to increase the number of randomised controlled trials in paediatric practice, thereby guiding therapeutic regimens. Therefore, those clinical questions will be answered (to the high standards attained by our paediatric oncological colleagues) and clinical practice will become more evidence based, instead of the continued extrapolation of data produced from research in adult patients. Research in the past 5 years has been extensive in the field of paediatric nephrology, with an increased incidence of systematic reviews and meta‐analyses challenging current beliefs, and genetic testing making rapid diagnosis for patients, families and clinicians involved, which sometimes influences clinical decision making with respect to therapeutic interventions. In this article, I will highlight only some of the more relevant articles in the published literature that have affected clinical practice of the general paediatric and paediatric nephrology communities.     

近五年中国大陆神经母细胞瘤基础研究述评

神经母细胞瘤(neuroblastoma,NB)是幼儿期最常见的恶性实体肿瘤之一,国内外研究结果显示:NB的年发病率为0.3~5.5/10万,仅低于白血病和中枢神经系统肿瘤,其占据了15岁以下青少年恶性肿瘤的8%~10%,80%的NB病例发生于5岁以下的儿童[1-2].     

Twenty years of pulmonary tuberculosis in children: what has changed?

OBJECTIVES: To compare the frequency, clinical and radiologic manifestations and source of infection of pulmonary tuberculosis in children treated in our hospital during two decades (1978 through 1987 and 1988 through 1997) and to evaluate the influence of the emergence of HIV infection (since 1985) and the effect of the discontinuation of Calmette-Guérin bacillus (BCG) vaccination (since 1987) on childhood tuberculosis. METHODS: We reviewed 324 children diagnosed with pulmonary tuberculosis in our hospital during the 20 years (1978 through 1997). The data from 2 decades, 1978 through 1987 and 1988 through 1997, were compared. BCG vaccination in Spain was discontinued in 1987, and HIV infection emerged significantly as a public health problem. RESULTS: An increase in the number of children with single hilar adenopathy was observed (32.2% in 1978 through 1987 vs. 43.4%, in 1988 through 1997, P < 0.05) in comparison with those with parenchymal involvement or a mixed pattern (62.4% in 1978 through 1987 vs. 45.7% in 1988 to 1997). Frequency in extrapulmonary manifestations in both periods was similar, with a nonsignificant trend toward a lower rate of tuberculous meningitis in the latter decade (10.4 vs. 5.6%, P = 0.07). We were able to identify an adult source case for 67.1% of the children (100 of 149) in the first decade vs.58.3% (102 of 175) in the second (P = NS); 10.8% of adult contacts but only 2.3% of children (all of them in the second period) were HIV-positive.CONCLUSIONS: Discontinuation of BCG vaccination and emergence of HIV infection have had little influence on childhood tuberculosis in our area.     

新生儿颅脑磁共振检查临床实践的专家共识

颅脑磁共振成像（magnetic resonance imaging,MRI）技术的迅速发展为新生儿脑发育评估、脑损伤诊断和预后判断提供了客观依据,临床应用日益广泛。中国医师协会新生儿科医师分会基于国内外现有研究证据,结合临床实践经验,为新生儿颅脑MRI的适应证和临床实践规范制定专家共识,主要内容包括：（1）疑似新生儿缺氧缺血性脑病、颅内感染、脑卒中,以及原因不明惊厥者应行颅脑MRI;颅脑MRI不纳入早产儿常规脑损伤筛查管理,当颅脑超声筛查有明确损伤证据时应行颅脑MRI进一步评估;对于颅脑超声未见异常的超早产儿和超低出生体重儿,建议在纠正胎龄足月时行颅脑MRI;（2）新生儿颅脑MRI应尽量在非镇静状态下完成;（3）过程中需密切监测生命体征,优化检查条件,保障安全,危重患儿检查需严格评估检查的必要性,可应用磁共振兼容的转运培养箱和呼吸机;（4）目前新生儿颅脑MRI检查可选1.5 T或3.0 T设备,应用新生儿颅脑专用线圈以提高信噪比;常规扫描序列选择应遵循：至少包含轴位T1加权像、轴位T2加权像、弥散加权成像,以及矢状位T1加权像或T2加权像;（5）建议采用结构化或分级报告系统,通过双人审签报告、多中心协作等方式提高报告可靠性。     

Evidence‐based medicine: What has happened in the past 50 years?

Although the phrase ‘evidence‐based medicine’ (EBM) was used for the first time in the medical literature less than 25 years ago, the history of EBM goes back for centuries. What is remarkable is how popular and how globally accepted the EBM movement has become in such a short time. Many famous, past clinicians have played major roles in the disciplines that preceded EBM, particularly ‘clinical epidemiology’. It soon became clear to the early EBM champions that ‘evidence’ was only part of the clinical decision‐making process. Consequently, both clinical expertise and the patient's values and preferences were rapidly incorporated into the concept we now know as ‘EBM’. The current need for high‐quality, easily accessible ‘evidence‐based summaries’ for busy clinicians is now apparent, as traditional EBM requires both considerable time and skill. Consequently, there is a progressive move away from the primary literature (such as randomised controlled trials) to systematic reviews and other ‘evidence‐based summaries’. The future of EBM will almost certainly involve widespread utilisation of ‘clinical (computer)‐based decision support systems’.     

Neurocognitive late effects of chemotherapy in children: the past 10 years of research on brain structure and function

Advances in the treatment of childhood cancers have greatly improved survivorship. Success has not come without cost, however, as survivors are at risk for late effects of treatment, including neurocognitive late effects (e.g., difficulties with thinking and reasoning). In the advent of chemotherapy-only protocols, researchers are examining neurocognitive sequelae of these agents to understand the specific role of chemotherapy in neurocognitive changes and the mechanism through which these occur. In this review, we examine the state of the literature on neurocognitive late effects after chemotherapy and their proposed neural mechanisms.     

Hypoxic/ischaemic cerebral injury in the neonatal brain

Ultrasound has been used in 11 neonates whose history or clinical features suggested the possibility of hypoxic/ischaemic lesions. The ultrasound findings were correlated with computed tomographic findings in nine infants and with pathological findings in two. On ultrasound scan, areas of increased echoes represented both hypoxic/ischaemic and haemorrhagic lesions. However, the distinction between them could not be made with certainty. Cystic changes were shown clearly by ultrasound as were cerebral vascular pulsations in and adjacent to the areas of increased echoes. With computed tomography, hypoxic/ischaemic lesions were represented by areas of decreased density and haemorrhagic lesions by areas of increased density. Computed tomography failed to clearly demonstrate the cystic changes. Three types of lesions, viz. diffuse, focal and periventricular were based on the location of brain injury, the former two occurring in term infants and the latter in premature infants. Ultrasound has been shown to be of value for definition of the site and extent of hypoxic/ischaemic cerebral lesions in the newborn and for observation of their evolution.     

新生儿疾病临床研究进展

1 新生儿脑损伤 新生儿脑损伤的评估及预后判断一直是被关注的热点.王瑾等[1]研究了最大长度序列脑干听觉诱发电位(MLS BAEP)对早期判断新生儿缺氧缺血性脑病(HIE)及程度的意义.103例窒息新生儿于生后3 d内分别行常规BAEP和MLS BAEP检查,并根据HIE程度分组.结果显示,常规BAEP和MLS BAEP检查中,V波潜伏期,Ⅰ-Ⅲ、Ⅲ-Ⅴ、Ⅰ-Ⅴ峰间期随HIE程度加重而逐渐延长的差异较明显,尤其在MLS BAEP中随声刺激速度的加快,这种差异也越显著.     

Translating childhood brain tumour research into clinical practice: the experience of molecular classification and diagnostics

Diagnosis and treatment of paediatric brain tumours has shown limited progress over the last half century. However, in the past 10 years the development of molecular techniques for investigating these tumours has expanded exponentially. The use of methylation profiling, gene expression analysis and the identification of gene fusions are forming the basis for improved diagnostic criteria and new treatment approaches. Knowledge and practice in this area is now beginning to expand beyond the research field and into the clinical setting. As the Chief Medical Officer highlighted in July 2017, an understanding of molecular medicine and its implications for both patients and the health economy is important for all clinicians. In this article, we summarise important recent advances in molecular medicine in childhood brain tumour research using the three most common types of paediatric brain tumour; pilocytic astrocytoma, medulloblastoma and ependymoma as illustrative examples.