What’s new in surfactant?

Surfactant therapy has significantly changed clinical practice in neonatology over the last 25 years. Recent trials in infants with respiratory distress syndrome (RDS) have not shown superiority of any natural surfactant over another. Advancements in the development of synthetic surfactants are promising, yet to date none has been shown to be superior to natural preparations. Ideally, surfactant would be administered without requiring mechanical ventilation. An increasing number of studies investigate the roles of alternative modes of administration and the use of nasal continuous positive airway pressure to minimise the need for mechanical ventilation. Whether children with other lung diseases benefit from surfactant therapy is less clear. Evidence suggests that infants with meconium aspiration syndrome and children with acute lung injury/acute respiratory distress syndrome may benefit, while no positive effect of surfactant is seen in infants with congenital diaphragmatic hernia. However, more research is needed to establish potential beneficial effects of surfactant administration in children with lung diseases other than RDS. Furthermore, genetic disorders of surfactant metabolism have recently been linked to respiratory diseases of formerly unknown origin. It is important to consider these disorders in the differential diagnosis of unexplained respiratory distress although no established treatment is yet available besides lung transplantation for the most severe cases. Conclusion: Research around surfactant is evolving and recent developments include further evolution of synthetic surfactants, evaluation of surfactant as a therapeutic option in lung diseases other than RDS and the discovery of genetic disorders of surfactant metabolism. Ongoing research is essential to continue to improve therapeutic prospects for children with serious respiratory disease involving disturbances in surfactant. Funding: Jasper Been is supported by a Profileringsfonds grant from the Maastricht University Hospital.     

What’s new in autism?

This review on autism spectrum disorder (ASD) focusses on recent insights in the clinical picture, such as continuity of the phenotype and the concept of broader phenotype, on epidemiology and on clinical issues relevant to physicians, including new methods for early screening and diagnosis, psychiatric and somatic co-morbidity, and the expansion of so-called complementary and alternative treatments. ASD is a disorder with mainly genetic causes and recent insights show that a variety of genetic mechanisms may be involved, i.e. single gene disorders, copy number variations and polygenic mechanisms. Technological advances in genetics have lead to a number of promising findings, which, together with other lines of fundamental research, suggest that ASD may be a disorder of connectivity in the brain, at least in a subgroup of patients. It is possible that part of the genetic load in autism actually reflects gene-environment interaction, but there is no evidence for purely environmental causes in a substantial number of cases. Clinical research suggests that ASD may be a multi-system disorder in at least a subgroup of subjects, affecting the gastro-intestinal (GI) tract, the immune system and perhaps other systems. Behavioural treatments remain the cornerstone of management, and are mainly aimed at stimulation of the domains of impaired development and reducing secondary behaviours. These treatments are constantly being refined, but the main progress in this area may be the increase of research on effectiveness.     

Fatty Liver Disease in Children—What Should One Do?

The world’s population is increasingly overweight and obese. According to the World Health Organization (WHO) as of 2010, 43 million children under the age of five were overweight. Once considered to be limited to developed countries, overweight and obese children are now found in low- and middle-income countries, though most commonly in urban areas. Furthermore the WHO now cites the conditions of overweight and obesity as being associated with more deaths around the globe than those associated with being underweight. With this increased prevalence of overweight and obese children has come a host of other medical problems including nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). This review will focus on NAFLD and NASH, their definitions, epidemiology, diagnosis and treatment. The authors will also discuss NAFLD in the Indian subcontinent, and the future of NAFLD and NASH.     

What’s new in hypophosphataemic rickets?

Although relatively uncommon individually, the various causes of hypophosphataemic rickets have provided an impetus for unravelling the mechanisms of phosphate homeostasis and bone mineralisation. Over the past 10 years, considerable advances have been made in establishing the gene mutations responsible for a number of the inherited causes and in understanding the mechanisms responsible for tumour-induced osteomalacia/rickets. The most exciting aspects of these discoveries have been the discovery of a whole new class of hormones or phosphatonins which are thought to control phosphate homoeostasis and 1 alpha-hydroxylase activity in the kidney, through a bone–kidney–intestinal tract axis. Although our understanding of the interrelationships is far from complete, it raises the possibilities of improved therapeutic agents in the long-term, and has resulted in improved diagnostic abilities in the short-term.     

Manuscript: You have a Message from Illi! The Mobile Diary in Researching Children’s Daily Experiences

Thus far, daily diary studies have mostly focused on adults and adolescents, while only a few have researched young children. In this methodological article, we introduce and evaluate a mobile diary application, “You have a message from Illi”, designed to capture young, under-school-age children’s daily experiences at home and in day care, in the context of a 24 h economy where parents work nonstandard hours and child care is arranged accordingly. We also compare childrens’ mood ratings reported by both the children themselves and adults. Children recruited either from day care centers (N?=?15) or day and night and care centers (N?=?17) carried smartphones with them for 1 week and reported their daily moods and activities three times a day by mobile phone as motivated by “Illi”, a fairy-tale character. The questions concerned daily activities, moods and transitions as well as good and challenging moments. The study demonstrated children’s ability and motivation to participate in a mobile diary and produce valuable information about their daily lives. The method captured fluctuations in children’s daily moods, as reported by both children and adults. The mood evaluations of adults and the children themselves correlated. Parents and day care staff perceived participation in the mobile diary study as practical, relevant and not over-demanding, and that the method was easy to integrate into daily life.     

Feeding intolerance in very-low-birthweight infants: what is it and what can we do about it?

The increased survival of very-low-birth-weight infants has resulted in the need to better understand the immaturities that challenge optimal nutrition for these infants and how to surmount them. This is critical if we are to prevent short and long term morbidity associated with poor nutrition. Here we describe several of these immaturities including those related to digestion and absorption, suck-swallow incoordination, delayed gastric emptying, and intestinal motility and how they lead to the common problem of feeding intolerance. Scientifically based strategies for introducing, stopping and continuing enteral feedings in association with parenteral nutrition are presented.     

What’s new in the neuro-cardio-facial-cutaneous syndromes?

The RAS-MAPKinase pathway is a signal transduction cascade which has been studied extensively during the last decades for its role in human oncogenesis. Activation of this cascade is controlled by cycling of the RAS protein between an inactive and an active state and by phosphorylation of downstream proteins. The signalling cascade regulates cell proliferation, differentiation and survival. Disturbed RAS signalling in malignancies is caused by acquired somatic mutations in RAS genes or other components of this pathway. Recently, germline mutations in genes coding for different components of the RAS signalling cascade have been recognized as the cause of several phenotypically overlapping disorders, recently referred to as the neuro-cardio-facial-cutaneous syndromes. Neurofibromatosis type 1, Noonan, LEOPARD, Costello and cardiofaciocutaneous syndromes all present with variable degrees of psychomotor delay, congenital heart defects, facial dysmorphism, short stature, skin abnormalities and a predisposition for malignancy. These findings point to important roles for this evolutionary conserved pathway in oncogenesis, development, cognition and growth. Conclusion: it has become obvious in recent years that the neuro-cardio-facial-cutaneous syndromes all share a common genetic and pathophysiologic basis. Dysregulation of the RAS-MAPKinase pathway is caused by germline mutations in genes involved in this pathway. Undoubtedly more genes causing related syndromes will be discovered in the near future since there are still a substantial number of genes in the pathway that are not yet associated with a known syndrome. Human genes and proteins are written in capital letters; murine genes and proteins in small letters. Genes are written in italic, proteins are written straight.     

What’s new in haemolytic uraemic syndrome?

Recent advances in understanding the aetiology of the disorders that make up the haemolytic uraemic syndrome (HUS) permit a revised classification of the syndrome. With appropriate laboratory support, an aetiologically-based subgroup diagnosis can be made in all but a few cases. HUS caused by enterohaemorrhagic Escherichia coli remains by far the most prevalent subgroup, and new insights into this zoonosis are discussed. The most rapidly expanding area of interest is the subgroup of inherited and acquired abnormalities of complement regulation. Details of the pathogenesis are incomplete but it is reasonable to conclude that local activation of the alternative pathway of complement in the glomerulus is a central event. There is no evidence-based treatment for this diagnostic subgroup. However, in circumstances where there is a mutated plasma factor such as complement factor H, strategies to replace the abnormal protein by plasmapheresis or more radically by liver transplantation are logical, and anecdotal successes are reported. In summary, the clinical presentation of HUS gives a strong indication as to the underlying cause. Patients without evidence of EHEC infection should be fully investigated to determine the aetiology. Where complement abnormalities are suspected there is a strong argument for empirical and early plasma exchange, although rapid advances in this field may provide more specific treatments in the near future.     

Barrett’s esophagus in children: what is the evidence?

Background

This study systematically reviewed etiology, prevalence, treatment and outcome of Barrett’s esophagus (BE) in the pediatric population.

Methods

PubMed^® was searched for terms “Barrett’s esophagus” and “children”. End points were age of patients, etiology, association with other syndromes, treatment, incidence of carcinoma and outcome. This review was conducted according to the PRISMA guidelines. Data were collected, entered and analyzed into a Microsoft Excel^® spreadsheet database.

Results

Search revealed 278 articles published between 1984 and 2017, of which 18 met the inclusion criteria. There were 130 patients for analysis with a mean age 10.6 years (0.8–17.2 years). BE was diagnosed in 80 patients with confirmed gastroesophageal reflux (GER) only; further 20 patients were neurologically impaired and had GER, 13 after esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) repair with associated GER, 6 post-chemotherapy, 1 after post caustic burns, 1 after esophageal replacement with stomach, 1 after peptic esophageal stricture, 1 with secretory diarrhea, 1 with Fanconi anemia, 1 tetralogy of Fallot, and 5 healthy children. Regarding treatment, 26 were on medical treatment only, 16 had surgeries combined with medical treatment, 80 patients underwent surgery only, 1 was on diet management, 4 were on surveillance only and 2 were never treated for BE as death occurred because of associated conditions. Fundoplication was the most commonly performed surgery (82.2%). Adenocarcinoma was found in one 23-year-old patient. Mean follow-up was 3.45 years (10 months–13 years) and long-term outcome showed recurrences in 8 and esophago-mediastinal fistula and proximal esophagus ulcer in 1. There were 7 lethal outcomes which were not directly associated with BE.

Conclusions

Although BE is considered a premalignant condition; incidence of carcinoma in pediatric population is low. Long-term follow-up with endoscopies and biopsies seems to be advisable for BE evidence and malignant alterations.