Current Opinion in Pediatrics

Published by Lippincott, Williams & Wilkins
Print ISSN: 1040-8703
Publications
Increasing evidence supports the view that infants exposed to perinatal infection are at increased risk for brain injury. We suggest that elevated cytokines in the amniotic fluid or in the fetal circulation be viewed as a humoral expression and that inflammatory cells in chorionic plate or umbilical cord blood vessel walls be viewed as a morphologic expression of the fetal inflammatory response. We discuss the evidence supporting the hypothesis that the fetal inflammatory response contributes to neonatal brain injury and later developmental disability. Little support has been found for a maternal contribution. Intervention should be designed with the fetus in mind.
 
Inactive cortisone is converted to active cortisol by the reductase activity of 11 beta-hydroxysteroid dehydrogenase type 1, which can thus increase glucocorticoid effects in target tissues. This paper reviews the functional role(s) of 11 beta-hydroxysteroid dehydrogenase type 1 and examines factors influencing its activity. In obese humans, 11 beta-hydroxysteroid dehydrogenase type 1 is relatively highly expressed in adipose tissue. In mice, overexpression of 11 beta-hydroxysteroid dehydrogenase type 1 in adipose or liver causes obesity or insulin resistance, respectively, whereas mice lacking 11 beta-hydroxysteroid dehydrogenase type 1 resist diet-induced obesity and are insulin-sensitive. Thus, 11 beta-hydroxysteroid dehydrogenase type 1 is a promising drug target for treating the metabolic syndrome and type 2 diabetes. Studies in vitro and in mutant mice demonstrate that the reductase activity of 11 beta-hydroxysteroid dehydrogenase type 1 depends on reduced nicotinamide adenine dinucleotide phosphate synthesized within the endoplasmic reticulum by hexose-6-phosphate dehydrogenase. Apparent cortisone reductase deficiency is characterized by androgen excess in women or children and decreased urinary excretion of cortisol metabolites. Although polymorphisms in the genes encoding 11 beta-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase were initially implicated in this condition, subsequent reports have not confirmed this. Hexose-6-phosphate dehydrogenase and 11 beta-hydroxysteroid dehydrogenase type 1 may play important roles in the pathogenesis of obesity and metabolic syndrome. Although the importance of polymorphisms in the corresponding genes remains uncertain, rare mutations have not been ruled out.
 
Purpose of review: At the time of diagnosis of the trisomy 18 and trisomy 13, parents and care providers face difficult and challenging decisions regarding management. Because of the increased infant mortality and developmental outcome associated with both conditions, the conventional approach to management has been to withhold technological support. In recent years, an active dialogue on this topic has emerged. The purpose of this review is to summarize the literature on the outcome of infants with trisomy 18 and 13 and to discuss the key themes in this emerging dialogue. Recent findings: In recent years, several important studies have appeared that have analyzed the issues relevant to this topic, including parental autonomy, best interest of the child standard, and quality of life. Some authorities state that in areas of ambiguity it is best to defer to parents' views, whereas others indicate concern that the best interest standard has given way to parental autonomy. Information on the actual experience of parents of children with trisomy 18 and 13 has been limited until recently. Summary: The author recommends a balanced approach to counseling families of the newborn with trisomy 18 and 13 at the time of diagnosis. The counseling process should include presentation of accurate survival figures, avoidance of language that assumes outcome, communication of developmental outcome that does not presuppose perception of quality of life, and respect for the family's choice, whether it be comfort care or intervention.
 
Purpose of review: To provide an updated overview of autism spectrum disorders (ASDs), with particular attention to the pediatrician's role in assessing and managing patients with ASDs. Recent findings: Clinical perspectives on ASDs continue to evolve. The prevalence of ASDs in the United States continues to rise, and pediatricians are being tasked with the responsibility for universal screening. Further changes in its epidemiology will undoubtedly result from anticipated changes in the diagnostic criteria put forth in the upcoming revision to the Diagnostic and Statistical Manual (5th edition). Although there have been considerable advances in identifying a genetic cause in many more cases, the cause remains elusive in most cases. Recent studies of concordant twins suggest there is a stronger environmental component than previously believed. Research suggests earlier diagnosis may be feasible in some cases, and a new treatment approach has been shown to be effective in very young children. Although there have not been any large-scale advances in the medical treatment, some isolated successes have been reported and other promising therapies are now being investigated. Summary: Clinical guidelines for ASDs are evolving, with updated diagnostic criteria expected and revised recommendations for evaluation also imminent. This article provides pediatricians with a clinical overview of ASD - with an emphasis on the clinical considerations relating to screening, evaluation, and management.
 
Superior mesenteric artery (SMA) syndrome describes vascular compression of the third portion of the duodenum and presents with nausea, postprandial vomiting, and epigastric abdominal pain. The syndrome is rare and may be missed if appropriate radiologic studies are not performed or the clinical presentation is atypical. The clinical contexts in which SMA syndrome develops usually involve rapid weight loss, alterations in spine anatomy, or external increases in abdominal pressure. Diagnostic methods for identifying duodenal obstruction by the SMA include upper gastrointestinal barium contrast studies, computed tomography scans, or angiography of the aorta with either contrast or magnetic resonance angiography. Medical therapy relies upon nutritional rehabilitation with either jejunal tube feedings or parenteral nutrition until weight gain results in relief of the obstruction. In instances where this approach fails, surgical correction is necessary, most often with laparoscopic duodenojejunostomy.
 
Activation of phosphoinositide 3-kinase (PI3K) leads to downstream activation of Akt and inactivation of glycogen synthase kinase-3b (GSK-3b), thereby stabilizing Mycn 
Advances in tumor genetics have increasingly linked pediatric neoplasms with disordered mechanisms of normal development, supporting the model of embryonal tumorigenesis. We provide a detailed discussion of two pediatric neural tumors, medulloblastoma and neuroblastoma, addressing tumorigenic causality and similarities within a pharmacological context. Expression profiling, elegant murine models, and chemical blockades of oncogenic signaling pathways have encouraged a new generation of therapeutic approaches for tumor treatment. Recent data have further clarified regulation of neural developmental and factors triggering malignancy. Medulloblastoma and neuroblastoma exemplify the current embryonal tumor model. Sonic hedgehog signaling is required for cerebellar development and its dysregulation is implicated in formation of medulloblastoma. The transcription factor Mycn orchestrates proliferation and differentiation of the developing peripheral neural crest. Amplification of the MYCN gene is the predominant marker for aggressive neuroblastoma, and correlates with poor prognosis. Current evidence suggests that Mycn is also the primary executor of Sonic hedgehog signaling in the cerebellum and that the Sonic hedgehog pathway regulates levels of both MYCN mRNA and Mycn protein product independently. Destabilization of Myc through inhibition of phosphoinositide 3-kinase signaling exhibits promise not only in medulloblastoma and neuroblastoma, but in a wide range of Myc-driven tumors.
 
To review the evolving management of infants/children with trisomy 18, the prognosis with and without medical intervention, the factors that have contributed to the evolving management strategies, and an approach to the formulation of healthcare management plans for newborns with trisomy 18. There has been a trend from nonintervention for infants/children with trisomy 18 toward management to prolong life. It has become clear that the prognosis for infants/children with trisomy 18 is not as 'hopeless' as was once asserted. However, case series of patients with trisomy 18 managed with a goal of prolonging life are not adequate to evaluate the efficacy of these interventions. They are also not adequate to support the contention that they have no efficacy. In fact, anecdotal evidence and medical plausibility suggest that treatment can prolong life in some cases. This trend has been supported by a change in emphasis from a largely physician-directed model of medical decision-making to a collaborative model, which respects parents' rights to make healthcare decisions for their children and recognizes that judgments about outcomes are often subjective, and social networks, which support and advocate for children with trisomy 18 and their families. An approach to collaborative medical decision-making that is goal-directed is recommended. Healthcare management approaches or policies that reject out of hand the goal of prolonging the life of any infant/child with trisomy 18 are not defensible. Management plans should be goal-directed, based on the physician-parent evaluation of the benefits and burdens of care options for the individual child.
 
Psychological factors affecting pediatric inflammatory bowel disease, intervention and other therapeutic resources are reviewed. Children with inflammatory bowel disease are at risk for more difficulties in psychosocial functioning than healthy children, particularly depression, anxiety and social difficulties. Psychosocial difficulties are generally similar to those found in other pediatric chronic illnesses and are clinically significant in only a subset of those with inflammatory bowel disease. Conflicting results have been reported for the areas of family dysfunction and body image, and few studies have been published in the areas of stress/coping and eating disorders. One pilot study suggests psychotherapy is effective for depressed adolescents with inflammatory bowel disease. The scant existing research limits conclusions about which children are most at risk for experiencing problems. Future research should investigate a range of psychosocial outcomes and risk factors for developing problems. Prevention and intervention strategies aimed at improving psychosocial functioning in children with inflammatory bowel disease should be developed and evaluated.
 
This article reviews the contraceptive methods levonorgestrel implants and depot medroxyprogesterone acetate. These methods provide effective and safe contraception for adolescents and adults. This review focuses on the use of these contraceptive techniques in the adolescent population, discussing patient selection, side effects, and controversies concerning the methods. Future hormonal contraceptive methods are also discussed. PIP In the US, the 90% of women, at risk of pregnancy, who use contraceptives account for 47% of all unplanned pregnancies. Thus, if women using no contraceptives or using user-dependent methods were to switch to long-acting hormonal contraceptives like Norplant or injectables, unplanned pregnancy rates would drop. Norplant was approved for use in the US in 1992. The device consists of six rods that release levonorgestrel over a period of five years to suppress the luteinizing hormone surge responsible for ovulation and thicken cervical mucus to prevent sperm penetration. Norplant is highly effective, results in few metabolic changes in users, and can be used by lactating mothers. Side effects (most prevalent in the first six months) include abnormal bleeding, weight gain, depression, and headaches. Adolescents studied reported overall satisfaction with the method. Difficulties with removal can be minimized if the implants are inserted properly. The injectable use of depot medroxyprogesterone acetate (DMPA) was approved in the US in 1992. Contraceptive plasma levels are reached within 24 hours of the injection and are maintained for 14 weeks. DMPA inhibits ovulation and is highly effective when administered once every three months. DMPA is associated with a longer delay in return to fertility than other methods. The side effects of DMPA are similar to those seen in Norplant users. Concern about changes in bone density are currently being investigated. DMPA users have increased low-density lipoprotein cholesterol levels and decreased high-density lipoprotein cholesterol levels as compared to IUD users. DMPA (unlike Norplant) can be used effectively in women using anticonvulsant medications or antibiotics. It is also safe during lactation. Research into hormonal methods is being concentrated on the development of a two-rod and one-rod Norplant delivery system, on biodegradable delivery systems, and on various injectable formulations, including once-a-month estrogen/progesterone combination methods.
 
School-based health clinics have grown in number from one or two in the early 1970s to more than 600 in the 1990s. The main focus of school-based clinics is to provide primary health care and psychosocial counseling to children and adolescents in schools. This article reviews the distribution and availability of school-based clinics in 1994, discussing various models and definitions for school-based health services, the health and educational impact of school-based clinics on adolescents, and the policy issues of concern to school-based health clinics in the current era of health care and health financing reform.
 
The biology of human breast milk, and the policy of encouraging breastfeeding, continue to be the object of much scientific inquiry. The past year has seen several advances in these fields of nutrition, and this article reviews some of the most interesting and pertinent studies. Four general themes have been apparent in the recent literature: 1) the role of breastfeeding and breast milk in the incidence of infectious diseases; 2) the effect of breastfeeding on neurodevelopmental outcome; 3) the nutritional composition of breast milk; and 4) the determinants of breastfeeding among adolescents and ethnic minority mothers. Review of these studies will assist the office-based pediatrician in knowing the scientific rationale, and the best methodology, for the promotion of breastfeeding.
 
The evolution of the guidelines for selective intrapartum chemoprophylaxis (SIC) of group B streptococcal early-onset disease is reviewed here. To assess the benefits of the risk-based and culture-based strategies for prevention, observational studies since 1996 are summarized. The effect of chorioamnionitis on group B streptococcal early-onset disease, despite SIC, is emphasized. Optimal management remains controversial, and alternative strategies for the selection of women for chemoprophylaxis and for the management of infants are discussed.
 
Although the vast majority of pediatricians agree that breastfeeding is the preferred form of infant feeding, a large number of infants are still exclusively formula-fed or rarely breastfed for an extended period of time. This review explores focuses on data that speak to mothers' decisions to initiate and continue breastfeeding. Current research focuses on the immunomodulatory effects of breast milk, especially its protective benefits as relates to infection and allergy. The evidence clearly indicates that pediatricians must continue to play a critical role in the promotion of breastfeeding.
 
A review on atopic dermatitis is given, considering as basic information articles published over the period of February 1, 2000 to January 31, 2001. Atopic dermatitis is a chronic, inflammatory, primarily genetic-determined skin disease of which the cause is unknown. Its prevalence is rising in the industrialized countries, and no one knows why. The hygienic theory is most promising. Although most cases of atopic dermatitis are mild, the disease may be severe and widespread, with much impact on morbidity and social life. Mild cases usually clear and compromise 60% of the cases. Atopic dermatitis may always turn back. The clinical features are age related. Recently, a new subgroup was noted by several dermatologists in different parts of the world, consisting of people who suffer from atopic dermatitis for the first time at adult age. Food allergy, intolerance, and diet are still controversial and play a role especially in children until the age of 5 years. Diagnostic tests, such as the Atopy Patch Test, using food allergens, adds 10% or more positives and imitates the late-phase clinical manifestations. The Atopy Patch Test is still experimental as a diagnostic tool and has shortcomings, like difficulty in reading. Financial costs of treating and caring for atopic dermatitis may be high, stressing the importance of health care.
 
Many genodermatoses have been linked in recent years to their respective genes. The underlying biology and integrative nature of these genes with other genes and organ systems is beginning to be understood. This paper reviews recent advances in neurocutaneous disorders, ectodermal dysplasias, and the phenomenon of revertant gene mosaicism. In neurofibromatosis type 1, molecular assays are being developed to distinguish malignant from benign and premalignant lesions. Clinical mutation analysis for the NF1 gene has been problematic; a sensitive new assay using automated comparative sequence analysis may be helpful. Revision of clinical care guidelines is ongoing. New data for the prospective management of optic pathway gliomas is reviewed. The two genes that underlie tuberous sclerosis complex, tuberin and hamartin, lie at the center of an important signal transduction pathway with significant implications for pharmacologic treatment. Issues in genetic counseling for this highly variable disease are updated. Extensive progress has been made in understanding the basis of several forms of ectodermal dysplasia. Disorders caused by mutations in p63 and the connexin and NF-kappaB gene families will be reviewed. Finally, phenotypic in vivo amelioration of genodermatoses via revertant gene mosaicism will be discussed as a possible mechanism to be exploited in directed therapeutic approaches. This paper reviews recent developments in the molecular and biologic bases of neurofibromatosis type 1, tuberous sclerosis, and ectodermal disorders related to p63 and the connexin and NF-kappaB gene families. The concept of revertant gene mosaicism is also discussed as a potential model for gene therapy.
 
The decline in adolescent pregnancy rates noted in the 1990s has been attributed to more teenagers choosing abstinence, the availability of long-acting contraceptive options, and the increased use of condoms. Many adolescents remain at risk of unplanned pregnancy, however, because of method failure, inconsistent or incorrect use, or discontinuation of a method without choosing another method. Practitioners who care for adolescents and young women have access to several new methods in 2003. Recent additions include a contraceptive transdermal patch, a hormone-releasing intravaginal ring, new formulations of pills, and a new intrauterine device. Additionally, the World Health Organization has updated its guidelines to provide the practitioner with evidence-based recommendations to assist in selecting the most appropriate contraceptive method for each patient.
 
The fields of pediatric and congenital cardiac interventions continue to expand at a rapid pace. The last few years have witnessed a tremendous explosion in procedures such as the transcatheter closure of secundum atrial septal defects, patent foramen ovale, patent ductus arteriosus, stent placement for pulmonary artery stenosis, and coarctation of the aorta. The purpose of this review is to highlight important publications in the last year and the direction the field is taking. Research data over the last year has concentrated on six main themes: (a) mid-to-long-term data for device closure of atrial septal defects, the incidence of late cardiac erosions, thrombus formation and heart block; (b) the transcatheter closure of muscular ventricular septal defects; (c) the transcatheter closure of perimembranous ventricular septal defects; (d) the placement of bioprosthetic valves in the pulmonary and aortic positions; (e) the 'hybrid' approach that combines surgical and interventional techniques in the management of various congenital cardiac defects; and (f) fetal interventions. This review outlines the key data presented in the literature involving interventional cardiology for pediatric and congenital cardiac defects over the last year. It illustrates that in close collaboration with industry, together with bioengineers and cardiothoracic surgeons, adult cardiac interventionists and perinatologists should continue to expand the role of pediatric catheter interventions. Fetal interventions have the potential to alter the natural history of abnormal cardiac development.
 
Acne vulgaris is a common skin disorder among children and young adults that carries enormous financial and psychosocial impact. Contemporary therapies attempt to address factors underlying acne as a disorder of the pilosebaceous unit. These longstanding paradigms regarding pathogenesis and treatment continue to evolve in light of recent work on this ubiquitous disease. This review focuses on new literature that has emerged regarding the biology of the folliculosebaceous unit, the identification of particular mediators responsible for inflammatory acne, the use of topical and systemic retinoids in acne therapy, and approaches to address the emergence of antibiotic-resistant Propionibacterium acnes strains. In addition, the use of several novel therapeutic avenues is discussed, including combination therapies, lipoxygenase inhibitors, and lasers. As the understanding of the factors that initiate and exacerbate acne vulgaris continues to increase, so does the diversity of therapeutic options. Rational use of available treatment options based on the type and severity of acne lesions is a key component of successful acne therapy and allows the physician who treats adolescents with acne to provide optimum care.
 
Diamond Blackfan anemia (DBA) is an inherited bone marrow failure syndrome characterized by erythroid failure, congenital anomalies and predisposition to cancer. Recently, the notion of DBA as a disorder of ribosome biogenesis has been clarified. Correlations between molecular underpinnings and disease pathophysiology, while elusive, are beginning to emerge. Advances in these areas will be explored in this review. All known genes mutated in DBA encode ribosomal proteins associated with either the small (RPS) or large (RPL) subunit and in these cases ribosomal protein haploinsufficiency gives rise to the disease. The number of genes affected, their potential interactions with the environment and modifier genes, and the myriad of potential signaling pathways linking abortive ribosome synthesis to cell-cycle regulators may all contribute to disease heterogeneity. Genotype/phenotype relationships emerging over the past year promise to shed light on these complex interrelationships and their role in DBA pathophysiology. The nosology of DBA has recently expanded to include two distinct disease categories: a classical inherited bone marrow failure syndrome and a 'ribosomopathy'. The description of DBA as a ribosomopathy has provided a context for scientific inquiry analogous to the description of Fanconi anemia as a disorder of DNA repair.
 
A review of influenza is particularly relevant this year due to the ongoing novel H1N1 influenza pandemic. Surveillance and clinical data including risk factors for infection and complications due to the current H1N1 pandemic are reviewed. New evidence on the safety of antiviral agents in children and studies on interventions to reduce community transmission of influenza are included. Influenza vaccine efficacy and improving immunization coverage have also been addressed by recent studies. These studies from the early phase of the pandemic identify the population that are at high risk for complications, and affirm that active surveillance and prevention are important aspects of a public health response. Appropriate use of antiviral agents and improving influenza immunization coverage for all ages continue to be a challenge. Further studies are underway to improve the public health response, and the pandemic H1N1 strain is being incorporated into the 2010 seasonal influenza vaccine.
 
To provide an updated review of the epidemiology, clinical presentations, and outcomes of the 2009 pandemic influenza A H1N1 in children. The majority of cases of 2009 pandemic influenza A H1N1 in children have been mild. However, neurological complications, hospitalization, and even deaths have been reported in children. Death and severe illnesses have mostly occurred in children below 5 years of age and children with high-risk conditions. Coinfections with bacteria have also been reported. Most strains are sensitive to oseltamivir and all to zanamivir. Even though the majority of cases of 2009 pandemic influenza A H1N1 are mild, severe disease does occur in children. In addition, neurological complications and coinfection with bacteria exist. Treatment with antiviral medications should be initiated within 48 h to be most effective. When pandemic H1N1 vaccines become available, the safety and efficacy of these vaccines in this vulnerable population will be important to document.
 
Pediatric interventional cardiology has evolved quite dramatically over the past few decades and now, in 2009, the published literature continues to evolve new percutaneous strategies for managing patients with congenital heart disease, both simple and complex. Our goal for this review was to highlight new techniques and the new devices available to the pediatric interventional cardiologist, and to review the outcomes from past endeavors. Manuscripts published in the past year continue to demonstrate innovation; indicating an exciting and increasing experience of transcatheter treatment of septal communications using either new occluder devices or novel techniques. Bioabsorbable devices and percutaneously implanted valves are leading examples of technological improvements and creativity that will ultimately improve patient outcomes while minimizing invasiveness. Reports on procedural outcomes show technically safe early follow-up, with promising mid-term and long-term results for balloon valvuloplasty, balloon atrial septostomy and pulmonary artery stent implantation. As well, fetal and hybrid interventions have become important new arenas for the pediatric interventionist. Pediatric interventions have grown far beyond the early stages of the 1980s as mid-term and long-term outcome data are being reported, and many previously insurmountable hurdles have been overcome by developing new strategies and devices.
 
This review summarizes new findings in the field of maltreatment, addressing epidemiology, physical abuse, abusive head trauma, sexual abuse, sequelae, and prevention. Many articles this year focus on establishing a framework for thinking about how to evaluate a child for maltreatment, the consequences of maltreatment, and the current understanding of prevention efforts. Interestingly, some research has helped to reinforce some concepts that were clinically appreciated, especially related to retinal hemorrhages. The volume, quality, and breadth of research relating to child maltreatment continue to improve and expand our understanding of child abuse pediatrics. These authors summarize notable advances in our understanding of child maltreatment over the past year.
 
To review the recent publications on pediatric heart failure and pediatric transplantation. Little progress has been made in the chronic medical management of pediatric heart failure. Basic science studies demonstrating disparate regulation of β2-adrenergic receptors and microRNA between pediatric and adult heart failure may give clues to the lack of improvement in pediatric outcomes. Pediatric ventricular assist devices have significantly improved survival of bridge-to-transplant, but currently have too many limitations for destination therapy for children. Several areas of pediatric heart transplant have had significant developments over the last few years: the role of antibodies in mediating graft dysfunction after transplantation, ABO-incompatible transplant, extending the pediatric limits on acceptable pulmonary vascular resistance, and risk prediction of pediatric transplant outcomes. Failed single-ventricle palliation is a growing indication for heart transplantation with its own unique challenges. Pediatric heart transplantation can have excellent outcomes with survival beyond 20 years after transplant common, especially in the infant. However, the growing population of children and young adults being referred for heart transplantation after failed congenital heart surgery, especially after failed single-ventricle palliation, is presenting new obstacles that may start reducing the survival rates for pediatric heart transplantation. This may in part be ameliorated by earlier referral for transplant evaluation.
 
Spinal fusion procedures that are the mainstay of the treatment of progressive or severe curves in adolescents and adults are not suitable for most young children as there is a large magnitude of remaining growth. Early spinal fusion stunts the growth of the thorax and may interfere with the development of the lungs. Therefore, in children with early-onset scoliosis, 'growth friendly' instrumentation systems have been utilized to control the deformity while allowing the growth of the spine and the thoracic cage. The experience with growing rods has been increasing, along with expanding indications. Several self-lengthening instrumentation systems have been introduced aiming for guided spinal growth. There has been considerable progress in the clinical and laboratory studies using magnetically controlled growing rod constructs. Growing rods and vertical expandable prosthetic titanium rib (VEPTR) systems provide deformity control while allowing for spinal growth along with a risk of spontaneous vertebral fusions. VEPTR may cause rib fusions as the implants overlie the thoracic cage and, therefore, the use in pure spinal deformities is controversial. There have been exciting recent advances concerning the treatment of spinal deformities in young children. Despite these advances, the surgical treatment of early-onset scoliosis remains far from optimal and more development is on the way.
 
Supracondylar humerus fractures are the most common elbow fractures in children. Choice of treatment may be guided by the Gartland classification. Recent studies recommend conservative management for non or minimally displaced fractures, whereas there seems to be a trend towards surgical intervention for all displaced fractures. The purpose of this review is to discuss the various treatment options for displaced supracondylar humerus fractures. Closed reduction and percutaneous pinning are the preferred treatment options for most displaced pediatric supracondylar fractures of the humerus. The ideal pin configuration has always been subject to great controversy. It is well known that placement of a medial pin carries the risk of iatrogenic ulnar nerve injury, whereas lateral pinning carries an increased risk of median neuropathy. Therefore, given the potential risk, it is recommended to avoid medial pinning to prevent damage to the ulnar nerve and stabilize the fracture with two or three lateral pins. Today, the preferred treatment of displaced supracondylar humerus fractures in children is immediate closed reduction and percutaneous fixation with two or three lateral pins. In case of instability of the medial column, a medial pin may be used, but possibility of iatrogenic ulnar nerve injury should be considered.
 
A patent ductus arteriosus (PDA) in premature infants is common and is associated with a number of adverse outcomes. The purpose of this review is to discuss recent literature in PDA diagnosis and management. The diagnosis of a 'hemodynamically significant' PDA is challenging and a robust definition is lacking. The risks and benefits of therapies, either medical or surgical, designed to close the PDA, are controversial. Oral acetaminophen has gained increasing attention as an alternative pharmaceutical agent for PDA closure in premature infants, although safety concerns remain. Compared to surgical ligation, transcatheter PDA closure may be associated with less risk and fewer adverse events. Both aggressive and conservative management of PDA has similar clinically important outcomes, although the strength of evidence is derived mostly from cohort studies. Clinicians should weigh the potential adverse effects of pharmaceutical or surgical PDA closure against the likelihood of spontaneous closure. The infant population most likely to benefit from PDA closure remains ill-defined and clinical context is recommended.
 
FGF21 has emerged as a hormone involved in energy homeostasis. A large number of recent reports have expanded the role of FGF21 from a response factor to prolonged fasting to a key hormone that regulates free fatty acid (FFAs) levels. The therapeutic role of recombinant human FGF21 for type 2 diabetes and dyslipidemia is under study. Recent evidence suggests that supraphysiological concentrations of FFAs induce FGF21 secretion (i.e., starvation and intense physical activity) through the peroxisome proliferator-activated receptor alpha (PPARα) pathway. The rise in FGF21 levels is aimed at improving energy production (ketogenesis) and utilization (oxidation) of FFAs. FGF21 increment may protect against chronic exposure to high concentrations of FFAs, which causes lipotoxicity in muscle, pancreas, and liver. In addition, FGF21 induces appetite and inhibits growth, probably as part of the adaptive starvation response. The autocrine function of FGF21 in adipose tissue increases PPARγ activity and glucose uptake. Increased plasma FGF21 levels have been found in insulin resistance states in humans. However, the reason for this rise in FGF21 values is still under study. We propose that FGF21 serves as a defense mechanism against supraphysiological concentrations of FFAs. In addition, FGF21 might have a therapeutic indication in humans.
 
Congenital adrenal hyperplasia (CAH) due to a CYP21A2 deficiency results in prenatal androgen exposure and virilization of the external genitalia. The surgical procedures, indications, timing, and methods used have come under debate during the past decade. The androgen effect on later behaviors adds to the complexity of the situation for these women. The purpose of this review is to update physicians on recent findings regarding the outcome of feminizing surgery, infertility, quality of life (QoL), and psychosexual aspects in women with CAH. Surgical outcome, also for the more modern techniques used today, has not been entirely satisfactory and QoL assessments paint a dark picture. All psychological effects assessed show a spectrum of severity correlating with the CYP21A2 genotype or disease severity. The prevailing recommendation for sex of rearing is to let all patients with the 46,XX karyotype grow up as girls. This notion has now been challenged regarding patients with the most extreme virilization of genitalia. There are large differences in outcome depending on the severity of the disease or CYP21A2 mutation. Care needs to be individualized and centralized to specialized multidisciplinary teams. Feminizing surgery is still not satisfactory for all patients. More studies regarding sex identity are needed.
 
Purpose of review: This review highlights the recent identification of human interleukin-21 (IL-21) and interleukin-21 receptor (IL-21R) deficiencies as novel entities of primary immunodeficiency. Recent findings: We recently described the first patients with IL-21R deficiency who had cryptosporidial infections associated with chronic cholangitis and liver disease. All IL-21R-deficient patients suffered from recurrent respiratory tract infections. Immunological work-up revealed impaired B cell proliferation and immunoglobulin class-switch, reduced T cell effector functions, and variable natural killer cell dysfunctions. Recently, these findings have been extended by the discovery of one patient with a mutation in the IL21 gene. This patient predominantly manifested with very early onset inflammatory bowel disease and recurrent respiratory infections. Laboratory examination showed reduced circulating B cells and impaired B cell class-switch. Summary: Human IL-21 and IL-21R deficiencies cause severe, primary immunodeficiency reminiscent of common variable immunodeficiency. Early diagnosis is critical to prevent life-threatening complications, such as secondary liver failure. In view of the critical role of IL-21 in controlling immune homeostasis, early hematopoietic stem cell transplantation might be considered as therapeutic intervention in affected children.
 
Trisomy 21 (Down syndrome) is a common condition encountered by the pediatric surgeon. The surgical anomalies associated with Down syndrome now have treatment options that were previously considered futile. An effective surgical team approach to these children involves knowledge of the unique pathophysiology of trisomy 21 and an appreciation for the desires of the family and the needs of the child. Surgical techniques benefit children with Down syndrome equally as typical children. Pessimism regarding the outcome of surgical treatment of colorectal anomalies is fading, with evidence of nearly equivalent outcomes. Several autoimmune disorders impact children with Down syndrome. Idiosyncratic susceptibility to infections and malignancy is noted. Unique anesthetic complications and aerodigestive tract disorders have been identified. Many anomalies have surgical options that enhance the quality of life. There is optimism in the surgical treatment of children with Down syndrome. Improved operations, better anesthetic management and recognition of problems specific to the child with trisomy 21 make it safer and ethical to offer surgical solutions. Societal acceptance and mainstream participation are on the rise. The astute, compassionate pediatric surgeon does much to enhance the quality of life of these children and of the families who love them.
 
Top-cited authors
Daniel W Green
  • Hospital for Special Surgery
David C Bellinger
  • Harvard University
Karin B Nelson
  • National Institutes of Health
Roger Widmann
  • Weill Cornell Medical College
Katherine Biagas
  • Stony Brook University