Current Pediatric Reviews - Volume 11, Issue 2, 2015

The surgical treatment of tetralogy of Fallot can be considered as a success story in the history of congenital heart diseases. Since the early outcome is no longer the main issue, the focus moved to the late sequelae of TOF repair, i.e. the pulmonary insufficiency and the secondary adaptation of the right ventricle. This review provides recent insights into the pathophysiological alterations of the right ventricle in relation to the reconstruction of the right ventricular outflow tract after repair of tetralogy of Fallot. Its clinical relevance is documented by addressing the policy changes regarding the optimal management at the time of surgical repair as well as properly defining criteria and timing for late pulmonary valve implantation.

Non-transfusion-dependent thalassemias (NTDT) encompass a group of hereditary chronic hemolytic anemia, which, as the name indicates, not require regular blood transfusion for survival. These include β-thalassemia intermedia, hemoglobin E/β-thalassemia, and Hemoglobin H disease (α- thalassemia intermedia). Individuals with structural variant of hemoglobin especially Hemoglobin S and Hemoglobin C associated with “α” or “β” thalassemia in heterozygous condition may also present with similar features of NTDT. NTDT patients are not immune to the development of transfusion unrelated complications in the long run. These hereditary chronic hemolytic anemias are still under-recognized in developing countries like India, where the disease burden might be high causing significant morbidity. The pathophysiologic hallmark that characterizes this group of disorders (ineffective erythropoiesis, hemolysis, chronic anemia) leads to a number of serious complications, similar to transfusion dependent thalassemia. So, timely diagnosis and institution of appropriate preventive/remedial measures as well as education of patient population can help decrease the morbidity to a significant extent. In the present review, focus will be on the pathophysiological mechanisms and available management options of NTDT from a developing country perspective like India.

In this review, we discuss the evidence supporting the causative role of increased FGF21 expression in reduced GH action and impaired longitudinal bone growth. Fibroblast Growth Factor (FGF) 21 (FGF21) is a member of a subfamily of FGFs which lack the FGF heparin-binding domain. Thus, these FGFs can function as endocrine as well as paracrine factors. During fasting, increased expression of FGF21 induces gluconeogenesis, fatty acid oxidation, and ketogenesis: as a result, FGF21 is considered a key regulator of the metabolic adaptation to fasting. In addition, recent evidence indicates that FGF21 may regulate longitudinal bone growth. It has been shown that transgenic mice overexpressing FGF21 exhibit reduced bone growth and hepatic Growth Hormone (GH) insensitivity. FGF21 knock-out mice exposed to chronic food restriction experience greater body and tibial growth than their food-restricted wild-type littermates, suggesting that the increased FGF21 expression in wild-type mice during undernutrition leads to reduced skeletal growth. The FGF21-mediated attenuation of bone growth appears to be secondary to reduced GH sensitivity, both systemically and locally in the long bones’ growth plate. The effects of FGF21 on GH action are direct, and may result from the reduced translocation of GH receptors from the cytoplasm to the cell membrane. Lastly, we discuss recent studies which have shown that FGF21 in infancy is inversely correlated with linear growth rate. In conclusion, all the evidence discussed in this review indicates that FGF21 may be an important negative regulator of mammalian growth.

Medulloblastoma, the most common primary pediatric malignant brain tumor is a molecularly heterogeneous disease with different developmental origins, distinct phenotypes, diverse biological behaviour, and contrasting clinical outcomes. The current clinico-radiological risk-classification fails to take account of this heterogeneity and existent prognostic variability. It is widely accepted that dysregulation of normal developmental processes constitute a key mechanism of tumorigenesis in at least a subset of medulloblastomas. Several attempts at biological classification have successfully identified distinct subgroups with subgroup-specific gene signatures, demographics, histologic subtypes, and rates of metastases. Several research groups have classified medulloblastoma into molecular subgroups using a variety of different genomic approaches and platforms such as gene expression profiling, microRNA profiling and methylation arrays. Recently, a consensus has emerged that classifies medulloblastoma into four distinct molecular subgroups named as wingless (WNT), sonic hedgehog (SHH), Group 3 and Group 4 respectively. However, such integrative approaches have limited applicability in the clinic due to the need of fresh-frozen tissues and elaborate molecular biology tools. In parallel, some groups have proposed and validated traditional antibody-based approaches using immunohistochemistry on archival specimen for rapid and reliable molecular subgrouping to be applied in any basic neuropathology laboratory. Heterogeneity within each of these four consensus subgroups has also been demonstrated that needs to be considered in the design of future clinical trials. There is a compelling need to integrate molecular biomarkers with clinico-pathologic outcome indicators to refine risk-stratification as well as develop novel molecularly targeted agents for optimizing therapeutic index and personalizing therapy.

Exercise is important in the management of type 1 diabetes mellitus (T1DM). Modern diabetes care includes the goal that all youth meet guidelines for regular physical activity. Evidence suggests regular physical activity improves cardiovascular health, lipid profiles, psychosocial wellbeing and, possibly, glycemic control in youth with T1DM. However, exercise is especially problematic for children and adolescents because wide glycemic excursions commonly occur during and after exercise and may increase the risk of severe hypoglycemia. In addition, youth with T1DM have abnormal counterregulatory hormone responses, further increasing the risk of exercise-associated hypoglycemia. Recent studies have demonstrated that this risk is present during, and many hours after exercise, and have tested strategies to prevent exercise-induced hypoglycemia in youth. Despite these recent studies, the fear of hypoglycemia remains a major impediment to achieving target glycemic control in youth, targets that have recently been tightened. Equally, data suggests fear of hypoglycemia is the major impediment to participation in regular daily exercise in T1DM. Recent advances in insulin delivery systems and in real time continuous glucose monitoring have improved care for youth with T1DM, allowing safer participation in exercise programs. The impending development and approval of “closed loop” insulin delivery systems (the artificial pancreas) holds great promise for the safe participation in exercise for all youth with T1DM.

Objectives: Clinicians often refer to published or local guidelines when counselling expectant parents on perinatal care decisions at the limits of viability. The objectives of this study are to systematically review the literature and assess the quality of published international guidelines regarding perinatal care of 22-25 week gestational age infants. Study Design: MEDLINE, Pre-MEDLINE and TRIP databases were systematically searched for guidelines on perinatal management of extremely premature infants. Included guidelines were: created by an institution that regularly cared for extremely premature infants; offered comprehensive care plans; and, published after 1999 in English. The final selected guidelines were appraised using the validated AGREE-II (Appraisal of Guidelines for Research & Evaluation) tool which consists of six quality domains (Scope and Purpose, Stakeholder Involvement, Rigour of Development, Clarity of Presentation, Applicability, and Editorial Independence). Overall guideline quality was rated and each appraiser was asked whether they recommended the guideline for use. Results: Electronic and grey searches yielded 263 publications. Screening left 37 guidelines, 16 of which met inclusion criteria. Appraisal revealed deficits within all quality domains, predominantly ‘Applicability’, ‘Editorial Independence’ and ‘Rigour of Development’. A wide range of mean domain scores within each guideline was observed. Overall quality scores ranged from 11%-61%; no guideline was assessed as suitable for use without modifications. Conclusion: Based on the AGREE-II criteria, we identified deficits in the quality of all of the published international guidelines, highlighting the need for rigorously and transparently developed guidelines to inform practice related to perinatal care of 22-25 week gestational age infants.

Objective: To assess the effect of chronic middle ear effusion (CMEE) on balance and equilibrium. Material and Methods: Prospective study controlling two groups of children. The active arm consisted of children having a unilateral or bilateral CMEE that persisted for at least 3 months. The control group consisted of children presenting with normal middle ear. Children and parents in both groups were questioned about any symptom of vertigo, dizziness, disequilibrium or child’s tendency to fall. ENT exam included an assessment with pneumatic and microscopic otoscopy, evaluation of the vestibular system with the Romberg test, the Fukuda test, the head-shaking test and the Starwalk test. Results: The study group consisted of 15 children (mean = 6.5 years, SD = 2; 10 females and 5 males). The control group consisted also of 15 children (mean = 7.2 years, SD = 1.8; 8 females and 7 males). The duration of MEE was between 3 and 12 months (mean = 8 months). Three children (20%) in the study group had a history of vertigo, imbalance, disequilibrium and/or tendency to fall. None of the children in the control group had such a history (p = 0.22); Five children in the study group had abnormal head-shaking test, Fukuda and/or Starwalk tests (33.33%). Two children in the control group had such a finding (13.33%) (p = 0.39). Romberg test was normal in all children in both groups. In the study group, one child showed positional and spontaneous nystagmus on VNG testing. Another one showed positional nystagmus. Hence, 2 children had abnormal findings on VNG (13.33%). In the control group, VNG was normal in all children (p = 0.46). Tympanometry showed a type B curve in 26 ears, a type C curve in 3 ears and type A in one ear. In the control group all patients presented a type A curve. Conclusion: This paper describes the first study using VNG in a population of children with CMEE. The presence of balance disturbances associated or not with hearing loss is of paramount importance to the clinician as to the indications of myringotomy with a tube intervention.