Adolescent and young adult (AYA) survivors of pediatric oncology related cerebral insult are vulnerable to numerous treatment-induced deficits that significantly enhance cardiovascular disease risk. ...Regular exercise improves endothelial function, fitness, body composition and musculoskeletal function which may reduce predisposition for cardiovascular disease. Here we assessed the feasibility and effectiveness of a 24-week exercise intervention on cardiovascular, physical and metabolic outcomes in this population. Thirteen survivors (6 male, 7 female; median age 19 y (range 16-23 y) were recruited to participate in a 48-week study consisting of a 24-week control period (regular care) followed by a 24-week exercise intervention. Outcome measures were collected at entry (week 0) and following regular care (24-week) and exercise (48-week). Assessed variables included endothelial function (flow mediated dilation, FMD), blood pressure, heart rate (HR), aerobic capacity, anthropometry, body composition, muscular strength (3 repetition maximum testing), muscular endurance (repetitions/min) and physical activity levels (accelerometry). Compared to baseline, delta diameter (p = 0.008) and FMD (p = 0.029) of the brachial artery increased following exercise. Bicep-curl strength also increased following exercise compared to baseline (p = 0.019), while submaximal (6 min mark) measures of ventilation (p = 0.012), rating of perceived exertion (p = 0.012), HR (p = 0.001), absolute (p = 0.000) and relative (p = 0.000) aerobic capacity decreased. Breaks in sedentary time increased (p = 0.043) following exercise compared to regular care. Although the sample was small and heterogeneous, this study demonstrates that exercise is achievable and has positive effects on vascular function, submaximal fitness, local strength and physical activity in a population of AYA survivors of pediatric oncology related cerebral insult.
Aim
A retrospective audit was undertaken to evaluate modes of presentation and treatment outcomes for craniopharyngioma in a single paediatric institution over a 20‐year period.
Methods
A search of ...the neurosurgical and histopathological databases for patients under 21 years of age treated for craniopharyngioma between 1990 and 2010 was performed at our institution. The clinical records of eligible patients were reviewed and information regarding presentation, medical and surgical management and post‐treatment outcome were extracted and collated.
Results
Of 10 evaluable patients, the commonest presenting symptoms were headache and visual impairment. Clinical and biochemical evaluation undertaken prior to surgery revealed visual dysfunction in 70% and pituitary deficit in 30%. Gross total resection was achieved in 40% but was curative in only 20%. The remaining 80% required further surgical and/or radiotherapeutic intervention. Seven patients had radiation therapy with stabilisation in 70%. Multiple Pituitary Hormone Deficiency evolved in all patients over time, while visual impairment worsened in 30% post‐operatively and improved in 20%. Obesity was present in 50% after a mean follow‐up interval of 5.6 years and was apparent within 1 year of initial surgery in 30%. Although neurocognitive, psychological and behavioural problems were noted for some patients during medical review, only 20% of patients were formally assessed.
Conclusions
Craniopharyngioma is associated with significant long‐term morbidity. Attention to an integrated care pathway that includes standardised neurocognitive and psychological and behavioural assessment would facilitate early appropriate intervention and support leading to an improved quality of life for children with craniopharyngioma.
Context:
Intronic DNA frequently encodes potential exonic sequences called pseudoexons. In recent years, mutations resulting in aberrant pseudoexon inclusion have been increasingly recognized to ...cause disease.
Objectives:
To find the genetic cause of familial glucocorticoid deficiency (FGD) in two siblings.
Patients:
The proband and his affected sibling, from nonconsanguineous parents of East Asian and South African origin, were diagnosed with FGD at the ages of 21 and 8 months, respectively.
Design:
Whole exome sequencing was performed on genomic DNA (gDNA) of the siblings. Variants in genes known to cause FGD were assessed for causality. Further analysis of gDNA and cDNA was performed by PCR/RT-PCR followed by automated Sanger sequencing.
Results:
Whole exome sequencing identified a single, novel heterozygous variant (p.Arg71*) in nicotinamide nucleotide transhydrogenase (NNT) in both affected individuals. Follow-up cDNA analysis in the proband identified a 69-bp pseudoexon inclusion event, and Sanger sequencing of his gDNA identified a 4-bp duplication responsible for its activation. The variants segregated with the disease: p.Arg71* was inherited from the mother, the pseudoexon change was inherited from the father, and an unaffected sibling had inherited only the p.Arg71* variant.
Conclusions:
FGD in these siblings is caused by compound heterozygous mutations in NNT; one causing pseudoexon inclusion in combination with another leading to Arg71*. Discovery of this pseudoexon activation mutation highlights the importance of identifying sequence changes in introns by cDNA analysis. The clinical implications of these findings include: facilitation of antenatal genetic diagnosis, early institution of potentially lifesaving therapy, and the possibility of preventative or curative intervention.
Background Survivors of paediatric brain cancer and/or cranial radiotherapy (CRT) are at an increased risk of developing serious comorbidities. Established risk factors for chronic disease include ...central obesity, endothelial abnormalities and diminished fitness. Objectives Here we characterised anthropometry, body composition, bone mineral density (BMD), heart rate (HR), blood pressure (BP), endothelial function, muscular strength and endurance and aerobic fitness in adolescent and young adult (AYA) survivors. Methods Twenty survivors (10 male, 10 female; 20 ± 2 years) were compared with 19 matched controls. Muscular strength was assessed using three repetition maximum tests, while muscular endurance was determined as number of repetitions performed per minute. Peak oxygen uptake (VO2 peak) was assessed on a treadmill using a modified chronotropic protocol. Anthropometric measurements, HR and BP were taken using standard clinical protocols, while body composition and BMD were determined using dual X-ray absorptiometry (DXA). Endothelial function was measured using the flow mediated dilation technique. Results Survivors demonstrated deficits in muscular strength (latissimus dorsi pull-down, p = 0.020; bicep curl, p = 0.009), muscular endurance (squats, p = 0.012; sit-ups, p = 0.030; push-ups, p = 0.013), minute ventilation at peak exericse (p = 0.002) and VO2peak (L/min, p = 0.002; mL/kg/min, p = 0.008; mL/kg LBM/min, p = 0.010). Additionally, survivors had greater waist-to-hip ratios (p = 0.032), resting HR (p = 0.048) and higher percentage of total body (p = 0.017), central (p = 0.009) and peripheral (p = 0.032) fat. Lean body mass (p = 0.004) and BMD (p = 0.005) were lower in the survivor group. Conclusion AYA survivors of paediatric brain cancer and/or CRT exhibit altered body composition, increased resting HR and reduced BMD, muscular strength, muscular endurance and cardiorespiratory fitness compared to controls.
To assess metabolic function among adolescent and young adult (AYA) survivors of childhood cancer-related brain surgery or cranial irradiation (CRT) and to determine feasibility, safety, and ...metabolic as well as psychological impact of a 6-month exercise program in this cohort.
Twenty AYAs aged 15-23 years were recruited. All had completed cancer treatment by age 15.5 and were more than 1 year after end of treatment. Metabolic function was assessed at baseline (T1), after a 6-month non-intervention period (T2), and after the 6-month intervention (T3). Psychological assessments were performed at T1 and T3. Eight to 12 months after the program (T4), its lasting impact was assessed by questionnaire. The 6-month intervention consisted of small group-based, tailored, supervised exercise sessions combining resistance and aerobic exercise. Sessions were offered up to thrice per week and adherence defined as participation in ≥24 sessions. Flexibility was built into the design with an alternative home-based program offered to those who could not attend the gymnasium.
Thirteen of the 20 recruited participants were adherent to the program. There was one fall during exercise, but no injury was sustained. Higher rates of metabolic impairment than would be expected in a healthy cohort were found at baseline both among brain tumor survivors and survivors of total body irradiation. Central adiposity reduced post-intervention (p = 0.014) and improvements in adaptive function were seen. Participants enjoyed the program, but work and study commitments limited attendance.
AYA survivors of childhood brain tumors and CRT should be screened for metabolic and psychological well-being. Small group-based exercise is safe, feasible, and enjoyable for this cohort and may benefit them both metabolically and psychologically.
ACTRN12614000796684. Retrospectively registered July 28, 2014.
Objective & Design. We undertook a retrospective review of children diagnosed with acute lymphoblastic leukemia (ALL) and treated with modern COG protocols (n=80) to determine longitudinal changes in ...body mass index (BMI) and the prevalence of obesity compared with a healthy reference population. Results. At diagnosis, the majority of patients (77.5%) were in the healthy weight category. During treatment, increases in BMI z-scores were greater for females than males; the prevalence of obesity increased from 10.3% to 44.8% (P<0.004) for females but remained relatively unchanged for males (9.8% to 13.7%, P=0.7). Longitudinal analysis using linear mixed-effects identified associations between BMI z-scores and time-dependent interactions with sex (P=0.0005), disease risk (P<0.0001), age (P=0.0001), and BMI z-score (P<0.0001) at diagnosis and total dose of steroid during maintenance (P=0.01). Predicted mean BMI z-scores at the end of therapy were greater for females with standard risk ALL irrespective of age at diagnosis and for males younger than 4 years of age at diagnosis with standard risk ALL. Conclusion. Females treated on standard risk protocols and younger males may be at greatest risk of becoming obese during treatment for ALL. These subgroups may benefit from intervention strategies to manage BMI during treatment for ALL.
Aim
A retrospective audit was undertaken to evaluate modes of presentation and treatment outcomes for craniopharyngioma in a single paediatric institution over a 20‐year period.
Methods
A search of ...the neurosurgical and histopathological databases for patients under 21 years of age treated for craniopharyngioma between 1990 and 2010 was performed at our institution. The clinical records of eligible patients were reviewed and information regarding presentation, medical and surgical management and post‐treatment outcome were extracted and collated.
Results
Of 10 evaluable patients, the commonest presenting symptoms were headache and visual impairment. Clinical and biochemical evaluation undertaken prior to surgery revealed visual dysfunction in 70% and pituitary deficit in 30%. Gross total resection was achieved in 40% but was curative in only 20%. The remaining 80% required further surgical and/or radiotherapeutic intervention. Seven patients had radiation therapy with stabilisation in 70%.
M
ultiple
P
ituitary
H
ormone
D
eficiency evolved in all patients over time, while visual impairment worsened in 30% post‐operatively and improved in 20%. Obesity was present in 50% after a mean follow‐up interval of 5.6 years and was apparent within 1 year of initial surgery in 30%. Although neurocognitive, psychological and behavioural problems were noted for some patients during medical review, only 20% of patients were formally assessed.
Conclusions
Craniopharyngioma is associated with significant long‐term morbidity. Attention to an integrated care pathway that includes standardised neurocognitive and psychological and behavioural assessment would facilitate early appropriate intervention and support leading to an improved quality of life for children with craniopharyngioma.
: Sulfonylureas are commonly prescribed for type 2 diabetes mellitus; however, overdose or accidental ingestion may result in profound and prolonged hypoglycaemia with permanent neurological ...sequelae and death. We describe two cases of children with hypoglycaemia due to presumed accidental ingestion of sulfonylureas, where traditional methods of raising blood sugar levels were unsatisfactory. Two studies describe Octreotide for adults with hypoglycaemia, but there are no studies examining the use of Octreotide in children for this indication. Given that Octreotide has been shown to be safe in children when used for other indications, we used Octreotide to safely restore euglycaemia.
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