BACKGROUND Central giant cell granulomas (CGCG) are rare osteolytic, benign but often locally agg... more BACKGROUND Central giant cell granulomas (CGCG) are rare osteolytic, benign but often locally aggressive tumours of bone. Surgical curettage may not be possible in extensive lesions and resection carries high morbidity, especially in growing children, and previous medical therapies have had variable efficacy and high recurrence rates. Interruption of receptor activator of nuclear factor-kappa B ligand (RANKL) signalling holds promise as an effective therapeutic strategy for these tumours. AIMS To evaluate the efficacy and safety of our protocol for denosumab treatment of CGCG in children. METHODS Retrospective review of 4 patients treated with denosumab using a standardised protocol for CGCG in a tertiary paediatric centre. Denosumab 70 mg/m2 was given 4-weekly, followed by 2 doses of zoledronate 0.025 mg/kg, aimed at preventing rebound hypercalcaemia. RESULTS Treatment of CGCG resulted in metabolic remission in all patients, but recurrence, detected by positron emission tomography (PET), occurred at 6 months in three patients and 12 months in one patient. Three patients developed symptomatic hypercalcaemia 4-5 months and one patient asymptomatic hypercalcaemia 7 months after cessation of denosumab, with 3 requiring additional bisphosphonate treatment. CONCLUSIONS Denosumab produced a radiological and metabolic response in our patients, but metabolic recurrence occurred in all patients. PET imaging was effective for monitoring treatment response and early detection of recurrence. Incidence of rebound hypercalcaemia in this paediatric cohort was high. We present proposed changes to our protocol with the aim of producing sustained remission and preventing rebound hypercalcaemia.
Clinical studies from Australia and the Asia-Pacific region support an association between type 1... more Clinical studies from Australia and the Asia-Pacific region support an association between type 1 diabetes and several viruses, including rubella, RV and EV. Meta-analysis has demonstrated a significant association between EV infection and type 1 diabetes globally, as well as in this region. Detailed studies of EV outbreaks have identified genotypes distinct to the region. In particular, an outbreak of EV71 in 1997–1999 was temporally associated with the most common virus isolated from an Australian incident cohort of children with type 1 diabetes. In this study, EV infection was more common in young people without high-risk HLA genotypes, suggesting that there may be a subgroup of virus-induced type 1 diabetes. Fulminant diabetes is a unique form of diabetes found predominantly in Asian patients with rapid onset, ketosis-prone diabetes. Concurrent viral infections, in particular EV, are also associated with this form of diabetes. Further evaluation of the clinical characteristics of young people and adults with virus-induced diabetes in the region, in parallel with examination of molecular characteristics of isolates, may provide innovative insights into the pathogenesis of type 1 diabetes and fulminant diabetes.
Changes in retinal geometric parameters predict risk and progression of diabetic retinopathy (DR)... more Changes in retinal geometric parameters predict risk and progression of diabetic retinopathy (DR). We have shown that vitamin D deficiency (VDD) is associated with DR. We hypothesized that VDD mediates changes in retinal geometric parameters. Retinal vascular geometric parameters were assessed using a semiautomated computer program in photographs from young people with type 1 diabetes (T1D)(n=481)and summarized as central retinal arteriolar and venular equivalents (CRAE, CRVE), fractal dimension, length-diameter ratio, branching angle and curvature tortuosity. Parameters were compared between those with and without DR and VDD (25-hydroxyvitamin D concentration ≤ 50 nmol/L). Retinal vascular geometric parameters were also compared across quartiles of vitamin D levels. Median CRVE was higher in patients with DR compared with those without (median (IQR) CRVE 247.3 μm (31.3) versus 238.8 μm (23.5),P=0.01). Fractal dimension was marginally greater in patients without VDD (1.49 (0.06) ver...
Objective: Microvascular complications occur in adolescents with type 1 diabetes, although guidel... more Objective: Microvascular complications occur in adolescents with type 1 diabetes, although guidelines vary as to when screening should commence and prevalence data for those with ≤5-yr duration are limited. We therefore investigated trends in prevalence of early microvascular complications over 17 yr. Research design and methods: 819 adolescents (54% female) aged 11-17 yr with 2-to 5-yr diabetes duration were assessed for complications at a tertiary pediatric diabetes clinic between 1990 and 2006. Early retinopathy was detected using seven-field fundal photography, albumin excretion rate (AER) by timed overnight urine collections and peripheral nerve function by thermal/vibration threshold at the foot. Results were analyzed by age, time period of assessment, and duration. Results: Early retinopathy declined from 1990 to 2002 (16-7%, p < 0.01), then remained unchanged until 2006. Early elevation of AER (≥7.5 μg/min) and microalbuminuria (≥20 μg/min) did not change over time, whereas peripheral nerve abnormalities increased (14-28%, p < 0.01). Median hemoglobin A1c improved (8.7-8.2%, p < 0.01), in parallel with increased total daily insulin dose and injections per day (p < 0.01). Body mass index standard deviation score increased over time (0.55-0.79, p < 0.01). In multivariate logistic regression, early retinopathy was associated with earlier time period [odds ratio (OR) 0.68, confidence interval (CI) 0.55-0.85, p < 0.01] and older age (OR 1.19, CI 1.02-1.39, p = 0.03). AER ≥ 7.5 μg/min was associated with older age (1.19, 1.06-1.34, p < 0.01) and longer diabetes duration (OR 1.28, CI 1.02-1.62, p = 0.04) and height-adjusted peripheral nerve abnormalities with later time period (OR 1.26, CI 1.05-1.50, p = 0.01). Conclusions: Early complications are not uncommon in adolescents with 2to 5-yr diabetes duration, despite more intensive management in recent years.
BACKGROUND Central giant cell granulomas (CGCG) are rare osteolytic, benign but often locally agg... more BACKGROUND Central giant cell granulomas (CGCG) are rare osteolytic, benign but often locally aggressive tumours of bone. Surgical curettage may not be possible in extensive lesions and resection carries high morbidity, especially in growing children, and previous medical therapies have had variable efficacy and high recurrence rates. Interruption of receptor activator of nuclear factor-kappa B ligand (RANKL) signalling holds promise as an effective therapeutic strategy for these tumours. AIMS To evaluate the efficacy and safety of our protocol for denosumab treatment of CGCG in children. METHODS Retrospective review of 4 patients treated with denosumab using a standardised protocol for CGCG in a tertiary paediatric centre. Denosumab 70 mg/m2 was given 4-weekly, followed by 2 doses of zoledronate 0.025 mg/kg, aimed at preventing rebound hypercalcaemia. RESULTS Treatment of CGCG resulted in metabolic remission in all patients, but recurrence, detected by positron emission tomography (PET), occurred at 6 months in three patients and 12 months in one patient. Three patients developed symptomatic hypercalcaemia 4-5 months and one patient asymptomatic hypercalcaemia 7 months after cessation of denosumab, with 3 requiring additional bisphosphonate treatment. CONCLUSIONS Denosumab produced a radiological and metabolic response in our patients, but metabolic recurrence occurred in all patients. PET imaging was effective for monitoring treatment response and early detection of recurrence. Incidence of rebound hypercalcaemia in this paediatric cohort was high. We present proposed changes to our protocol with the aim of producing sustained remission and preventing rebound hypercalcaemia.
Clinical studies from Australia and the Asia-Pacific region support an association between type 1... more Clinical studies from Australia and the Asia-Pacific region support an association between type 1 diabetes and several viruses, including rubella, RV and EV. Meta-analysis has demonstrated a significant association between EV infection and type 1 diabetes globally, as well as in this region. Detailed studies of EV outbreaks have identified genotypes distinct to the region. In particular, an outbreak of EV71 in 1997–1999 was temporally associated with the most common virus isolated from an Australian incident cohort of children with type 1 diabetes. In this study, EV infection was more common in young people without high-risk HLA genotypes, suggesting that there may be a subgroup of virus-induced type 1 diabetes. Fulminant diabetes is a unique form of diabetes found predominantly in Asian patients with rapid onset, ketosis-prone diabetes. Concurrent viral infections, in particular EV, are also associated with this form of diabetes. Further evaluation of the clinical characteristics of young people and adults with virus-induced diabetes in the region, in parallel with examination of molecular characteristics of isolates, may provide innovative insights into the pathogenesis of type 1 diabetes and fulminant diabetes.
Changes in retinal geometric parameters predict risk and progression of diabetic retinopathy (DR)... more Changes in retinal geometric parameters predict risk and progression of diabetic retinopathy (DR). We have shown that vitamin D deficiency (VDD) is associated with DR. We hypothesized that VDD mediates changes in retinal geometric parameters. Retinal vascular geometric parameters were assessed using a semiautomated computer program in photographs from young people with type 1 diabetes (T1D)(n=481)and summarized as central retinal arteriolar and venular equivalents (CRAE, CRVE), fractal dimension, length-diameter ratio, branching angle and curvature tortuosity. Parameters were compared between those with and without DR and VDD (25-hydroxyvitamin D concentration ≤ 50 nmol/L). Retinal vascular geometric parameters were also compared across quartiles of vitamin D levels. Median CRVE was higher in patients with DR compared with those without (median (IQR) CRVE 247.3 μm (31.3) versus 238.8 μm (23.5),P=0.01). Fractal dimension was marginally greater in patients without VDD (1.49 (0.06) ver...
Objective: Microvascular complications occur in adolescents with type 1 diabetes, although guidel... more Objective: Microvascular complications occur in adolescents with type 1 diabetes, although guidelines vary as to when screening should commence and prevalence data for those with ≤5-yr duration are limited. We therefore investigated trends in prevalence of early microvascular complications over 17 yr. Research design and methods: 819 adolescents (54% female) aged 11-17 yr with 2-to 5-yr diabetes duration were assessed for complications at a tertiary pediatric diabetes clinic between 1990 and 2006. Early retinopathy was detected using seven-field fundal photography, albumin excretion rate (AER) by timed overnight urine collections and peripheral nerve function by thermal/vibration threshold at the foot. Results were analyzed by age, time period of assessment, and duration. Results: Early retinopathy declined from 1990 to 2002 (16-7%, p < 0.01), then remained unchanged until 2006. Early elevation of AER (≥7.5 μg/min) and microalbuminuria (≥20 μg/min) did not change over time, whereas peripheral nerve abnormalities increased (14-28%, p < 0.01). Median hemoglobin A1c improved (8.7-8.2%, p < 0.01), in parallel with increased total daily insulin dose and injections per day (p < 0.01). Body mass index standard deviation score increased over time (0.55-0.79, p < 0.01). In multivariate logistic regression, early retinopathy was associated with earlier time period [odds ratio (OR) 0.68, confidence interval (CI) 0.55-0.85, p < 0.01] and older age (OR 1.19, CI 1.02-1.39, p = 0.03). AER ≥ 7.5 μg/min was associated with older age (1.19, 1.06-1.34, p < 0.01) and longer diabetes duration (OR 1.28, CI 1.02-1.62, p = 0.04) and height-adjusted peripheral nerve abnormalities with later time period (OR 1.26, CI 1.05-1.50, p = 0.01). Conclusions: Early complications are not uncommon in adolescents with 2to 5-yr diabetes duration, despite more intensive management in recent years.
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Papers by Myra Poon