Impact of Time to Diagnosis on Morbidity and Survival in Children With Malignant Central Nervous System Tumors.

OBJECTIVE: The aim was to determine the impact of time to diagnosis (TTD) on morbidity and mortality and to identify factors associated with overall survival (OS) in pediatric patients with malignant central nervous system (CNS) tumors. METHODS: This is a retrospective review of all malignant CNS tumors presenting to 2 tertiary care pediatric hospitals from 2000 to 2019. Cox proportional hazard model analysis outcomes included TTD and OS as well as morbidity; stratified by tumor category, age, relapse, and presence of metastatic disease. RESULTS: There were 197 children with malignant CNS tumors (mean age 8.7 y, 61% male). Tumors included medulloblastoma (N=58, 29.4%), ependymoma (N=27, 13.7%), high-grade glioma (N=42, 21.3%), germ cell tumors (N=47, 23.9%), and other embryonal tumors (N=23, 11.7%). Median TTD from symptom onset was 62 (interquartile range: 26.5 to 237.5 d) and 28% had metastatic disease. Three-year progression free survival was 55% and 3-year OS was 73.1%. Increased OS was associated with increased TTD (parameter estimate 0.12; confidence interval [CI]: 0.019-7.06; P =0.019), high-grade glioma (hazard ratio [HR]: 2.46; CI [1.03-5.86]; P =0.042), other embryonal tumor (HR: 2.84; CI [1.06-7.56]; P =0.037), relapse (HR: 10.14; CI: 4.52-22.70; P <0.001) and metastatic disease (HR: 3.25; CI: 1.51-6.96; P =0.002). Vision change (HR: 0.58; CI: 0.313-1.06; P =0.078), hearing loss (HR: 0.71; CI: 0.35-1.42; P =0.355), and cognitive impairment (HR: 0.73; CI: 0.45-1.19; P =0.205) were not associated with TTD in this model. CONCLUSIONS: Increased median TTD is associated with higher OS in pediatric patients treated for malignant CNS tumors. Tumor biology and treatment modality are more important factors than TTD for predicting morbidity and long-term outcomes in pediatric patients with CNS tumors.

Optimized Infliximab Induction Predicts Better Long-Term Clinical and Biomarker Outcomes Compared to Standard Induction Dosing.

OBJECTIVES: To evaluate the efficacy of standard and optimized infliximab induction dosing in attaining corticosteroid (CS) free clinical remission at week 52 and the effect that post-induction trough levels have on long-term outcome. METHODS: Inflammatory bowel disease (IBD) patients ≤18 years commenced on infliximab between August 1, 2016, and August 1, 2018, from Vancouver, Canada, and Glasgow, Scotland, were included. The Glasgow cohort followed standard induction while the Vancouver cohort undertook induction optimization based on clinical, biomarker, and proactive infliximab trough levels. Baseline characteristics and laboratory values were documented. RESULTS: In total, 140 children were included [median age 14.1 years (interquartile range (IQR) 12.0-16.0)]; 54% male. CS-free clinical remission at week 52 was higher in the optimized group compared to the standard cohort [65/78 (83%) vs. 32/62 (52%), P < 0.001]. Combined CS-free clinical and biomarker remission (CRP < 5 mg/L) was also higher in the optimized compared to the standard cohort [65/78 (83%) vs 25/62 (40%), P < 0.001]. The median post-induction trough level was higher in children who were in CS-free clinical remission at week 52 [3.6 mg/L (1.5-7.1)] vs. those who were not [2.0 mg/L (0.8-4.1), P = 0.04]. The odds of attaining a therapeutic post-induction trough level were almost 4-fold higher in the optimized group than the standard cohort (OR 3.97, 95% CI: 1.89-8.68, P < 0.001). CONCLUSIONS: Standard infliximab induction resulted in less favorable long-term outcomes for pediatric IBD patients. Optimizing induction using clinical, biomarker, and proactive trough levels resulted in higher post-induction trough levels and a greater odds of attaining long-term clinical remission.

Glomerular Filtration Rate Abnormalities in Children With Type 1 Diabetes.

OBJECTIVES: Type 1 diabetes (T1D) increases the risk of chronic kidney disease (CKD) development. The primary objective of this study was to assess the prevalence of abnormalities in estimated glomerular filtration rate (eGFR) in children with T1D. As a secondary objective, we sought to explore the relationship between clinical characteristics and abnormalities in eGFR. METHODS: This cross-sectional study involved children ≤18 years of age with T1D followed in the diabetes clinic at a pediatric tertiary care centre. Data were collected from health records between 2016 and 2020. Using the Bedside Schwartz, Chronic Kidney Disease in Children Under 25 (CKiD U25) and European Kidney Function Consortium (EKFC) equations, eGFR was categorized as CKD (<60 mL/min/1.73 m2), mildly decreased (60 to <90 mL/min/1.73 m2), normal (90 to <158 mL/min/1.73 m2) and hyperfiltration (≥158 mL/min/1.73 m2). Linear regression analysis was used to describe the relationship between eGFR and clinical characteristics. RESULTS: Of the 420 participants, 225 were male (54%); the median age at diagnosis and duration of T1D were 6.1 and 4.8 years, respectively. The proportion of participants with mildly decreased eGFR was similar regardless of eGFR equation, with 11% to 14% of participants with an eGFR <90 mL/min/1.73 m2. When analyzed as a function of duration of T1D, eGFR was 1.4 mL/min/1.73 m2 lower per year duration of T1D. CONCLUSIONS: A notable proportion of children with T1D demonstrates eGFR abnormalities early in their T1D course. This finding along with evidence of lower eGFR in adolescence is concerning for long-term risk of CKD and warrants systematic serum creatinine monitoring at diagnosis and regular intervals thereafter in children with T1D.

Diagnostic reference levels for mammography in BreastScreen Queensland.

Diagnostic reference levels assist in the optimisation of radiation exposure parameters within a medical imaging facility. As no Australian DRLs currently exist, radiation doses from mammography in BreastScreen Queensland are analysed. Program-based DRLs of 1.1 and 1.4 mGy are proposed for digital radiography and computed radiography mammography systems, respectively.