Diagnosis of vertebral fractures in children: is a simplified algorithm-based qualitative technique reliable?

Background Identification of osteoporotic vertebral fractures allows treatment opportunity reducing future risk. There is no agreed standardised method for diagnosing paediatric vertebral fractures. Objective To evaluate the precision of a modified adult algorithm-based qualitative (ABQ) technique, applicable to children with primary or secondary osteoporosis. Materials and methods Three radiologists independently assessed lateral spine radiographs of 50 children with suspected reduction in bone mineral density using a modified ABQ scoring system and following simplification to include only clinically relevant parameters, a simplified ABQ score. A final consensus of all observers using simplified ABQ was performed as a reference standard for fracture characterisation. Kappa was calculated for interobserver agreement of the components of both scoring systems and intraobserver agreement of simplified ABQ based on a second read of 29 randomly selected images. Results Interobserver Kappa for modified ABQ scoring for fracture detection, severity and shape ranged from 0.34 to 0.49 Kappa for abnormal endplate and position assessment was 0.27 to 0.38. Inter- and intraobserver Kappa for simplified ABQ scoring for fracture detection and grade ranged from 0.37 to 0.46 and 0.45 to 0.56, respectively. Inter- and intraobserver Kappa for affected endplate ranged from 0.31 to 0.41 and 0.45 to 0.51, respectively. Subjectively, observers’ felt simplified ABQ was easier and less time-consuming. Conclusion Observer reliability of modified and simplified ABQ was similar, with slight to moderate agreement for fracture detection and grade/severity. Due to subjective preference for simplified ABQ, we suggest its use as a semi-objective measure of diagnosing paediatric vertebral fracture

Importance of dynamic contrast enhanced magnetic resonance imaging for targeting biopsy and salvage treatments after prostate cancer recurrence

Purpose: Evaluate T2 weighted MRI (T2W), diffusion weighted imaging (DWI), and dynamic contrast enhanced MRI (DCE-MRI) for determining areas of prostate cancer recurrence to target biopsy or salvage treatment in patients previously treated with I-125 seed brachytherapy. Material and methods: MRI data from 15 patients, whose primary treatment was I-125 seed brachytherapy and who were subsequently treated with partial gland salvage high-dose-rate brachytherapy were retrospectively analyzed. Two radiologists independently reviewed imaging on two occasions blinded to clinical and biopsy information. At first review, the T2W and DWI sequences were assessed for likely presence of tumor and at second review, the additional DCE-MRI sequence was assessed. Results were recorded and compared on a prostate diagram divided into 12 sectors (quadrants at each of base, mid-gland, and apex) plus seminal vesicles (SV). Results: Number of patients for whom recurrence was visible was 7/15 for T2W, 6.5/15 for DWI, and 15/15 for DCE-MRI (average of results for the two radiologists). Approximately, half of the sectors identified as showing recurrence were at the anterior base of the prostate. Conclusions: In prostate cancer patients previously treated with I-125 permanent seed implants, DCE-MRI is superior to T2W and DWI in defining areas of recurrence, and should be used to target biopsy and for treatment planning of focal salvage therapies

Diagnostic accuracy of DXA compared to conventional spine radiographs for the detection of vertebral fractures in children

Objectives In children, radiography is performed to diagnose vertebral fractures and dual energy x-ray absorptiometry (DXA) to assess bone density. In adults, DXA assesses both. We aimed to establish whether DXA can replace spine radiographs in assessment of paediatric vertebral fractures. Methods Prospectively, lateral spine radiographs and lateral spine DXA of 250 children performed on the same day were independently scored by three radiologists using the simplified algorithm based qualitative technique and blinded to results of the other modality. Consensus radiograph read and second read of 100 random images were performed. Diagnostic accuracy, inter/intraobserver and intermodality agreements, patient/carer experience and radiation dose were assessed. Results Average sensitivity and specificity (95% confidence interval) in diagnosing one or more vertebral fractures requiring treatment was 70% (58%-82%) and 97% (94%- 100%) respectively for DXA and 74% (55%-93%) and 96% (95%-98%) for radiographs. Fleiss’ kappa for interobserver and average kappa for intraobserver reliability were 0.371 and 0.631 respectively for DXA and 0.418 and 0.621 for radiographs. Average effective dose was 41.9µSv for DXA and 232.7µSv for radiographs. Image quality was similar. Conclusion Given comparable image quality and non-inferior diagnostic accuracy, lateral spine DXA should replace conventional radiographs for assessment of vertebral fractures in children

Efficacy and toxicity outcomes for patients treated with focal salvage high dose rate brachytherapy for locally recurrent prostate cancer

Introduction Isolated local recurrence of prostate cancer following primary radiotherapy or brachytherapy may be treated with focal salvage high dose rate brachytherapy, although there remains an absence of high quality evidence to support this approach. Methods Men with prostate cancer treated consecutively between 2015 and 2018 using 19 Gy in a single fraction high dose rate brachytherapy (HDR) for locally recurrent prostate cancer were identified from an institutional database. Univariable analysis was performed to evaluate the relationship between patient, disease and treatment factors with biochemical progression free survival (bPFS). Results 43 patients were eligible for evaluation. Median follow up duration was 26 months (range 1–60). Median bPFS was 35 months (95% confidence interval 25.6–44.4). Kaplan-Meier estimates for bPFS at 1, 2 and 3 years post salvage were 95.2%, 70.6% and 41.8% respectively. On univariable Cox regression analysis, only nadir PSA was significantly associated with bPFS although the majority of patients were also treated with androgen deprivation therapy. Only one late grade 3 genitourinary toxicity was observed. Conclusion Focal salvage HDR brachytherapy may provide good biochemical control with a low risk of severe toxicity. Further evaluation within clinical trials are needed to establish its role in the management of locally recurrent prostate cancer

A comparison of outcomes for patients with intermediate and high risk prostate cancer treated with low dose rate and high dose rate brachytherapy in combination with external beam radiotherapy

Introduction There is evidence to support use of external beam radiotherapy (EBRT) in combination with both low dose rate brachytherapy (LDR–EBRT) and high dose rate brachytherapy (HDR–EBRT) to treat intermediate and high risk prostate cancer. Methods Men with intermediate and high risk prostate cancer treated using LDR–EBRT (treated between 1996 and 2007) and HDR–EBRT (treated between 2007 and 2012) were identified from an institutional database. Multivariable analysis was performed to evaluate the relationship between patient, disease and treatment factors with biochemical progression free survival (bPFS). Results 116 men were treated with LDR-EBRT and 171 were treated with HDR–EBRT. At 5 years, bPFS was estimated to be 90.5% for the LDR–EBRT cohort and 77.6% for the HDR–EBRT cohort. On multivariable analysis, patients treated with HDR–EBRT were more than twice as likely to experience biochemical progression compared with LDR–EBRT (HR 2.33, 95% CI 1.12–4.07). Patients with Gleason ≥8 disease were more than five times more likely to experience biochemical progression compared with Gleason 6 disease (HR 5.47, 95% CI 1.26–23.64). Cumulative incidence of ≥grade 3 genitourinary and gastrointestinal toxicities for the LDR–EBRT and HDR–EBRT cohorts were 8% versus 4% and 5% versus 1% respectively, although these differences did not reach statistical significance. Conclusion LDR–EBRT may provide more effective PSA control at 5 years compared with HDR–EBRT. Direct comparison of these treatments through randomised trials are recommended to investigate this hypothesis further

Association of early postnatal transfer and birth outside a tertiary hospital with mortality and severe brain injury in extremely preterm infants: observational cohort study with propensity score matching

Objective To determine if postnatal transfer or birth in a non-tertiary hospital is associated with adverse outcomes. Design Observational cohort study with propensity score matching. Setting National health service neonatal care in England; population data held in the National Neonatal Research Database. Participants Extremely preterm infants born at less than 28 gestational weeks between 2008 and 2015 (n=17 577) grouped based on birth hospital and transfer within 48 hours of birth: upward transfer (non-tertiary to tertiary hospital, n=2158), non-tertiary care (born in non-tertiary hospital; not transferred, n=2668), and controls (born in tertiary hospital; not transferred, n=10 866). Infants were matched on propensity scores and predefined background variables to form subgroups with near identical distributions of confounders. Infants transferred between tertiary hospitals (horizontal transfer) were separately matched to controls in a 1:5 ratio. Main outcome measures Death, severe brain injury, and survival without severe brain injury. Results 2181 infants, 727 from each group (upward transfer, non-tertiary care, and control) were well matched. Compared with controls, infants in the upward transfer group had no significant difference in the odds of death before discharge (odds ratio 1.22, 95% confidence interval 0.92 to 1.61) but significantly higher odds of severe brain injury (2.32, 1.78 to 3.06; number needed to treat (NNT) 8) and significantly lower odds of survival without severe brain injury (0.60, 0.47 to 0.76; NNT 9). Compared with controls, infants in the non-tertiary care group had significantly higher odds of death (1.34, 1.02 to 1.77; NNT 20) but no significant difference in the odds of severe brain injury (0.95, 0.70 to 1.30) or survival without severe brain injury (0.82, 0.64 to 1.05). Compared with infants in the upward transfer group, infants in the non-tertiary care group had no significant difference in death before discharge (1.10, 0.84 to 1.44) but significantly lower odds of severe brain injury (0.41, 0.31 to 0.53; NNT 8) and significantly higher odds of survival without severe brain injury (1.37, 1.09 to 1.73; NNT 14). No significant differences were found in outcomes between the horizontal transfer group (n=305) and controls (n=1525). Conclusions In extremely preterm infants, birth in a non-tertiary hospital and transfer within 48 hours are associated with poor outcomes when compared with birth in a tertiary setting. We recommend perinatal services promote pathways that facilitate delivery of extremely preterm infants in tertiary hospitals in preference to postnatal transfer