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

In vivo investigation of female reproductive functions and parameters in nonpregnant mice models and mass spectrometric analysis of the methanol leaf extract of Emilia Coccinea (Sims) G Dons

In Southern Nigeria, the leaves of Emilia coccinea (Sims) G Dons are used traditionally for birth control. This study was therefore aimed at evaluating the activities of the methanolic leaf extract of Emilia coccinea (EM) on parameters that affect reproduction as well as the acute toxic effects of the plant using nonpregnant female mice models. Leaves of EM were extracted by maceration with 99.8% methanol. Oral acute toxicity profiles were examined. The effects of EM on female reproductive cycle were determined after oral treatment with EM at 1000 and 100 mg/kg/day daily for 6 days using stilbesterol (1 mg/kg/day) and normal saline as controls. The activities of EM (1000 mg/kg/day and 100 mg/kg/day p.o) on reproductive hormones and organs were also studied using estradiol valerat (100 mg/kg/day p.o), progesterone (10 mg/kg/day s.c.), and normal saline as controls. The extract did not induce any observable toxic effect after 24 h. At 1000 mg/kg, the extract significantly shortened the estrus cycle (P < 0.05) while prolonging the estrus phase which were comparable to that observed with stilbesterol. The extract also increased uterine weight and altered the histology of uterine and ovarian tissues. The female reproductive hormones were additionally altered at 1000 mg/kg and the effects were comparable to that of estradiol valerat such as to indicate possible antifertility effects. LC-HRFTMS analysis showed 9 putatively identified compounds with pyrrolizidine alkaloid occurring at the highest intensity among the identified compounds. In conclusion, the leaf extracts of EM has been shown in this study to exhibit antiovulatory and estrogenic activities which would support the traditional use of the plant in Nigeria

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

Cross-talk between human T cells, mast cells and conjunctival epithelial cells

The ocular surface is continually exposed to the outside environment and is a common site of inflammation. Conjunctival epithelial cells are thought to play a role in innate responses at the ocular surface. The hypothesis of my study is that conjunctival epithelial cells also contribute to T cell and mast cell effector mechanisms in chronic allergic eye disease via secretion of cytokines. In this study we initially demonstrate that the conjunctiva expresses TLRs, and that the TLR3 ligand (poly I:C) activates conjunctival epithelial cells in vitro to secrete inflammatory mediators as part of the innate immune response. Conjunctival tissues were also shown to express the Th2 associated cytokine, IL-13 as well as TSLP – a cytokine thought to be involved in Th2 differentiation. Conjunctival tissues from chronic allergic eye disease subjects were found to have increased IL-13 and TSLP expression compared to normal controls. Using a human conjunctival epithelial cell line, cells could be induced to express increased levels of TSLP following exposure to poly I:C or pro-inflammatory cytokines. Th17 cells, identified by coexpression of CD4 and IL-17, were also detected in CAED tissues and a high level of expression of IL-17A was localised to the epithelium. However, although capable of secreting IL- 25, IL-17A was not secreted by conjunctival epithelial cells, indicating that the IL-17 observed histologically may have been IL-17 binding to the surface of the epithelium. IL-17 receptor C (IL-17RC) expression was found to be increased in CAED tissues whilst IL-17RA was upregulated when conjunctival epithelial cells were stimulated with pro-inflammatory cytokines together with poly I:C. Blockade of IL-17RA and subsequent stimulation with IL-17 led to increased IL-8 and decreased TGF-β secretion. Although being implicated in the immunopathogenesis of certain diseases, IL-17 and its other family members may potentially serve to play an immunoregulatory role in immunity at the ocular surface

Neuromodulation for Pelvic and Urogenital Pain

Chronic pain affecting the pelvic and urogenital area is a major clinical problem with heterogeneous etiology, affecting both male and female patients and severely compromising quality of life. In cases where pharmacotherapy is ineffective, neuromodulation is proving to be a potential avenue to enhance analgesic outcomes. However, clinicians who frequently see patients with pelvic pain are not traditionally trained in a range of neuromodulation techniques. The aim of this overview is to describe major types of pelvic and urogenital pain syndromes and the neuromodulation approaches that have been trialed, including peripheral nerve stimulation, dorsal root ganglion stimulation, spinal cord stimulation, and brain stimulation techniques. Our conclusion is that neuromodulation, particularly of the peripheral nerves, may provide benefits for patients with pelvic pain. However, larger prospective randomized studies with carefully selected patient groups are required to establish efficacy and determine which patients are likely to achieve the best outcomes.</jats:p

Present status and advances in bladder pain syndrome: central sensitisation and the urinary microbiome

Key content Bladder pain syndrome (BPS) presents as a spectrum of urological symptoms with poorly understood pathophysiology. Bladder mucosal injury secondary to low grade sub-clinical infection is a possible trigger, leading to nociceptive upregulation and, subsequently, central sensitisation. Brain abnormalities associated with BPS suggest that neuropathological brain alterations exist, which may contribute to the perceived pain. Central sensitisation plays a role in the disease pathophysiology via an augmentation in the responsiveness of the central pain signalling neurons. The urinary microbiome is implicated as a trigger for the development and maintenance of BPS. Future directions to improve treatment strategies include stratification of patients with BPS into subtypes such as peripheral or central disease and investigation of the urinary microbiome and bladder barrier replacement. Learning objectives To update clinicians’ knowledge of current research into the urinary microbiome and pain sensitisation in BPS pathophysiology. To understand the biodiversity and abundance of urinary microbes and the role of peripheral and central pain sensitisation, which will help identify future management techniques for BPS. Ethical issues What are the consequences of long-term antibiotics use for BPS management on bacterial resistance

Diagnostic performance of morphometric vertebral fracture analysis (MXA) in children using a 33-point software program

Background There is significant inter and intraobserver variability in diagnosing vertebral fractures in children. Purpose We aimed to evaluate the diagnostic accuracy of morphometric vertebral fracture analysis (MXA) using a 33-point software program designed for adults, on dual-energy x-ray absorptiometry (DXA) images of children. Materials and methods Lateral spine DXA images of 420 children aged between 5 and 18 years were retrospectively reviewed. Vertebral fracture assessment (VFA) by an expert pediatric radiologist using Genant's semiquantitative scoring system served as the gold standard. All 420 DXA scans were analyzed by a trained radiographer, using semi-automated software (33-point morphometry). VFA of a random sample of 100 DXA was performed by an experienced pediatric clinical scientist. MXA of a random sample of 30 DXA images were analyzed by three pediatric radiologists and the pediatric clinical scientist. Diagnostic accuracy and inter and intraobserver agreement (kappa statistics) were calculated. Results Overall sensitivity, specificity, false positive (FP) and false negative (FN) rates for the radiographer using the MXA software were 80%, 90%, 10%, and 20% respectively and for mild fractures alone were 46%, 92%, 8%, and 54% respectively. Overall sensitivity, specificity, FP, and FN rates for the four additional observers using MXA were 89%, 79%, 21%, and 11% respectively and for mild fractures alone were 36%, 86%, 14%, and 64% respectively. Agreement between two expert observers was fair to good for VFA and MXA [kappa = 0·29 to 0·76 (95% CI: 0·17–0·88) and 0·29 to 0·69 (95% CI: 0·17–0·83)] respectively. Conclusion MXA using a 33-point technique developed for adults is not a reliable method for the identification of mild vertebral fractures in children. A pediatric standard is required which not only incorporates specific vertebral body height ratios but also the age-related physiological changes in vertebral shape that occur throughout childhood