Cerebrospinal fluid dynamics in pediatric pseudotumor cerebri syndrome

Funder: University of CambridgeAbstract: Purpose: There is a growing body of evidence highlighting the importance of comprehensive intracranial pressure (ICP) values in pseudotumor cerebri syndrome (PTCS). Due to the highly dynamic nature of ICP, several methods of ICP monitoring have been established, including the CSF infusion study. We have performed a retrospective review of the CSF dynamics measurements for all pediatric patients investigated for PTCS in our center and examined their diagnostic value compared with clinical classification. Methods: We retrospectively recruited 31 patients under 16 years of age investigated for PTCS by CSF infusion test. We used the clinically provided Friedman classification 13/31 patients with definite PTCS (group A), 13/31 with probable PTCS (group B), and 5/31 not PTCS (group C), to compare CSF dynamics in the 3 groups. Results: CSF pressure (CSFp) was significantly increased in group A (29.18 ± 7.72 mmHg) compared with B (15.31 ± 3.47 mmHg; p = 1.644e-05) and C (17.51 ± 5.87; p = 0.01368). The amplitude (AMP) was higher in the definite (2.18 ± 2.06 mmHg) than in group B (0.68 ± 0.37; p = 0.01382). There was no in either CSFp or AMP between groups B and C. No lower breakpoint of the AMP-P line was observed in group A but was present in 2/13 and 2/5 patients in groups B and C. In group A, sagittal sinus pressure (SSp) and elasticity were the only parameters above threshold (p = 4.2e-06 and p = 0.001953, respectively), In group B, only the elasticity was significantly higher than the threshold (p = 004257). Group C did not have any of the parameters raised. The AUC of CSFp, elasticity, and SSp for the 3 groups was 93.8% (84.8–100% CI). Conclusions: Monitoring of CSFp and its dynamics, besides providing a more precise methodology for measuring CSFp, could yield information on the dynamic parameters of CSFp that cannot be derived from CSFp as a number, accurately differentiating between the clinically and radiologically derived entities of PTCS

Fructose transport-deficient Staphylococcus aureus reveals important role of epithelial glucose transporters in limiting sugar-driven bacterial growth in airway surface liquid.

Hyperglycaemia as a result of diabetes mellitus or acute illness is associated with increased susceptibility to respiratory infection with Staphylococcus aureus. Hyperglycaemia increases the concentration of glucose in airway surface liquid (ASL) and promotes the growth of S. aureus in vitro and in vivo. Whether elevation of other sugars in the blood, such as fructose, also results in increased concentrations in ASL is unknown and whether sugars in ASL are directly utilised by S. aureus for growth has not been investigated. We obtained mutant S. aureus JE2 strains with transposon disrupted sugar transport genes. NE768(fruA) exhibited restricted growth in 10 mM fructose. In H441 airway epithelial-bacterial co-culture, elevation of basolateral sugar concentration (5-20 mM) increased the apical growth of JE2. However, sugar-induced growth of NE768(fruA) was significantly less when basolateral fructose rather than glucose was elevated. This is the first experimental evidence to show that S. aureus directly utilises sugars present in the ASL for growth. Interestingly, JE2 growth was promoted less by glucose than fructose. Net transepithelial flux of D-glucose was lower than D-fructose. However, uptake of D-glucose was higher than D-fructose across both apical and basolateral membranes consistent with the presence of GLUT1/10 in the airway epithelium. Therefore, we propose that the preferential uptake of glucose (compared to fructose) limits its accumulation in ASL. Pre-treatment with metformin increased transepithelial resistance and reduced the sugar-dependent growth of S. aureus. Thus, epithelial paracellular permeability and glucose transport mechanisms are vital to maintain low glucose concentration in ASL and limit bacterial nutrient sources as a defence against infection

Modelling outcomes after paediatric brain injury with admission laboratory values: a machine-learning approach.

BACKGROUND: Severe traumatic brain injury (TBI) is a leading cause of mortality in children, but the accurate prediction of outcomes at the point of admission remains very challenging. Admission laboratory results are a promising potential source of prognostic data, but have not been widely explored in paediatric cohorts. Herein, we use machine-learning methods to analyse 14 different serum parameters together and develop a prognostic model to predict 6-month outcomes in children with severe TBI. METHODS: A retrospective review of patients admitted to Cambridge University Hospital's Paediatric Intensive Care Unit between 2009 and 2013 with a TBI. The data for 14 admission serum parameters were recorded. Logistic regression and a support vector machine (SVM) were trained with these data against dichotimised outcomes from the recorded 6-month Glasgow Outcome Scale. RESULTS: Ninety-four patients were identified. Admission levels of lactate, H+, and glucose were identified as being the most informative of 6-month outcomes. Four different models were produced. The SVM using just the three most informative parameters was the best able to predict favourable outcomes at 6 months (sensitivity = 80%, specificity = 99%). CONCLUSIONS: Our results demonstrate the potential for highly accurate outcome prediction after severe paediatric TBI using admission laboratory data

Radiological Correlates of Raised Intracranial Pressure in Children: A Review.

Radiological assessment of the head is a routine part of the management of traumatic brain injury. This assessment can help to determine the requirement for invasive intracranial pressure (ICP) monitoring. The radiological correlates of elevated ICP have been widely studied in adults but far fewer specific pediatric studies have been conducted. There is, however, growing evidence that there are important differences in the radiological presentations of elevated ICP between children and adults; a reflection of the anatomical and physiological differences, as well as a difference in the pathophysiology of brain injury in children. Here in, we review the radiological parameters that correspond with increased ICP in children that have been described in the literature. We then describe the future directions of this work and our recommendations in order to develop non-invasive and radiological markers of raised ICP in children

Thresholds for identifying pathological intracranial pressure in paediatric traumatic brain injury.

Intracranial pressure (ICP) monitoring forms an integral part of the management of severe traumatic brain injury (TBI) in children. The prediction of elevated ICP from imaging is important when deciding on whether to implement invasive ICP monitoring for a patient. However, the radiological markers of pathologically elevated ICP have not been specifically validated in paediatric studies. Here in, we describe an objective, non-invasive, quantitative method of stratifying which patients are likely to require invasive monitoring. A retrospective review of patients admitted to Cambridge University Hospital's Paediatric Intensive Care Unit between January 2009 and December 2016 with a TBI requiring invasive neurosurgical monitoring was performed. Radiological biomarkers of TBI (basal cistern volume, ventricular volume, volume of extra-axial haematomas) from CT scans were measured and correlated with epochs of continuous high frequency variables of pressure monitoring around the time of imaging. 38 patients were identified. Basal cistern volume was found to correlate significantly with opening ICP (r = -0.53, p < 0.001). The optimal threshold of basal cistern volume for predicting high ICP ([Formula: see text]20 mmHg) was a relative volume of 0.0055 (sensitivity 79%, specificity 80%). Ventricular volume and extra-axial haematoma volume did not correlate significantly with opening ICP. Our results show that the features of pathologically elevated ICP in children may differ considerably from those validated in adults. The development of quantitative parameters can help to predict which patients would most benefit from invasive neurosurgical monitoring and we present a novel radiological threshold for this.We gratefully acknowledge financial support as follows. Research support: the Medical Research Council (MRC, Grant Nos. G0600986 ID79068 and G1002277 ID98489) and the National Institute for Health Research Biomedical Research Centre (NIHR BRC) Cambridge (Neuroscience Theme; Brain Injury and Repair Theme). Authors’ support: Peter J Hutchinson – NIHR Research Professorship, Academy of Medical Sciences/Health Foundation Senior Surgical Scientist Fellowship, NIHR Global Health Research Group on Neurotrauma, and NIHR Cambridge BRC. Joseph Donnelly is supported by a Woolf Fisher Scholarship. MC- NIHR BRC

A restatement of the natural science evidence base concerning grassland management, grazing livestock and soil carbon storage

Approximately a third of all annual greenhouse gas emissions globally are directly or indirectly associated with the food system, and over a half of these are linked to livestock production. In temperate oceanic regions, such as the UK, most meat and dairy is produced in extensive systems based on pasture. There is much interest in the extent to which such grassland may be able to sequester and store more carbon to partially or completely mitigate other greenhouse gas emissions in the system. However, answering this question is difficult due to context-specificity and a complex and sometimes inconsistent evidence base. This paper describes a project that set out to summarize the natural science evidence base relevant to grassland management, grazing livestock and soil carbon storage potential in as policy-neutral terms as possible. It is based on expert appraisal of a systematically assembled evidence base, followed by a wide stakeholders engagement. A series of evidence statements (in the appendix of this paper) are listed and categorized according to the nature of the underlying information, and an annotated bibliography is provided in the electronic supplementary material.</p

Shunt infusion studies: impact on patient outcome, including health economics

Funder: University of CambridgeAbstract: Objectives: The diagnosis of shunt malfunction is often not straightforward. We have explored, in symptomatic shunted patients with hydrocephalus or pseudotumour cerebri syndrome (PTCS), the accuracy of CSF infusion tests in differentiating a functioning shunt from one with possible problems, and the health economic consequences. Methods: Participants: hydrocephalus/PTCS patients with infusion tests performed from January 2013 until December 2015. We followed patients up after 6 and 12 months from the test to determine whether they had improved, had persisting symptoms or had required urgent revision. We calculated the total cost savings of revision versus infusion tests and standard protocol of revision and ICP monitoring versus infusion tests. Results: Three hundred sixty-five shunt infusion tests had been performed where a shunt prechamber/reservoir was present. For hydrocephalus patients, more than half of the tests (~ 55%, 155 out of 280) showed no shunt malfunction versus 125 with possible malfunction (ages 4 months to 90 years old). For PTCS patients aged 10 to 77 years old, 47 had possible problems and 38 no indication for shunt malfunction. Overall, > 290 unnecessary revisions were avoided over 3 years’ time. Two hundred fifty-eight (> 85%) of those non-surgically managed, remained well, did not deteriorate and did not require surgery. No infections were associated with infusion studies. For Cambridge, the overall savings from avoiding revisions was £945,415 annually. Conclusions: Our results provide evidence of the importance of shunt testing in vivo to confirm shunt malfunction. Avoiding unnecessary shunt revisions carries a strong health benefit for patients that also translates to a significant financial benefit for the National Health Service and potentially for other healthcare systems worldwide

Shunt infusion studies: impact on patient outcome, including health economics

Funder: University of CambridgeAbstract: Objectives: The diagnosis of shunt malfunction is often not straightforward. We have explored, in symptomatic shunted patients with hydrocephalus or pseudotumour cerebri syndrome (PTCS), the accuracy of CSF infusion tests in differentiating a functioning shunt from one with possible problems, and the health economic consequences. Methods: Participants: hydrocephalus/PTCS patients with infusion tests performed from January 2013 until December 2015. We followed patients up after 6 and 12 months from the test to determine whether they had improved, had persisting symptoms or had required urgent revision. We calculated the total cost savings of revision versus infusion tests and standard protocol of revision and ICP monitoring versus infusion tests. Results: Three hundred sixty-five shunt infusion tests had been performed where a shunt prechamber/reservoir was present. For hydrocephalus patients, more than half of the tests (~ 55%, 155 out of 280) showed no shunt malfunction versus 125 with possible malfunction (ages 4 months to 90 years old). For PTCS patients aged 10 to 77 years old, 47 had possible problems and 38 no indication for shunt malfunction. Overall, > 290 unnecessary revisions were avoided over 3 years’ time. Two hundred fifty-eight (> 85%) of those non-surgically managed, remained well, did not deteriorate and did not require surgery. No infections were associated with infusion studies. For Cambridge, the overall savings from avoiding revisions was £945,415 annually. Conclusions: Our results provide evidence of the importance of shunt testing in vivo to confirm shunt malfunction. Avoiding unnecessary shunt revisions carries a strong health benefit for patients that also translates to a significant financial benefit for the National Health Service and potentially for other healthcare systems worldwide