Admission PaO2 and Mortality in Critically Ill Children: A Cohort Study and Systematic Review.

OBJECTIVE: To describe the relationship between PaO2 at intensive care admission and mortality in critically ill children and to review systematically the literature describing this relationship. DESIGN: Cohort study: A review of consecutive tertiary pediatric intensive care admissions (January 2004 to December 2014) in a single center. The relationship between admission Pao2 and crude and standardized mortality was explored using nonlinear regression. Systematic review: A search of MEDLINE (1950 to January 2015), EMBASE (1980 to January 2015), Cochrane and Database of Abstracts of Reviews of Effects databases was undertaken using the following terms: "hyperoxia," "hypoxia," "critically ill children," "pediatric intensive care," "mortality," and/or "survival." SETTING: Tertiary PICU. PATIENTS: Patients younger than 18 years of age. INTERVENTIONS: The association of hyperoxia (PaO2, > 300 torr [40 kPa]) and hypoxia (PaO2, 40 kPa). Nonlinear regression displayed a "U-shaped" relationship between PaO2 and crude and case-mix adjusted mortality. Systematic review: Fourteen studies and one conference abstract were eligible for inclusion. Eleven studies (n = 5,280) relate to hypoxia with combined odds ratio for death, of 3.13 (95% CI, 1.79-5.48; p < 0.001) compared to normoxia. Six studies (n = 2,012) relate to hyperoxia and suggest no effect on mortality compared to normoxia (odds ratio, 1.15; 95% CI, 0.42-3.17; p = 0.77). CONCLUSIONS: Hypoxia at admission is associated with increased mortality in critically ill children, whereas the association with hyperoxia is less clear. The cohort study demonstrated a U-shaped association between admission PaO2 and mortality. Further examination is needed to explore the effect of hyperoxia upon mortality prediction accuracy

Genomic Prognosticators and Extent of Resection in Molecularly Subtyped World Health Organization Grade II and III Gliomas–A Single-Institution, Nine-Year Data

BACKGROUND: WHO grade II and III IDH wild-type (IDH-wt) gliomas are often treated as WHO grade IV glioblastomas. However, cumulative evidence indicates that IDH mutation status alone is insufficient in predicting survival. The current study examines molecular and clinical markers to further prognostically stratify WHO grade II and III gliomas, in particular, IDH-wt. METHODS: A single institution's records were retrospectively reviewed for molecularly stratified WHO grade II and grade III gliomas over a nine-year period (2010-2019). Clinical data, IDH1/IDH2 status, EGFR amplification and other molecular markers were recorded and correlated to the study outcomes. These were defined as progression-free survival (PFS), overall survival (OS) and time to malignant progression (TtMP). RESULTS: 167 and 42 WHO grade II and III gliomas, respectively, were identified, totalling 209 cases with 157 IDH1/2 mutated and 52 IDH wild-type tumours. The presence of IDH1/2 mutation was associated with longer OS (p<0.0001) and PFS (p<0.0001) but not with TtMP (p=0.314). Lack of EGFR amplification, younger age, greater extent of resection (EOR) (≥80%) were identified as independent, favourable prognostic factors. In the IDH-wt cohort, multivariate analysis indicated that older age (p=0.003) and lesser EOR (<80%) (p=0.007) are associated with worse OS. Additionally, EGFR amplification showed a trend toward shorter OS in the IDH-wt cohort (p=0.073). CONCLUSIONS: IDH1/2 mutation favours longer OS and PFS but does not protect from malignant progression. Lack of EGFR amplification, older age and greater EOR are favourable OS prognosticators. In the IDH-wt cohort, older age and lesser EOR were linked to worse OS

Pathology-MRI correlations in diffuse low-grade epilepsy associated tumors

It is recognized that IDH mutation negative, low-grade epilepsy associated tumors (LEAT) can show diffuse growth patterns and lack the diagnostic hallmarks of either classical dysembryoplastic neuroepithelial tumors (DNT) or typical ganglioglioma. “Nonspecific or diffuse DNT” and more recently “polymorphous low-grade neuroepithelial tumor of the young” have been terms used for these entities. There are few reports on the MRI recognition of these diffuse glioneuronal tumors (dGNT), which is important in planning the extent of surgical resection. In 27 LEATs T1, T2, FLAIR, and postcontrast T1 MRI were evaluated and the pathology reviewed, including immunostaining for NeuN, CD34, MAP2, and IDH1. Each case was then independently classified by pathology or MRI as simple DNT, complex DNT, or dGNT. There was agreement in 23/27 (85%; Kappa score 0.62; p < 0.01). In 4 cases, there was discrepancy in the diagnosis of simple versus complex DNT but 100% agreement achieved for dGNT. DNT showed significantly more expansion of the cortex, cystic change and ventricle extension than dGNT. dGNT showed significantly more subcortical T2w hyperintensity and focal cortical atrophy which correlated on pathology with CD34 expression, cortical neuronal loss and white matter rarefaction. There was no distinct cortical dysplasia component identified by MRI or pathology in any case. This study highlights that dGNT can be reliably discriminated on MRI from DNT

Pathophysiology, diagnosis, and management of neuroinflammation in covid-19

Although neurological complications of SARS-CoV-2 infection are relatively rare, their potential long term morbidity and mortality have a significant impact, given the large numbers of infected patients. Covid-19 is now in the differential diagnosis of a number of common neurological syndromes including encephalopathy, encephalitis, acute demyelinating encephalomyelitis, stroke, and Guillain-Barré syndrome. Physicians should be aware of the pathophysiology underlying these presentations to diagnose and treat patients rapidly and appropriately. Although good evidence has been found for neurovirulence, the neuroinvasive and neurotropic potential of SARS-CoV-2 is limited. The pathophysiology of most complications is immune mediated and vascular, or both. A significant proportion of patients have developed long covid, which can include neuropsychiatric presentations. The mechanisms of long covid remain unclear. The longer term consequences of infection with covid-19 on the brain, particularly in terms of neurodegeneration, will only become apparent with time and long term follow-up

Frequent central nervous system, pachymeningeal and plexus MRI changes in POEMS syndrome

OBJECTIVE: Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes (POEMS) syndrome is a rare multisystem disease associated with a plasma-cell dyscrasia. Although pachymeningeal involvement has occasionally been described, MRI of the central nervous system (CNS) has not yet been extensively investigated. METHODS: We retrospectively evaluated CNS MRI in Europe’s largest single-center cohort of POEMS syndrome. Of 77 patients who have been formally diagnosed with POEMS, 41 had MRI brain and 29 had MRI spine. A control group of 33 patients with chronic inflammatory demyelinating polyneuropathy (CIDP) was used as this is the major differential diagnosis. Of these CIDP patients, 12 underwent both MRI brain and spine, 7 had solely MRI brain and 14 had MRI spine. RESULTS: In 41 POEMS patients with MRI brain, we identified frequent smooth, diffuse meningeal thickening of the cerebral convexities and falx (n = 29, 71%), of which 4 had meningeal collections. 17 (41%) had vascular abnormalities including white-matter disease, of which 4 had established infarcts. Of 29 patients with MRI spine, 17 (59%) had thickening of the brachial and lumbosacral plexus. Conversely in 19 CIDP patients with MRI brain, none had meningeal thickening (p < 0.0001); however, 8 (42%) had vascular abnormalities (p = 0.85). Of 26 patients with MRI spine, 9 (35%) had brachial or lumbosacral plexus thickening (p = 0.06). CONCLUSIONS: In contrast to CIDP, POEMS patients frequently have pachymeningeal thickening. Vascular abnormalities and plexus thickening were also common but not statistically different to CIDP

Validation of the Brief Developmental Assessment in pre-school children with heart disease

INTRODUCTION: The objective of this study was to prospectively validate the “Brief Developmental Assessment”, which is a new early recognition tool for neurodevelopmental abnormalities in children with heart disease that was developed for use by cardiac teams. METHODS: This was a prospective validation study among a representative sample of 960 pre-school children with heart disease from three United Kingdom tertiary cardiac centres who were analysed grouped into five separate age bands. RESULTS: The “Brief Developmental Assessment” was successfully validated in the older four age bands, but not in the youngest representing infants under the age of 4 months, as pre-set validation thresholds were met – lower 95% confidence limit for the correlation coefficient above 0.75 – in terms of agreement of scores between two raters and with an external measure the “Mullen Scales of Early Learning”. On the basis of American Association of Pediatrics Guidelines, which state that the sensitivity and specificity of a developmental screening tool should fall between 70 and 80%, “Brief Developmental Assessment” outcome of Red meets this threshold for detection of Mullen scores >2 standard deviations below the mean. CONCLUSION: The “Brief Developmental Assessment” may be used to improve the quality of assessment of children with heart disease. This will require a training package for users and a guide to action for abnormal results. Further research is needed to determine how best to deploy the “Brief Developmental Assessment” at different time points in children with heart disease and to determine the management strategy in infants younger than 4 months old

Development and preliminary testing of the Brief Developmental Assessment: an early recognition tool for children with heart disease

Introduction: Neurodevelopmental abnormalities are common in children with CHD and are the highestpriority concerns for parents and professionals following cardiac surgery in childhood. There is no additional routine monitoring of development for children with CHD in the United Kingdom; hence, neurodevelopmental concerns may be detected late, precluding early referral and intervention. Methods: An early recognition tool – the “Brief Developmental Assessment” – was developed using quality improvement methodology involving several iterations and rounds of pilot testing. Our requirements were for a tool covering important developmental domains and practicable for use within inpatient and outpatient settings by paediatric cardiac health professionals who are nondevelopmental specialists, without specialised equipment and which involved direct observation, as well as parental report. Results: Items were included in the tool based on existing developmental measures, covering the domains of gross and fine motor skills, daily living skills, communication, socialisation, and general understanding. Items were developed for five age bands – 0–16 weeks, 17–34 weeks, 35–60 weeks, 15 months–2.9 years, and 3–4.9 years – and the final versions included a traffic light scoring system for identifying children with possible delay in any or all domains. Preliminary testing indicated excellent inter-rater reliability, an ability to detect children with a diagnosis known to be associated with developmental delay, and largely acceptable internal reliability. Conclusion: We report the evolution and preliminary testing of an early recognition tool for assessing the development of children with heart disease; this was encouraging and sufficiently good to support further validation in a larger study

Canonical correlation analysis in the study of cerebral and peripheral haemodynamics interrelations with systemic variables in neonates supported on ECMO.

Neonates supported on extracorporeal membrane oxygenation (ECMO) are at high risk of brain injury due to haemodynamic instability. In order to monitor cerebral and peripheral (muscle) haemodynamic and oxygenation changes in this population we used a dual-channel near-infrared spectroscopy (NIRS) system. In addition, to assess interrelations between NIRS and systemic variables, collected simultaneously, canonical correlation analysis (CCA) was employed. CCA can quantify the relationship between a set of variables and assess levels of dependency. In four out of five patients, systemic variables were found to be less inter-related with cerebral rather than peripheral NIRS measurements. Moreover, during ECMO flow manipulations, we found that the interrelation between the systemic and the NIRS cerebral/peripheral variables changed. The CCA method presented here can be used to assess differences between NIRS cerebral and NIRS peripheral responses due to systemic variations which may be indicative of physiological differences in the mechanisms that regulate oxygenation and/or haemodynamics of the brain and the muscle