The CELTIC ranges project (comprehensive and effective laboratory test reference intervals for Irish children) methodology and results for renal profile tests in plasma on the Roche modularTM system.

BACKGROUND: The CELTIC ranges project aims to deliver a comprehensive range of reference intervals for commonly ordered laboratory investigations suitable for use in an Irish population as well as enabling comparison with relevant international studies. In this paper, we describe our methodology used throughout the entire project and present paediatric reference intervals for renal profile tests in plasma (sodium, potassium, urea and creatinine). METHODS: 1023 children aged up to 17 years were recruited from our hospital's general practitioner paediatric phlebotomy clinic. Clinical chemistry analyses were performed on the Roche modular system and statistical analysis was completed in line with CLSI guideline EP28-A3c. RESULTS: The plasma reference interval for sodium for ages 0.45-16.99 years was 137-143 mmol/L in 1000 subjects (combined genders). For plasma potassium, the corresponding ranges between 1 and 16.99 years (combined genders) were 3.6-4.8 mmol/L. Apart from neonates and in keeping with other studies, age partitioning for electrolytes was not required. Data for plasma creatinine (enzymatic methodology) and urea is also presented and, as anticipated, required partitioning for both age and gender. CONCLUSIONS: Our renal profile findings are broadly consistent with those of international studies, for example, CALIPER, HAPPI, NORDIC, PRINCE and KiGGs. Moreover, the CELTIC ranges study is also based on over 1000 subjects whose samples were analysed on the widely used Roche modular analytics system. We also expect the findings will improve knowledge of children's metabolic health in Ireland.

Mild-to-severe traumatic brain injury in children: altered cytokines reflect severity.

BACKGROUND: Paediatric traumatic brain injury (TBI) is recognised to have significant longer-term neurocognitive effects. Childhood is a time of high risk for head injury. Functional recovery is variable with a combination of any or all of physical, cognitive and emotional impairment. Immune activation and alteration in cytokine levels are present following TBI which may differ from adults. METHODS: Pro- and anti-inflammatory cytokines including Interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, IL-17A, Tumor Necrosis Factor (TNF)-α and Interferon (IFN)-γ were examined at baseline and following in vitro treatment with endotoxin of whole blood, in the following children: severe TBI (sTBI: initial Glasgow coma scale(GCS) ≤ 8), mild TBI (mTBI; GCS 14/15) at 0-4d and at 10-14d post-TBI and compared to healthy age-matched controls. RESULTS: The study enrolled 208 children, including 110 with TBI cohort (n = 104 mild; 6 severe) and controls (n = 98). At baseline all children with TBI had increased IL-6. The mTBI group had significantly increased IFN-γ versus controls. In sTBI at baseline, IFN-γ was decreased compared to controls. At baseline IL-8, IL-10, IL-17A, and TNF-α were decreased in mTBI compared to controls. This persisted at 2 week post-mTBI. The AUC for detecting mTBI was 0.801 CI (0.73-086) using IL6/IL10 ratio. mTBI showed a greater fold change in IL-8 and TNF-α in response to endotoxin stimulation, a response that persisted at 2 weeks. Children with sTBI did not have a significant IL-6 response to endotoxin, but did show an increase in IL-17A. CONCLUSION: Children with all TBI including mTBI show altered cytokine profiles and altered endotoxin responses. Although cytokines increased in sTBI especially in response to endotoxin, suppressed responses were found in mTBI coupled with persistent immune dysfunction post-injury.

Traumatic Brain Injury in Children: Glial fibrillary Acidic Protein and Clinical Outcomes.

OBJECTIVES: Glial fibrillary acidic protein (GFAP) is a neuronal protein released after traumatic brain injury (TBI) and detectable in serum samples. GFAP correlates with symptom severity in adults and may be a marker of brain injury in children with milder symptoms or preverbal children. METHODS: GFAP was examined in children with severe TBI (initial Glasgow Coma Scale score <8), with mild TBI (Glasgow Coma Scale score 14/15), and at 0 to 4 and at 10 to 14 days after TBI and was compared with healthy age-matched controls. Mechanism, time points from injury, and symptoms were recorded. RESULTS: The study enrolled 208 children including 110 with TBI (n = 104 mild, 6 severe) and controls (n = 98). GFAP was higher in mild TBI than in controls and highest in the severe TBI cohort, with a maximum value at 6 hours from injury. Vomiting was significantly associated with higher GFAP levels, but no association was found with amnesia, loss of consciousness, and the Sports Concussion Assessment Tool. Children reporting >1-point changes from their preinjury functioning on the Post-Concussive Symptom Inventory had higher initial GFAP but not total Post-Concussive Symptom Inventory score changes. CONCLUSIONS: GFAP identifies children with TBI, even at the milder end of the spectrum, and is strongly associated with postinjury vomiting. It may be a useful marker of pediatric TBI; however, sampling is time critical.

The 'Jedward' versus the 'Mohawk': a prospective study on a paediatric distraction technique.

OBJECTIVE: To examine the use of a standard hospital glove, inflated as a balloon with a face drawn on it, as a distraction technique in children with an acute injury. METHODS: We designed a study to assess the 'best' way to orientate the glove when drawing a face on it. A prospective study was performed in the authors' institution, where all children between the ages of 2 and 8 years presenting during the study period were given the option of playing with one of two glove balloons with a face drawn on it in two different ways. RESULTS: 149 paediatric patients were assessed, of whom 136 picked a glove, 75 picked the 'Jedward' version and 61 the 'Mohawk' version. CONCLUSIONS: A standard hospital glove, inflated as a balloon with a face drawn on it, is a useful distraction for children with an acute injury. The face drawn should be drawn 'Jedward' style.

Response to IL-1-receptor antagonist in a child with familial cold autoinflammatory syndrome.

Familial cold auto-inflammatory syndrome, Muckle-Wells syndrome and chronic infantile neurologic, cutaneous, articular syndrome are related disorders associated with mutations in the CIAS1 gene. They appear to represent a continuum of one disease characterized by IL-1-mediated inflammation. Until recently, these conditions have been difficult to treat; however, with the advent of IL-1-receptor antagonist therapy, many reports of successful treatment of patients with these autoinflammatory diseases have emerged in the past 2 years. We describe an 8-year-old girl, diagnosed with Familial cold auto-inflammatory syndrome, confirmed by presence of a novel CIAS1 mutation, who was refractory to symptomatic treatment. As frequent attacks of urticaria and associated arthralgia had a debilitating effect on the child's lifestyle, a trial of IL-1-receptor antagonist (anakinra) was instituted. Dramatic sustained clinical improvement was evident within days and serum amyloid and C-reactive protein levels normalized within a month. Although several authors have reported successful use of this agent in children with chronic infantile neurologic, cutaneous, articular syndrome, we believe ours is the first report of successful treatment with anakinra in a young child with familial cold auto-inflammatory syndrome.