Administering analgesia sublingually is a suitable option for children with acute abdominal pain in the emergency department.

AIM: Acute abdominal pain is a frequent complaint in children attending emergency departments. The aim of this study was to investigate the pain score reductions when children with acute abdominal pain received medication sublingually. METHODS: We carried out a multicentre randomised controlled trial in three children's hospitals in Italy between March 2015 and June 2017. Children from four to 18 years of age with acute abdominal pain were recruited if their self-reported pain was at least six on a scale from 0-10. The children were randomised to receive ketorolac 0.5 mg/kg (n = 70) or tramadol 2 mg/kg (n = 70) sublingually or a melt in the mouth powder of 20 mg/kg paracetamol (n = 70). The main study outcome was the pain scores for the three drugs after two hours. RESULTS: The 210 children (58.6% girls) had a median age of 12 years with an interquartile range of 9-14.3. The median pain scores at two hours were not significantly different between ketorolac 2.0 (interquartile ranges, IQR 0.0-4.3) and tramadol 3.0 (IQR 1.0-5.0) vs paracetamol 3.0 (IQR 0.8-5.0). The median pain reductions were all 5.0 points. CONCLUSION: Delivering analgesia sublingually was a suitable option for pain relief in children with acute abdominal pain in the emergency department.

Intranasal Nerve Growth Factor administration improves cerebral functions in a child with severe traumatic brain injury: A case report.

BACKGROUND: Nerve growth factor (NGF) promotes neural recovery after experimental traumatic brain injury (TBI) supporting neuronal growth, differentiation and survival of brain cells and up-regulating the neurogenesis-associated protein Doublecortin (DCX). Only a few studies reported NGF administration in paediatric patients with severe TBI. METHODS: A four-year-old boy in a persistent unresponsive wakefulness syndrome (UWS) was treated with intranasal murine NGF administration 6 months after severe TBI. The patient received four cycles of intranasal NGF (0.1 mg/kg, twice a day for 10 consecutive days). RESULTS: NGF administration improved functional [Positron Emission Tomography/Computed Tomography (PET/CT); Single photon emission/Computed Tomography (SPECT/CT) and Magnetic Resonance Imaging (MRI)] assessment, electrophysiological [Electroencephalogram (EEG) and Visual Evoked Potential (VEP)] studies and clinical conditions. He showed improvements in voluntary movements, facial mimicry, phonation, attention and verbal comprehension, ability to cry, cough reflex, oral motility, feeding capacity, and bowel and urinary functions. After NGF administration, raised levels of both NGF and DCX were found in the cerebrospinal fluid of the patient. No side effects were reported. CONCLUSIONS: Although further studies are needed for better understanding the neuroprotective role of this neurotrophin, intranasal NGF administration appears to be a promising and safe rescuing strategy treatment in children with neurological impairment after TBI.

Contact urticaria on eczematous skin by kiwifruit allergy. In vivo component-resolved diagnosis.

BACKGROUND: Kiwifruit allergy has been responsible for a variety of clinical manifestations, ranging from mild reactions, such as localised oral symptoms, to severe systemic symptoms, such as anaphylaxis. No cases of isolated contact urticaria (ICU) due to IgE-mediated allergy to kiwifruit have been reported in the literature so far. Here we describe the first three cases of ICU due to kiwi and we hypothesise about a kiwifruit allergen not described yet. METHODS: Using the available in vivo allergy tests, we performed a component-resolved diagnosis to detect the allergen involved. All the patients underwent prick-by-prick with raw and boiled kiwi pulp and latex glove, skin prick test with commercial extracts of kiwifruit, birch, latex, palm profilin and peach lipid transfer protein, rub test with raw and boiled kiwi and oral food challenges with the raw fruit. RESULTS: We found that, in our patients, the kiwifruit allergen responsible for ICU is thermolabile, gastrosensitive, and it does not show any of the most common kiwi-attributed cross-reactivity (latex, birch, profiling and lipid transfer protein). None of the 13 kiwifruit allergens already known shows all these features. CONCLUSIONS: Kiwifruit allergy can also occur with ICU, probably due to a native protein that is not yet identified. In this case the elimination diet is not required.

Increased levels of neurotrophins in the cerebrospinal fluid of children with Epstein-Barr virus meningoencephalitis.

OBJECTIVE: The aim of this study was to evaluate the expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in the cerebrospinal fluid (CSF) of children with Epstein-Barr virus (EBV)-induced meningoencephalitis (ME) in order to establish a possible correlation with laboratory findings and neurological manifestations. METHODS: A prospective observational clinical study was performed on 10 children with viral ME, five of them with EBV-induced ME. As controls, we used CSF samples collected from children admitted with febrile seizures. Neurotrophin levels were measured using an enzyme immunoassay. RESULTS: Significantly higher levels of BDNF and NGF were detected in all patients with viral ME compared to controls. Moreover, in patients with EBV-induced ME, the neurotrophin levels were higher than in those with other viral ME. Of note, in children with EBV-induced ME, we found a significant correlation between neurotrophic factor levels and the number of lymphocytes in the CSF (p<0.001). In these patients we also found a significant correlation between BDNF expression and the blood platelet count (p<0.001). Interestingly, two patients with EBV-induced ME showed a correlation between neurotrophin increase and persistent brain abnormalities, such as prolonged alteration of mental status, psychomotor agitation, and athetosis. CONCLUSIONS: Viral ME induces an early and strong increased biosynthesis of neurotrophic factors. This neurotrophin over-expression is likely to play a key role in the mechanisms of neuronal inflammation and in the severity of brain damage, particularly in EBV-induced ME.

Neuroprotective role of nerve growth factor in hypoxic-ischemic brain injury.

Hypoxic-ischemic brain injuries (HIBI) in childhood are frequently associated with poor clinical and neurological outcome. Unfortunately, there is currently no effective therapy to restore neuronal loss and to determine substantial clinical improvement. Several neurotrophins, such as Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF), and Glial Derived Neurotrophic Factor (GDNF), play a key role in the development, differentiation, and survival of the neurons of the peripheral and central nervous system. Experimental animal studies demonstrated their neuroprotective role in HIBI, while only a few studies examined the neuroprotective mechanisms in patients with severe HIBI. We report two cases of children with HIBI and prolonged comatose state who showed a significant improvement after intraventricular NGF administration characterized by amelioration of electroencephalogram (EEG) and cerebral perfusion at single-photon emission computed tomography (SPECT). The improvement in motor and cognitive functions of these children could be related to the neuroprotective role exerted by NGF in residual viable cholinergic neurons, leading to the restoration of neuronal networks in the damaged brain.

Effects of nerve growth factor in experimental model of focal microgyria.

AIM: The effects on neural repair of intraparenchymal nerve growth factor (NGF) administration were evaluated in neonate Wistar rats with experimentally induced focal microgyria. METHODS: A freezing focal polymicrogyric lesion was induced on the frontal cortex in 35 newborn Wistar rats on postnatal day 1. NGF was administered in 15 cases, with 20 pups as controls. Animals were sacrificed at 72 h and 7 days after NGF administration. Real-time PCR was used for the quantification of the expression of TrkA, p75, and doublecortin (DCX) at the level of the cortical lesion in seven different groups of animals: control 72 h (n = 5), control 7 days (n = 5), microgyria 72 h (n = 5), microgyria 7 days (n = 5), microgyria + NGF 72 h (n = 5), microgyria + NGF 7 days (n = 5), and control + NGF (n = 5). RESULTS: A significant increase in TrkA expression was found in the microgyria + NGF 7 days group compared to the others. TrkA upregulation was already visible 72 h after NGF administration. Unlike TrkA, p75 expression increased in animals subjected to the experimental focal microgyria and decreased markedly after NGF administration. DCX expression in injured animals was observed to increase strongly 7 days after NGF administration compared with other groups. CONCLUSIONS: NGF administration interferes with neural repair mechanisms at the polymicrogyric lesion site by means of TrkA and DCX upregulation which possibly counteracts the process of apoptosis caused by the brain injury.

Neuroprotective role of nerve growth factor in hypoxicischemic injury. From brain to skin.

Hypoxic-ischemic injuries (HII) of the brain, optic pathways, and skin are frequently associated with poor neurological and clinical outcome. Unfortunately, no new therapeutic approaches have been proposed for these conditions. Recently, experimental and clinical studies showed that nerve growth factor (NGF) can improve neurological deficits, visual loss and skin damage after HII. Based on these studies, we report the effects of NGF administration in different lesions of the brain, optic pathways and skin. 2.5S NGF purified and lyophilized from male mouse submaxillary glands was utilized for the treatment. NGF administration was started in absence of recovery after conventional and standardized treatment. One mg NGF was administered via the external catheter into the brain, by drop administration in the eye, and by subcutaneous administration in the skin. We treated 4 patients: 2 children with hypoxic-ischemic brain damage, an adult patient with an optic glioma-induced visual loss and a child with a severe crush syndrome of the lower left limb. After NGF treatment, we observed an amelioration of both neurological and electrophysiological function of the brain, a subjective and objective improvement of visual function, and a gradual improvement of ischemic skin lesion. No side effects were related to NGF treatment in all patients studied. Our observation shows that NGF administration may be an effective and safe adjunct therapy in patients with severe HII. The beneficial and prolonged effect on nerve function suggests a neuroprotective mechanism exerted by NGF on the residual viable neurological pathways of these patients.

Comparison of propofol versus propofol-ketamine combination in pediatric oncologic procedures performed by non-anesthesiologists.

BACKGROUND: Limited data are available on the best option (short acting sedatives, opioids, or ketamine) in oncologic procedural sedation performed by non-anesthesiologists. The aim of the present prospective study is to compare the safety and efficacy of propofol-ketamine versus propofol alone, managed by trained pediatricians, in children with cancer undergoing painful procedures. PROCEDURES: Data on 121 children with acute lymphatic leukemia (ALL) undergoing procedural sedations (lumbar punctures and bone marrow aspirations) were prospectively collected and included drug doses, side effects, pain assessment, and sedation degree. Children were randomly assigned to one of the two groups: P (n = 62) receiving propofol alone and K (n = 59) in whom a ketamine-propofol combination was used. RESULTS: In group K, the total dose of propofol required was significantly lower than in group P (3.9 ± 3.6 mg/kg vs. 5.1 ± 3.6 mg/kg; P < 0.001). The incidence of hypotension was also significantly lower (11% vs. 39%; P < 0.001). Major O(2) desaturations (defined as SatO(2) < 88%) occurred principally in group P (7 vs. 1; P = 0.05). Both best analgesia and shorter recovery time were obtained with the propofol-ketamine association. No differences were observed in the degree of sedation and in the awakening quality score between the two groups. CONCLUSIONS: The combination of propofol and ketamine produced statistically significant clinical advantages combined with a higher profile of safety in children with cancer undergoing painful procedures.