Guideline on management of the acute asthma attack in children by Italian Society of Pediatrics.

BACKGROUND: Acute asthma attack is a frequent condition in children. It is one of the most common reasons for emergency department (ED) visit and hospitalization. Appropriate care is fundamental, considering both the high prevalence of asthma in children, and its life-threatening risks. Italian Society of Pediatrics recently issued a guideline on the management of acute asthma attack in children over age 2, in ambulatory and emergency department settings. METHODS: The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was adopted. A literature search was performed using the Cochrane Library and Medline/PubMed databases, retrieving studies in English or Italian and including children over age 2 year. RESULTS: Inhaled ß2 agonists are the first line drugs for acute asthma attack in children. Ipratropium bromide should be added in moderate/severe attacks. Early use of systemic steroids is associated with reduced risk of ED visits and hospitalization. High doses of inhaled steroids should not replace systemic steroids. Aminophylline use should be avoided in mild/moderate attacks. Weak evidence supports its use in life-threatening attacks. Epinephrine should not be used in the treatment of acute asthma for its lower cost / benefit ratio, compared to β2 agonists. Intravenous magnesium solphate could be used in children with severe attacks and/or forced expiratory volume1 (FEV1) lower than 60% predicted, unresponsive to initial inhaled therapy. Heliox could be administered in life-threatening attacks. Leukotriene receptor antagonists are not recommended. CONCLUSIONS: This Guideline is expected to be a useful resource in managing acute asthma attacks in children over age 2

Budd-Chiari Syndrome Imaging Diagnosis: State of the Art and Future Perspectives

Budd-Chiari syndrome (BCS) is a rare hepatic vascular disorder defined by the presence of partial or complete impairment of hepatic venous drainage in the absence of right heart failure or constrictive pericarditis. Several conditions can lead to BCS, from hypercoagulable states to malignancies. Primary BCS is the most common subtype, and usually bartends hypercoagulability states, while secondary BCS involves tumor invasion or extrinsic compression. A combination of clinical and imaging features leads to the diagnosis of BCS, including (1) direct signs: occlusion or compression of the hepatic veins and/or inferior vena cava, and the presence of venous collaterals; (2) indirect signs: morphological hepatic changes with caudate lobe enlargement; inhomogeneous enhancement, and hypervascular nodules. From a clinicopathological point of view, two forms of BCS can be distinguished: acute and subacute/chronic BCS, although asymptomatic and fulminant forms are also possible. Acute presentations are rare, and symptoms include hepatomegaly, ascites, and hepatic insufficiency. Subacute/chronic forms are the most common presentation, with dysmorphic liver and variable degrees of fibrosis deposition. Patients with chronic BCS can develop benign regenerative nodules (large regenerative nodules or FNH [Focal Nodular Hyperplasia]-like lesions), but are also at a higher risk of hepatocellular carcinoma (HCC). The radiologist role is therefore fundamental in both diagnosis and surveillance of BCS. The aim of this review is to present all clinical and imaging signs that can help to reach the diagnosis of BCS, with their clinical significance, providing tips and tricks for the cross-sectional diagnosis of this condition

Hydroxyindole-O-methyltransferase (HIOMT) activity in the retina of melatonin-proficient mice

Numerous pieces of evidence support the expression by the mammalian retina of Hydroxyindole-O-methyltransferase (HIOMT, EC 2.1.1.4), the enzyme directly responsible for the biosynthesis of the pineal chronobiotic hormone melatonin (MLT). However, conflicting results obtained so far by enzyme-kinetic and immune-detection techniques still make HIOMT presence and relevance in the eye a matter of debate. This work aimed at evaluating unambiguously HIOMT activity in the mouse retina, a valuable model for studying the effects of MLT variations on ocular pathophysiology. Since laboratory mouse strains can bear genetic polymorphisms yielding defective enzymes of MLT biosynthesis, retinas and control pineal glands used in this study were obtained in a MLT-proficient crossing of A/J mice, the A/J/C57BL/10 strain. To improve the radiochemical reference assay, we tested different homogenization procedures coupled with HPLC detection. Concomitantly, we quantified MLT, and its precursor N-acetyl-serotonin (NAS) by HPLC coupled to electrochemical detection in retinas isolated from either light- or dark-adapted mice. Results showed that the standard radio-chemical assay was successful for pineal HIOMT only, whereas specific homogenization buffers and HPLC were required to detect retinal activity, presumably due to interfering methyl-transferases inhibited by NAS. Under present conditions, retinal HIOMT Vmax accounted for by ≈ 40 fmol/h/mg protein, 2.6-hundreds-fold lower than the pineal counterpart, displaying equivalent KMs (≈10 μM). Moreover, NAS and MLT rapidly decreased in light-exposed isolated retinas, corroborating light-sensitive in-situ MLT formation. Conclusively, we measured mouse retinal HIOMT kinetics under basal conditions, a useful result to elucidate the regulatory patterns, the possible impact on eye health, and therapeutic approaches related to this enzyme

Analytical and pharmacological aspects of therapeutic drug monitoring of mTOR inhibitors

Mammalian Target Of Rapamycin (mTOR) inhibitors represent a new class of immunosuppressant drugs extensively used for the prevention and the treatment of graft rejection in organ transplant recipients. Their current use is due to referred low nephrotoxic effects, particularly important in kidney transplanted and/or patients with renal failure. The most representative drugs of such class are Sirolimus (Siro) and Everolimus (Rad). Both drugs show a narrow therapeutic window, therefore, monitoring of whole-blood drug levels is recommended in order to optimize the therapy. Among the available assays, Liquid Chromatography coupled with UltraViolet or Electrospray Tandem Mass Spectrometry methods (LC/UV or LC/ESI-MSMS) are the most accurate and specific ones. A reliable alternative is represented by immunoassays, which offer the opportunity to minimize sample pre-treatment, thus reducing the time between drawing blood sample and measuring the drug concentration, an important aspect in high-throughput analyses. Despite this, a limitation in the use of immunoassays for therapeutic drug monitoring is the lower specifity compared with the chromatographic methods when analysing structurally-related drugs. New insights to optimize mTOR inhibitors regimens seem to be offered by the evaluation of CYP450 3A activity by using the probe drug approach. To such purpose, there are a number of major probe drugs used for in vivo studies including: midazolam, cortisol, lidocaine, nifedipine, dextromethorphan, erythromycin, dapsone and alfentanil. The aim of the present paper is to report the most recent knowledge concerning this issue, supplying a critical and comprehensive review for whom are involved both in the clinical and analytical areas

Resilience of systems by value of information and SHM

Critical infrastructure systems such as energy provision and distribution systems, transport systems and the built environment in general are subject to and sensitive to deterioration processes. Structural Health Monitoring (SHM) strategies have been increasingly employed as a means to detect deterioration, facilitate timely and efficient interventions – and thereby to enhance resilience of critical infrastructure. However, in specific situations, it is generally not obvious if and to what degree different SHM strategies are efficient and sufficient for enhancing the resilience of critical infrastructure systems. In response to this challenge, the present contribution puts forwards a novel approach, taking basis in the concept of value of information analysis from Bayesian pre-posterior decision. Utilizing a principal model framework we show how the proposed approach is implemented with due consideration of the resilience governing characteristics and interdependencies between infrastructure systems, social/organisational systems, regulatory systems, ecological systems as well as anthropological and geological hazard systems

Advanced magnetic resonance imaging of cortical laminar necrosis in patients with stroke

Purpose: The aim of this study was to assess the novel advanced magnetic resonance imaging findings of acute stage cortical laminar necrosis developing after complicated cardiovascular or abdominal surgery. Materials and methods: This institutional review board-approved study included patients with postoperative stroke due to cortical laminar necrosis imaged with magnetic resonance in the acute stage. Brain magnetic resonance imaging examinations were obtained on a 3T magnetic resonance scanner within 48 hours of the neurological symptoms, including diffusion-weighted images (b value, 1000 s/mm2) and arterial spin labelling using a pseudo-continuous arterial spin labelling method in four patients. Conventional and advanced magnetic resonance images were analysed to assess the imaging features in acute stage cortical laminar necrosis. Results: The final population consisted of 14 patients (seven men and seven women, mean age 61 years, range 32–79 years) diagnosed with stroke and acute phase cortical laminar necrosis. All the patients presented with cortical lesions showing restricted diffusion on diffusion-weighted images and hypointensity on the apparent diffusion coefficient map. Cortical hyperintensity on T2-weighted or fluid-attenuated inversion recovery images was found in three (21%) and six (43%) patients, respectively. Reduced perfusion was noted in three out of four patients imaged with arterial spin labelling, while in one case no corresponding perfusion abnormality was noted on the arterial spin labelling maps. Arterial spin labelling abnormalities were much more extensive than diffusion restriction in two patients, and they were associated with a poor outcome. Conclusion: Cortical hyperintense abnormalities on diffusion-weighted imaging may be the only sign of developing cortical laminar necrosis injury. The acquisition of arterial spin labelling helps to identify perfusion alterations and the extension of the ischaemic injury