The future outlook on allergen immunotherapy in children: 2018 and beyond.

Allergen immunotherapy (AIT) is the only currently available immune-modifying and aetiological treatment for patients suffering from IgE-mediated diseases. In childhood, it represents a suitable therapeutic option to intervene during the early phases of respiratory allergic diseases such as rhino-conjunctivitis and asthma, which is when their progression may be more easily influenced. A growing body of evidence shows that oral immunotherapy represents a promising treatment option in children with persistent IgE- mediated food allergy. The efficacy of AIT is under investigation also in patients with extrinsic atopic dermatitis, currently with controversial results. Furthermore, AIT might be a strategy to prevent the development of a new sensitization or of a (new) allergic disease. However, there are still some methodological criticisms, such as: a) the regimen of administration and the amount of the maintenance dose are both largely variable; b) the protocols of administration are not standardized; c) the description and classification of side effects is variable among studies and needs to be standardized; d) quality of life and evaluation of health economics are overall missing. All these aspects make difficult to compare each study with another. In addition, the content of major allergen(s) remains largely variable among manufacturers and the availability of AIT products differences among countries. The interest and the attention to AIT treatment are currently fervent and increasing. Well-designed studies are awaited in the near future in order to overcome the current gaps in the evidence and furtherly promote implementation strategies

A convergent strategy for the pamamycin macrodiolides:Total synthesis of pamamycin-607, pamamycin-593, and pamamycin-621D precursors

International audienc

Nigerian Psychoactive Alcoholic Herbal Mixture Impacts Behavioural Performance and Caused Brain Biochemical and Histopathological Alterations in Mice

Psychoactive alcoholic herbal mixture is popularly consumed because of the belief on its stimulant and curative effects. This study investigated the neurobehavioral, biochemical and histopathological consequences following its single and repeated co-administration with ethanol to mice. Mice were assessed for sensorimotor, anxiety and memory functions following acute and repeated administration of alcohol herbal mixture (AHM). Alterations in brain acetylcholineterase, nitrite, reduced glutathione (GSH) and malondialdehyde levels were assessed in striatum, prefrontal cortex (PFC) and hippocampus. Neuronal cells counts were determined in the prefrontal cortex and hippocampal tissues. In the acute study, AHM significantly impaired locomotor activity and motor coordination in mice. Repeated administration of AHM and AHM combined with ethanol caused significant impairment of locomotor and motor coordination, increased anxiety-like behavior and impaired memory in mice. Acetylcholinesterase activity was significantly increased in the PFC while nitrite level was elevated in the striatum and PFC. There was significant elevation of malondialdehyde and depletion of GSH in all brain regions as well as reduced neuronal cell counts in the PFC and hippocampus. This study showed evidences of behavioral perturbation and brain biochemical changes in mice, hence repeated consumption of alcoholic herbal mixture might produce substance-attributable harm and quicken neurodegenerative diseases in humans

Metabolomics, microbiota, and in vivo and in vitro biomarkers in type 2 severe asthma: A perspective review

Precision medicine refers to the tailoring of therapeutic strategies to the individual characteristics of each patient; thus, it could be a new approach for the management of severe asthma that considers individual variability in genes, environmental exposure, and lifestyle. Precision medicine would also assist physicians in choosing the right treatment, the best timing of administration, consequently trying to maximize drug efficacy, and, possibly, reducing adverse events. Metabolomics is the systematic study of low molecular weight (bio)chemicals in a given biological system and offers a powerful approach to biomarker discovery and elucidating disease mechanisms. In this point of view, metabolomics could play a key role in targeting precision medicine

[Turner-like syndrome: a case report].

A prepubescent 11 year-old girl came to our attention for short stature. Auxological evaluation showed peculiar phenotype. In order to exclude Turner syndrome standard karyotype was performed with normal result. Because of anemia and selective deficiency of the erythroid lineage further investigations were performed and a diagnosis of Blackfan-Diamond anemia was made

Is it possible to make a diagnosis of raw, heated and baked egg allergy in children using cut-offs? A systematic review

The diagnosis of IgE-mediated egg allergy lies both on a compatible clinical history and on the results of skin prick tests (SPTs) and IgEs levels. Both tests have good sensitivity but low specificity. For this reason, oral food challenge (OFC) is the ultimate gold standard for the diagnosis. The aim of the present paper is to systematically review the literature in order to identify, analyze and synthesize the predictive value of SPT and specific IgEs both to egg white and main egg allergens and to review the cut-offs suggested in the literature

IgE antibody repertoire in nasal secretions of children and adults with seasonal allergic rhinitis: a molecular analysis

Background: There is growing interest both in testing IgE in nasal secretions (NS) and in molecular diagnosis of seasonal allergic rhinitis (SAR). Yet, the reliability of nasal IgE detection with the newest molecular assays has never been assessed in a large cohort of pollen allergic patients. Objective: To investigate with microarray technology and compare the repertoires of specific IgE (sIgE) antibodies in NS and sera of a large population of children and adults with SAR. Methods: Nasal secretions were collected with an absorbent device (Merocel 2000®, Medtronic) and a minimal dilution procedure from 90 children and 71 adults with SAR. Total IgE (tIgE) (ImmunoCAP, Thermo Fisher Scientific (TFS)) and sIgE antibodies against 112 allergen molecules (ISAC-112, TFS) were measured in NS and serum. Results: Nasal sIgE was detectable in 68.3% of the patients. The detected nasal sIgE antibodies recognized airborne (88%), vegetable (10%), and animal food or other (<1%) allergen molecules. The prevalence and average levels of sIgE in NS and serum were highly interrelated at population level. A positive nasal sIgE antibody to a given molecule predicted the detection of the same antibody in the patient's serum with a specificity of 99.7% and a sensitivity of 40%. Conclusions: The concentration of sIgE is much lower in nasal secretions than in the serum. sIgE assays with very high analytical sensitivity and sampling methods with minimal dilution will be therefore needed to validate nasal secretions as alternative to serum in testing the sIgE repertoire

Cross-sectional and prospective study of the effects of GH therapy on metabolic panel in children with GH deficiency

Background: Numerous studies have shown that GH, in addition to promoting linear growth, exerts a key role in many metabolic processes. However, there are only few studies aiming at evaluating the metabolic panel of children with GH deficiency (GHD). The aims of the study were: to verify the presence of metabolic alterations in GHD children in comparison with age-matched controls and to check the possible effects of two year GH therapy on the metabolic parameters in GHD. Study design: cross-sectional and prospective; one center experience Population and Methods: We enrolled 32 pediatric GHD patients (group A) and 33 sex- and age-matched healthy controls (group B). Baseline serum assays (lipid, insulin, glucose) were performed in both groups. GHD children underwent replacement therapy with GH. The same assays were repeated after 12 and 24 months of GH treatment. Results: No differences, in basal assays were found between the two groups. In group A, after initiation of GH, there was a significant increase of basal insulin and HOMA- insulin resistance (IR) index (p <0.001). In children with severe GHD (peak GH <3 ng / ml), after beginning of GH therapy a significant improvement in the lipid profile was found (p < 0.05). Conclusions: a) At the time of diagnosis GHD children had a metabolic picture that was not different from non- GHD group; b) in children with severe GHD, the metabolic profile showed a trend towards at improvement after the initiation of replacement therapy with GH, with beneficial effects in terms of total cholesterol, LDL cholesterol and cardiovascular risk indices; c) GHD patients with unfavorable metabolic profile (high BMI and hypercholestorolemia) need a monitoring of glucose metabolism by periodical evaluations of insulin and HOMA – IR

Heterogeneous validity of daily data on symptoms of seasonal allergic rhinitis recorded by patients using the e-diary AllergyMonitor®

Background: Patient-generated symptom and medication scores are essential for diagnostic and therapeutic decisions in seasonal allergic rhinitis (SAR). Previous studies have shown solid consistencies between different scores at population level in real-life data and trials. For clinicians, the evaluation of individual data quality over time is essential to decide whether to rely on these data in clinical decision-making. Objective: To analyze the consistency of different symptom (SS) and symptom medication scores (SMSs) at individual level in two study cohorts with different characteristics and explore individual patient trajectories over time. Methods: Within the pilot phase of the @IT.2020 project on diagnostic synergy of mobile health and molecular IgE assessment in patients with SAR, we analyzed data of 101 children and 93 adults with SAR and instructed them to record their symptoms and medication intake daily via the mobile app AllergyMonitor®. We then assessed the correlation between different SMS and a visual analogue scale (VAS) on the impact of allergy symptoms on daily life at population and individual level. Results: At population level, the Rhinoconjunctivitis total symptom score (RTSS) correlated better with VAS than the combined symptom and medication score (CSMS). At individual level, consistency among RTSS and VAS was highly heterogeneous and unrelated to disease severity or adherence to recording. Similar heterogeneity was observed for CSMS and VAS. Conclusions: The correlation of clinical information provided by different disease severity scores based on data collected via electronic diaries (e-diaries), is sufficient at population level, but broadly heterogeneous for individual patients. Consistency of the recorded data must be examined for each patient before remotely collected information is used for clinical decision making