Energetic α-particle sources produced through proton-boron reactions by high-energy high-intensity laser beams.

In an experiment performed with a high-intensity and high-energy laser system, α-particle production in proton-boron reaction by using a laser-driven proton beam was measured. α particles were observed from the front and also from the rear side, even after a 2-mm-thick boron target. The data obtained in this experiment have been analyzed using a sequence of numerical simulations. The simulations clarify the mechanisms of α-particle production and transport through the boron targets. α-particle energies observed in the experiment and in the simulation reach 10-20 MeV through energy transfer from 20-30 MeV energy incident protons. Despite the lower cross sections for protons with energy above the sub-MeV resonances in the proton-boron reactions, 10^{8}-10^{9}α particles per steradian have been detected.

Risk factors for recurrent acute otitis media: a real-life clinical experience.

Acute otitis media (AOM) is the most common bacterial infection in children. Some children with AOM tend to be otitis-prone, such as frequent recurrence of AOM (RAOM). Possible RAOM risk factors are widely debated. The current study was performed in a real-life setting, such as an otorhinolaryngologic (ORL) clinic, to identify predictive factors, including clinical data and endoscopic findings, for RAOM in children. In this study, 1,002 children (550 males, 452 females, mean age 5.77 + 1.84 years) complaining of upper airway symptoms were consecutively visited. Detailed clinical history and nasal endoscopy were performed. Throughout the ORL visit, it was possible to define some factors involved in the recurrence of AOM, including female gender, artificial feeding, tonsillar and adenoid hypertrophy. Adenoid and tonsillar hypertrophy, female gender, and artificial are factors significantly associated with RAOM. Therefore, reducing adenoid and tonsil size, also using topical corticosteroids or glycyrrhizin, could be a reasonable strategy to potentially reduce adenoid and tonsil size. The current study suggests that also in a primary care setting, it is possible to achieve meaningful information that is relevant in clinical practice.

Hexavalent vaccines in preterm infants: an update by Italian Society of Pediatric Allergy and Immunology jointly with the Italian Society of Neonatology.

Hexavalent vaccines, protecting against six diseases (diphtheria, tetanus, pertussis [DTaP], poliovirus, hepatitis B virus [HBV], and Haemophilus influenzae type b [Hib], are routinely the standard of care in Europe. The use of combined vaccines allows the reduction of number of injections and side effects, the reduction of costs, and the increase in adherence of the family to the vaccination schedule both in terms of the number of doses and timing. The safety profile, efficacy and effectiveness of hexavalent vaccines have been extensively documented in infants and children born at term, and data are accumulating in preterm infants. Hexavalent vaccines are particularly important for preterm infants, who are at increased risk for severe forms of vaccine preventable diseases. However, immunization delay has been commonly reported in this age group. All the three hexavalent vaccines currently marketed in Italy can be used in preterm infants, and recent data confirm that hexavalent vaccines have a similar or lower incidence of adverse events in preterm compared to full-term infants; this is likely due to a weaker immune system response and reduced ability to induce an inflammatory response in preterm infants. Apnoea episodes are the adverse events that can occur in the most severe preterm infants and / or with history of respiratory distress. The risk of apnoea after vaccination seems to be related to a lower gestational age and a lower birth weight, supporting the hypothesis that it represents an unspecific response of the preterm infant to different procedures. High seroprotection rates have been reported in preterm infants vaccinated with hexavalent vaccine. However, a lower gestational age seems to be associated with lower antibody titres against some vaccine antigens (e.g. HBV, Hib, poliovirus serotype 1, and pertussis), regardless of the type of hexavalent vaccine used. Waiting for large effectiveness studies, hexavalent vaccines should be administered in preterm infants according to the same schedule recommended for infants born at term, considering their chronological age and providing an adequate monitoring for cardio-respiratory events in the 48-72 h after vaccination, especially for infants at risk of recurrence of apnoea.

Can an otorhinolaryngological visit induce the suspect of allergic rhinitis in children?

Summary: Allergic rhinitis (AR) is very frequent in childhood. AR is commonly associated with some co-morbidities and typical clinical features. This study aimed to test the hypothesis whether an otorhinolaryngological (ORL) visit could induce the suspect of AR. Globally, 1,002 children (550 males, mean age 5.77 years) were consecutively visited at an ORL clinic. Clinical visit, nasal endoscopy, and skin prick test were performed in all patients. In particular, history investigated atopic familiarity, birth, feeding type, passive smoking, comorbidities, including asthma, respiratory infections, otitis media, respiratory sleep disorder. Endoscopy assessed the tonsil and adenoid volume, turbinate contacts, mucosal color, and nasal discharge. Univariate and multivariate analysis were performed. The study showed that 547 (54.6%) children had AR. Some parameters were predicting factor for suspecting AR: middle turbinate contact (OR = 9.27), familial atopy (OR = 6.24), pale nasal mucosa (OR = 4.95), large adenoid volume (OR = 3.02 for score 4), and asthma co-morbidity (OR = 2.95). In conclusion this real-life study showed that during an ORL visit it is possible to suspect AR in children with turbinate hypertrophy, familial atopy, nasal pale mucosa, adenoid enlargement, and asthma comorbidity.

Bet v 1 sensitization modulates allergenic molecular immune response.

Summary: Background Allergy is characterized by allergen-specific IgE production. Molecular-based allergy diagnostic allows to define the precise sensitization profile. Bet v 1 is the major allergen of the PR-10 family. It has been reported that pan-allergens could affect the sensitization panel in adults. This study aimed to evaluate the impact of Bet v 1 sensitization on sensitization pattern in a large sample of children. Methods Serum IgE molecular components were assessed by ISAC method. Sera from 1,205 children, 708 males (58.76%) and 497 females (41.24%), median age 8.61 years (4.93 - 12.54 years) were analyzed. Results A total of 354 PR-10-positive subjects were detected out of 1,205 subjects. Bet v 1 positive children were significantly more frequently sensitized to other molecules belonging to PR-10 family and noteworthy also to other allergenic families than Bet v 1 negative children. Conclusions The present study demonstrates that Bet v 1 sensitization may significantly affect the sensitization pattern in children living in Genoa, a Mediterranean city located in a birch-free area.

Diagnostic relevance of IgE sensitization profiles to eight recombinant Phleum pratense molecules.

BACKGROUND: Grass pollen-related seasonal allergic rhinoconjunctivitis (SARg) is clinically heterogeneous in severity, comorbidities, and response to treatment. The component-resolved diagnostics disclosed also a high heterogeneity at molecular level. Our study aimed at analyzing the characteristics of the IgE sensitization to Phleum pratense molecules and investigating the diagnostic relevance of such molecules in childhood. METHODS: We examined 1120 children (age 4-18 years) with SARg. Standardized questionnaires on atopy were acquired through informatics platform (AllergyCARD™). Skin prick tests were performed with pollen extracts. Serum IgE to airborne allergens and eight P. pratense molecules (rPhl p 1, rPhl p 2, rPhl p 4, rPhl p 5b, rPhl p 6, rPhl p 7, rPhl p 11, rPhl p 12) were tested by ImmunoCAP FEIA. RESULTS: The analysis of IgE responses against eight P. pratense molecules showed 87 profiles. According to the number of molecules recognized by IgE, the more complex profiles were characterized by higher serum total IgE, higher grass-specific serum IgE, and higher number and degree of sensitization to pollens. The most frequent IgE sensitization profile was the monomolecular Phl p 1. Sensitization to Phl p 7 was a reliable biomarker of asthma, whereas Phl p 12 of oral allergy syndrome. Sensitization to Phl p 7 was associated with a higher severity of SARg, and complex profiles were associated with longer disease duration. CONCLUSIONS: In a large pediatric population, the complexity of IgE sensitization profiles against P. pratense molecules is related to high atopic features although useless for predicting the clinical severity. The detection of serum IgE to Phl p 1, Phl p 7, and Phl p 12 can be used as clinical biomarkers of SARg and comorbidities. Further studies in different areas are required to test the impact of different IgE molecular profiles on AIT response.

The impact of age on serum allergen-specific IgE to inhaled molecular components.

BACKGROUND: Respiratory allergy is characterised by an IgE-mediated reaction. The immune system functions, including IgE production, progressively decline over time, such as growing up and ageing. Molecular-based allergy diagnostic defines sensitisation profile. This study aimed to evaluate the impact of age on serum allergen-specific IgE to molecular component levels in a large sample of subjects. METHODS: Serum IgE to: Phl p1, Bet v1, Ole e1, Cup a1, Par j2, Can f1, Der p2, and Fel d1 were assessed by ISAC method. Sera from 2788 patients, 1230 males (44.1%) and 1558 females (55.9%), median age 23 years (1st and 3rd quartiles: 9.7-49.7 years; age range: 1 month-103 years) were analysed. RESULTS: The number of positive tests (i.e. sensitisation) tended to increase between birth and school-age till young adulthood and then decreased (p<0.0001) with the exception of Fel d 1 (p=0.14). A similar age-dependent trend was observed considering the levels of each allergen components: the levels of each allergen component, with the exception of Fel d 1, tended to increase till early adulthood and then to decrease reaching the lowest levels in the elderly. CONCLUSIONS: Allergen-specific IgE production to inhaled molecular components trend to reduce with ageing, but with differences between allergens. This phenomenon should be adequately evaluated managing allergic patients.

Sequential treatment with immunotherapy and BRAF inhibitors in BRAF-mutant advanced melanoma

Purpose. Immunotherapy (IT) agents and BRAF inhibitors (BRAFi) are effective treatments for patients with advanced BRAF-mutant melanoma although the optimal sequence remains to be elucidated. The aim of this study was to compare the outcomes of two different cohorts of patients treated with BRAFi first, then IT or the reverse sequence. Patients and methods. This is a retrospective study on two groups of patients: a cohort was treated first with BRAFi followed by immunotherapy (BRAFi-IT) and the other cohort with the reverse sequence (IT-BRAFi). Baseline characteristics and clinical outcomes were compared between the two cohorts. Results. A total of 25 patients were included in the study. Sixteen patients were given BRAFi-IT sequence and nine received IT-BRAFi sequence. No differences were observed in the characteristics of patients prior to each treatment between cohorts. Objective response rate (ORR) achieved by BRAFi were not different among groups. ORR achieved by IT was higher when administered after BRAFi (43.8 vs 0 %). Survival rates at 1-2 years were similar in both cohorts and median overall survival was not different for BRAFi-IT and IT-BRAFi (log rank test p = 0.97). Conclusions. No differences were observed in OS between the two cohorts. These results support the indistinct use of IT or BRAFi as initial treatment in patients with metastatic BRAF-mutant melanoma, although higher rate of response to IT was observed when administered after BRAFi. Prospective randomized clinical trials are needed on this issue (AU)

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Allergen-specific IgE to food molecular components and age: From early childhood to adulthood.

BACKGROUND: Respiratory allergy is characterised by an IgE-mediated reaction. The immune system functions, including IgE production, progressively decline over time with growing up and ageing. Molecular-based allergy diagnostic defines sensitisation profile. This study aimed to evaluate the impact of age on serum allergen-specific IgE to molecular component levels in a large sample of subjects. METHODS: Serum IgE to: rCor a11, rPru p3, nJug r3, rAra h8, rGly m4, rCor a8, nPen m1, nAct d8, Bos d 8, and nGal d2 were assessed by ISAC method. Sera from 2795 patients, 1234 males (44.1%) and 1561 females (55.9%), median age 23 years (1st and 3rd quartiles: 9.7-43.7 years; age range: 1 month-103 years) were analysed. RESULTS: The number of positive tests (i.e. sensitisation) tended to increase between birth and school-age until young adulthood and then decreased. A similar age-dependent trend was observed considering the levels of each allergen components: the levels of each allergen component tended to increase until early adulthood, but Gal d 2 and Bos d 8 (rapidly diminishing), and then to decrease over time. However, the pattern is significantly dependent on each single tested food. CONCLUSIONS: Allergen-specific IgE production to food molecular components tend to reduce with ageing, but with differences between allergens. This phenomenon should be adequately evaluated managing allergic patients.

Sequential treatment with immunotherapy and BRAF inhibitors in BRAF-mutant advanced melanoma.

PURPOSE: Immunotherapy (IT) agents and BRAF inhibitors (BRAFi) are effective treatments for patients with advanced BRAF-mutant melanoma although the optimal sequence remains to be elucidated. The aim of this study was to compare the outcomes of two different cohorts of patients treated with BRAFi first, then IT or the reverse sequence. PATIENTS AND METHODS: This is a retrospective study on two groups of patients: a cohort was treated first with BRAFi followed by immunotherapy (BRAFi-IT) and the other cohort with the reverse sequence (IT-BRAFi). Baseline characteristics and clinical outcomes were compared between the two cohorts. RESULTS: A total of 25 patients were included in the study. Sixteen patients were given BRAFi-IT sequence and nine received IT-BRAFi sequence. No differences were observed in the characteristics of patients prior to each treatment between cohorts. Objective response rate (ORR) achieved by BRAFi were not different among groups. ORR achieved by IT was higher when administered after BRAFi (43.8 vs 0 %). Survival rates at 1-2 years were similar in both cohorts and median overall survival was not different for BRAFi-IT and IT-BRAFi (log rank test p = 0.97). CONCLUSIONS: No differences were observed in OS between the two cohorts. These results support the indistinct use of IT or BRAFi as initial treatment in patients with metastatic BRAF-mutant melanoma, although higher rate of response to IT was observed when administered after BRAFi. Prospective randomized clinical trials are needed on this issue.