Heterogeneity of sensitization profiles and clinical phenotypes among patients with seasonal allergic rhinitis in Southern European countries-The @IT.2020 multicenter study.

BACKGROUND: Pollen allergy poses a significant health and economic burden in Europe. Disease patterns are relatively homogeneous within Central and Northern European countries. However, no study broadly assessed the features of seasonal allergic rhinitis (SAR) across different Southern European countries with a standardized approach. OBJECTIVE: To describe sensitization profiles and clinical phenotypes of pollen allergic patients in nine Southern European cities with a uniform methodological approach. METHODS: Within the @IT.2020 multicenter observational study, pediatric and adult patients suffering from SAR were recruited in nine urban study centers located in seven countries. Clinical questionnaires, skin prick tests (SPT) and specific IgE (sIgE) tests with a customized multiplex assay (Euroimmun Labordiagnostika, Lübeck, Germany) were performed. RESULTS: Three hundred forty-eight children (mean age 13.1 years, SD: 2.4 years) and 467 adults (mean age 35.7 years SD: 10.0 years) with a predominantly moderate to severe, persistent phenotype of SAR were recruited. Grass pollen major allergenic molecules (Phl p 1 and/or Phl p 5) ranged among the top three sensitizers in all study centers. Sensitization profiles were very heterogeneous, considering that patients in Rome were highly poly-sensitized (sIgE to 3.8 major allergenic molecules per patient), while mono-sensitization was prominent and heterogeneous in other cities, such as Marseille (sIgE to Cup a 1: n = 55/80, 68.8%) and Messina (sIgE to Par j 2: n = 47/82, 57.3%). Co-sensitization to perennial allergens, as well as allergic comorbidities also broadly varied between study centers. CONCLUSIONS: In Southern European countries, pollen allergy is heterogeneous in terms of sensitization profiles and clinical manifestations. Despite the complexity, a unique molecular, multiplex, and customized in-vitro IgE test detected relevant sensitization in all study centers. Nevertheless, this geographical diversity in pollen allergic patients imposes localized clinical guidelines and study protocols for clinical trials of SAR in this climatically complex region.

Acute chest syndrome in children with sickle cell disease: Data from a national AIEOP cohort identify priority areas of intervention in a hub-and-spoke system.

Acute chest syndrome (ACS) is a frequent cause of hospitalization in sickle cell disease (SCD). Despite advances in acute care, many settings still lack knowledge about ACS best practices. After the AIEOP Guidelines were published in 2012, suggesting standardized management in Italy, a retrospective study was performed to assess the diagnostic and therapeutic pathways of ACS in children. From 2013 to 2018, 208 ACS episodes were presented by 122/583 kids in 11 centres. 73 were male, mean age 10.9 years, 85% African, 92% HbSS or Sß°. In our hub-and-spoke system, a good adherence to Guidelines was documented, but discrepancies between reference centres and general hospitals were noted. Improvement is needed for timely transfer to reference centres, use of incentive spirometry, oxygen therapy and pain management.

Factors predicting the outcome of allergen-specific nasal provocation test in children with grass pollen allergic rhinitis.

Background: Nasal provocation testing (NPT) is a reference methodology to identify the culprit allergen in patients with allergic rhinitis. Selecting the right allergen for NPT is particularly difficult in poly-sensitized patients with seasonal allergic rhinitis (SAR). Predictors of NPT outcomes may facilitate the proper use of this test or even substitute it. Objective: To identify predictors of grass pollen NPT outcome from an array of clinical data, e-diary outcomes, and allergy test results in poly-sensitized pediatric patients with SAR. Methods: Poly-sensitized, SAR patients with grass pollen allergy, participating in the @IT.2020 pilot project in Rome and Pordenone (Italy), participated in a baseline (T0) visit with questionnaires, skin prick testing (SPT), and blood sampling to measure total (ImmunoCAP, TFS, Sweden) and specific IgE antibodies to grass pollen extracts and their major allergenic molecules (ESEP, Euroimmun Labordiagnostika, Germany). During the pollen season, patients filled the AllergyMonitor® e-diary app measuring their symptoms, medication intake, and allergy-related well-being via the Visual Analogue Scale (VAS). After the pollen season (T1), patients answered clinical questionnaires and underwent a nasal provocation test (NPT) with grass pollen extract. Results: We recruited 72 patients (age 14.3 ± 2.8 years, 46 males) sensitized to grass and/or other pollens, including olive (63; 87.5%) and pellitory (49; 68.1%). Patients positive to grass pollen NPT (61; 84.7%), compared to the negative ones, had worse VAS values in the e-diary, larger SPT wheal reactions, and higher IgE levels, as well as specific activity to timothy and Bermuda grass extracts, rPhl p 5 and nCyn d 1. A positive NPT to grass pollen was predicted by an index combining the specific activity of IgE towards Phl p 5 and Cyn d 1 (AUC: 0.82; p < 0.01; best cut-off ≥7.25%, sensitivity 70.5%, specificity: 90.9%). VAS results also predicted NPT positivity, although with less precision (AUC: 0.77, p < 0.01; best cut-off ≥7, sensitivity: 60.7%, specificity: 81.8%). Conclusions: An index combining the specific activity of IgE to rPhl p 5 and nCyn d 1 predicted with moderate sensitivity and high specificity the outcome of a grass pollen NPT in complex, poly-sensitized pediatric patients with seasonal allergic rhinitis. Further studies are needed to improve the index sensitivity and to assess its usefulness for NPT allergen selection or as an alternative to this demanding test procedure.

Lipomatous Hypertrophy: An Accidental Finding in Heart.

Lipomatous hypertrophy is an uncommon benign lesion of the atrium, generally asymptomatic, characterized by unencapsulated accumulation of adipose tissue entrapping cardiomyocytes. This pathology generally remains unnoticed and often emerges as an occasional finding. Here, we report two cases from our hospital including a review of the available literature.

Cooking influence in tolerance acquisition in egg-induced acute food protein enterocolitis syndrome

Background: Few studies on the age of resolution of Food Protein Induced Enterocolitis Syndrome (FPIES) induced by solid foods are available. In particular, for FPIES induced by egg, the mean age of tolerance acquisition reported in the literature ranges from 42 to 63 months. Objective: We have assessed whether the age of tolerance acquisition in acute egg FPIES varies depending on whether the egg is cooked or raw. Methods: We conducted a retrospective and multicentric study of children with diagnosis of acute egg FPIES seen in 10 Italian allergy units between July 2003 and October 2017. The collected data regarded sex, presence of other allergic diseases, age of onset of symptoms, kind and severity of symptoms, cooking technique of the ingested egg, outcome of the allergy test, age of tolerance acquisition. Results: Sixty-one children with acute egg FPIES were enrolled, 34 (56%) males and 27 (44%) females. Tolerance to cooked egg has been demonstrated by 47/61 (77%) children at a mean age of 30.2 months. For 32 of them, tolerance to raw egg has been demonstrated at a mean age of 43.9 months. No episodes of severe adverse reaction after baked egg ingestion have been recorded. Conclusions: It is possible to perform an OFC with baked egg, to verify the possible acquisition of tolerance, at about 30 months of life in children with acute egg FPIES

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Cooking influence in tolerance acquisition in egg-induced acute food protein enterocolitis syndrome.

BACKGROUND: Few studies on the age of resolution of Food Protein Induced Enterocolitis Syndrome (FPIES) induced by solid foods are available. In particular, for FPIES induced by egg, the mean age of tolerance acquisition reported in the literature ranges from 42 to 63 months. OBJECTIVE: We have assessed whether the age of tolerance acquisition in acute egg FPIES varies depending on whether the egg is cooked or raw. METHODS: We conducted a retrospective and multicentric study of children with diagnosis of acute egg FPIES seen in 10 Italian allergy units between July 2003 and October 2017. The collected data regarded sex, presence of other allergic diseases, age of onset of symptoms, kind and severity of symptoms, cooking technique of the ingested egg, outcome of the allergy test, age of tolerance acquisition. RESULTS: Sixty-one children with acute egg FPIES were enrolled, 34 (56%) males and 27 (44%) females. Tolerance to cooked egg has been demonstrated by 47/61 (77%) children at a mean age of 30.2 months. For 32 of them, tolerance to raw egg has been demonstrated at a mean age of 43.9 months. No episodes of severe adverse reaction after baked egg ingestion have been recorded. CONCLUSIONS: It is possible to perform an OFC with baked egg, to verify the possible acquisition of tolerance, at about 30 months of life in children with acute egg FPIES.

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.

Anisakis sensitivity in Italian children: a prospective study

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Endotypes of pollen-food syndrome in children with seasonal allergic rhinoconjunctivitis: a molecular classification.

BACKGROUND: Pollen-food syndrome (PFS) is heterogeneous with regard to triggers, severity, natural history, comorbidities, and response to treatment. Our study aimed to classify different endotypes of PFS based on IgE sensitization to panallergens. METHODS: We examined 1271 Italian children (age 4-18 years) with seasonal allergic rhinoconjunctivitis (SAR). Foods triggering PFS were acquired by questionnaire. Skin prick tests were performed with commercial pollen extracts. IgE to panallergens Phl p 12 (profilin), Bet v 1 (PR-10), and Pru p 3 (nsLTP) were tested by ImmunoCAP FEIA. An unsupervised hierarchical agglomerative clustering method was applied within PFS population. RESULTS: PFS was observed in 300/1271 children (24%). Cluster analysis identified five PFS endotypes linked to panallergen IgE sensitization: (i) cosensitization to ≥2 panallergens ('multi-panallergen PFS'); (ii-iv) sensitization to either profilin, or nsLTP, or PR-10 ('mono-panallergen PFS'); (v) no sensitization to panallergens ('no-panallergen PFS'). These endotypes showed peculiar characteristics: (i) 'multi-panallergen PFS': severe disease with frequent allergic comorbidities and multiple offending foods; (ii) 'profilin PFS': oral allergy syndrome (OAS) triggered by Cucurbitaceae; (iii) 'LTP PFS': living in Southern Italy, OAS triggered by hazelnut and peanut; (iv) 'PR-10 PFS': OAS triggered by Rosaceae; and (v) 'no-panallergen PFS': mild disease and OAS triggered by kiwifruit. CONCLUSIONS: In a Mediterranean country characterized by multiple pollen exposures, PFS is a complex and frequent complication of childhood SAR, with five distinct endotypes marked by peculiar profiles of IgE sensitization to panallergens. Prospective studies in cohorts of patients with PFS are now required to test whether this novel classification may be useful for diagnostic and therapeutic purposes in the clinical practice.

The smartphone: a novel diagnostic tool in pollen allergy?

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The oral food desensitization in the Italian allergy centres.

BACKGROUND: Attempts aimed at inducing food tolerance through oral food desensitization (OFD) for the treatment of IgE-mediated food allergies are increasing. In Italy, a number of allergy centres offer this procedure. OBJECTIVE: To collect information on how these centres are organized, how patients are selected, the methods used to administer OFD and how adverse reactions are managed. METHODS: A questionnaire was e-mailed to all the Italian allergy centres offering OFD. RESULTS: The survey shows a high degree of variability between centres. A correct diagnosis of food allergy is crucial for selecting patients for OFD. In the Italian allergy centres, oral food challenges are mostly open label (84%), but in 16% of cases they are single-blind (8%) or double-blind (8%). A high proportion of allergy centres (83%) offer OFD to children presenting forms of anaphylaxis triggered by traces--or very low doses--of food allergen. The majority of allergy centres (76%) enroll patients over 3 years of age, with 44% enrolling patients above the age of 5. Not-controlled asthma, unreliability of parents in the management of OFD and/or risk of adverse events, are the main reasons for exclusion from the procedure. CONCLUSION: Although OFD may sometimes be successful and may be considered a valid alternative to an elimination diet, further randomized controlled trials are needed, in order to clarify some controversial points, such as the characteristics of the child undergoing OFD, and the methods of food preparation and administration. Moreover, further studies should further investigate OFD safety, efficacy and costs.

Pilot study on the short-term prediction of symptoms in children with hay fever monitored with e-Health technology.

Forecasting symptoms of pollen-related allergic rhinoconjunctivitis at the level of individual patients would be useful to improve disease control and plan pharmacological intervention. Information Technology nowadays facilitates a more efficient and easier monitoring of patients with chronic diseases. We aimed this study at testing the efficiency of a model to short-term forecast symptoms of pollen-AR at the "individual" patient level. We analysed the data prospectively acquired from a group of 21 Italian children affected by pollen-related allergic rhinoconjunctivitis and recorded their symptoms and medication "Average Combined Score" (ACS) on a daily basis during April-June 2010-2011 through an informatics platform (Allergymonitor™). The dataset used for prediction included 15 variables in four categories: (A) date, (B) meteo-climatic, (C) atmospheric concentration of 5 pollen taxa, and (D) intensity of the patient's IgE sensitization. A Partial Least Squares Discriminant Analysis approach was used in order to predict ACS values above a fixed threshold value (0.5). The best performing predicting model correctly classified 77.8% ± 10.3% and 75.5% ± 13.2% of the recorded days in the model and test years, respectively. In this model, 9/21 patients showed ≥ 80% correct classification of the recorded days in both years. A better performance was associated with a higher degree of patient's atopic sensitization and a time lag > 1. Symptom forecasts of seasonal allergic rhinitis are possible in highly polysensitised patients in areas with complex pollen exposure. However, only predictive models tailored to the individual patient's allergic susceptibility are accurate enough. Multicenter studies in large population samples adopting the same acquisition data system on smart phones are now needed to confirm this encouraging outcome.

The impact of telemonitoring on adherence to nasal corticosteroid treatment in children with seasonal allergic rhinoconjunctivitis.

BACKGROUND: Adherence to controller therapy in allergic diseases is low. Telemonitoring has been proposed to improve adherence to treatment in chronic diseases. However, this strategy has never been tested in allergic rhinoconjunctivitis. OBJECTIVE: To test whether Internet-based telemonitoring during the grass-pollen season of children with allergic rhinoconjunctivitis may enhance adherence to treatment. METHODS: Children and adolescents, 5-18 years old, with moderate-to-severe seasonal allergic rhinoconjunctivitis to grass pollen requiring daily administration of nasal corticosteroid (NCS) (mometasone) were recruited (April 2013) in a paediatric allergy practice. Participants were randomized to Internet-based monitoring (AllergyMonitor(™) , AM) or to usual care (no diary at all, controls) and followed from 13 May (T0) to 15 June 2013 (T2). An intermediate visit (T1) was performed between 31 May and 2 June. Optimal adherence to therapy was expressed as the use of at least 0.190 g/day of mometasone, corresponding to 1 puff/nostril/day, and it was measured by canister weights during (T1) and at the end (T2) of the study period. Main secondary outcomes included the reported disease severity (validated self-questionnaire) and quality of life (AdoIRQLQ questionnaire), disease knowledge (multiple-choice questionnaire), nasal flow and resistance at baseline and at T2. RESULTS: The use of mometasone, expressed as both optimal adherence rate (48.4% vs. 12.5%; P = 0.002) and average daily use (0.20 ± 0.12 g/day vs. 0.15 ± 0.07 g/day; P = 0.037), was higher in the AM group (n = 31) than among controls (n = 32). Disease knowledge improved among the patients using AM (83.3% vs. 68.3%; P < 0.001) but not among controls (68.2% vs. 67.7% right answers; P > 0.05). No differences were observed in the reported severity of disease, nasal flow and resistance and quality of life both at baseline and at follow-up visits. CONCLUSIONS: Internet-based telemonitoring improves adherence to NCS treatment and disease knowledge among children and adolescents with seasonal allergic rhinoconjunctivitis.

Cystic gastrointestinal stromal tumors of the pancreas simulating cystoadenocarcinoma. Report of three cases and short review of the literature.

Gastrointestinal stromal tumors (GISTs) represent a distinct subset of mesenchymal tumours of the gastrointestinal tract. They are more common in the stomach and small intestine, and are characterized by the proliferation of spindle or epithelioid cells and by the expression of CD117. Extra-gastrointestinal stromal tumors are rare and only 13 cases of pancreatic GISTs have been reported in the literature, only 1 of which presented as a cystic lesion. Mutational analysis of KIT and Platelet derived growth factor receptor-α genes was performed only in two out of the 13 cases. We report 3 cases of cystic GISTs of the pancreas, radiologically mimicking a cystoadenocarcinoma. Routine histopathology and molecular characterization of the tumours have been performed. In two of them, molecular analysis showed unusual genetic alterations (the internal repeat of codon 502 and 503 in exon 9 of the KIT gene and the KIT exon 9 single nucleotide substitution c.1427G⟩T). Pancreatic GIST should be included in the differential diagnosis of both cystic and solid masses of the pancreas. The diagnosis should be accomplished by a combination of radiology, histology, immunohistochemistry and molecular biology. The evaluation of CD117 expression and the sequence analysis of KIT and Platelet derived growth factor receptor-α gene is mandatory for therapy.

Risk of adverse IgE-mediate reaction at the first egg ingestion in children with atopic dermatitis. Results of a case-control study

BACKGROUND: Studies have reported that children with atopic dermatitis (AD) have a high risk of adverse reactions at first egg ingestion. METHODS: We enrolled 79 children with AD retrospectively and 45 children without AD (control group) prospectively, who had never eaten egg. All children underwent skin prick tests (SPT) with commercial extracts and prick by prick with natural food (raw and boiled egg). Oral food challenge (OFC) was performed in SPT positive patients. RESULTS: Sixty-six percent (52/79) of AD group and 11% (5/45) of Control group had at least one positive SPT (p < 0.001), Relative Risk (RR) = 5.9 and Odds Ratio = 15.4. Of the 46/52 sensitised children in the AD group, 36 children ate egg for the first time in hospital during an OFC and 10 children ate egg at home because of their parents' choice, with 19/46 (41%) resulting in allergic reactions to raw and/or boiled egg. Four/five sensitised children in the control group underwent OFC and three of them (75%) showed an allergic reaction to raw, but not boiled egg. Thirty percent (14/46) of AD group had a systemic reaction vs. 25% (1/4) of Control group. CONCLUSION: A child with AD has a RR of sensitisation to egg six times higher than a child without AD, before the first known ingestion. We propose to test sensitisation to egg in every child with AD who has never eaten egg, and to perform OFC in those with positive SPT in hospital setting

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Immunolocalisation of ghrelin and obestatin in human testis, seminal vesicles, prostate and spermatozoa.

The role of ghrelin and obestatin in male reproduction has not completely been clarified. We explored ghrelin and obestatin localisation in the male reproductive system. Polyclonal antibodies anti-ghrelin and anti-obestatin were used to detect the expression of these hormones in human testis, prostate and seminal vesicles by immunocytochemistry, while in ejaculated and swim up selected spermatozoa by immunofluorescence. Sertoli cells were positive for both peptides and Leydig cells for ghrelin; germ cells were negative for both hormones. Mild signals for ghrelin and obestatin were observed in rete testis; efferent ductules were the most immune reactive region for both peptides. Epididymis was moderately positive for ghrelin; vas deferens and seminal vesicles showed intense obestatin and moderate ghrelin labelling; prostate tissue expressed obestatin alone. Ejaculated and selected spermatozoa were positive for both peptides in different head and tail regions. This study confirms ghrelin localisation in Leydig and Sertoli cells; the finding that ghrelin is expressed in rete testis, epididymis, vas deferens and seminal vesicles is novel, as well as the localisation of obestatin in almost all tracts of the male reproductive system. This research could offer insights for stimulating other studies, particularly on the role of obestatin in sperm physiology, which is still obscure.