The lncRNA HOTAIR has been implicated in several human cancers. Here, we evaluated the molecular alterations and upstream regulatory mechanisms of HOTAIR in glioma, the most common primary brain tumors, and its clinical relevance. HOTAIR gene expression, methylation, copy-number and prognostic value were investigated in human gliomas integrating data from online datasets and our cohorts. High levels of HOTAIR were associated with higher grades of glioma, particularly IDH wild-type cases. Mechanistically, HOTAIR was overexpressed in a gene dosage-independent manner, while DNA methylation levels of particular CpGs in HOTAIR locus were associated with HOTAIR expression levels in GBM clinical specimens and cell lines. Concordantly, the demethylating agent 5-Aza-2′-deoxycytidine affected HOTAIR transcriptional levels in a cell line-dependent manner. Importantly, HOTAIR was frequently co-expressed with HOXA9 in high-grade gliomas from TCGA, Oncomine, and our Portuguese and French datasets. Integrated in silico analyses, chromatin immunoprecipitation, and qPCR data showed that HOXA9 binds directly to the promoter of HOTAIR. Clinically, GBM patients with high HOTAIR expression had a significantly reduced overall survival, independently of other prognostic variables. In summary, this work reveals HOXA9 as a novel direct regulator of HOTAIR, and establishes HOTAIR as an independent prognostic marker, providing new therapeutic opportunities to treat this highly aggressive cancer.

restriction fragment length polymorphism (RFLP). No statistically significant differences were found in the genotype or allele distributions of either rs920778 or rs12826786 between glioma patients and controls, suggesting these SNPs are not associated with glioma risk. No significant associations were found between rs920778 variants and HOTAIR expression levels, while rs12826786 CT genotype was associated with increased intratumoral HOTAIR RNA levels when compared to TT genotype (p-value = 0.04). Univariate (Log-rank) and multivariate (Cox proportional) analyses showed both rs920778 CT and rs12826786 CT genotypes were significantly associated with longer overall survival of WHO grade III anaplastic oligodendroglioma patients. Our results suggest that HOTAIR SNPs rs920778 and rs12826786 do not play a significant role in glioma susceptibility, but may be important prognostic factors in anaplastic oligodendroglioma patients. Future studies are warranted to validate and expand these findings, and to further dissect the importance of these SNPs in glioma.

Introduction: Adherence in allergen immunotherapy is crucial for its efficacy. At least 3 years of treatment are recommended for achieving a long-term modifying effect. Objectives: To assess patient's adherence and to identify determinant factors for allergen subcutaneous immunotherapy (SCIT) suspension in patients with respiratory allergy. Methods: Retrospective analysis of the medical record of patients submitted to SCIT between January 2013 and December 2016 in our Department. Results: 323 patients were included: 52% female; mean age 30±13 years; average treatment time 19±13 months. 52 patients (16%) stopped SCIT: 54% female; mean age 30±9 years; average treatment time 12±6 months; 67% dropped the treatment during the 1 st year, 27% in the 2 nd and 6% during the 3rd year of treatment. Adherence rate determined was 77%. The most frequent reasons for withdrawal were due to economic reasons (47.9%), followed by patients' perception of no clinical improvement (23%) and change to sublingual immunotherapy (11.6%). Conclusion: Adherence rate in our study was 77%. Economic reasons were the main cause of abandonment in the first year, while the perception of non-improvement was the main reason for abandonment in subsequent years. Adequate information on SCIT prescribing and rigorous monitoring of patients during the treatment can improve adherence.

Chlorhexidine is a commonly used antiseptic and disinfectant in the health-care setting. Anaphylaxis to chlorhexidine is a rare but potentially life-threatening complication. Epidemiologic data suggest that the cases of chlorhexidine allergy appears to be increasing. In this article we report a life-threatening anaphylactic shock with cardiorespiratory arrest, during urethral catheterization due to chlorhexidine. The authors also performed a literature review of PubMed library of anaphylactic cases reports due to this antiseptic between 2014 and 2018, demonstrating the increase in the number of cases occurring worldwide and the importance of detailed anamnesis and appropriate diagnostic workup of allergic reactions to disinfectants.

Systemic reactions to bee stings are potentially fatal in bee venom (BV)-allergic patients (1). Although not always known by doctors of other specialties and namely by emergency physicians (2), immunotherapy with bee venom (bVIT) is a well established therapy that has been shown to improve the quality of life of patients with systemic reactions (3) and, more importantly, prevent lifethreatening reactions following an accidental sting (4). Accepted criteria for starting bVIT are the presence of a systemic reaction following a bee sting together with a certain degree of probability of the patient being stung again, along with the unequivocal demonstration of a IgE-mediated reaction to bee venom either by skin tests or serum specific IgE to whole BV extracts. The availability of component resolved diagnosis allowed the identification of major species-specific allergens, which can contribute to more accurate diagnosis in some patients (5). In recent years recombinant BV allergens, such as Api m4, have been suggested to be associated with a higher frequency of adverse reaction to bVIT (6) or with lesser effectiveness of bVIT, such as Api m10 (7). Api m10 is a major BV allergen, being recognized by more than 50% of BV allergic patients of different populations (8,9) and inclusively in some patients that are negative to Api m1. In an unselected population of BV allergic patients followed in our Hospital, positivity to Api m10 was present in 70%, being second only to Api m1 (positive in 86%) (9). Since it has been reported that several bVIT extracts lack Api m10 or have this allergen only in very small quantities (10), the predominance of Api m10 sensitization has been proposed as a possible predictive marker of bVIT failure (7). Significant differences in Api m10 concentrations between different manufacturers and, in one case, significant differences between batches of the same manufacturer have been reported (7,11). These reports suggest differences in the quality of therapeutic BV extracts, which could also be related to different manufacturing processes, a fact that might be of major importance at least for patients with particular sensitization profiles (11).

Introduction: Severe systemic reactions (SR) to allergen subcutaneous immunotherapy (SCIT) are rare but local reactions (LR) are common. We aimed to characterize the type of reactions and safety profile.Methods: Retrospective analysis of medical record from patients under SCIT between 2013- 2016.Results: Total of 7372 SCIT injections in 323 patients: 52% female; mean age 30 years(SD 13); mean treatment time 19 months(SD 13). There were 57 patients (17.6% of population, 70% female) with at least one adverse reaction, for 93 reactions described(1.3% injections). There were 79 LR(1.1% injections) in 46(14.2%) patients: 36 in build-up, 43 in maintenance. There were 14 SR(0.19% injections) in 12(3.7%) patients: 12 in build-up, 2 in maintenance. All SR were grade 1. The majority of reactions were caused by mite SCIT(69.9%). Conclusion:SCIT is safe and well tolerated, with no report of SR grade>1.

Table of contentsOral AbstractsO1 Functionally distinct HMGB1 isoforms correlate with physiological processes in drug-induced SJS/TENDaniel F. Carr, Wen-Hung Chung, Rosalind E. Jenkiins, Mas Chaponda, Gospel Nwikue, Elena M. Cornejo Castro, Daniel J. Antoine, Munir PirmohamedO2 Hypersensitivity reactions to beta-lactams, does the t cell recognition pattern influence the clinical picture?Natascha Wuillemin, Dolores Dina, Klara K. Eriksson, Daniel YerlyO3 Specific binding characteristics of HLA alleles associated with nevirapine hypersensitivityRebecca Pavlos, Elizabeth Mckinnin, David Ostrov, Bjoern Peters, Soren Buus, David Koelle, Abha Chopra, Craig Rive, Alec Redwood, Susana Restrepo, Austin Bracey, Jing Yuan, Silvana Gaudieri, Mary Carrington, David Haas, Simon Mallal, Elizabeth PhillipsO4 Do we need to measure total ige for the interpretation of analytical results of ImmunoCAP dnd 3gAllergy specific IgE?Douwe De Boer, Paul Menheere, Chris Nieuwhof, Judith BonsO5 Neutrophil activation in systemic anaphylaxis: results from the multicentric NASA studyFriederike Jonsson, Luc De Chaisemartin, Vanessa Granger, Caitlin Gillis, Aurelie Gouel, Catherine Neukirch, Fadia Dib, Pascale Roland Nicaise, Dan Longrois, Florence Tubach, Sylvie Martin, Pierre Bruhns, NASA Study GroupO6 Purpuric drug eruptions due to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for non-small-cell lung cancer (NSCLC): a clinic-pathological study of 32 casesKai-Lung Chen, Shu-Ling Liao, Yi-Shuan Sheen, Yung-Tsu Cho, Che-Wen Yang, Jau-Yu Liau, Chia-Yu ChuPoster presentations: Poster Walk 1—Anaphylaxis (P01–P09)P1 Anaphylactic reactions during anaesthesia and the perioperative periodRita Aguiar, Anabela Lopes, Natália Fernandes, Leonor Viegas, M. A. Pereira-BarbosaP2 Anaphylaxis to chlorhexidine: is there a cross-reactivity to alexidine?Antonia Bünter, Nisha Gupta, Tatjana Pecaric Petkovic, Nicole Wirth, Werner J. Pichler, Oliver HausmannP3 Cefotaxime-induced severe anaphylaxis in a neonateMehtap Yazicioglu, Pinar G. Ozdemir, Gokce Ciplak, Ozkan KayaP4 Clinical features and diagnosis of anaphylaxis resulting from exposure to chlorhexidinePeter John CookeP5 Drug-induced anaphylaxis: five-year single-center surveyInês Mota, Ângela Gaspar, Filipe Benito-Garcia, Marta Chambel, Mário Morais-AlmeidaP6 Intraoperative severe anaphylactic reaction due to patent blue v dyeLuis Marques, Eva Alcoceba, Silvia LaraP7 Kounis syndrome in the setting of anaphylaxis to diclofenacLeonor Carneiro-Leão, Carmen Botelho, Eunice Dias-Castro, Josefina CernadasP8 Perioperative anaphylaxis audit: Royal Melbourne HospitalKatherine Nicholls, William Lay, Olivia Smith, Christine Collins, Gary Unglik, Kymble Spriggs, Priscilla Auyeung, Jeremy McComish, Jo A. DouglassP9 Recurrent peri-operative anaphylaxis: a perfect stormJonny G. Peter, Paul PotterPoster Walk 2: DH regions and patient groups (P10–P19)P10 A rare presentation of amoxicillin allergy in a young childFabrícia Carolino, Eunice Dias De Castro, Josefina R. CernadasP11 Adverse drug reactions in ...

Background: Delayed food anaphylaxis upon consumption of red meat is attributed to specific IgE-antibodies directed to galactose-α-1,3-galactose (α-Gal). Anaphylactic reactions may occur after ingestion of meat from different mammals, mainly beef and pork, but reactions to lamb, rabbit or horse have also been reported. In particular, pork kidney has been shown to trigger symptoms that were more severe and occurred within a shorter delay. The objective of the present study was the identification and characterization of pork kidney proteins carrying α-Gal carbohydrates and mediating delayed allergic reactions through specific IgE to α-Gal. Materials and methods: A cohort of 59 patients with specific IgE to α-Gal was screened by immunoblot for IgE-reactive proteins in pork kidney extract. Proteins were purified by affinity chromatography and identified by Edman sequencing and peptide mass fingerprinting. Isolated proteins were used in immunoassays using patient sera and α-Gal specific antibodies. Allergenicity was assayed in basophil activation and skin prick test. Results: Multiple IgE-binding proteins were detected in protein extracts of pork kidney by immunoblot using patient sera and an anti-α-Gal antibody. Reactive bands were located in the high molecular weight range of 100 to ≥200 kDa. Two major IgE-binding proteins were identified as porcine angiotensin I converting enzyme (ACE I) and aminopeptidase N (AP-N). IgE-binding to both proteins was lost by periodate treatment, resulting in oxidation of carbohydrates. Addition of α-Gal inhibited IgE-reactivity to both peptidases. Allergenicity was confirmed by activation of patient basophils and positive skin prick tests. Conclusions: Two IgE-reactive cell membrane peptidases carrying α-Gal epitopes were identified in pork kidney, a tissue which is known as potent inducer of red meat-induced anaphylaxis. Allergenicity and clinical relevance of these proteins were confirmed in patients with delayed anaphylaxis to red meat by skin prick test and basophil activation.