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).