Untangling the truth: User engagement with misinformation in toothache-related Facebook posts.

OBJECTIVE: Social media is a platform for sharing views on aspects of life, including oral health. This study aimed to characterize Facebook posts related to toothache information. METHODS: Two independent investigators retrieved 500 English-language posts with the highest level of interaction using CrowdTangleTM and analyzed their facticity, motivation, author's profile, content, sentiment, and type of post. Data were analysed descriptively and using Pearson's Chi-square and Mann-Whitney U tests and multiple logistic regression models. RESULTS: Most posts were produced by regular users and were not financially motivated, although commercial posts had significantly higher total interaction among users. While link- or video-containing posts (OR = 1.66) and posts with positive sentiments (OR = 1.53) were associated with users' total interaction, older (OR = 1.81) and link- or video-containing posts (OR = 2.04) were associated with overperforming scores. Misinformation was positively associated with financial motivation (OR = 2.03) and positive sentiments (OR = 3.79). CONCLUSION: This study highlights the importance of addressing the spread of misinformation related to oral health on social media and taking steps to ensure that accurate and reliable information is readily available. Toothache-related misinformation was associated with positive sentiments and financial motivation. Links, videos, and positive sentiments awakened greater user engagements with toothache-related posts.

Why is Pet (cat/dog) allergen immunotherapy (ait) such a controversial topic? current perspectives and future directions.

Summary: Dogs and cats are the most common pets worldwide. In Italy, the prevalence of allergic sensitization to cats and dogs is 16% and 9% respectively. The limited standardization of allergenic extracts, especially for dogs, emphasizes the importance of Component Resolved Diagnosis (CRD) for accurate diagnosis and subsequent prescription of allergen immunotherapy (AIT). However, this low standardization is the main factor contributing to the unsatisfactory clinical efficacy of traditional AIT, AIT with modified allergens, and intralymphatic allergen-specific immunotherapy (ILAIT). Emerging immunological approaches, particularly for controlling the primary cat allergen, show promise but are hindered by high costs (e.g., use of anti-Fel d 1 monoclonal antibodies in humans) or by exclusively targeting Fel d 1 produced by one's own animal (e.g., immunizing cats to induce neutralizing antibodies against Fel d 1 or including an egg product with anti Fel d 1 IgY antibodies in feline diet). Further studies are imperative for standardizing pet allergens, enhancing the efficacy of various AIT modalities, and exploring other immunological approaches, to optimize the relationship between pets and their owners and prevent distressing "forced removals."

Biophysical Analysis to Assess the Interaction of CRAC and CARC Motif Peptides of Alpha Hemolysin of Escherichia coli with Membranes.

Alpha hemolysin of Escherichia coli (HlyA) is a pore-forming protein, which is a prototype of the "Repeat in Toxins" (RTX) family. It was demonstrated that HlyA-cholesterol interaction facilitates the insertion of the toxin into membranes. Putative cholesterol-binding sites, called cholesterol recognition/amino acid consensus (CRAC), and CARC (analogous to CRAC but with the opposite orientation) were identified in the HlyA sequence. In this context, two peptides were synthesized, one derived from a CARC site from the insertion domain of the toxin (residues 341-353) (PEP 1) and the other one from a CRAC site from the domain between the acylated lysines (residues 639-644) (PEP 2), to study their role in the interaction of HlyA with membranes. The interaction of peptides with membranes of different lipid compositions (pure POPC and POPC/Cho of 4:1 and 2:1 molar ratios) was analyzed by surface plasmon resonance and molecular dynamics simulations. Results demonstrate that both peptides interact preferentially with Cho-containing membranes, although PEP 2 presents a lower KD than PEP 1. Molecular dynamics simulation results indicate that the insertion and interaction of PEP 2 with Cho-containing membranes are more prominent than those caused by PEP 1. The hemolytic activity of HlyA in the presence of peptides indicates that PEP 2 was the only one that inhibits HlyA activity, interfering in the binding between the toxin and cholesterol.

Sterol, tocopherol, and bioactive fatty acid differences between conventional, high-quality, and organic cow milk.

Milk contains several components that are important for human nutrition and health. To date, studies on organic and conventional milk have focused on their gross composition and fatty acid content, but little attention has been paid to the differences between other minor components, such as sterols and vitamins that may have functional actions. The aim of this study was to investigate the nutritional differences among 3 types of milk from a dairy plant: conventional, high-quality, and organic (in compliance with European regulations) milk, focusing on minor components such as sterols of animal and plant origin (phytosterols), tocopherols, and bioactive fatty acids. Cholesterol ranged from 271.37 mg/100 g of fat in conventional milk to 278.76 mg/100 g of fat in organic milk. Lanosterol was the main minor animal sterol in cow milk (ranging from 3.41 to 4.37 mg/100 g of fat), followed by desmosterol. The amount of total plant sterols in the analyzed milk ranged from 4.43 mg/100 g of fat in organic to 4.71 mg/100 g of fat in high-quality milk. Brassicasterol was the main sterol of plant origin which varied from 2.6 mg/100 g of fat in conventional and organic milk, to 2.93 mg/100 g of fat in high-quality milk. The second most present phytosterol was ß-sitosterol, which ranged from 0.86 mg/100 g of fat in conventional to 0.97 mg/100 g of fat in high-quality, and organic milk. The results of the study showed no significant differences in gross and sterol composition between the 3 types of milk. However, the only significant difference found was in the fatty acid profile, with a higher n-3 content found in high-quality milk than in conventional and organic milk. These findings suggest that the investigated product categories and labels have minimal effect on the sterol and fatty acid profile of commercial cow milk.

COVID-19 lockdown, personal protective equipment, hyper-hygiene and allergy.

Summary: At the beginning of SARS-CoV 2 pandemic, in the absence of "targeted" therapies, the national health authorities have introduced some measures aimed at reducing the spread of infection in the community (lockdown, social distancing, personal protective equipment (PPE), personal hygiene and disinfection of living environments). All the containment measures have led to both positive and negative effects in patients with allergic diseases. We believe that further studies should be undertaken to investigate the possible correlations between SARS-CoV-2 infection and allergy, from a broader perspective. In particular, the risk factors for the development of undesirable effects should be investigated, especially in healthcare professionals forced to use PPE and sanitizing agents for a long time. However, since the COVID-19 pandemic probably will not be short-lived, the use of such protective aids will necessarily be widespread even in the general population. Therefore, further studies on the materials used for the production of PPE and sanitizing agents would be necessary to reduce their sensitizing and, in some cases, toxic potential.

Severe asthma: follow-up after one year from the Italian Registry on Severe Asthma (IRSA)

Summary: Background. Asthma affects millions of people worldwide, with a subgroup suffering from severe asthma (SA). Biologics have revolutionized SA treatment, but challenges remain in managing different patient traits. This study analyzed data from the Italian Registry on Severe Asthma (IRSA) to investigate changes in SA characteristics and effectiveness of treatments after one year of follow-up, and to identify factors associated with response to treatments in a real-world setting. Methods. Data on SA patients with one year of follow-up were extracted from IRSA. Asthma control, exacerbations, lung function, and treatments, were assessed at follow-up and analyzed against baseline characteristics. Results. After one year of follow-up, notable improvements were observed in all the outcomes of SA of the included patients (n = 570). The effectiveness of biologic therapies was particularly evident, as they contributed significantly to these positive outcomes. Additionally, certain factors were found to be associated with improvement, namely T2 phenotype, baseline eosinophil count (BEC), and area of residence. On the other hand, comorbidities (obesity, gastro-esophageal reflux disease) and poor lung function were risk factors. Notably, poor-responders to biologics exhibited lower level of education, BEC, and exacerbations, and higher frequency of atopy and ACT score ≥ 20. Conclusions. The findings demonstrate the effectiveness of biologics in asthma management, when implemented as part of a planned follow-up strategy aimed at optimizing and fine-tuning the therapy. Moreover, the study highlights the importance of considering key traits such as the T2 phenotype, BEC, education, and comorbidities when tailoring SA treatment. Overall, this study contributes to enhancing our understanding of SA management and guiding the development of personalized treatment approaches for patients with SA.

Smallpox vaccination and vaccine hesitancy in the Kingdom of the Two Sicilies (1801) and the great modernity of Ferdinand IV of Bourbon: a glimpse of the past in the era of the SARS-COV-2 (COVID-19) pandemic.

OBJECTIVE: The current health emergency caused by COVID-19 disease shows several correspondences with well-known epidemics of the past. The knowledge of their management and overcoming could give us useful tools to face the present COVID-19 pandemic and future epidemics. STUDY DESIGN: On 1 March 1801, the first smallpox vaccinations were carried out in Palermo, and a few weeks later, the vaccine was also administered in Naples and the various provinces of the Kingdom. We aim to study the mass vaccination programme initiated by the Bourbon king Ferdinand IV that was the first large-scale campaign to be conducted in Italy and one of the first in Europe. METHODS: The authors searched and examined historical testimony and different aspects linked to the public health issues on vaccination. It is a topical topic in the current period with the COVID pandemic. RESULTS: Albeit with the due differences determined by the passage of time and by the scientific and cultural advances of modern society, this testimony from the past can provide us with food for thought regarding how to face the present COVID-19 pandemic and to prepare for the future. Indeed, it shows us how the terrible smallpox epidemic was handled and finally overcome, thanks to vaccination.

From triggers to asthma: a narrative review on epithelium dysfunction.

Summary: It is currently recognized that the airway epithelium plays a pivotal role in orchestrating inflammatory, immune, and regenerative responses to allergens, viruses and environmental pollutants that contribute to asthma pathogenesis. The impact of pollen on respiratory epithelium is multifaceted and goes beyond the direct barrier damage driven by the best-known Type-2 response. After pollen-driven activation, airway epithelial cells play an active role in triggering several pathways. In particular, the release of epithelial cytokines (or alarmins) activates both innate and adaptive immunity, with downstream effects implicated to the pathogenesis of asthma. Pollutants also have a pleiotropic effect on respiratory epithelium. Diesel exhaust particles can directly damage the respiratory epithelium with consequent barrier dysfunction, increased permeability, and local inflammation, but they can also activate Th2 responses. Innate immune responses also are triggered by pollutants through release of epithelial cytokines and redox-sensitive pathways that generate mechanical and immunologic changes in the respiratory epithelium. In addition to the typical Type-1 immune response, respiratory virus infections stimulate type-2 innate lymphoid cells in the airway epithelium to release epithelial cytokines. Finally, the action of epithelial triggers on airway smooth muscle is the central element in the induction of remodeling and hyperreactivity of the airways in asthma. This article reviews the pathophysiology and functions of the airway epithelium and the role of epithelial damage by different triggers in the development, persistence, and exacerbations of asthma.

Lessons from peculiar cases of anaphylaxis: why allergists should be prepared for the unexpected.

Summary: Anaphylaxis is the most severe systemic hypersensitivity reaction, it can be caused by a number of well identified triggers such as foods, drugs, stinging insects and facilitated by predisposing clinical conditions. However, sometimes anaphylaxis shows up with uncommon or peculiar characteristics which could delay diagnosis and therapeutic treatment. In this report we aimed to describe less accounted / difficult-to-approach shapes of anaphylaxis to facilitate clinicians to suspect these severe reactions even in uncommon conditions. We choose to present data on anaphylaxis regarding simulation, mode of exposure to sensitizing agents, pregnancy, exposure to animals, intimate behaviour, psychological stress and other situations.

Sensitization to Gibberellin-Regulated Protein (Peamaclein) Among Italian Cypress Pollen-Sensitized Patients.

BACKGROUND AND OBJECTIVES: Peach gibberellin-regulated protein (peamaclein) has recently emerged as a relevant food allergen in cypress pollen-hypersensitive patients. Objective: We investigated monosensitization to peamaclein among Italian cypress pollen-allergic patients. MATERIAL AND METHODS: A total of 835 cypress pollen-hypersensitive patients from 28 Italian allergy centers underwent a thorough work-up to determine food-allergic reactions and performed skin prick testing with a commercial peach extract containing peamaclein. IgE to rPru p 3 was measured in peach reactors, and those with negative results were enrolled as potentially monosensitized to peamaclein. IgE reactivity to rPru p 7 was evaluated using immunoblot and an experimental ImmunoCAP with rPru p 7. RESULTS: Skin prick tests were positive to peach in 163 patients (19.5%); however, 127 (77.9%) were excluded because they reacted to Pru p 3. Twenty-four patients (14.7%) corresponding to 2.8% of the entire study population) were considered potentially monosensitized to peamaclein. No geographic preference was observed. Seventeen of the 24 patients (70.8%) had a history of food allergy, mainly to peach (n=15). Additional offending foods included other Rosaceae, citrus fruits, fig, melon, tree nuts, and kiwi. On peach immunoblot, only 3 of 18 putative peamaclein-allergic patients reacted to a band at about 7 kDa; an additional 4 patients reacted at about 50-60 kDa. Ten of 18 patients (56%) had a positive result for Pru p 7 on ImmunoCAP. CONCLUSION: Allergy and sensitization to peamaclein seem rare in Italy. Most patients react to peach, although other Rosaceae fruits and several citrus fruits may also be offending foods. Peach and cypress pollen probably also share cross-reacting allergens other than peamaclein.

A preliminary investigation into the unsaponifiable fraction of donkey milk: Sterols of animal origin, phytosterols, and tocopherols.

We investigated the main sterols, phytosterols, and the α- and γ-tocopherol content in donkey milk during the first 2 mo of lactation. Cholesterol was the main sterol in milk (mean ± standard deviation = 0.97 ± 0.443 g/100 g of fat). Lanosterol was the main minor sterol of animal origin, followed by desmosterol (0.003 ± 0.001 and 0.001 ± 0.001 g/100 g of fat, respectively). Of the phytosterols, ß-sitosterol was the main sterol of vegetal origin in donkey milk (0.005 ± 0.002 g/100 g of fat), but lower levels of campesterol, brassicasterol, and stigmasterol were also recorded. Mean levels of α- and γ-tocopherol were 0.01 ± 0.007 and 0.003 ± 0.001 g/100 g of fat, respectively. We observed no significant changes in sterol or tocopherol content during the first 2 mo of lactation. The presence of lanosterol in donkey milk is of particular interest, because lanosterol is a potential drug and has important physiological effects. The presence of phytosterols, which are considered nutraceutical molecules, enhances the nutritional quality of donkey milk fat for consumers.

Pathogenicity of Phytopythium chamaehyphon: A New Player in Kiwifruit Vine Decline Syndrome of Actinidia chinensis var. deliciosa 'Hayward' in Italy.

Kiwifruit vine decline syndrome (KVDS) is a serious soil-borne disease that degrades the fine roots of both Actinidia chinensis var. deliciosa and var. chinensis. The disease seems to be the result of an interaction between several soil-borne pathogens, mostly oomycetes, and waterlogging. This work investigates the pathogenicity of the oomycete Phytopythium chamaehyphon recently isolated from roots of diseased plants. Pathogenicity was tested in 6-month-old and 1-year-old plants that, after inoculation, were flooded up to three times to induce symptom appearance. Leaf wilting and root rot typical of KVDS was observed in all the plants inoculated with P. chamaehyphon strain KD-15 (PCHA) and in all the positive controls potted in a mix of peat and soils collected in KVDS-affected orchards, while negative controls remained symptomless. Disease development on 6-month-old plants was characterized by unusual degradation of the not-lignified collar, occurring even in absence of flooding. Conversely, on 1-year-old plants, symptoms faithfully reproduced KVDS dynamics observed in orchard. This work confirmed the pathogenicity of P. chamaehyphon and raised new questions about the actual role of waterlogging in KVDS etiology.

Anaphylaxis.

Summary: Anaphylaxis is the most severe systemic hypersensitivity reaction, and it can be life-threatening or even fatal. It involves the activation of multiple immune and non immune pathways beyond IgE, thus exhibiting different phenotypes. New symptoms of hypersensitivity caused by chemotherapy drugs, monoclonal antibodies, and biological agents have been suggested to be recognized as anaphylaxis phenotypes. No biomarker has been described that allows an unequivocal diagnosis of anaphylaxis. Moreover, more biomarkers for specific endotypes are needed to stratify severity, to predict risk, and to optimaze tretament choice in the individual patient. Food, drugs and stinging insects represent the most commly identified triggers. Idiopathic anaphylaxis is a diagnosis of exclusion and it can hide a clonal mast cell disorder. Individual risk factors and co-factors may influence the severity of anaphylaxis or its onset, and they should be identified to implement the appropriate measures to prevent recurrence. Prompt recognition and treatment are critical in anaphylaxis, adrenaline being the first-line saving therapy. Individualized anaphylaxis action plan should include avoidance measures, prescription of an adrenaline autoinjector, education, optimal management of relevant comorbidities, venom specific immunotherapy, food oral immunotherapy, and drug desensitization, when appropriate. However, the quality of acute and long-term anaphylaxis management is variable influencing the poor outcomes experienced by many patients. Clinical practice guidelines have the potential to improve outcomes, but they often prove challenging to implement in routine clinical care.

Differential Stability of Aurein 1.2 Pores in Model Membranes of Two Probiotic Strains.

Aurein 1.2 is an antimicrobial peptide from the skin secretion of an Australian frog. In the previous experimental work, we reported a differential action of aurein 1.2 on two probiotic strains Lactobacillus delbrueckii subsp. bulgaricus (CIDCA 331) and Lactobacillus delbrueckii subsp. lactis (CIDCA 133). The differences found were attributed to the bilayer compositions. Cell cultures and CIDCA 331-derived liposomes showed higher susceptibility than the ones derived from the CIDCA 133 strain, leading to content leakage and structural disruption. Here, we used molecular dynamics simulations to explore these systems at the atomistic level. We hypothesize that if the antimicrobial peptides organized themselves to form a pore, it will be more stable in membranes that emulate the CIDCA 331 strain than in those of the CIDCA 133 strain. To test this hypothesis, we simulated preassembled aurein 1.2 pores embedded into bilayer models that emulate the two probiotic strains. It was found that the general behavior of the systems depends on the composition of the membrane rather than the preassemble system characteristics. Overall, it was observed that aurein 1.2 pores are more stable in the CIDCA 331 model membranes. This fact coincides with the high susceptibility of this strain against antimicrobial peptide. In contrast, in the case of the CIDCA 133 model membranes, peptides migrate to the water-lipid interphase, the pore shrinks, and the transport of water through the pore is reduced. The tendency of glycolipids to make hydrogen bonds with peptides destabilizes the pore structures. This feature is observed to a lesser extent in CIDCA 331 due to the presence of anionic lipids. Glycolipid transverse diffusion (flip-flop) between monolayers occurs in the pore surface region in all the cases considered. These findings expand our understanding of the antimicrobial peptide resistance properties of probiotic strains.

Evaluation of PD1 and PD-L1 expression in high-grade sarcomas of the limbs in the adults: possible implications of immunotherapy.

Sarcomas are a heterogeneous group of rare tumours. Improvements in immunotherapy and the important role of PD1 and PD-L1 expression in advancement and prognosis have opened new fields of research for the treatment of these neoplasia. We evaluated the immunohistochemistry of PD1 and PD-L1 expression in 60 adults' patients affected by high-grade sarcomas of the limbs. PD1 expression was 65% while PD-L1 was 68.3%. PD-L1 expression seems to correlate to Ki67 in liposarcomas, fibrosarcoma's and pleomorphic sarcomas, while it does not show any correlation to chondrosarcomas, while in rhabdomyosarcomas there is a correlation but, given the small sample size, it was not possible to perform a statistic analysis. Our study shows positivity among the different subgroups of positive PD1 lymphocytes infiltration and PD-L1 expression in high-grade sarcomas of the limbs.

[Hypoglossal nerve palsy after follicle puncture]. / Hypoglossusparese nach Follikelpunktion.

A 42-year-old female patient suffered an infranuclear hypoglossal nerve paresis with right-sided swelling and weakness of the tongue following a short duration mask anesthesia for a follicle puncture. This resulted in dysarthria and dysphagia persisting for more than 3 months. A return to work was initially impossible. Etiopathogenetically, a mechanical compression of the peripheral hypoglossal nerve by positioning or reclination during mask ventilation is discussed. Conclusion for clinical practice: In order to protect against lesions of the hypoglossal nerve, the pre-anaesthesiological examination should ask specifically about cervical problems as an indication of individual sensitivity to reclination. In such cases, special attention should be paid to careful patient positioning. Even shorter periods of reclination or compression of the soft tissues of the neck can result in lesions, therefore tolls such as a Wendl or Guedel tube should be used accordingly.

[Deodorants and antiperspirants]. / Déodorants et antitranspirants.

The terms deodorants and antiperspirants very frequently used interchangeably despite the fact that they employ completely different active substances and mechanisms of action. Antiperspirants are necessarily deodorants due to the lack of substrate to decompose. They nevertheless represent a group of very specific substances that create particular problems due to the presence of aluminium chlorohydrate, or ACH, (Al2(OH)5Cl, 2H2O), aluminium sesquichlorohydrate and aluminium-zirconium complex, which, after hydrolysis, causes intense acidification of the skin, hence the importance of inclusion of emollients and pH regulators in formulations. Moreover, systemic aluminium is thought to be genotoxic and to promote breast cancer, and it is thus at the centre of numerous scientific controversies. Nevertheless, its potential toxicity following topical application is related to its ability to penetrate skin, which is as yet poorly understood but considered very low, a fact that may provide some degree of reassurance regarding its use in cosmetic products. Its role in Alzheimer's disease has not been proven. On the other hand, zirconium salts are considered toxic and are partly regulated in Europe. The problems associated with deodorants are those arising from the presence of antiseptics (triclosan, usnic acid) capable of inducing bacterial resistance, but more particularly, the presence of axillary dermatitis due to the allergenic potential of the fragrances and essential oils used (e.g. isoeugenol, citronellal, lyral, cinnamic aldehyde, etc.).

Frozen section accurately allows pathological characterization of endometrial cancer in patients with a preoperative ambiguous or inconclusive diagnoses: our experience.

BACKGROUND: The aim of this study was to assess the agreement rate between intraoperative evaluation (IOE) and final diagnosis (FD) in a series of surgically resected endometrial carcinoma (EC), with a preoperative ambiguous or inconclusive diagnosis by endometrial biopsies and imaging. METHODS: A retrospective study was performed selecting patients who underwent surgery with IOE for suspected EC at our institution from 2012 to 2018. A K coefficient was determined with respect to the histotype, tumor grade, myometrial infiltration and cervical involvement. RESULTS: Data analysis has been performed on 202 women. The IOE evaluation was distributed as Endometrioid (n = 180) and Non-Endometrioid (n = 22). The comparison between the frozen section (FS) and the definitive histological subtype showed an overall agreement rate of 93,07% (k = 0.612) and an agreement of 97.2% for Endometrioid vs 59% for Non-Endometrioid tumors. The FIGO system grading was the same in 91,1% of patients, none was upgraded and in 8,9% downgraded. Observed agreements were 89,11% and 95,54% for myometrial and cervical involvement, respectively. CONCLUSIONS: The good agreement between intraoperative grading, myometrial invasion and their histological definition on permanent sections highlights that FS is a good predictor for surgical outcome, in particular in presence of a preoperative ambiguous or inconclusive diagnostic evaluation.

Evaluation of quinoxaline compounds as ligands of a site adjacent to S2 (AS2) of cruzain.

The binding of ten quinoxaline compounds (1-10) to a site adjacent to S2 (AS2) of cruzain (CRZ) was evaluated by a protocol that include a first analysis through docking experiments followed by a second analysis using the Molecular Mechanics-Poisson-Boltzmann Surface Area method (MM-PBSA). Through them we demonstrated that quinoxaline compounds bearing substituents of different sizes at positions 3 or 4 of the heterocyclic ring might interact with the AS2, particularly interesting site for drug design. These compounds showed docking scores (ΔGdock) which were similar to those estimated for inhibitors that bind to the enzyme through non-covalent interactions. Nevertheless, the free binding energies (ΔG) values estimated by MM-PBSA indicated that the derivatives 8-10, which bear bulky substituents at position 3 of the heterocycle ring, became detached from the binding site under a dynamic study. Surprisingly, the evaluation of the inhibitory activity of cruzipain (CZ) of some derivatives showed that they increase the enzymatic activity. These results lead us to conclude about the relevance of AS2 as a pocket for compounds binding site, but not necessarily for the design of anti-chagasic compounds.

Clinical aspects of hymenoptera venom allergy and venom immunotherapy.

Summary: Hymenoptera venom allergy (HVA) is the most frequent cause of anaphylaxis in Europe, accounting for most of the severe reactions occurring in adults, and being the second cause of anaphylaxis in children. Prevention of further episodes in patients who developed a systemic reaction (SR) is based on the correct management of the allergic emergency, the referral to an allergist for a correct diagnosis, prescription of adrenaline auto-injectors (AAI) and specific venom immunotherapy (VIT), if recommended. Diagnosis is based on the classification of the type of reaction, confirmation of an IgE-mediated pathogenesis and the identification of the offending insect. The use of component resolved diagnostics may be helpful in case of poly-sensitization or negative allergy tests with a proven history of previous SRs. When a severe SR occurs, baseline serum tryptase levels should always be assessed. The prescription of AAI is recommended or suggested for untreated patients, patients undergoing VIT and after discontinuation of treatment, according to multiple evidence. VIT is the most effective treatment available for HVA patients, as confirmed by recent European guidelines. VIT has an early, sustained and persistent protective effect and modifies the natural course of the disease. Moreover, VIT proved to be safe and well tolerated. According to a recent systematic review, no treatment-related fatalities were recorded to date. Compared to AAI, VIT significantly improves the quality of life of HVA patients by reducing the anxiety and limitations in daily activities caused by the fear of stinging insects. The memory of a life-threatening experience is the most likely reason why adherence to VIT is higher compared to immunotherapy with inhalant allergens. Several risk factors in HVA have been identified that can influence not only the severity of sting reactions in untreated patents, but also the occurrence of side effects, treatment effectiveness and the risk of relapse after discontinuation of VIT. Patient and treatment-related risk factors must be considered while selecting the best candidates for VIT, the type and duration of treatment. In this paper we address the most important issues related to HVA and VIT that may have an impact on daily clinical practice.