360° approach to the patient with mite allergy: from scientific evidence to clinical practice.

In the recent years, several important advances have been made in the diagnosis of allergy using molecular techniques. The aetiological diagnosis of allergy using molecular components of allergens allows a more precise definition of the patient's IgE repertoire. Precision medicine is a structural model aimed at personalising healthcare and places the patient at the centre of the specialist's decision-making process. To this end, an accurate characterisation of the external exposome at a molecular level and their putative role as clinically relevant allergens is essential to elucidate the phenotypic diversity of atopic disease, with a view to personalising diagnosis and therapy. It has been proposed a decision algorithm, the Top-Down approach, where the clinical history is set first and is followed by the use of skin tests or specific IgE techniques, which facilitates the clinicians to make decisions. The therapeutic intervention driven by the standard diagnostic approach, but supported by these innovative tools, can lead to a better phenotyping of highly complex patients, and a more appropriate prescription of AIT. To this end, the allergen extracts used for diagnosis require to be of proven quality and contain the most relevant allergens. Likewise, allergen vaccines must gather efficacy, safety, duration, and patient compliance, hence the demand for new vaccines to overcome these drawbacks.

Quality of Life of Allergic Dogs Treated with Allergen-Specific Immunotherapy-A Retrospective Study.

BACKGROUND: The quality of life (QoL) of dogs with canine atopic dermatitis (CAD) treated with allergen-specific immunotherapy (ASIT) was studied to determine whether the QoL of dogs treated with ASIT (AG) improved compared with dogs not treated with ASIT (CG). METHODS: The power of the study was calculated in advance assuming that the AG would assess QoL 20% better than the CG. The CG consisted of 21 dogs with CAD and the AG of 46 dogs with CAD. Validated QoL1 (pre-treatment) and QoL2 (post-treatment) questionnaires were emailed to owners. RESULTS: AG dogs were significantly less disturbed during mealtimes (i.e., had better appetites and scratched less during mealtimes) and caused significantly less physical discomfort to their owners (due to unpleasant odor, the impression of a dirty apartment) than CG dogs. Owners of dogs treated with ASIT were able to significantly improve their daily activities (leisure, vacation, walks, work, hunting), significantly reduce their expenses (treatment costs, veterinary costs), feel significantly less emotional distress (less guilt, powerlessness, sadness, regret, fear, anger, disgust, rage, frustration), and experience less influence on relationships with family members and friends compared to owners of dogs not treated with ASIT. CONCLUSIONS: According to our results, the quality of life of dogs treated with ASIT and their owners seemed to improve significantly.

Role of microRNAs in type 2 diseases and allergen-specific immunotherapy.

MicroRNAs (miRs) have gained scientific attention due to their importance in the pathophysiology of allergic diseases as well as their potential as biomarkers in allergen-specific treatment options. Their function as post-transcriptional regulators, controlling various cellular processes, is of high importance since any single miR can target multiple mRNAs, often within the same signalling pathway. MiRs can alter dysregulated expression of certain cellular responses and contribute to or cause, but in some cases prevent or repress, the development of various diseases. In this review article, we describe current research on the role of specific miRs in regulating immune responses in epithelial cells and specialized immune cells in response to various stimuli, in allergic diseases, and regulation in the therapeutic approach of allergen-specific immunotherapy (AIT). Despite the fact that AIT has been used successfully as a causative treatment option since more than a century, very little is known about the mechanisms of regulation and its connections with microRNAs. In order to fill this gap, this review aims to provide an overview of the current knowledge.

Long-term clinical course and prognosis of vaccine-related persistent itching nodules (1997-2019): An observational study.

Background: Vaccines adsorbed to aluminium can induce long-lasting intensely itching subcutaneous nodules (granulomas) at the injection site as well as contact allergy to aluminium. In clinical trials of a new acellular pertussis vaccine performed in the 1990s (Gothenburg, Sweden) with 76 000 participants, itching nodules were reported in 745 children. A positive patch test to aluminium was verified in 77% of the tested children with itchy nodules. Aim: To describe the long-term clinical course and prognosis of vaccine-related itching nodules caused by aluminium-containing pediatric vaccines and to estimate the risk for new symptoms after future vaccination with aluminium-containing vaccines. Methods: 745 children with vaccine-related itching nodules were followed by regular interviews/questionnaires for more than 20 years. 723 of them received a booster dose of diphtheria/tetanus vaccine either with or without aluminium adjuvant during the follow-up time. Results: Most study participants (86%) reported a full recovery from their itching nodules after a median duration of 6.6 years. Only a few of the diphtheria/tetanus-booster-vaccinated children (3%) reported mild transient itching and swelling at the new injection site. Conclusion: Vaccine-induced itching granulomas caused by an aluminium-adsorbed acellular pertussis toxoid vaccine seem to disappear over time. Future vaccinations with aluminium-adsorbed vaccines can be performed with little risk for new itching nodules later in life.

Clinical efficiency of allergen-specific immunotherapy with fungal allergens in patients with chronic polypous rhinosinusitis against the background of fungal sensitization.

Fungal flora is one of the causes of inflammatory, including polypous, processes in the nasal cavity. In this regard, studies aimed at reducing the effect of fungal sensitization (FS) on the course of chronic polypous rhinosinusitis (CPRS) are relevant. The objective of the study was to evaluate the effect of various treatment options on the clinical course of the disease in patients with chronic polypous rhinosinusitis against the background of sensitization to fungi. The study included 90 patients with chronic polypous rhinosinusitis in combination with FS. The patients were divided into two groups - the first clinical group (G1) and the second clinical group (G2). G1 patients received allergen-specific immunotherapy (ASIT) according to the scheme. G2 patients received basic treatment. Evaluation of the clinical efficiency of ASIT was made based on complaints, assessment of symptom severity on a visual analog scale (VAS), and rhinoendoscopic examination. The treatment outcomes were evaluated on a 4-point scale, with excellent results (4 points) - complete remission of the disease during the follow-up period (6-12 months); good (3 points) - exacerbation of the disease 1-2 times a year, in mild form and removed by expectant treatment; satisfactory (2 points) - the number of exacerbations did not decrease. The use of ASIT therapy is pathogenetically justified and leads to a significant improvement in the clinical condition of patients with CPRS with FS.

Self-reported surgeon health behaviours: A multicentre, cross-sectional exploration into the modifiable factors that impact surgical performance with the association of surgeons in training.

INTRODUCTION: Surgeons regularly educate patients on health promoting behaviours including diet, sleep and exercise. No study thus far has explored surgeons' personal compliance with these health behaviours and their relationship with surgical performance. The primary outcomes of this study were self-reported health, health related behaviours, wellbeing, fatigue and surgical performance. METHODS: A survey of validated themes on health related behaviours, workplace variables and performance was distributed to surgical trainees and consultants in the UK and Ireland through the Association for Surgeons in Training (ASiT). Non-parametric analysis was used to determine inferential associations. RESULTS: Ninety five surgeons (51.5% female, 39.9% registrars) completed the survey. 94% and 74% reported 'good' or better overall health and mental wellbeing respectively. The majority (54.7%) reported inconsistent sleep patterns. Less than a quarter engage in regular exercise. Sixty two and 64.2% reported being regularly fatigued and bothered by feelings of anxiety and/or depression respectively. Poor self-reported health and wellbeing were associated with poorer reported off-call performance (p < .01). Higher levels of fatigue negatively impacted self-reported surgical and non-surgical task proficiency (p < .01). DISCUSSION AND CONCLUSION: Surgeons reported high levels of overall health. However, healthy behaviours around sleep, diet and exercise were not consistently reported. Fewer reported good mental health and emotional well-being. Self-reported health behaviours including sleep and physical activity were associated with surgical performance. Strategies to improve modifiable lifestyle factors which will optimise physical health, mental wellbeing and levels of fatigue may optimise surgical performance.

Biological drug and drug delivery-mediated immunotherapy.

The initiation and development of major inflammatory diseases, i.e., cancer, vascular inflammation, and some autoimmune diseases are closely linked to the immune system. Biologics-based immunotherapy is exerting a critical role against these diseases, whereas the usage of the immunomodulators is always limited by various factors such as susceptibility to digestion by enzymes in vivo, poor penetration across biological barriers, and rapid clearance by the reticuloendothelial system. Drug delivery strategies are potent to promote their delivery. Herein, we reviewed the potential targets for immunotherapy against the major inflammatory diseases, discussed the biologics and drug delivery systems involved in the immunotherapy, particularly highlighted the approved therapy tactics, and finally offer perspectives in this field.

Bullying and undermining behaviours in surgery: A qualitative study of surgical trainee experiences in the United Kingdom (UK) & Republic of Ireland (ROI).

BACKGROUND: Bullying and undermining (B/U) behaviours are documented in the international surgical workplace. This study is the largest assessment of prevalence of B/U behaviours within UK & ROI surgical training to date. MATERIALS AND METHODS: UK & ROI surgical trainees were electronically surveyed in July 2017. The survey was open for one month and sent to all registered trainees at Core and Specialty level by the Joint Committee on Surgical Training (JCST) along with email and social media dissemination by the Association of Surgeons in Training (ASiT) and the British Orthopaedic Trainees Association (BOTA). A consensus session on the topic was conducted at the ASiT Conference in Edinburgh in March 2018. Standards for reporting of Qualitative Research were followed. RESULTS: 1412 responses were received (26.6% response rate). All training regions, grades and specialties were represented. 60% of trainees (n = 837) reported witnessing or experiencing B/U behaviours in the surgical workplace. The most common reports related to sexism; 42% (n = 568) reported witnessing or experiencing sexist language/attitudes in the workplace. This was reported more by female respondents (66% compared to 27% male). 21% (n = 291) and 13% (n = 180) reported witnessing or personally experiencing racist and homophobic language or attitudes respectively. Consultants were identified as the most frequent perpetrators. The surgical wards or theatres were the most frequently reported areas that trainees either witnessed or experienced B/U behaviours. Of those trainees who had reported a personal experience of B/U behaviours (n = 344), 20% described their experiences of reporting as negative or very negative. 48.1% of respondents felt that surgery as a whole had a moderate, high or very high degree of a concern about B/U behaviours. CONCLUSION: B/U behaviours are prevalent in the surgical domain. Urgent action is required to eradicate this unacceptable behaviour. A cross-specialty, intercollegiate response is required to tackle this issue and improve the working culture in surgery for all.

Consensus recommendations on balancing educational opportunities and service provision in surgical training: Association of Surgeons in Training Delphi qualitative study.

BACKGROUND: Ensuring the highest quality of surgical training remains a challenge as demands on health service provision rise. This study aimed to explore the differences and potential conflicts between service provision and dedicated training activity provided by surgical trainees, and recommend solutions. METHODS: Participants were drawn from the Association of Surgeons in Training (ASiT) national council. Nominal Group Technique (NGT) was employed by members of the ASiT executive addressing 3 key domains (1) defining differences between training and service tasks, (2) impact of service-provision on training and (3) ways to improve training. A two-round Delphi process was conducted via electronic survey to ASiT council. Consensus was considered achieved for any statement where 80% or more of respondents indicated agreement. RESULTS: 47 statements were generated through NGT which were put to the Delphi process. Consensus was reached on a total of 24/47 statements. Educational or training tasks were identified as being activities which progressed a trainee's skill set, could be tailored to a trainee's own ability, and involved acting as a trainer to more junior colleagues. The negative impact of excess service provision included training quality, trainee mental health, and surgical trainee recruitment. Potential measures to improve training included increasing hospital staffing and resources, protected training times, trainee-specific or competency-based learning and training or incentivising trainers. CONCLUSION: This trainee-based study provides several consensus recommendations on the characteristics that define surgical training and how a balance between service provision and training can potentially be achieved. Policy makers and health systems may be guided by these to ensure high quality training and a satisfied workforce.

Basophil biomarkers as useful predictors for sublingual immunotherapy in allergic rhinitis.

Prevalence of allergic diseases is increasing worldwide. Allergen-specific immunotherapy (ASIT) is potentially the only curative treatment for allergy, but there is a lack of reliable methods to monitor the immune responses to ASIT and to predict clinical efficacy. Recently, the definition of allergen sensitivity threshold (CD-Sens) by Basophil Activation Tests has been suggested as potential method in this context. The aim of this study was to compare trends of CD-Sens, measured by the markers CD63 and CD203c, and clinical symptoms in subjects with allergic rhinitis receiving Sublingual Immunotherapy (SLIT). 26 rhinitis patients allergic to Parietaria were selected and matched into two groups; a SLIT treated group (SG) and a reference group (RG) treated by traditional anti-allergic medications. Visual Analogue Scale (VAS) score for the four cardinal symptoms of rhinitis and peripheral blood was collected before the first dose of SLIT (T0) and after 12 months (T12) to define the severity of the symptoms and the sensitivity of basophils to Parietaria. The comparison between T0 and T12 in SG patients showed a significant decrease of symptom severity (VAS score) and an increased tolerability of basophils to Parietaria (CD-Sens) both by CD63 and CD203c. But, only CD203c seems to be correlated with the clinical symptoms. These data corroborate the hypothesis that SLIT could change the immunological course of allergic sensitization already in the first year, and that an immunological parameter as CD-Sens measured by CD63 and CD203c expression on stimulated basophils could be useful to monitor the changes in the immune system.

Addressing the recruitment shortfall in surgery - How do we inspire the next generation?

•Application rates to surgery by medical students have declined in recent years.•More hands-on experience, information and mentorship is needed in medical schools.•Within surgery, gendered stereotyping of roles and environments must be challenged.•Reform of the current systems of outcome reporting is necessary.

DermAll nanomedicine for allergen-specific immunotherapy.

Allergen-specific immunotherapy (ASIT) the only disease-modifying treatment for IgE-mediated allergies is characterized with long treatment duration and high risk of side effects. We investigated the safety, immunogenicity and efficacy of a novel ASIT, called DermAll, in an experimental allergic rhinitis model. We designed and characterized DermAll-OVA, a synthetic plasmid pDNA/PEIm nanomedicine expressing ovalbumin (OVA) as model allergen. DermAll-OVA was administered topically with DermaPrep device to target Langerhans cells. To detect the clinical efficacy of DermAll ASIT we quantified the nasal symptoms and characterized the immunomodulatory activity of DermAll ASIT by measuring cytokine secretion after OVA-stimulation of splenocytes and antibodies from the sera. In allergic mice DermAll ASIT was as safe as Placebo, balanced the allergen-induced pathogenic TH2-polarized immune responses, and decreased the clinical symptoms by 52% [32%, 70%] compared to Placebo. These studies suggest that DermAll ASIT is safe and should significantly improve the immunopathology and symptoms of allergic diseases. FROM THE CLINICAL EDITOR: A novel allergen-specific immunotherapy for IgE-mediated allergies is presented in this paper, using an experimental allergic rhinitis model and a synthetic plasmid pDNA/PEIm nanomedicine expressing ovalbumin as model allergen. Over 50% reduction of symptoms was found as the immune system's balance was favorably altered toward more TH2-polarized immune responses.