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Reintroduction failure after negative food challenges in adults is common and mainly due to atypical symptoms

BACKGROUND:Reintroduction of a food after negative food challenge (FC) faces many obstacles. There are no studies available about this subject in adults.OBJECTIVE:To investigate the frequency, reasons and risk factors of reintroduction failure in adults.METHODS:In this prospective study, adult patients received standardized follow-up care after negative FCs including a reintroduction scheme and supportive telephone consultations. Data were collected by telephone interview (2 weeks after FC) and questionnaires (at baseline and 6 months after FC(s)): food habits questionnaire, State-Trait Anxiety Inventory, Food Allergy Quality of Life Questionnaire-Adult Form and Food Allergy Independent Measure. Frequency and reasons of reintroduction failure were analysed using descriptive statistics and risk factors with univariate analyses.RESULTS:Eighty patients were included with, in total, 113 negative FCs. Reintroduction failed on short-term (2 weeks after FC) in 20% (95% CI: 13%-28%). Common reasons were symptoms upon ingestion during the reintroduction scheme (50%) and no need to eat the food (23%). On the long-term (5-12 months after FC(s)), reintroduction failure increased to 40% (95% CI: 28%-53%). Common reasons were atypical symptoms after eating the food (59%) and fear for an allergic reaction (24%). Five risk factors for long-term reintroduction failure were found: if culprit food was not one of the 13 EU regulated allergens, reintroduction failure at short-term, atypical symptoms during FC, a lower quality of life and a higher state anxiety.CONCLUSIONS AND CLINICAL RELEVANCE:Reintroduction failure after negative FCs in adults is common, increases over time, and is primarily due to atypical symptoms. This stresses the need for more patient-tailored care before and after negative food challenges.cc-by-nc-sa

The efficacy of oral and subcutaneous antigen-specific immunotherapy in murine cow's milk- and peanut allergy models

From Pubmed: " BACKGROUND: Antigen-specific immunotherapy (AIT) is a promising therapeutic approach for both cow's milk allergy (CMA) and peanut allergy (PNA), but needs optimization in terms of efficacy and safety. AIM: Compare oral immunotherapy (OIT) and subcutaneous immunotherapy (SCIT) in murine models for CMA and PNA and determine the dose of allergen needed to effectively modify parameters of allergy. METHODS: Female C3H/HeOuJ mice were sensitized intragastrically (i.g.) to whey or peanut extract with cholera toxin. Mice were treated orally (5 times/week) or subcutaneously (3 times/week) for three consecutive weeks. Hereafter, the acute allergic skin response, anaphylactic shock symptoms and body temperature were measured upon intradermal (i.d.) and intraperitoneal (i.p.) challenge, and mast cell degranulation was measured upon i.g. challenge. Allergen-specific IgE, IgG1 and IgG2a were measured in serum at different time points. Single cell suspensions derived from lymph organs were stimulated with allergen to induce cytokine production and T cell phenotypes were assessed using flow cytometry. RESULTS: Both OIT and SCIT decreased clinically related signs upon challenge in the CMA and PNA model. Interestingly, a rise in allergen-specific IgE was observed during immunotherapy, hereafter, treated mice were protected against the increase in IgE caused by allergen challenge. Allergen-specific IgG1 and IgG2a increased due to both types of AIT. In the CMA model, SCIT and OIT reduced the percentage of activated Th2 cells and increased the percentage of activated Th1 cells in the spleen. OIT increased the percentage of regulatory T cells (Tregs) and activated Th2 cells in the MLN. Th2 cytokines IL-5, IL-13 and IL-10 were reduced after OIT, but not after SCIT. In the PNA model, no differences were observed in percentages of T cell subsets. SCIT induced Th2 cytokines IL-5 and IL-10, whereas OIT had no effect. CONCLUSION: We have shown clinical protection against allergic manifestations after OIT and SCIT in a CMA and PNA model. Although similar allergen-specific antibody patterns were observed, differences in T cell and cytokine responses were shown. Whether these findings are related to a different mechanism of AIT in CMA and PNA needs to be elucidated."

Accidental allergic reactions to food in adolescents and adults An overview of the factors involved and implications for prevention

Accidental allergic reactions to food are one of the major problems in adult patients diagnosed with food allergy. Such reactions occur frequently, are often severe and are associated with higher medical and non-medical costs. The aim of this Perspective is to provide insight into the different factors involved in the occurrence of accidental allergic reactions and to present an overview of practical implications for effective preventive measures. Several factors affect the occurrence of accidental reactions. These factors are related to the patient, health care, or food. The most important patient-related factors are age, social barriers to disclosing their allergy and non-adherence to the elimination diet. With regards to healthcare, the degree to which clinical practice is tailored to the individual patient is an important factor. The major food-related factor is the absence of adequate precautionary allergen labeling (PAL) guidelines. Since many factors are involved in accidental allergic reactions, different preventive strategies are needed. It is highly recommended that health care be tailored to the individual patient, with regard to education about the elimination diet, support on behavioral and psychosocial aspects, usage of shared decision-making and taking into account health literacy. In addition, it is crucial that steps are taken to improve policies and guidelines for PAL.

Application of the adverse outcome pathway (AOP) concept to structure the available in vivo and in vitro mechanistic data for allergic sensitization to food proteins

From the publisher: "Background: The introduction of whole new foods in a population may lead to sensitization and food allergy. This constitutes a potential public health problem and a challenge to risk assessors and managers as the existing understanding of the pathophysiological processes and the currently available biological tools for prediction of the risk for food allergy development and the severity of the reaction are not sufficient. There is a substantial body of in vivo and in vitro data describing molecular and cellular events potentially involved in food sensitization. However, these events have not been organized in a sequence of related events that is plausible to result in sensitization, and useful to challenge current hypotheses. The aim of this manuscript was to collect and structure the current mechanistic understanding of sensitization induction to food proteins by applying the concept of adverse outcome pathway (AOP). Main body: The proposed AOP for food sensitization is based on information on molecular and cellular mechanisms and pathways evidenced to be involved in sensitization by food and food proteins and uses the AOPs for chemical skin sensitization and respiratory sensitization induction as templates. Available mechanistic data on protein respiratory sensitization were included to fill out gaps in the understanding of how proteins may affect cells, cell-cell interactions and tissue homeostasis. Analysis revealed several key events (KE) and biomarkers that may have potential use in testing and assessment of proteins for their sensitizing potential. Conclusion: The application of the AOP concept to structure mechanistic in vivo and in vitro knowledge has made it possible to identify a number of methods, each addressing a specific KE, that provide information about the food allergenic potential of new proteins. When applied in the context of an integrated strategy these methods may reduce, if not replace, current animal testing approaches. The proposed AOP will be shared at the www.aopwiki.org platform to expand the mechanistic data, improve the confidence in each of the proposed KE and key event relations (KERs), and allow for the identification of new, or refinement of established KE and KERs." Authors: Jolanda H. M. van BilsenEmail author, Edyta Sienkiewicz-Szłapka, Daniel Lozano-Ojalvo, Linette E. M. Willemsen, Celia M. Antunes, Elena Molina, Joost J. Smit, Barbara Wróblewska, Harry J. Wichers, Edward F. Knol, Gregory S. Ladics, Raymond H. H. Pieters, Sandra Denery-Papini, Yvonne M. Vissers, Simona L. Bavaro, Colette Larré, Kitty C. M. Verhoeckx and Erwin L. Roggen

Using artificial intelligence to create diverse and inclusive medical case vignettes for education

Abstract Aims: Medical case vignettes play a crucial role in medical education, yet they often fail to authentically represent diverse patients. Moreover, these vignettes tend to oversimplify the complex relationship between patient characteristics and medical conditions, leading to biased and potentially harmful perspectives among students. Displaying aspects of patient diversity, such as ethnicity, in written cases proves challenging. Additionally, creating these cases places a significant burden on teachers in terms of labour and time. Our objective is to explore the potential of artificial intelligence (AI)-assisted computer-generated clinical cases to expedite case creation and enhance diversity, along with AI-generated patient photographs for more lifelike portrayal. Methods: In this study, we employed ChatGPT (OpenAI, GPT 3.5) to develop diverse and inclusive medical case vignettes. We evaluated various approaches and identified a set of eight consecutive prompts that can be readily customized to accommodate local contexts and specific assignments. To enhance visual representation, we utilized Adobe Firefly beta for image generation. Results: Using the described prompts, we consistently generated cases for various assignments, producing sets of 30 cases at a time. We ensured the inclusion of mandatory checks and formatting, completing the process within approximately 60 min per set. Conclusions: Our approach significantly accelerated case creation and improved diversity, although prioritizing maximum diversity compromised representativeness to some extent. While the optimized prompts are easily reusable, the process itself demands computer skills not all educators possess. To address this, we aim to share all created patients as open educational resources, empowering educators to create cases independently.

Het tragische misverstand van Dave Eggers' The Circle