Interferon-γ signaling in eosinophilic esophagitis has implications for epithelial barrier function and programmed cell death.

Objective: Eosinophilic esophagitis (EoE) is a chronic esophageal inflammatory disorder characterized by eosinophil-rich mucosal inflammation and tissue remodeling. Transcriptional profiling of esophageal biopsies has previously revealed upregulation of type I and II interferon (IFN) response genes. We aim to unravel interactions between immune and epithelial cells and examine functional significance in esophageal epithelial cells. Design: We investigated epithelial gene expression from EoE patients using single-cell RNA sequencing and a confirmatory bulk RNA-sequencing experiment of isolated epithelial cells. The functional impact of interferon signaling on epithelial cells was investigated using in vitro organoid models. Results: We observe upregulation of interferon response signature genes (ISGs) in the esophageal epithelium during active EoE compared to other cell types, single-cell data, and pathway analyses, identified upregulation in ISGs in epithelial cells isolated from EoE patients. Using an esophageal organoid and air-liquid interface models, we demonstrate that IFN-γ stimulation triggered disruption of esophageal epithelial differentiation, barrier integrity, and induced apoptosis via caspase upregulation. We show that an increase in cleaved caspase-3 is seen in EoE tissue and identify interferon gamma (IFNG) expression predominantly in a cluster of majority-CD8+ T cells with high expression of CD69 and FOS. Conclusion: These findings offer insight into the interplay between immune and epithelial cells in EoE. Our data illustrate the relevance of several IFN-γ-mediated mechanisms on epithelial function in the esophagus, which have the potential to impact epithelial function during inflammatory conditions.

ChatGPT's performance in dentistry and allergy-immunology assessments: a comparative study.

Large language models (LLMs) such as ChatGPT have potential applications in healthcare, including dentistry. Priming, the practice of providing LLMs with initial, relevant information, is an approach to improve their output quality. This study aimed to evaluate the performance of ChatGPT 3 and ChatGPT 4 on self-assessment questions for dentistry, through the Swiss Federal Licensing Examination in Dental Medicine (SFLEDM), and allergy and clinical immunology, through the European Examination in Allergy and Clinical Immunology (EEAACI). The second objective was to assess the impact of priming on ChatGPT's performance. The SFLEDM and EEAACI multiple-choice questions from the University of Bern's Institute for Medical Education platform were administered to both ChatGPT versions, with and without priming. Performance was analyzed based on correct responses. The statistical analysis included Wilcoxon rank sum tests (α=0.05). The average accuracy rates in the SFLEDM and EEAACI assessments were 63.3% and 79.3%, respectively. Both ChatGPT versions performed better on EEAACI than SFLEDM, with ChatGPT 4 outperforming ChatGPT 3 across all tests. ChatGPT 3's performance exhibited a significant improvement with priming for both EEAACI (p=0.017) and SFLEDM (p=0.024) assessments. For ChatGPT 4, the priming effect was significant only in the SFLEDM assessment (p=0.038). The performance disparity between SFLEDM and EEAACI assessments underscores ChatGPT's varying proficiency across different medical domains, likely tied to the nature and amount of training data available in each field. Priming can be a tool for enhancing output, especially in earlier LLMs. Advancements from ChatGPT 3 to 4 highlight the rapid developments in LLM technology. Yet, their use in critical fields such as healthcare must remain cautious owing to LLMs' inherent limitations and risks.

ChatGPT's performance in dentistry and allergyimmunology assessments: a comparative study.

Large language models (LLMs) such as ChatGPT have potential applications in healthcare, including dentistry. Priming, the practice of providing LLMs with initial, relevant information, is an approach to improve their output quality. This study aimed to evaluate the performance of ChatGPT 3 and ChatGPT 4 on self-assessment questions for dentistry, through the Swiss Federal Licensing Examination in Dental Medicine (SFLEDM), and allergy and clinical immunology, through the European Examination in Allergy and Clinical Immunology (EEAACI). The second objective was to assess the impact of priming on ChatGPT's performance. The SFLEDM and EEAACI multiple-choice questions from the University of Bern's Institute for Medical Education platform were administered to both ChatGPT versions, with and without priming. Performance was analyzed based on correct responses. The statistical analysis included Wilcoxon rank sum tests (alpha=0.05). The average accuracy rates in the SFLEDM and EEAACI assessments were 63.3% and 79.3%, respectively. Both ChatGPT versions performed better on EEAACI than SFLEDM, with ChatGPT 4 outperforming ChatGPT 3 across all tests. ChatGPT 3's performance exhibited a significant improvement with priming for both EEAACI (p=0.017) and SFLEDM (p=0.024) assessments. For ChatGPT 4, the priming effect was significant only in the SFLEDM assessment (p=0.038). The performance disparity between SFLEDM and EEAACI assessments underscores ChatGPT's varying proficiency across different medical domains, likely tied to the nature and amount of training data available in each field. Priming can be a tool for enhancing output, especially in earlier LLMs. Advancements from ChatGPT 3 to 4 highlight the rapid developments in LLM technology. Yet, their use in critical fields such as healthcare must remain cautious owing to LLMs' inherent limitations and risks.

Case report: ETS1 gene deletion associated with a low number of recent thymic emigrants in three patients with Jacobsen syndrome.

Jacobsen syndrome is a rare genetic disorder associated with a terminal deletion in chromosome 11. The clinical presentation is variable. Although immunodeficiency has been described in patients with Jacobsen syndrome, a clear genotype-phenotype correlation has not yet been established. Here, we report on the immunologic phenotypes of four patients with Jacobsen syndrome. All four patients showed one or more atypical immunologic features. One patient suffered from recurrent viral infections, two patients had experienced a severe bacterial infection and one had received antibiotic prophylaxis since early childhood. One patient had experienced severe, transient immune dysregulation. Hypogammaglobulinemia and low B cell counts were found in two patients, while the number of recent thymic emigrants (CD31+CD45RA+ CD4 cells) was abnormally low in three. When considering the six immune-related genes located within the affected part of chromosome 11 (ETS1, TIRAP, FLI1, NFRKB, THYN1, and SNX19), only the ETS1 gene was found be deleted in the three patients with low numbers of recent thymic emigrants and non-switched memory B cells. Our findings support the hypothesis whereby Jacobsen syndrome is associated with a combined immunodeficiency with variable presentation. Further investigations of potential genotype-phenotype correlations are warranted and might help to personalize patient management in individuals lacking immune-related genes. In addition, we recommend immunologic follow-up for all patients with Jacobsen syndrome, as immune abnormalities may develop over time.

[Food Allergy in Childhood]. / Nahrungsmittelallergien im Kindesalter.

Food Allergy in Childhood Abstract. Food allergies in childhood are on the rise and are therefore a topical issue in practice. In this article, we describe the most common allergens and risk factors for the development of a food allergy. The classification of IgE- and non-IgE-mediated food allergies and their respective clinical manifestations are highlighted. The importance of a careful diagnosis with targeted history taking and allergy testing and finally the performance of oral provocation for the diagnosis will be presented in a practical manner. We will discuss the care of families of children with food allergies, whereby support through nutritional counselling as well as equipping families with an emergency kit, including appropriate instructions for use, are important. Finally, the latest therapeutic approaches of specific immunotherapy, which aims to induce tolerance, are presented and the prognosis of food allergies is discussed.

Does superior caval vein pressure impact head growth in Fontan circulation?

BACKGROUND: Patients with bidirectional cavopulmonary anastomosis have unphysiologically high superior caval vein pressure as it equals pulmonary artery pressure. Elevated superior caval vein pressure may cause communicating hydrocephalus and macrocephaly. This study analysed whether there exists an association between head circumference and superior caval vein pressure in patients with single ventricle physiology. METHODS: We carried out a retrospective analysis of infants undergoing Fontan completion at our institution from 2007 to 2013. Superior caval vein pressures were measured during routine catheterisation before bidirectional cavopulmonary anastomosis and Fontan completion as well as head circumference, adjusted to longitudinal age-dependent percentiles. RESULTS: We included 74 infants in our study. Median ages at bidirectional cavopulmonary anastomosis and Fontan were 4.8 (1.6-12) and 27.9 (7-40.6) months, respectively. Head circumference showed significant growth from bidirectional cavopulmonary anastomosis until Fontan completion (7th (0-100th) versus 20th (0-100th) percentile). There was no correlation between superior caval vein pressure and head circumference before Fontan (R2=0.001). Children with lower differences in superior caval vein pressures between pre-bidirectional cavopulmonary anastomosis and pre-Fontan catheterisations showed increased growth of head circumference (R2=0.19). CONCLUSIONS: Patients with moderately elevated superior caval vein pressure associated with single ventricle physiology did not have a tendency to develop macrocephaly. There is no correlation between superior caval vein pressure before Fontan and head circumference, but between bidirectional cavopulmonary anastomosis and Fontan head circumference increases significantly. This may be explained by catch-up growth of head circumference in patients with more favourable haemodynamics and concomitant venous pressures in the lower range. Further studies with focus on high superior caval vein pressures are needed to exclude or prove a correlation.