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Background: Esophageal food impactions (EFI) often precede a diagnosis of eosinophilic esophagitis (EOE). Current guidelines suggest obtaining esophageal biopsies upon suspicion of EOE, treating with proton pump inhibitor (PPI), and repeating esophagogastroduodenoscopy (EGD). This study was conducted to determine provider practice patterns with these mentioned recommendations at the time of EFI. Methods: In this retrospective study, key outcomes were the proportion of patients who had EOE mucosal biopsies, EOE diagnosis, PPI initiation, and recommendations and completions of repeat EGD. Differences in outcomes among age, sex, race, off-hours time of procedure, and trainee involvement were examined. EOE diagnosis predictors were explored with logistic regression. Results: Twenty-nine percent of the patients had esophageal biopsies taken at the time of index EGD (iEGD). Sixteen patients were diagnosed with EOE at the time of index EFI, while fourteen patients were diagnosed on subsequent EGDs. Among those diagnosed with EOE at iEGD, 94% were placed on PPI. Of patients with confirmed EOE on index biopsy, 63% of patients were recommended repeat EGD, of which 50% completed it within 90 days. Older age was protective of EOE diagnosis while no GERD history and endoscopist suspicion of EOE predicted diagnosis of EOE. Conclusions: Endoscopists uncommonly take biopsies at the time of EFI, which may delay diagnosis and treatment of EOE. [ABSTRACT FROM AUTHOR]

Background Eosinophilic esophagitis (EoE) is an esophageal inflammatory disease associated with atopic diseases. Thymic stromal lymphopoietin (TSLP) and calpain 14 (CAPN14) genetic variations contribute to EoE, but how this relates to atopy is unclear. Objective The purpose of this study was to explore the relationship between EoE, atopy, and genetic risk. Methods EoE-atopy enrichment was tested by using 700 patients with EoE and 801 community control subjects. Probing 372 single nucleotide polymorphisms (SNPs) in 63 atopy genes, we evaluated EoE associations using 412 nonatopic and 868 atopic disease control subjects. Interaction and stratified analyses of EoE-specific and atopy-related SNPs were performed. Results Atopic disease was enriched in patients with EoE ( P < .0001). Comparing patients with EoE and nonatopic control subjects, EoE associated strongly with IL-4/kinesin family member 3A ( IL4 / KIF3A) ( P = 2.8 × 10 −6 ; odds ratio [OR], 1.87), moderately with TSLP ( P = 1.5 × 10 −4 ; OR, 1.43), and nominally with CAPN14 ( P = .029; OR, 1.35). Comparing patients with EoE with atopic disease control subjects, EoE associated strongly with ST2 ( P = 3.5 × 10 −6 ; OR, 1.77) and nominally with IL4/KIF3A ( P = .019; OR, 1.25); TSLP 's association persisted ( P = 4.7 × 10 −5 ; OR, 1.37), and CAPN14' s association strengthened ( P = .0001; OR, 1.71). Notably, there was gene-gene interaction between TSLP and IL4 SNPs ( P = .0074). Children with risk alleles for both genes were at higher risk for EoE ( P = 2.0 × 10 −10 ; OR, 3.67). Conclusions EoE genetic susceptibility is mediated by EoE-specific and general atopic disease loci, which can have synergistic effects. These results might aid in identifying potential therapeutics and predicting EoE susceptibility. [ABSTRACT FROM AUTHOR]

Background: Poor adherence to clinical practice guidelines for eosinophilic esophagitis (EoE) has been described and the diagnostic delay of the disease continues to be unacceptable in many settings., Objective: To analyze the impact of improved knowledge provided by the successive international clinical practice guidelines on reducing diagnostic delay and improving the diagnostic process for European patients with EoE., Methods: Cross-sectional analysis of the EoE CONNECT registry based on clinical practice. Time periods defined by the publication dates of four major sets of guidelines over 10 years were considered. Patients were grouped per time period according to date of symptom onset., Results: Data from 1,132 patients was analyzed and median (IQR) diagnostic delay in the whole series was 2.1 (0.7-6.2) years. This gradually decreased over time with subsequent release of new guidelines (p < 0.001), from 12.7 years up to 2007 to 0.7 years after 2017. The proportion of patients with stricturing of mixed phenotypes at the point of EoE diagnosis also decreased over time (41.3% vs. 16%; p < 0.001), as did EREFS scores. The fibrotic sub-score decreased from a median (IQR) of 2 (1-2) to 0 (0-1) when patients whose symptoms started up to 2007 and after 2017 were compared (p < 0.001). In parallel, symptoms measured with the Dysphagia Symptoms Score reduced significantly when patients with symptoms starting before 2007 and after 2012 were compared. A reduction in the number of endoscopies patients underwent before the one that achieved an EoE diagnosis, and the use of allergy testing as part of the diagnostic workout of EoE, also reduced significantly over time (p = 0.010 and p < 0.001, respectively)., Conclusion: The diagnostic work-up of EoE patients improved substantially over time at the European sites contributing to EoE CONNECT, with a dramatic reduction in diagnostic delay., (© 2022 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Purpose of Review: As the rising prevalence and incidence of eosinophilic esophagitis (EoE) has quickly outpaced the rate of esophageal biopsies, particularly in Westernized countries, several studies have suggested a link between intrinsic genetic and extrinsic environmental risk factors and the development, presentation, and diagnosis of EoE. This review aims to critically assess existing studies describing the role of the environment on the development, symptomatic presentation, and diagnosis of this recently recognized chronic immune-mediated disease. Recent Findings: We present and critically evaluate the working hypotheses and supportive studies thus far on environmental factors on EoE, describe sources of potential bias in diagnosis due to socioeconomic factors and thus undermining studies of EoE etiology, and highlight opportunities for future research. Summary: As genetics alone do not explain the rapid rise of EoE, we must look to environmental, or extrinsic, factors both in the early-life period which shape the development of the gut microbiome, as well as later life contributing to diagnosis of this new disease. Future etiologic studies linking risk factors to EoE development in individual patients are needed. [ABSTRACT FROM AUTHOR]

Background and Aim: Our primary aim was to describe the prevalence of immunoglobulin G (IgG) and its subclass IgG4 in immunohistochemistry staining in esophageal biopsy specimens of children with eosinophilic esophagitis (EoE) compared with that of specimens from children with gastroesophageal reflux disease (GERD). Methods: Esophageal biopsy specimens from children with EoE or GERD were stained prospectively for IgG and IgG4 antibodies. Subjects with EoE were divided into cohorts with either active EoE or EoE in remission. Active EoE cases were further divided into proton pump inhibitor responsive (PPI‐r) and PPI‐nonresponsive (PPI‐nr) subgroups. Demographic, clinical, and histologic data were compared among groups, including quantified IgG and IgG4 staining, peak eosinophil count, eosinophil‐derived neurotoxin levels, and EoE endoscopic reference score. Results: Seventy‐nine children (aged 10.6 ± 5.6 years; 68% male) were enrolled. IgG‐positive cell counts were significantly elevated in those with active EoE (n = 29, 3 [interquartile range, IQR: 2–6]/high‐powered field [HPF]), compared with those having EoE remission (n = 25, 1 [IQR: 0–2]/HPF; P = 0.002) and those with GERD (n = 25, 0 [IQR: 0–0.25]/HPF, P = <0.0001). IgG‐positive cell counts were significantly higher in the PPI‐r (n = 15, 5 [IQR: 2.5–11]/HPF) subgroup, compared with the PPI‐nr subgroup (n = 11, 3 [IQR: 1.5–3.5]/HPF; P = 0.041) at baseline endoscopy. Conclusion: Initial esophageal tissue biopsy specimens from pediatric subjects with active EoE showed a significant increase in IgG‐positive staining compared with tissue from subjects in EoE remission or with GERD. There was higher positivity of IgG‐stained cells in the PPI‐r subgroup compared with the PPI‐nr subgroup. [ABSTRACT FROM AUTHOR]

Background: Observational studies have indicated a possible connection between Helicobacter pylori (H. pylori) infection and eosinophilic esophagitis (EoE), but their causal relationship has yet to be established. To investigate the causal associations between H. pylori infection and EoE, we performed a Mendelian randomization (MR) analysis. Methods: Firstly, we conducted both univariable and multivariable Mendelian randomization (MR) analyses. Furthermore, a two-step MR was carried out to ascertain the potential underlying pathways of these associations, particularly the involvement of inflammatory cytokines. We employed the inverse-variance weighted (IVW) method as the main analysis in our MR study. To enhance the credibility of the results, we also conducted several sensitivity analyses. Results: Our study demonstrated a noteworthy correlation between genetically predicted anti-H. pylori IgG antibody levels and a reduced risk of EoE (OR=0.325, 95% CI=0.165--0.643, P value=0.004, adj p value=0.009). No significant causal associations were detected between other H. pylori antibodies and EoE in our study. When it comes to multivariable MR analysis controlling for education attainment, household income, and deprivation individually, the independent causal impact of anti-H. pylori IgG on EoE persisted. Surprisingly, the two-step MR analysis indicated that inflammatory factors (IL-4, IL-5, IL-13, IL-17, and IFN-g) did not appear to mediate the protective effect of H. pylori infection against EoE. Conclusion: Findings suggested that among the range of H. pylori-related antibodies, anti-H. pylori IgG antibody is the sole causal factor associated with protection against EoE. Certain inflammatory factors may not be involved in mediating this association. These findings make a significant contribution to advancing our understanding of the pathogenesis of EoE and its evolving etiology. [ABSTRACT FROM AUTHOR]

Coordinated cell interactions within the esophagus maintain homeostasis, and disruption can lead to eosinophilic esophagitis (EoE), a chronic inflammatory disease with poorly understood pathogenesis. We profile 421,312 individual cells from the esophageal mucosa of 7 healthy and 15 EoE participants, revealing 60 cell subsets and functional alterations in cell states, compositions, and interactions that highlight previously unclear features of EoE. Active disease displays enrichment of ALOX15+ macrophages, PRDM16+ dendritic cells expressing the EoE risk gene ATP10A, and cycling mast cells, with concomitant reduction of TH17 cells. Ligand–receptor expression uncovers eosinophil recruitment programs, increased fibroblast interactions in disease, and IL-9+IL-4+IL-13+ TH2 and endothelial cells as potential mast cell interactors. Resolution of inflammation-associated signatures includes mast and CD4+ TRM cell contraction and cell type-specific downregulation of eosinophil chemoattractant, growth, and survival factors. These cellular alterations in EoE and remission advance our understanding of eosinophilic inflammation and opportunities for therapeutic intervention. Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus with unclear immune cell involvement. Here the authors generate a single cell transcriptomic dataset with 400k cells from the esophageal mucosa of active EoE patients, remission EoE patients, and healthy individuals to characterise esophageal cellular composition, phenotype and interaction in this disease. [ABSTRACT FROM AUTHOR]

Introduction: Benzotriazine-1,4-dioxides (BTDOs) such as tirapazamine (TPZ) and its derivatives act as radiosensitizers of hypoxic tissues. The benzotriazine-1-monoxide (BTMO) metabolite (SR 4317, TPZMO) of TPZ also has radiosensitizing properties, and via unknown mechanisms, is a potent enhancer of the radiosensitizing effects of TPZ. Unlike their 2-nitroimidazole radiosensitizer counterparts, radiolabeled benzotriazine oxides have not been used as radiopharmaceuticals for diagnostic imaging or molecular radiotherapy (MRT) of hypoxia. The radioiodination chemistry for preparing model radioiodinated BTDOs and BTMOs is now reported. Hypothesis: Radioiodinated 3-(2-iodoethoxyethyl)-amino-1,2,4-benzotriazine-1,4-dioxide (I-EOE-TPZ), a novel bioisosteric analogue of TPZ, and 3-(2-iodoethoxyethyl)-amino-1,2,4-benzotriazine-1-oxide (I-EOE-TPZMO), its monoxide analogue, are candidates for in vivo and in vitro investigations of biochemical mechanisms in pathologies that develop hypoxic microenvironments. In theory, both radiotracers can be prepared from the same precursors. Methods: Radioiodination procedures were based on classical nucleophilic [131I]iodide substitution on Tos-EOE-TPZ (P1) and by [131I]iodide exchange on I-EOE-TPZ (P2). Reaction parameters, including temperature, reaction time, solvent and the influence of pivalic acid on products’ formation and the corresponding radiochemical yields (RCY) were investigated. Results: The [131I]iodide labeling reactions invariably led to the synthesis of both products, but with careful manipulation of conditions the preferred product could be recovered as the major product. Radioiodide exchange on P2 in ACN at 80 ± 5 °C for 30 min afforded the highest RCY, 89%, of [131I]I-EOE-TPZ, which upon solid phase purification on an alumina cartridge gave 60% yield of the product with over 97% of radiochemical purity. Similarly, radioiodide exchange on P2 in ACN at 50 ± 5 °C for 30 min with pivalic acid afforded the highest yield, 92%, of [131I]I-EOE-TPZMO exclusively with no trace of [131I]I-EOE-TPZ. In both cases, extended reaction times and/or elevated temperatures resulted in the formation of at least two additional radioactive reaction products. Conclusions: Radioiodination of P1 and P2 with [131I]iodide leads to the facile formation of [131I]I-EOE-TPZMO. At 80 °C and short reaction times, the facile reduction of the N-4-oxide moiety was minimized to afford acceptable radiochemical yields of [131I]I-EOE-TPZ from either precursor. Regeneration of [131I]I-EOE-TPZ from [131I]I-EOE-TPZMO is impractical after reaction work-up.

Background: The prevalence rate of eosinophilic esophagitis (EoE) between Japan and Western countries is quite different. Although multiple factors, including the genetic background, lifestyle and dietary habits, may account for the difference, the pathogenic mechanism of EoE has not been fully clarified in Japanese. To elucidate whether EoE's pathogenic mechanisms differ between those populations, we performed transcriptome analysis of esophageal biopsy specimens from Japanese EoE patients and compared the identified gene signatures with published microarray data for EoE patients in the US. Methods: We prospectively enrolled adult Japanese EoE patients (n = 4) according to the 2011 consensus guidelines for diagnosis of EoE. Age-matched healthy volunteer subjects (n = 4) were also enrolled as controls. We assessed the gene expression profiles of esophageal biopsies using microarray technology and then compared the identified gene signatures with earlier data generated in the US. Results: Of 42,545 transcripts represented on the microarray, 385 were differentially expressed between the EoE and control samples (≥2 fold change and adjusted p-value of

Introduction: Eosinophilic esophagitis (EoE) is a chronic, inflammatory, antigendriven disease of the esophagus. Tissue EoE pathology has previously been extensively characterized by novel transcriptomics and proteomic platforms, however the majority of surface marker determination and screening has been performed in blood due to mucosal tissue size limitations. While eosinophils, CD4+ T cells, mast cells and natural killer (NK) T cells were previously investigated in the context of EoE, an accurate picture of the composition of peripheral blood mononuclear cells (PBMC) and their activation is missing. Methods: In this study, we aimed to comprehensively analyze the composition of peripheral blood mononuclear cells and their activation using surface marker measurements with multicolor flow cytometry simultaneously in both blood and mucosal tissue of patients with active EoE, inactive EoE, patients with gastroesophageal reflux disease (GERD) and controls. Moreover, we set out to validate our data in co-cultures of PBMC with human primary esophageal epithelial cells and in a novel inducible mouse model of eosinophilic esophagitis, characterized by extensive IL-33 secretion in the esophagus. Results: Our results indicate that specific PBMC populations are enriched, and that they alter their surface expression of activation markers in mucosal tissue of active EoE. In particular, we observed upregulation of the immunomodulatory molecule CD38 on CD4+ T cells and on myeloid cells in biopsies of active EoE. Moreover, we observed significant upregulation of PD-1 on CD4+ and myeloid cells, which was even more prominent after corticosteroid treatment. With coculture experiments we could demonstrate that direct cell contact is needed for PD-1 upregulation on CD4+ T cells. Finally, we validated our findings of PD-1 and CD38 upregulation in an inducible mouse model of EoE. Discussion: Herein we show significant alterations in the PBMC activation profile of patients with active EoE in comparison to inactive EoE, GERD and controls, which could have potential implications for treatment. To our knowledge, this study is the first of its kind expanding the multi-color flow cytometry approach in different patient groups using in vitro and in vivo translational models. [ABSTRACT FROM AUTHOR]

Background/Aims: Asymptomatic esophageal eosinophilia (aEE) is considered to be a potential precursor of eosinophilic esophagitis (EoE). However, there are few clinical parameters that can be used to evaluate the disease. Therefore, we aimed to clarify the factors involved in the symptoms of EoE by examining the clinicopathological differences between aEE and EoE. Methods: We reviewed 41 patients with esophageal eosinophilia who underwent endoscopic ultrasonography and high-resolution manometry. They were divided into the aEE group (n=16) and the EoE group (n=25) using the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease score. The patients’ clinicopathological findings were collected and examined. Results: The median Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease score was 3.0 in the aEE group and 10.0 in the EoE group. There was no significant difference in patient characteristics, endoscopic findings and pathological findings. The cutoff value for wall thickening was 3.13 mm for the total esophageal wall thickness and 2.30 mm for the thickness from the surface to the muscular layer (total esophageal wall thickness: 84.0% sensitivity, 75.0% specificity; thickness from the surface to the muscular layer: 84.0% sensitivity, 68.7% specificity). The high-resolution manometry study was abnormal in seven patients (43.8%) in the aEE group and in 12 (48.0%) in the EoE group. The contractile front velocity was slower in the EoE group (p=0.026). Conclusions: The esophageal wall thickening in the lower portion of the esophagus is an important clinical factors related to the symptoms in patients with EoE. [ABSTRACT FROM AUTHOR]

Eosinophilic esophagitis (EoE) is an atopic disease of the esophagus that has shown a significant increase in incidence and prevalence in the last 20 years. The etiology of EoE is unclear, and few studies explore the esophageal microbiota in EoE. The local microbiome has been implicated in the pathogenesis of several allergic and inflammatory diseases, such as asthma and eczema. In this study, we performed a systematic review to evaluate differences in the microbiota profile of patients with EoE compared with controls. MEDLINE, Embase, Cochrane Library, Scopus, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) databases were searched to identify studies investigating the microbiota composition in EoE. Three reviewers screened the articles for eligibility and quality. Seven articles underwent full‐text review, and a narrative synthesis was undertaken. The microbiota of the mouth and esophagus are correlated. Patients with active EoE present increased esophageal microbial load and increased abundance in particular species, such as Haemophilus and Aggregatibacter. On the other hand, EoE patients present a decrease in Firmicutes. High microbial load and abundance of Haemophilus are observed in EoE patients, but little evidence exists to demonstrate their influence on inflammation and disease. Understanding microbial signatures in EoE might contribute to the development of novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background/Aims: Asymptomatic esophageal eosinophilia (aEE), characterized by eosinophil infiltration in the esophagus without clinical symptoms, has been reported as a precursor of eosinophilic esophagitis (EoE). Nevertheless, no report exists on the long-term clinical course of the disease. Therefore, this study aimed to investigate the long-term clinical course of aEE over 5 years, including the symptomatic conversion rate and the effect of treatments. Methods: We reviewed 28 patients with aEE who had been followed up for over 5 years with endoscopic monitoring. The basal characteristics of patients were compared with those of 58 patients diagnosed with EoE during the same period. Patients’ clinicopathological findings were collected and examined. Results: No significant differences in basal characteristics and histopathological findings were observed between the patients with aEE and those with EoE. The median follow-up duration was 64 months. Among the 28 patients with aEE, seven were treated with proton pump inhibitor or potassium-competitive acid blocker and the remaining 21 opted for follow-up with no medication. Among the treated patients, six (85.7%) exhibited endoscopic and pathologic improvements. Among the cases followed up without medication, the findings worsened in two (9.5%), improved spontaneously in seven (33.3%), and were unchanged in 12 (57.1%), and three (14.3%) developed symptoms at a mean time of 40 months. Symptoms developed in cases where endoscopic and pathologic findings remained unchanged or worsened during follow-up. Conclusions: Some patients with aEE had improved findings without treatment, whereas others developed symptoms, emphasizing the importance of long-term monitoring and individualized treatment decisions. [ABSTRACT FROM AUTHOR]

As part of the research conducted by the two authors on Occitanism in Aquitaine, this contribution focuses on the founders of the Occitan summer school (created in Lot-et-Garonne in 1974), who were fully aware of the urgency of teaching the Oc language: Marceau Esquieu, Jean Rigouste, Christian Rapin, who became true cultural actors in the Agenais. Developing an intermediate level between the school and university levels, this IEO-affiliated association offers workshops each year, makes resources available and creates teaching materials in order to train speakers and teach Occitan culture and literacy.

Eosinohilic esophagitis (EoE) and gastroesophageal reflux diseases (GERD) are closely related esophageal disorders, and both accumulate eosinophils in the esophagus. However, origin of both these diseases are very different. The evidence indicates that acid reflux is the main cause of GERD; whereas EoE is induced in response to food or environment allergens exposed accumulation of inflammatory cells like eosinophils, mast cells and T cell subsets. EoE is a global problem, and effect even 1 year old children to adult population. Currently, mepolizumab (anti-IL-5) neutralization therapy sdata showed reduced epithelial layer eosinophilia in EoE, 1, 2 and most recently FDA approved FDA has also approved Dupixent (anti-IL4R and anti-IL-13) for EoE following Phase 3 randomized, double-blind, placebo-controlled trial. The efficacy and safety of Dupixent 300 mg weekly patients 12 year or older on limited patient number, 69% and 64% reduction in EoE symptoms from baseline compared to 32% and 41% for placebo (FDA, 2022). In this commentary, we raised few concerns to be considered on these therapies based on the significance of IL-5, IL-4 in maintaining the innate immunity of the young children are mostly effected by EoE that require long term immunotherapy of mepolizumab (anti-IL-5) or Dupixent (anti-IL4R and anti-IL-13).

Purpose of review: The aim of this review is to provide practical guidance for clinicians to support the optimal use of endoscopy in both the diagnosis and the evaluation of treatment response in patients with eosinophilic esophagitis (EoE). Recent findings: The systematic and high-quality assessment and grading of EoE endoscopic features improves EoE detection. Fibrotic complications of EoE that negatively impact patients' symptoms and quality of life can be detected and treated through endoscopy. The correlation between endoscopic features of EoE and histological activity remains challenging. However, assessment of endoscopic activity is fast and reliable in the evaluation of treatment response and, therefore, is supported by current guidelines. New modalities such as FLIP panometry and molecular markers for diagnosis and monitoring of EoE are promising, but whether they may replace endoscopy in guiding treatment of EoE needs to be ascertained. Summary: Endoscopy plays a central role in EoE management, both in routine practice and in clinical trials. Endoscopy is pivotal in EoE diagnosis and response evaluation since it allows the direct assessment of endoscopic disease activity and, indirectly, the histological evaluation. Consequently, together with clinical and histological evaluation, endoscopy is rapidly becoming essential in monitoring the effectiveness of therapy in patients with EoE. [ABSTRACT FROM AUTHOR]

Purpose. The present study aimed to improve the aqueous solubility, permeability, bioavailability, and nootropic potential of standardized Emblica officinalis extract (EOE) by developing a novel phytosomal formulation. Method. Emblica officinalis extract-loaded phytosomes (EOPs) were prepared using solvent evaporation. The EOP was prepared at different molar ratios of extract and phospholipid. Herein, the effects of phospholipid extract ratio (A), temperature (B), and reaction time (C) were systematically investigated on entrapment efficiency using Box-Behnken design. In vitro and in vivo characterizations of the optimized formulation were performed. Results. Optimized EOP formulation (89.90 ± 0.24 μg/ml) exhibited improved aqueous solubility than plain EOE (11.85 ± 0.25 μg/ml). The optimized formulation's particle size and Zeta potential were 198.4 ± 0.20 nm and −39.0 ± 0.40 mv. DSC and XRD studies confirmed the partial amorphization of EOE in phytosomes. Optimized formulation exhibited 69.82 ± 0.17% of EOE release at 12 h and followed zero-order release kinetics. Moreover, the phytosomal formulation of EOE exhibited its rationality with an improvement of bioavailability by 2.7 folds compared with pure EOE. Compared to EOE, EOP showed significantly ( p < 0.05 lower escape and transfer latencies on both days in MWMT and EPMT, indicating more effective memory-enhancing activity. Furthermore, EOP-treated rats exhibited improved acetylcholine (Ach) levels than EOE. Brain tissue concentrations measured following EOP oral administration (1.06 ± 0.04 μg/ml) were substantially greater (p < 0.05) than those following EOE (0.32 ± 0.07 μg/ml). The brain dopamine and serotonin concentration were found to be higher (16.27 ± 1.209 and 43.28 ± 1.550 ng/ml) in the EOP-treated group as compared to the pure extract-treated group (10.40 ± 1.185 and 32.79 ± 1.738 ng/ml). Conclusion. Improvement of aqueous solubility, permeability, dissolution, bioavailability, and narrower particle size distribution could facilitate enhancement in the nootropic potential of EOE phytosomal formulation. [ABSTRACT FROM AUTHOR]

Background and Aim: The DanEoE is a previously described population‐ and register‐based cohort of 236 adult patients with eosinophilic esophagitis (EoE) in a well‐defined Danish region with a population of 580 000 and free medical treatment. The aim of the study was to compare the phenotype and treatment response between EoE patients with complications to patients without complications at diagnosis. Methods: A retrospective cross‐sectional study of the DanEoE cohort's 236 adult EoE patients diagnosed between 2007 and 2017 in the North Denmark Region. Patients were divided into a group who had had complications (dilated or food bolus obstruction [FBO]) before or at the diagnosis, and a group without. Results: At the diagnostic endoscopy, 61% had never had a complication, and 39% had either had FBO (n = 77) or been dilated (n = 15). The complicated group had the same mean age at symptom debut (37 [SD = 16] vs 37 [SD = 17] years, P = 1.0), but were diagnosed significantly later with a resulting longer diagnostic delay (13 [SD = 13] vs 7.9 [SD = 11] years, P = 0.01). Almost half of all patients were never treated to symptomatic remission (uncomplicated 40%, complicated 49%). The histological remission was not secured in the majority (uncomplicated 68%, complicated 70%). Despite this, <15% of patients with previous FBO experienced this after the diagnosis. Conclusion: In the population‐based DanEoE cohort, results indicated that the complicated EoE phenotype was a patient with a 5‐year longer diagnostic delay. In the current study, the complication status did not predict the treatment response. This population‐based DanEOE cohort study indicates that the complicated eosinophilic esophagitis phenotype is a patient with a 5‐year longer diagnostic delay. [ABSTRACT FROM AUTHOR]

Background: Food-specific immunoglobulin G4 (FS-IgG4) is associated with eosinophilic esophagitis (EoE); however, it is not clear whether production is limited to the esophagus. Aims: To assess FS-IgG4 levels in the upper gastrointestinal tract and plasma and compare these with endoscopic disease severity, tissue eosinophil counts, and patient-reported symptoms. Methods: We examined prospectively banked plasma, throat swabs, and upper gastrointestinal biopsies (esophagus, gastric antrum, and duodenum) from control (n = 15), active EoE (n = 24), and inactive EoE (n = 8) subjects undergoing upper endoscopy. Patient-reported symptoms were assessed using the EoE symptom activity index (EEsAI). Endoscopic findings were evaluated using the EoE endoscopic reference score (EREFS). Peak eosinophils per high-power field (eos/hpf) were assessed from esophageal biopsies. Biopsy homogenates and throat swabs were normalized for protein content and assessed for FS-IgG4 to milk, wheat, and egg. Results: Median FS-IgG4 for milk and wheat was significantly increased in the plasma, throat swabs, esophagus, stomach, and duodenum of active EoE subjects compared to controls. No significant differences for milk- or wheat-IgG4 were observed between active and inactive EoE subjects. Among the gastrointestinal sites sampled, FS-IgG4 levels were highest in the esophagus. Esophageal FS-IgG4 for all foods correlated significantly across all sites sampled (r ≥ 0.59, p < 0.05). Among subjects with EoE, esophageal FS-IgG4 correlated significantly with peak eos/hpf (milk and wheat) and total EREFS (milk). EEsAI scores and esophageal FS-IgG4 levels did not correlate. Conclusions: Milk and wheat FS-IgG4 levels are elevated in plasma and throughout the upper gastrointestinal tract in EoE subjects and correlate with endoscopic findings and esophageal eosinophilia. [ABSTRACT FROM AUTHOR]

Whether obesity is protective against progression of EoE is unknown. The aim of this study was to assess factors that alter the progression of EoE and determine if BMI is correlated with reduced disease severity. In this retrospective analysis of the Department of Veterans Affairs electronic health records, patients with EoE who received at least one dilation were identified using ICD and CPT codes. Kaplan–Meier curves determined the relationship between BMI and time to second esophageal dilation as a measurement of severity of disease. Cox proportional hazards models assessed the risk of second dilation adjusted for potential confounders. Of 2890 patients with EoE and at least one dilation, 40% were obese (n = 1165). There were no clinically significant differences in demographics between obese and non-obese patients. Non-obese patients were more likely to be smokers and had a higher mean average of the number of dilation visits compared to obese patients (p < 0.05). When stratified by obesity, non-obese individuals had a median time to next dilation of 6.53 years (95% CI (5.83, 7.79)) compared to 9.24 years for obese individuals (95% CI (7.40, 15.04)). When stratified by six BMI categories, median time to second dilation increased with increasing BMI. The hazard ratio of second dilation for obese individuals was 0.81 (95% CI (0.72–0.92)). EoE patients with a higher BMI were less likely to undergo a second dilation compared to those with a lower BMI. Obesity may have a protective role in EoE or severe strictures may lead to malnourishment. Further research into these possibilities is needed. [ABSTRACT FROM AUTHOR]

A recent study conducted by researchers from the University of North Carolina School of Medicine suggests that subcutaneous immunotherapy (SCIT) may be beneficial for individuals with eosinophilic esophagitis (EoE) who also have comorbid allergic rhinitis. The study found that SCIT did not worsen EoE symptoms and could potentially be helpful. The researchers compared characteristics and treatment outcomes between individuals with EoE and allergic rhinitis who were receiving SCIT and those who were not. The study, which is the largest of its kind to date, found no adverse effects of SCIT on EoE. [Extracted from the article]

Background and Aims: Ultrasonography has shown that eosinophils accumulate in each segment of the esophageal mucosa in human EoE, ultimately promoting esophageal motility dysfunction; however, no mechanistic evidence explains how or why this accumulation occurs. Methods: Quantitative PCR, ELISA, flow cytometry, immunostaining, and immunofluorescence analyses were performed using antibodies specific to the related antigens and receptors. Results: In deep esophageal biopsies of EoE patients, eosinophils and mast cells accumulate adjacent to nerve cell-derived VIP in each esophageal segment. qRT-PCR analysis revealed five- to sixfold increases in expression levels of VIP, CRTH2, and VAPC2 receptors and proteins in human blood- and tissue-accumulated eosinophils and mast cells. We also observed a significant correlation between mRNA CRTH2 levels and eosinophil- and nerve cell-derived VIPs in human EoE (p < 0.05). We provide evidence that eosinophil and mast cell deficiency following CRTH2 antagonist treatment improves motility dysfunction in a chronic DOX-inducible CC10-IL-13 murine model of experimental EoE. Conclusions: CRTH2 antagonist treatment is a novel therapeutic strategy for inflammatory cell-induced esophageal motility dysfunction in IL-13-induced chronic experimental EoE. [ABSTRACT FROM AUTHOR]

Purpose of review: Eosinophilic esophagitis (EoE) is a chronic inflammatory disease triggered by food antigens, characterized by TH2 cell and cytokine-mediated inflammation. Dietary therapy has emerged as a cornerstone in managing EoE. Elemental diets, while effective, pose challenges including nutritional deficits, adherence difficulty, and social limitations. Allergen-directed diets are less favored due to limited efficacy in predicting food triggers. Empiric elimination diets, like the six-food elimination diet, show promise but face adherence burdens and are cumbersome. Collaboration with dietitians is crucial for tailored nutrition assessment and support. Assessing response to dietary therapy involves standardized endoscopic and histological evaluation. Recent findings: Less restrictive elimination diets (e.g., two-food elimination diet, 2–4-6 step-up diet, dairy-only elimination) offer promising alternatives with potentially fewer endoscopies. Emerging less invasive methods (e.g., esophageal string capsule test, Cytosponge, transnasal endoscopy) provide promising monitoring alternatives. Summary: Dietary therapy is the primary non-pharmaceutical EoE treatment. Challenges persist, but newer, less restrictive approaches show promise. Implementation of dietary therapy requires careful consideration of patient factors and collaboration with dietitians to mitigate nutritional risks and ensure adherence. Less invasive monitoring methods offer alternatives, minimizing procedural burdens. Ongoing research aims to optimize strategies and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Eosinophilic Esophagitis is a widely-recognized immune-mediated esophagus disease with distinct clinical and histopathological features, exhibiting an increased global incidence. Therapeutic options encompass either dietary measures or pharmacological approaches, including proton pump inhibitors and topical corticosteroids. The use of monoclonal antibodies is currently under comprehensive evaluation, with a plethora of ongoing clinical trials designed to determine their clinical efficacy. The present case report demonstrates an exceptional case of refractory Eosinophilic Esophagitis, unresponsive to conventional treatment, achieving both clinical and histopathological remission subsequent to initiation of benralizumab treatment. Concurrently, our case underscores the necessity for continued research in the field of monoclonal antibodies for their use as a future treatment approach against Eosinophilic Esophagitis. [ABSTRACT FROM AUTHOR]

Once considered a rare disease, eosinophilic oesophagitis (EoE) is becoming increasingly prevalent, yet many healthcare professionals (HCPs) remain unfamiliar with the underlying pathophysiology and optimal management approaches. For this study, we developed a faculty-led, online, continuing medical education activity on EoE. The effectiveness of this activity was evaluated according to Moore's framework, with changes in knowledge and competence (Moore's Levels 3 and 4) assessed for a cohort of gastroenterologists, dietitians, allergists and immunologists (N = 300), using questionnaires completed before and after participation. Changes in HCP confidence in treating EoE were also reported and remaining educational gaps were identified. The activity was viewed by a global audience of 5,330 participants within 6 months, and significant improvements in knowledge and competence were reported following participation in the activity across all specialities, regions and experience (mean [standard deviation] score pre- versus post-activity: 4.32 [1.38] versus 5.46 [0.82]; p < 0.001). Confidence in treating EoE also increased from pre- to post-activity, with the proportion of participants reporting that they felt moderately or extremely confident increasing from 53% to 82%. Several educational unmet needs were identified, which can be used to inform the design of future educational activities in EoE [ABSTRACT FROM AUTHOR]

Background: Eosinophilic esophagitis (EoE) is a T‐cell‐mediated disease that is caused by specific foods and results in esophageal dysfunction. Existing allergy testing modalities are not helpful when attempting to identify EoE‐causal foods necessitating empiric food elimination and recurrent endoscopy. The goal of this study was to identify and compare allergen‐specific immune features that can be assayed in a minimally invasive manner to predict clinical food allergy in EoE. Methods: We obtained blood samples from control subjects (n = 17), subjects with clinical EoE milk allergy (n = 17), and subjects with immunoglobulin E‐mediated milk allergy (n = 9). We measured total and milk‐specific plasma immunoglobulin G (IgG)4 levels and peripheral memory CD4+ T helper (TH) cell proliferation and cytokine production after stimulation with endotoxin‐depleted milk proteins. Sensitivity and specificity for predicting clinical EoE milk allergy were calculated and compared between approaches. Results: Total and milk‐specific IgG4 levels were not significantly different between control subjects and subjects with clinical EoE milk allergy. Stimulation with milk proteins caused TH lymphocytes from subjects with clinical EoE milk allergy to proliferate more (%P1 of 38.3 ± 4.6 vs. 12.7 ± 2.8, p < 0.0001), and produce more type 2 cytokines (%IL‐4+ of 33.7 ± 2.8 vs. 6.9 ± 1.6, p < 0.0001) than cells from control subjects. Milk‐dependent memory TH‐cell proliferation (sensitivity and specificity of 88% and 82%, respectively) and interleukin 4 (IL‐4) production (sensitivity and specificity of 100%) most strongly predicted clinical EoE milk allergy. Conclusions: Peripheral markers of allergen‐specific immune activation may be useful in identifying EoE‐causal foods. Assaying milk‐dependent IL‐4 production by circulating memory TH lymphocytes most accurately predicts clinical EoE milk allergy. [ABSTRACT FROM AUTHOR]

Eosinophilic esophagitis (EoE) is a chronic Th2 and food antigen-mediated disease characterized by esophageal eosinophilic infiltration. Thymic stromal lymphopoetin (TSLP), an epithelial derived cytokine which bridges innate and Th2-type adaptive immune responses in other allergic conditions, is overexpressed in esophageal biopsies of EoE subjects. However, the triggers of TSLP expression in the esophageal epithelium are unknown. The objective of the current study was to characterize TSLP expression in human esophageal epithelium in EoE in vivo and to determine the role of food antigens upon epithelial TSLP expression in vitro. Using immunohistochemistry (IHC), we localized TSLP in esophageal biopsies of active EoE (≥15 eos/hpf), inactive EoE (

Although most studies on treatments for eosinophilic esophagitis (EoE) have focused on effects in the epithelium, EoE is a transmural disease. Eosinophils that infiltrate the subepithelial layers of the esophagus lead to fibrosis and the serious complications of EoE, and current therapies have shown minimal effects on this fibrosis. We aimed to elucidate T helper (Th)2 cytokine effects on esophageal fibroblasts and to explore potential fibroblast-targeted therapies for EoE.We established telomerase-immortalized fibroblasts from human esophageal biopsies. We stimulated these esophageal fibroblasts with Th2 cytokines, and examined effects of omeprazole and inhibitors of the Janus kinase (JAK)-signal transducer and activator of transcription (STAT6) pathway (AS1517499, leflunomide, and ruxolitinib) on STAT6 phosphorylation, STAT6 nuclear translocation, and eotaxin-3 expression. We also measured the effects of these inhibitors in esophageal epithelial cells stimulated with Th2 cytokines.As in esophageal epithelial cells, Th2 cytokines increased STAT6 phosphorylation, STAT6 nuclear translocation, eotaxin-3 transcription and protein secretion in esophageal fibroblasts. Unlike in epithelial cells, however, omeprazole did not inhibit cytokine-stimulated eotaxin-3 expression in fibroblasts. In contrast, JAK-STAT6 pathway inhibitors decreased cytokine-stimulated eotaxin-3 expression in both fibroblasts and epithelial cells.Omeprazole does not inhibit Th2 cytokine-stimulated eotaxin-3 expression by esophageal fibroblasts, suggesting that PPIs will have limited impact on subepithelial EoE processes such as fibrosis. JAK-STAT6 pathway inhibitors block Th2 cytokine-stimulated eotaxin-3 expression both in fibroblasts and in epithelial cells, suggesting a potential role for JAK-STAT inhibitors in treating both epithelial inflammation and subepithelial fibrosis in EoE.

Aim. Compare EoE-AP with EoE-D for clinical, endoscopy (EGD), histology and outcomes and also with FAP-N. Method. Symptoms, physical findings, EGD, histology, symptom scores, and treatments were recorded for the three groups. Cluster analysis was done. Results. Dysphagia and abdominal pain were different in numbers but not statistically significant between EoE-AP and EoE-D. EGD, linear furrows, white exudates were more in the EoE-D and both combined were significant (p

Introduction: The incidence of eosinophilic esophagitis (EoE) is rapidly increasing in both children and adults. However, despite extensive research, data on disease pathogenesis and useful markers for predicting treatment response are still lacking. The aim of the study was to analyze matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) expression in the esophagus of pediatric patients with EoE. Material and methods: This single-center study included newly diagnosed children with EoE based on endoscopic and histopathological results, children with esophageal eosinophilia (EE) not meeting the EoE criteria and healthy controls. Immunohistochemistry for MMP-1 and TIMP-1 was performed. Results: Among the 30 children whose biopsy specimens were evaluated, 10 patients were diagnosed with EoE, 10 patients with EE and 10 were healthy controls. Weak expression of MMP-1 in esophageal samples was observed in half or more cases in each group. However, strong MMP-1 expression was noted in half of EoE patients before treatment with a decrease in number of cases after treatment. Interestingly, lack of TIMP-1 expression was noted in all EoE patients, in contrast to EE samples, or control cases. Children with strong MMP-1 expression at the time of EoE diagnosis appeared to respond less well to proton pump inhibitors (PPIs) either alone or in combination with an elimination diet. There were no differences in MMP-1 expression with PPI monotherapy as opposed to combination therapy. Conclusions: Our data revealed that children with EoE did not express TIMP-1 in esophageal tissue, unlike EE and healthy controls. More intense expression of MMP-1 at diagnosis was associated with a poor response to treatment. [ABSTRACT FROM AUTHOR]

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated esophageal disease. Symptoms are related to mucosal eosinophilic-predominant inflammation that leads to esophageal dysfunction. Recent data suggest that esophageal atresia (EA) patients may have an increased incidence of EoE compared to the general population. As EoE symptoms may be confused with EA-related symptoms, they may significantly worsen morbidity in this specific group of patients. We investigated specific characteristics of patients with AE and EoE compared to those with EoE only. We conducted an observational retrospective monocentric study including all patients diagnosed with EoE from 1 January 2010 to 31 December 2021. For each patient, demographic, clinical and histopathological data were collected and then compared between the two cohorts (EA-EoE vs. EoE only). During the study period, 62 patients were included: 17 children were in the follow-up because of EA (18.1% of 94 EA patients screened in that period), while the other 45 presented EoE only. The demographic and clinical features of EA-EoE patients demonstrate a lower prevalence of allergic subjects (23.5% vs. 80%, p < 0.05), a lower age of presentation (3.1 vs. 12.2 years, p < 0.05), non-specific symptoms and a higher resolution rate with PPI therapy (64.7% vs. 17.8%, p < 0.05) compared to EoE-only patients. Our data confirm that EA patients are at high risk for developing EoE. As symptoms may overlap with the EA spectrum, early recognition of EoE may prevent patients from receiving unnecessary invasive therapeutic interventions and from developing complications from untreated EoE. [ABSTRACT FROM AUTHOR]

This paper aims to investigate the molecules involved in development of Barrett's esophagus (BE) in human eosinophilic esophagitis (EoE). Histopathological, immunohistochemical, real-time PCR Immuno blot, and ELISA analyses are performed to identify the signature genes and proteins involved in the progression of BE in EoE. We detected characteristic features of BE like intermediate columnartype epithelial cells, induced BE signature genes like ErbB3, CDX1, ErbB2IP in the esophageal mucosa of patients with EoE. In addition, we had observed several BE-associated proteins such as TFF3, p53 and the progression markers like EGFR, p16, MICA, MICB, and MHC molecules in esophageal biopsies of patients with chronic EoE. Interestingly, we also detected mucin-producing columnar cells and MUC-2, MUC-4, and MUC5AC genes and proteins along with induced IL-9 in patients with chronic EoE. A strong correlation of IL-9 with mucin genes is observed that implicated a possible role for IL-9 in the transformation of esophageal squamous epithelial cells to columnar epithelial cells in patients with EoE. These findings indicate that IL-9 may have an important role in BE development in patients with chronic EoE. We also discovered that IL-9 stimulates mucin-producing and barrier cell transcripts and proteins such CK8/18, GATA4, SOX9, TFF1, MUC5AC, and tight junction proteins in primary esophageal epithelial cells when exposed to IL-9. Taken together, these findings provide evidence that indeed IL-9 has a role in the initiation and progression of BE characteristics like development of mucin-producing columnar epithelial cells in patients with chronic EoE. [ABSTRACT FROM AUTHOR]