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Background and Aim: Mental status such as anxiety and depression in patients with non‐esophageal eosinophilic gastrointestinal diseases (non‐EoE EGIDs) has not been studied. The aim of this study was to evaluate whether patients with non‐EoE EGIDs had mental disorders and decreased mental‐health‐related quality of life (QOL) similar to those in patients with disorders of gut–brain interaction (DGBI). Methods: We enrolled patients with non‐EoE EGIDs and DGBI visiting the Osaka Metropolitan University Hospital, and the measures listed below were compared between the groups. We collected data using the following questionnaires: hospital anxiety and depression scale, and short form (SF)‐8 including mental component summary (MCS)‐8. Results: We evaluated 21 and 17 patients with non‐EoE EGIDs and DGBI, respectively. The anxiety score was not significantly different between the groups. The proportion of patients with possible anxiety was not significantly different between the groups (19.0% vs 33.3%). These results show that patients with non‐EoE EGIDs had anxiety that might be equivalent to that of patients with DGBI. The depression score and proportion of patients with possible depression in the non‐EoE EGID group tended to be lower than those in the DGBI group. MCS‐8 scores were not significantly different between the non‐EoE EGID and DGBI groups, which might imply an equivalent decrease in mental‐health‐related QOL in both groups of patients. In patients with non‐EoE EGIDs, the anxiety score had a significant inverse association with the MCS‐8 score. Conclusions: Patients with non‐EoE EGIDs may have anxiety that correlates with decreased mental‐health‐related QOL. [ABSTRACT FROM AUTHOR]

Background and Aim: The prevalence of eosinophilic esophagitis (EoE) is rising in the West. However, data from the Indian subcontinent is limited. In this prospective cross‐sectional study, we estimated the prevalence of EoE among children undergoing elective upper gastrointestinal endoscopy (UGIE). Methods: We enrolled 200 consecutive children (123 boys, median age 10.25 years [interquartile range 8.25–14.5]) between March 2020 and November 2022 at our center. Clinical characteristics, endoscopic findings, and laboratory parameters were noted. A total of 12 mucosal biopsies (3 each from the middle and lower third of the esophagus, stomach, and duodenum) were obtained. EoE was diagnosed if the peak eosinophil count was ≥15/high‐power field (HPF) in absence of gastric and duodenal eosinophilia. Results: The commonest indications for UGIE were gastroesophageal reflux disease‐like symptoms (29%), inflammatory bowel disease (22.5%), celiac disease (15%), and abdominal pain (13%). EoE was detected in seven children, suggesting an overall prevalence of 3.5%. Of the 20 children evaluated for dysphagia, 4 (20%) had EoE. Also, two of three (67%) children presented with food bolus impaction along with dysphagia had EoE. Of the seven children with EoE, three (43%) had bronchial asthma, two (28.5%) had peripheral eosinophilia, and one (14%) had elevated serum IgE. Trachealization and linear furrows were found in 57% and 71% cases, respectively. Four children received high‐dose proton pump inhibitor (PPI) for 12 weeks, two received PPI+ stricture dilatation, and one received systemic steroids. All achieved clinical, endoscopic, and histopathological remission. Conclusion: Hospital‐based prevalence of EoE among children undergoing elective UGIE was 3.5%. EoE patients had favorable outcomes with PPI. [ABSTRACT FROM AUTHOR]

This article provides a summary of a Cochrane review on the medical treatment of eosinophilic esophagitis (EoE). EoE is a chronic inflammatory condition of the esophagus that can affect individuals of all ages, but is more common in males and adults. The review evaluated the efficacy and safety of different medical interventions for EoE, including corticosteroids and biologics. The findings suggest that corticosteroids improve clinical and histological outcomes, while biologics may improve clinical outcomes. However, the cost and availability of biologics should be considered. Further research and cost-effectiveness analyses are needed to fully evaluate and compare these treatments. [Extracted from the article]

Background: In addition to the elimination diet, dietary composition may influence disease severity in patients with eosinophilic esophagitis (EoE) through modulation of the immune response. Aim: To explore the immunomodulatory role of nutrition before and during elimination diet in adult EoE patients. Methods: Nutritional intake was assessed in 39 Dutch adult EoE patients participating in the Supplemental Elemental Trial (Dutch trial registry NL6014, NTR6778) using 3‐day food diaries. In this randomized controlled trial, diagnosed patients received either a four‐food elimination diet alone (FFED) or FFED with addition of an amino acid‐based formula for 6 weeks. Multiple linear regression analyses were performed to assess associations between the intake of nutrients and food groups per 1000 kCal and peak eosinophil count/high power field (PEC), both at baseline and after 6 weeks. Results: At baseline, we found a statistically significant negative (thus favorable) relationship between the intake of protein, total fat, phosphorus, zinc, vitamin B12, folate, and milk products and PEC (p <.05), while calcium (p =.058) and full‐fat cheese/curd (p =.056) were borderline (favorably) significant. In contrast, total carbohydrates, prepacked fruit juice, and white bread were significantly positively (unfavorable) related to PEC (p <.05), while ultra‐processed meals (p =.059) were borderline (unfavorably) significant. After dietary intervention, coffee/tea were significantly negatively (favorably) related to PEC, hummus/legumes were significantly positively (unfavorably) related with PEC, while peanuts were borderline significantly positively related (p =.058). Conclusion: Dietary composition may be related to inflammation in adult EoE patients. High‐quality and anti‐inflammatory diets may be a promising adjuvant therapy in the dietary management of EoE. [ABSTRACT FROM AUTHOR]

This article discusses the use of dupilumab, a monoclonal antibody, in the treatment of eosinophilic esophagitis (EoE). The study aimed to determine if dupilumab could improve the clinical and histologic features of EoE before 12 weeks of treatment. The researchers conducted a retrospective study on 79 patients and found that dupilumab induced histologic remission and clinical benefit even before 12 weeks of treatment. There were no significant differences in outcomes between patients on dupilumab for different durations. Further research is needed to determine the appropriate timing for repeat evaluations. [Extracted from the article]

Summary: Food allergies occur due to a lack of tolerance to the proteins found in foods. While IgE‐ and non‐IgE‐mediated food allergies have different clinical manifestations, epidemiology, pathophysiology, and management, they share dysregulated T cell responses. Recent studies have shed light on the contributions of different T cell subsets to the development and persistence of different food allergic diseases. This review discusses the role of T cells in both IgE‐ and non‐IgE‐mediated food allergies and considers the potential future investigations in this context. [ABSTRACT FROM AUTHOR]

Background Purpose Methods Results Conclusion Respiratory motion irregularities in lung cancer patients are common and can be severe during multi‐fractional (∼20 mins/fraction) radiotherapy. However, the current clinical standard of motion management is to use a single‐breath respiratory‐correlated four‐dimension computed tomography (RC‐4DCT or 4DCT) to estimate tumor motion to delineate the internal tumor volume (ITV), covering the trajectory of tumor motion, as a treatment target.To develop a novel multi‐breath time‐resolved (TR) 4DCT using the super‐resolution reconstruction framework with TR 4D magnetic resonance imaging (TR‐4DMRI) as guidance for patient‐specific breathing irregularity assessment, overcoming the shortcomings of RC‐4DCT, including binning artifacts and single‐breath limitations.Six lung cancer patients participated in the IRB‐approved protocol study to receive multiple T1w MRI scans, besides an RC‐4DCT scan on the simulation day, including 80 low‐resolution (lowR: 5 × 5 × 5 mm3) free‐breathing (FB) 3D cine MRFB images in 40 s (2 Hz) and a high‐resolution (highR: 2 × 2 × 2 mm3) 3D breath‐hold (BH) MRBH image for each patient. A CT (1 × 1 × 3 mm3) image was selected from 10‐bin RC‐4DCT with minimal binning artifacts and a close diaphragm match (<1 cm) to the MRBH image. A mutual‐information‐based Freeform deformable image registration (DIR) was used to register the CT and MRBH via the opposite directions (namely F1: CTSource→MRTargetBH${\mathrm{C}}{{{\mathrm{T}}}_{{\mathrm{Source}}}} \to {\mathrm{MR}}_{{\mathrm{Target}}}^{{\mathrm{BH}}}$ and F2: CTTarget←MRSourceBH${\mathrm{C}}{{{\mathrm{T}}}_{{\mathrm{Target}}}} \leftarrow {\mathrm{MR}}_{{\mathrm{Source}}}^{{\mathrm{BH}}}$) to establish CT‐MR voxel correspondences. An intensity‐based enhanced Demons DIR was then applied for MRSourceBH→MRTargetFB${\mathrm{MR}}_{{\mathrm{Source}}}^{{\mathrm{BH}}} \to {\mathrm{MR}}_{{\mathrm{Target}}}^{{\mathrm{FB}}}$, in which the original MRBH was used in D1: CTSource→(MRSourceBH→MRTargetFB)Target${\mathrm{C}}{{{\mathrm{T}}}_{{\mathrm{Source}}}} \to {{({\mathrm{MR}}_{{\mathrm{Source}}}^{{\mathrm{BH}}} \to {\mathrm{MR}}_{{\mathrm{Target}}}^{{\mathrm{FB}}})}_{{\mathrm{Target}}}}$, while the deformed MRBH was used in D2:(CTTarget←MRSourceBH)Source→MRTargetFB${{( \text{C}{{\text{T}}_{\text{Target}}}\leftarrow \text{MR}_{\text{Source}}^{\text{BH}} )}_{\text{Source}}}\to \text{MR}_{\text{Target}}^{\text{FB}}$. The deformation vector fields (DVFs) obtained from each DIR were composed to apply to the deformed CT (D1) and original CT (D2) to reconstruct TR‐4DCT images. A digital 4D‐XCAT phantom at the end of inhalation (EOI) and end of exhalation (EOE) with 2.5 cm diaphragmatic motion and three spherical targets (ϕ = 2, 3, 4 cm) were first tested to reconstruct TR‐4DCT. For each of the six patients, TR‐4DCT images at the EOI, middle (MID), and EOE were reconstructed with both D1 and D2 approaches. TR‐4DCT image quality was evaluated with mean distance‐to‐agreement (MDA) at the diaphragm compared with MRFB, tumor volume ratio (TVR) referenced to MRBH, and tumor shape difference (DICE index) compared with the selected input CT. Additionally, differences in the tumor center of mass (|∆COMD1–D2|), together with TVR and DICE comparison, was assessed in the D1 and D2 reconstructed TR‐4DCT images.In the phantom, TR‐4DCT quality is assessed by MDA = 2.0 ± 0.8 mm at the diaphragm, TVR = 0.8 ± 0.0 for all tumors, and DICE = 0.83 ± 0.01, 0.85 ± 0.02, 0.88 ± 0.01 for ϕ = 2, 3, 4 cm tumors, respectively. In six patients, the MDA in diaphragm match is –1.6 ± 3.1 mm (D1) and 1.0 ± 3.9 mm (D2) between the reconstructed TR‐4DCT and lowR MRFB among 18 images (3 phases/patient). The tumor similarity is TVR = 1.2 ± 0.2 and DICE = 0.70 ± 0.07 for D1 and TVR = 1.4 ± 0.3 (D2) and DICE = 0.73 ± 0.07 for D2. The tumor position difference is |∆COMD1–D2| = 1.2 ± 0.8 mm between D1 and D2 reconstructions.The feasibility of super‐resolution reconstruction of multi‐breathing‐cycle TR‐4DCT is demonstrated and image quality at the diaphragm and tumor is assessed in both the 4D‐XCAT phantom and six lung cancer patients. The similarity of D1 and D2 reconstruction suggests consistent and reliable DIR results. Clinically, TR‐4DCT has the potential for breathing irregularity assessment and dosimetry evaluation in radiotherapy. [ABSTRACT FROM AUTHOR]

Background: A combination of proton‐pump inhibitors (PPI) and topical steroids (TS) is used to treat children with eosinophilic esophagitis (EoE). However, a subset of children do not respond to this combination therapy. We aimed to identify the esophageal transcriptional, cell composition, and microbial differences between the non‐responders (EoE‐PPI‐TSnr; n = 7) and responders (EoE‐PPI‐TSr; n = 7) to the combination therapy for EoE and controls (n = 9) using metatranscriptomics. Methods: Differential gene expression analysis was used to identify transcriptional differences, validated using the EoE diagnostic panel (EDP). Deconvolution analysis was performed to identify differences in their cell type composition. Microbiome analysis was conducted from esophageal biopsies RNAseq data, and microbial abundance was correlated with esophageal gene expression. Results: In all, 3164 upregulated and 3154 downregulated genes distinguished EoE‐PPI‐TSnr from EoE‐PPI‐TSr. Eosinophilic inflammatory response, cytokine signaling, and collagen formation pathways were significantly upregulated in EoE‐PPI‐TSnr. There was a 56% overlap in dysregulated genes between EoE‐PPI‐TSnr and EDP, with a perfect agreement in the directionality of modulation. Eosinophils, dendritic cells (DCs), immature DCs, megakaryocytic‐erythroid progenitors, and T helper type 1 cells were significantly higher in EoE‐PPI‐TSnr. There was no significant difference in microbiome diversity. The relative abundance of Fusobacterium sp. and Acinetobacter sp. notably differed in EoE‐PPI‐TSnr and correlated with the key pathways. Conclusion: Our results provide critical insights into the molecular, cellular, and microbial factors associated with the lack of response to PPI and TS combination therapy in children with EoE. This study advances our understanding of the pathobiology of EoE while guiding personalized treatment strategies. [ABSTRACT FROM AUTHOR]

A 9‐month‐old male presented with vomiting and dehydration with mild hypernatremia in the context of failure to thrive. He was later diagnosed with nephrogenic diabetes insipidus (NDI) during this hospitalisation and was also found to have eosinophilic esophagitis (EoE). He has since been growing well after EoE and NDI were properly managed. Molecular genetic testing revealed an unreported deletion in AQP2 which was deemed pathogenic and of autosomal dominant inheritance when correlated with his clinical findings and family history. This case report describes the clinical course of this patient in comparison to his family members and reviews current literature on autosomal dominant NDI caused by AQP2 mutations. [ABSTRACT FROM AUTHOR]

Background: Sinonasal malignancies with orbital invasion have dismal prognosis even when treated with orbital exenteration (OE). Sugawara et al. developed a surgical strategy called "extended‐OE (EOE)," showing encouraging outcomes. We hypothesized that a similar resection is achievable under endoscopic guidance through the exenterated orbit (endoscopic‐EOE). Methods: The study was conducted in three institutions: University of Vienna; Mayo Clinic; University of Insubria; 48 orbital dissections were performed. A questionnaire was developed to evaluate feasibility and safety of each step, scoring from 1 to 10, ("impossible" to "easy," and "high risk" to "low risk," respectively), most likely complication(s) were hypothesized. Results: The step‐by‐step technique is thoroughly described. The questionnaire was answered by 25 anterior skull base surgeons from six countries. Mean, median, range, and interquartile range of both feasibility and safety scores are reported. Conclusions: Endoscopic‐EOE is a challenging but feasible procedure. Clinical validation is required to assess real‐life outcomes. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Noninvasive biomarkers for diagnosing and monitoring eosinophilic esophagitis (EoE) are currently lacking. This study evaluates 20 biomarkers in serum and saliva, aiming to assess their diagnostic potential in pediatric EoE patients and healthy individuals.Blood and saliva from children undergoing upper endoscopy were analyzed for biomarkers, including absolute eosinophil count (AEC), eosinophil‐derived neurotoxin (EDN), total and specific IgG4‐antibodies (sIgG4), specific IgE‐antibodies (sIgE) and 15‐hydroxyeicosatetraenoic acid (15(S)‐HETE). Some patients participated twice, forming a longitudinal cohort. The ability to use the biomarkers to predict the EoE diagnosis was evaluated.Analysis from 105 children divided into active EoE, remission, and healthy, revealed elevated levels of serum biomarkers (AEC, EDN, 15(S)‐HETE, sIgG4, and sIgE) in active EoE compared to healthy individuals. A combination of biomarkers (AEC, EDN, sIgE to egg white and wheat) and symptoms showed an AUC of 0.92 in distinguishing between the three groups. We further showed that optimal cutoff values for these biomarkers could discriminate between active EoE and healthy with a sensitivity of 88% and a specificity of 100% in distinguishing EoE (active and in remission) from healthy. Longitudinally, levels of EDN, sIgG4 to Bos d 4, Bos d 5, Bos d 8, gliadin, and birch, and sIgE to milk decreased in patients progressing from active EoE to remission (p <.05).This study identified novel biomarkers associated with EoE and proposes a panel, together with symptoms, for effective discrimination between active EoE, EoE in remission, and healthy individuals. The findings may contribute to a less invasive diagnostic method and may be a potential surveillance tool for pediatric EoE patients. [ABSTRACT FROM AUTHOR]

Eosinophilic esophagitis (EoE) is an increasingly prevalent immune‐mediated disease that leads to chronic changes in the oesophagus. These changes can include strictures, narrowing, and stenosis, mediated by an interleukin (IL)‐13 pathway, which leads to remodelling and fibrosis through increasing migration of fibroblasts and subepithelial fibrosis via collagen deposition 1. IL‐13 downregulates TSPAN12, a gene whose expression regulates fibrosis and causes changes in barrier function and higher rates of fibrostenosis in EoE. Dupilumab, a biologic therapy aimed at blocking IL‐13, has been shown to improve EoE‐related inflammation and fibrosis in clinical trials. We report here four unique patients with documented oesophageal stenosis with inability to pass a paediatric endoscope due to structuring disease, requiring dilation, who had resolution of their oesophageal narrowing following dupilumab therapy. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Recently, we have identified a dysregulated protein signature in the esophageal epithelium of eosinophilic esophagitis (EoE) patients including proteins associated with inflammation and epithelial barrier function; however, the effect of proton pump inhibitor (PPI) treatment on this signature is unknown. Herein, we used a proteomic approach to investigate: (1) whether PPI treatment alters the esophageal epithelium protein profile observed in EoE patients and (2) whether the protein signature at baseline predicts PPI response.We evaluated the protein signature of esophageal biopsies using a cohort of adult EoE (n = 25) patients and healthy controls (C) (n = 10). In EoE patients, esophageal biopsies were taken before (pre) and after (post) an 8‐week PPI treatment, determining the histologic response. Eosinophil count PostPPI was used to classify the patients: ≥15 eosinophils/hpf as non‐responders (non‐responder) and < 15 eosinophils/hpf as responders (R). Protein signature was determined and differentially accumulated proteins were characterized to identify altered biological processes and signaling pathways.Comparative analysis of differentially accumulated proteins between groups revealed common signatures between three groups of patients with inflammation (responder‐PrePPI, non‐responder‐PrePPI, and non‐responder‐PostPPI) and without inflammation (controls and responder‐PostPPI). PPI therapy almost reversed the EoE specific esophageal protein signature, which is enriched in pathways associated with inflammation and epithelial barrier function, in responder‐PostPPI. Furthermore, we identified a set of candidate proteins to differentiate responder‐PrePPI and non‐responder‐PrePPI EoE patients before treatment.These findings provide evidence that PPI therapy reverses the alterations in esophageal inflammatory and epithelial proteins characterizing EoE, thereby providing new insights into the mechanism of PPI clinical response. Interestingly, our results also suggest that PPI response could be predicted at baseline in EoE. [ABSTRACT FROM AUTHOR]

Allergic disease prevalence has increased globally with the subset of type 2 inflammatory diseases playing a substantial role. Type 2 inflammatory diseases may differ in clinical presentation, but they exhibit shared pathophysiology that is targeted by the unique pharmacology of dupilumab. Dupilumab binds to the interleukin (IL)‐4 receptor alpha subunit (IL‐4Rα) that blocks IL‐4 and IL‐13 signaling, two key drivers of type 2 inflammation. Herein, we review the mechanism of action and pharmacology of dupilumab, and the clinical evidence that led to the regulatory approvals of dupilumab for the treatment of numerous type 2 inflammatory diseases: atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis, eosinophilic esophagitis, and prurigo nodularis. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori may be found during upper gastrointestinal endoscopy (UGE) performed to diagnose celiac disease (CeD), inflammatory bowel disease (IBD), and eosinophilic esophagitis (EoE). We aimed to describe the frequency of H. pylori in children undergoing UGE for CeD, IBD, and EoE and the number of children receiving eradication treatment. Materials and Methods: A retrospective multicenter study from 14 countries included pediatric patients diagnosed with CeD, IBD, and EoE between January 2019 and December 2021. Data collected: age, gender, hematologic parameters, endoscopic, histologic, and H. pylori culture results, and information on eradication treatment. Results: H. pylori was identified in 349/3890 (9%) children [167 (48%) male, median 12 years (interquartile range 8.1–14.6)]. H. pylori was present in 10% (173/1733) CeD, 8.5% (110/1292) IBD and 7.6% (66/865) EoE patients (p = NS). The prevalence differed significantly between Europe (Eastern 5.2% (28/536), Southern 3.8% (78/2032), Western 5.6% (28/513)) and the Middle East 26.6% (215/809) [odds ratio (OR) 7.96 95% confidence interval (CI) (6.31–10.1) p < 0.0001]. Eradication treatment was prescribed in 131/349 (37.5%) patients, 34.6% CeD, 35.8% IBD, and 56.1% EoE. Predictors for recommending treatment included erosions/ulcers [OR 6.45 95% CI 3.62–11.47, p < 0.0001] and nodular gastritis [OR 2.25 95% CI 1.33–3.81, p 0.003]. Treatment rates were higher in centers with a low H. pylori prevalence (<20%) [OR 3.36 95% CI 1.47–7.66 p 0.004]. Conclusions: Identifying H. pylori incidentally during UGE performed for the most common gastrointestinal diseases varies significantly among regions but not among diseases. The indications for recommending treatment are not well defined, and less than 40% of children received treatment. [ABSTRACT FROM AUTHOR]

Background: Eosinophilic oesophagitis (EOE) is a known cause of food bolus obstruction (FBO) with rising incidence and prevalence. Aims: To assess the rates of EOE in adult cases presenting with an FBO via prospective biopsy collection during index endoscopy. Methods: Oesophageal FBO cases requiring gastroscopy between February 2014 and January 2021 at a single institution with a unified policy to perform biopsies on FBO cases were analysed using medical records, endoscopy and histology. Statistical analysis was undertaken to compare those with and without EOE as their final diagnosis, including the timing of oesophageal biopsy and the season that cases presented. Results: One hundred ninety FBO presentations were analysed, 15 patients presented twice and one patient presented four times within the 7‐year study period. Men represented 72% of cases. A total of 78% of cases had biopsies collected at an index or scheduled follow‐up endoscopy. EOE was the cause of the FBO in 28% (53/190) of presentations. FBO secondary to EOE was more likely to occur in the spring and summer months (Australian September to March), with 39% (19 of 49) of cases presenting in spring attributable to EOE. Conclusion: EOE affects a significant proportion of patients presenting with FBO (28%); a high biopsy rate of 78% in FBO cases provides an opportunity for prompt diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Background and Aim: Food/environmental allergens have been associated with eosinophilic esophagitis (EoE); however, the correlation between allergy profiles and disease responsiveness to proton pump inhibitor (PPI) therapy remains unclear. We aimed to assess the association between food/environmental allergies identified on allergen testing and histologic response to PPI in patients with treatment‐naive EoE. Methods: Adults with newly diagnosed EoE who underwent formal testing for food/environmental allergies at a tertiary center were included. All patients underwent twice‐daily PPI for 8 weeks with subsequent repeat endoscopy and biopsy to assess histologic response. Patients with <15 eosinophils/hpf on post‐PPI mucosal biopsies were classified as responders (PPI‐r‐EoE), while those with ≥15 eosinophils/hpf were nonresponders (PPI‐nr‐EoE). Results: Sixty‐one patients met inclusion criteria (21 PPI‐r‐EoE vs 40 PPI‐nr‐EoE). Demographic, clinical, and endoscopic finding variables were similar between groups. Positive food allergen test was more prevalent among PPI‐nr‐EoE patients (82.5% vs 42.9%, P = 0.003). On multivariable analysis, positive food allergen testing remained an independent predictor for PPI nonresponse (aOR 0.15, CI: 0.04–0.58, P = 0.0006). Positive environmental allergen testing was highly prevalent, with no significant differences between groups (77.5% vs 95.2%, P = 0.14). However, higher number of positive environmental allergens (23.3% [≥5 allergens] vs 73.3% [<5 allergens], P = 0.003) and specific aeroallergens correlated with PPI‐nr‐EoE. Conclusion: Positive food allergy testing and increased environmental allergens predicted lower likelihood of histologic response to PPI in EoE. Our findings support an allergic phenotype of EoE that may less likely respond to PPI therapy. Formal allergen testing may play a role in therapy selection and tailored management in EoE. [ABSTRACT FROM AUTHOR]

This article presents a study that explores the use of noninvasive biomarkers for diagnosing and monitoring pediatric eosinophilic esophagitis (EoE), a chronic allergic disorder affecting the esophagus. The study identifies interleukin (IL)-17, galectin (GAL)-10, and transforming growth factor (TGF)-β as potential biomarkers for EoE. However, more research is required to validate these biomarkers and incorporate them into clinical practice. The study was conducted ethically on children and adolescents. Overall, this research suggests that these biomarkers could enhance the diagnosis and management of EoE, but further investigation is necessary. [Extracted from the article]

This article discusses a case report of a pediatric patient with eosinophilic esophagitis (EoE) who developed neuropathy after using the medication dupilumab. Dupilumab is a new therapy approved for the treatment of EoE in adolescents and pediatric patients. The patient experienced significant improvement in gastrointestinal symptoms while on the medication, but developed paresthesias in his legs and torso after several months of use. The symptoms resolved after discontinuing the medication. The article also mentions two adult cases of neuropathy associated with dupilumab use. While the exact mechanism is unclear, it is suggested that the medication may cause a shift in inflammation that could contribute to the development of neuropathies. Physicians should be aware of this potential association and monitor patients for peripheral neurologic symptoms while on dupilumab. [Extracted from the article]

A study published in the journal Allergy suggests that salivary immunoinflammatory proteins could be used as a less invasive method for identifying children with eosinophilic esophagitis (EoE). Currently, EoE is diagnosed through invasive procedures. The study collected saliva samples from children with EoE and controls and used proximity extension analysis to analyze the proteins. The findings indicate that a panel of proteins could accurately distinguish children with EoE from controls and differentiate between different subtypes of EoE. This research suggests that salivary proteins have diagnostic potential and could serve as non-invasive biomarkers for EoE, but further research is needed to validate these findings. [Extracted from the article]

Summary: Background: Eosinophilic gastrointestinal diseases (EGIDs) are chronic, immune‐mediated disorders characterised clinically by gastrointestinal symptoms and histologically by a pathologic increase in eosinophil‐predominant inflammation in the gastrointestinal tract, in the absence of secondary causes of eosinophilia. Aims: To highlight emerging insights and research efforts into the epidemiology, pathophysiology, diagnostic and therapeutic aspects of eosinophilic oesophagitis (EoE) and non‐EoE EGIDs, and discuss key remaining knowledge gaps. Methods: We selected and reviewed original research, retrospective studies, case series, randomised controlled trials, and meta‐analyses. Results: Standardised nomenclature classifies EGIDs as EoE, eosinophilic gastritis (EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC). Incidence and prevalence of EoE are rising, emphasising the need to better understand how environmental risk factors and genetic features interact. Advances in understanding EoE pathophysiology have led to clinical trials of targeted therapy and the approval (in the United States) of dupilumab for EoE. Several therapies that are under investigation hope to satisfy both histologic and clinical targets. For non‐EoE EGIDs, efforts are focused on better defining clinical and histopathologic disease determinants and natural history, as well as establishing new therapies. Conclusions: Unmet needs for research are dramatically different for EoE and non‐EoE EGIDs. In EoE, non‐invasive diagnostic tests, clinicopathologic models that determine the risk of disease progression and therapeutic failure, and novel biologic therapies are emerging. In contrast, in non‐EoE EGIDs, epidemiologic trends, diagnostic histopathologic thresholds, and natural history models are still developing for these more rare disorders. [ABSTRACT FROM AUTHOR]

Summary: Background: Prior work suggests eosinophilic oesophagitis (EoE) is rare in those aged over 65 years. However, elderly patients with EoE experience a substantial diagnostic delay from symptom onset to diagnosis. Aims: To assess if age predicted whether oesophageal biopsies were obtained in patients with EoE symptoms, what clinical features predict EoE in the elderly, and if EoE phenotype differs between elderly and non‐elderly patients. Methods: We conducted a retrospective cohort study utilising the University of North Carolina (UNC) electronic medical record, EoE clinicopathologic database and UNC endoscopy software from July 2008 to April 2021. A sample of 193 elderly and non‐elderly patients with dysphagia, chest pain and/or heartburn were assembled. Patients with EoE were newly diagnosed per contemporaneous guidelines. Patient demographics, clinical characteristics and procedural data were extracted. Summary statistics, bivariate and multivariate analyses were performed. Results: Of 193 patients, we included 91 elderly (47%) and 102 non‐elderly (53%). Age independently predicted the odds of biopsies (adjusted odds ratio (aOR): 0.44 elderly vs. non‐elderly; 95% CI: 0.21–0.92). Endoscopic features of EoE, but not symptoms, were more common in elderly than non‐EoE elderly patients. Elderly patients with EoE differed from non‐elderly only by time to diagnosis (aOR per year of symptoms preceding diagnosis: 1.08, 95% CI: 1.04–1.11). Conclusions: Elderly patients with EoE have <50% the odds of oesophageal biopsies. There were no significant differences between elderly and non‐elderly EoE patients, although endoscopic features helped discriminate the two groups. Our findings suggest that older age represents a barrier to EoE diagnosis. [ABSTRACT FROM AUTHOR]

MicroRNA (miRNA)‐mediated mRNA regulation directs many homeostatic and pathological processes, but how miRNAs coordinate aberrant esophageal inflammation during eosinophilic esophagitis (EoE) is poorly understood. Here, we report a deregulatory axis where microRNA‐155 (miR‐155) regulates epithelial barrier dysfunction by selectively constraining tight junction CLDN7 (claudin‐7). MiR‐155 is elevated in the esophageal epithelium of biopsies from patients with active EoE and in cell culture models. MiR‐155 localization using in situ hybridization (ISH) in patient biopsies and intra‐epithelial compartmentalization of miR‐155 show expression predominantly within the basal epithelia. Epithelial miR‐155 activity was evident through diminished target gene expression in 3D organotypic cultures, particularly in relatively undifferentiated basal cell states. Mechanistically, generation of a novel cell line with enhanced epithelial miR‐155 stable overexpression induced a functionally deficient epithelial barrier in 3D air–liquid interface epithelial cultures measured by transepithelial electrical resistance (TEER). Histological assessment of 3D esophageal organoid cultures overexpressing miR‐155 showed notable dilated intra‐epithelial spaces. Unbiased RNA‐sequencing analysis and immunofluorescence determined a defect in epithelial barrier tight junctions and revealed a selective reduction in the expression of critical esophageal tight junction molecule, claudin‐7. Together, our data reveal a previously unappreciated role for miR‐155 in mediating epithelial barrier dysfunction in esophageal inflammation. [ABSTRACT FROM AUTHOR]

This article presents the findings of a multicenter retrospective study on eosinophilic esophagitis (EoE) in children in Italy. The study aimed to describe the characteristics, treatment, and outcomes of pediatric EoE patients in Italy. The study included 56 patients, with the majority being male and the median age at diagnosis being 12.1 years. Dysphagia and bolus impaction were the most common symptoms, and older children showed more endoscopic alterations and symptoms compared to younger children. The study concludes that short-term EoE evolution is generally favorable in most cases. The study found that males are most affected by EoE, and atopic comorbidities and family history are common. Older patients often experience dysphagia and food impaction, while younger children exhibit nonspecific symptoms. The study also found that normal esophagogastroduodenoscopy (EGDS) findings were present in about 20% of cases, emphasizing the importance of biopsies even when the endoscopic appearance is normal. The study highlights the variation in symptoms and endoscopic features based on age, with younger children showing an inflammatory pattern and older children showing a fibro-stenotic pattern. The study also reports high rates of clinical remission with topical corticosteroid treatment, although there was a dissociation between clinical and histologic remission at follow-up. The authors note that larger prospective studies are needed to determine the long-term prognosis of [Extracted from the article]

The article discusses the identification of salivary immunoinflammatory proteins that can help diagnose children with eosinophilic esophagitis (EoE). The study found that inflammatory cytokines, including interleukin-17, correlated with the severity of esophageal mucosal involvement, but not with peak eosinophil count. The research suggests that EoE pathophysiology involves more than just eosinophils, highlighting the need for a multidimensional assessment in disease monitoring and management. Additionally, IL-17 may play a role in EoE pathogenesis, but further studies are needed to confirm its utility as a noninvasive biomarker. [Extracted from the article]

This article discusses a study on children with severe cow's milk allergy who also have esophageal eosinophilia (EE). The study found that 45.4% of patients had EE, with 21.2% diagnosed with eosinophilic esophagitis (EoE) and 24.2% with asymptomatic esophageal eosinophilia (aEE). The article provides detailed information on the characteristics and outcomes of the patients in the study, including a table showing follow-up information for 15 patients. The study highlights the importance of screening for EE in patients with cow's milk allergy, but notes the challenges in diagnosing and treating the condition. Further research is needed to better understand EE in these patients. [Extracted from the article]

Belatedly, gastroenterologists have begun to pay attention to the role of diet in the exacerbation of gastrointestinal symptoms in many digestive disorders—a recognition that has spurred both high‐quality clinical trials and translational research into this area. It has become clear that multiple mechanisms acting either in isolation or together can induce gut symptoms and that appropriate interventions can lead to significant relief. What this review will explore is not the role of diet in the production of certain symptoms or symptom clusters, but rather whether a dietary intervention can beneficially alter the natural history of a gastrointestinal disease—a much more demanding expectation. Yet there are examples of where a diet, if sustained, can have a long‐term impact on at least some of those affected by conditions such as eosinophilic esophagitis, celiac disease, food allergy, and constipation. [ABSTRACT FROM AUTHOR]

Purpose: Neurodevelopmental disorders, such as autism spectrum disorder (ASD), have been increasingly associated with eosinophilic gastrointestinal disorders (EGID). However, the relationship between these diseases remains unclear. We performed a systematic review with meta‐analysis to address this issue. Methods: The search was performed according to the PRISMA guidelines using descriptors for ASD and EGIDs from the MEDLINE, Embase, PsycInfo, LILACS, and Web of Science databases. Observational studies with the prevalence of ASD in any EGID were included. The study protocol was registered on the PROSPERO platform under the number CRD42023455177. Results: The total dataset comprised 766,082 participants. The result of the single‐arm meta‐analysis showed an overall prevalence of ASD in the population with EGID of 21.59% (95% CI: 10.73–38.67). There was an association between EGID and ASD (OR: 3.44; 95% CI: 1.25–2.21), also significant when restricted only to EoE (OR: 3.70; 95% CI: 2.71–5.70). Discussion: Recent studies have implicated the influence of an inadequate epithelial barrier integrity in the pathogenesis of several diseases. The role of this mechanism can be extended to situations beyond allergic reactions, including other conditions with underlying immunological mechanisms. Several diseases are potentially related to the systemic effect of bacterial translocation in tissues with defective epithelial barriers. Conclusion: Our meta‐analysis provides evidence that supports the consideration of EGID in patients with ASD and ASD in patients with EGID. Despite its limitations, the results should also be validated by future studies, preferably using multicenter prospective designs in populations with low referral bias. [ABSTRACT FROM AUTHOR]

Background: Standard impedance catheters and balloon‐based mucosal impedance catheters (BBMI) have been used to assess mucosal integrity and diagnose mucosal diseases. The goal of this study was to determine the age‐related technical issues associated with mucosal balloon inflation, validate the BBMI measurement against a standard impedance probe, and compare software‐generated diagnoses to histologic diagnoses. Methods: We prospectively recruited patients undergoing endoscopy, during which patients underwent standard mucosal impedance catheters and BBMI measurements. Measurements were compared to each other, to the histologic diagnoses, and to the number of eosinophils per high power field. We then compared the patients' diagnosis to that assigned by the BBMI software. Key Results: Sixty‐two patients (mean age: 62 ± 62 months) were recruited, including non‐GERD (N = 40), GERD (N = 15), and EoE (N = 7) patients. There were significant differences between the impedance values measured by the two technologies at each esophageal height (p < 0.003). There were significant correlations between the mean impedance values taken by the two catheters in the distal (r2 = 0.272, p = 0.04), mid (r2 = 0.371, p < 0.001), and proximal (r2 = 0.259, p = 0.05) esophagus. There were significant differences in BBMI impedance values across diagnoses in the mid and proximal esophagus (p = 0.024 and 0.025, respectively). While not statistically significant (p = 0.061–0.073), the standard catheter showed similar trends by diagnosis. Using the BBMI diagnostic prediction software, 33%–72% of patients were misclassified. Conclusion and Inferences: While there was significant variability in impedance values between technologies within patients, regional measurements were consistent across catheters. Automated analyses lacked the sensitivity to diagnose inflammatory disorders. [ABSTRACT FROM AUTHOR]

The epithelial barriers of the skin, gut, and respiratory tract are critical interfaces between the environment and the host, and they orchestrate both homeostatic and pathogenic immune responses. The mechanisms underlying epithelial barrier dysfunction in allergic and inflammatory conditions, such as atopic dermatitis, food allergy, eosinophilic oesophagitis, allergic rhinitis, chronic rhinosinusitis, and asthma, are complex and influenced by the exposome, microbiome, individual genetics, and epigenetics. Here, we review the role of the epithelial barriers of the skin, digestive tract, and airways in maintaining homeostasis, how they influence the occurrence and progression of allergic and inflammatory conditions, how current treatments target the epithelium to improve symptoms of these disorders, and what the unmet needs are in the identification and treatment of epithelial disorders., (© 2024 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background and Aim: Globally, over 180,000 children develop cancers yearly, with about 80% residing in low‐ or middle‐income countries where cancer‐associated mortality is also high. In The Gambia, cumulative incidence rate of 27.6 childhood cancers/million population was reported between 2002 and 2011. The current study appraised newly‐established pediatric oncological services in The Gambia. Methods: In this prospective registry study, children with cancer who presented at the pediatric units, Edward Francis Small Teaching Hospital, Banjul, between November 2022 and October 2023 were assessed. Data on sociodemographic variables, mode of admission and presentation, tumor type, diagnostic methods, and challenges such as laboratory support, treatment, use of blood/blood products; and eventual outcome were analyzed. Results: The median (interquartile range, IQR) age at presentation of the 44 children was 36.0 (22.3–117.0) months. Wilms tumor was the most common tumor 12 (27.3%); followed by leukemia 11 (25.0%); germ cell tumor 8 (18.2%); lymphoma 6 (13.6%); retinoblastoma 4 (9.1%); rhabdomyosarcoma 2 (4.5%) and one central nervous system tumor (2.3%). The median(IQR) duration of symptoms before presentation was 48 (21–90) days, presentation to diagnosis 7.5 (3–20.8) days, and first symptom to diagnosis 62.5 (32–126.8) days. Treatment refusal and abandonment rates were 20.5% and 13.6%, respectively. Families of 93.8% of children could not procure cytotoxic drugs due to nonavailability, high cost, or both. Adequate laboratory monitoring was only available in 6.8%, and none had platelet concentrate transfusion or radiotherapy. The nine (20.5%) who completed treatment are currently being followed up, 10(22.7%) are still receiving chemotherapy, while 2(4.5%) were referred. Eight (18.2%) died, predominantly from metastasis (75%) and severe drug toxicities (25%). Conclusion: Late presentation and diagnosis, poverty, unavailability of drugs, suboptimal or lack of laboratory testing, blood product, adjuvant medications, and psychosocial supports contributed to high treatment refusal, abandonment, and mortality. These daunting challenges can be ameliorated with regular community sensitization, frequent cancer auditing, and strong political will. [ABSTRACT FROM AUTHOR]

Background and Aim: According to the European Society of Gastrointestinal Endoscopy (ESGE), gastroscopy should be conducted within 6 h for complete obstruction and 24 h for incomplete obstruction due to food bolus impaction. This study explores whether adults with acute esophageal food bolus (FB) impaction experience adverse outcomes when their time to esophagogastroduodenoscopy (EGD) deviates from the recommended guidelines. Methods: A retrospective review was performed on the records of 248 patients who presented at the study site between 2015 and 2022 with symptoms of FB impaction. Results: Two hundred and forty‐eight patients underwent EGD for FB impaction. Grade 1 (erosion, ulceration), Grade 2 (tear), and Grade 3 (perforation) complications were present in 31.6%, 6.9%, and 0.8% of cases, respectively. Of the 134 (54.0%) patients with complete obstruction, 51 (38.1%) received EGD within the recommended 6 h. Of the 114 (46%) patients with incomplete obstructions, 93 (81.6%) received EGD within the recommended 24 h. There was no statistically significant correlation between length of stay (LOS) post‐EGD and any of ingestion to presentation time, presentation to EGD time, or ingestion to EGD time. Age and complication level were greater predictors of longer LOS than presentation to EGD time. Patients who presented in hours were significantly more likely to receive EGD within the 6‐ and 24‐h guidelines than those who presented out of hours (50.7% vs 22.0%). Conclusion: Neither time to EGD from ingestion of food bolus nor time to EGD from hospital presentation correlated with complication rate, complication severity, or length of stay post‐EGD. [ABSTRACT FROM AUTHOR]

Aircraft coating process has been an important part in manufacturing process of modern aviation products. For coating defect detection, the manual observation with naked eyes is usually utilized, which leads to low production efficiency. In this paper, the authors propose the improved YOLOv5‐OBB with the channel‐spatial attention block (CSAB), feature pyramid non‐local module (FPNM) and structured sparsity slimming criterion (SSSC). The CSAB can pay more attention to effective channel information features from the channel dimension and the target information area from the spatial dimension. The effective non‐local module called FPNM is proposed to further improve the detection accuracy. The authors utilize the oriented bounding boxes (OBB) to reduce redundant background information for coating defect detection. In addition, the SSSC is proposed to achieve network slimming and trade‐off between the efficiency and accuracy. The experimental results on several datasets demonstrate the effectiveness of the authors' scheme, which achieves superior performance. [ABSTRACT FROM AUTHOR]

With increasing global urbanization, the proportion of the world's population engaged in the primary sector of the economy continues to decrease, leading to significant changes in the experience of nature (EoN). As a result, not only are opportunities for EoN reduced, but they are shifting structurally because the proportion of nature experiences that take place in leisure time increases relative to that which takes place in a work and production context.In order to understand the implications of this structural change, a new typology is introduced that defines experiences of nature by considering their social context: economic and recreational EoN.Economic EoN is predominantly purpose‐oriented, while recreational EoN is primarily experience‐driven. Compared to economic EoN, recreational EoN often requires less skill and knowledge while relying on stereotypical constructs of nature, demonstrated, for example, by traditional land uses and tourism, respectively. As urbanization continues, the proportion of recreational nature experiences will continue to increase, raising an important question: How can the experience‐driven, recreational relation to nature contribute to long‐term engagement and responsible stewardship?Long‐term engagement is evident in leisurely behaviour where people pursue hobbies. In urban societies, many people invest a considerable amount of time and material resources in their hobbies, while developing specific skill sets and acquiring extensive knowledge in the process. Furthermore, nature‐related hobbies enable the transformation of irrelevant economic EoN into meaningful recreational EoN, allowing the emergence of an individual perspective on and a lasting relationship with nature, as well as creating a skill‐based sense of place.Policy implications: As traditional economic EoN diminish and becomes irrelevant during the urbanization process, hobbies can help preserve ecological knowledge and skills with recreational EoN. Protected areas and other organizations curating nature experiences should create and promote experiences that relate to nature‐based hobbies and focus on supporting skill development. Read the free Plain Language Summary for this article on the Journal blog. Read the free Plain Language Summary for this article on the Journal blog. [ABSTRACT FROM AUTHOR]

SHR‐1819 is a novel anti‐IL‐4Rα monoclonal antibody currently under clinical development for use in patients with type 2 inflammatory diseases. In this randomized, double‐blind, placebo‐controlled, single‐dose escalation phase I trial, we evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of SHR‐1819 in healthy subjects. Subjects received a single subcutaneous injection of SHR‐1819 or placebo, with dose escalation starting at 60 mg and subsequently increasing to 120, 240, 360, and 720 mg. A total of 42 eligible subjects were randomized, and 33 received SHR‐1819 (1 subject in the 60 mg cohort and 8 subjects each in the 120, 240, 360 , and 720 mg cohorts) and 9 received placebo. SHR‐1819 was well‐tolerated, with the majority of adverse events being mild in severity. The exposure of SHR‐1819 increased in a manner greater than proportionally with a dose range of 120 to 720 mg. The median Tmax was within 4–7 days (60–720 mg), and the mean half‐life ranged from 2.88 to 5.97 days (120–720 mg). The clearance rate of SHR‐1819 exhibited a decrease with increasing dose level. Administration of SHR‐1819 resulted in a certain degree of reduction in the percentage change from baseline in concentrations of inflammatory biomarkers TARC/CCL17 and IgE, while the reduction of TARC/CCL17 concentrations showed a dose‐dependent trend. More than half of the total subjects treated with SHR‐1819 were reported antidrug antibody‐negative. The preliminary data from this phase I study support further development of SHR‐1819 for the treatment of type 2 inflammatory diseases. [ABSTRACT FROM AUTHOR]

Retort processing is a food preservation technique to address the challenge posed by Clostridium botulinum for commercial sterility of a food product to get microbiologically safe and stable products by heating. This review aims to explore the journey of retort processing, starting from its early use in single‐batch canned foods and progressing to its contemporary applications with different types of containers and heating mediums. Additionally, it will delve into the adaptability of retort equipment, including its ability to operate in stationary and various agitation states, as well as its flexibility in processing speed for both single‐batch and continuous operations. [ABSTRACT FROM AUTHOR]

Interleukin (IL)-5 is the key cytokine in the maturation, activation, proliferation, migration and survival of eosinophils, which are key effector cells in many upper and lower airway diseases. Through its effects on eosinophils, IL-5 indirectly contributes to various pathophysiological processes including tissue damage, repair and remodelling. Understanding the importance of IL-5 in eosinophil-associated diseases led to the development of anti-IL-5 therapies, which provide clinical benefits across a range of conditions. However, recent evidence suggests that eosinophil-depletion alone may not account for all of the therapeutic effects of anti-IL-5 therapy and that IL-5 may also contribute to disease independently of its effects on eosinophils. Indeed, evidence from ex vivo studies and targeted therapy in vivo demonstrates that IL-5 and its inhibition affects a much broader range of cells beyond eosinophils, including epithelial cells, plasma cells, mast cells, basophils, neutrophils, type 2 innate lymphoid cells, T regulatory cells and fibroblasts. This review will provide an update on the evidence supporting the breadth of IL-5 biology relevant to disease pathogenesis beyond eosinophil-associated inflammation, where there is a need for additional insight, and the clinical implications of a more central role of IL-5 in type 2 inflammation., (© 2024 GSK and The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Infantile bullous pemphigoid (BP) is a rare autoantibody-mediated skin disorder. We report the effective treatment of a 6-month-old infant with BP using baricitinib, a Janus kinase (JAK) inhibitor, after failure with steroids and intravenous immunoglobulin. The patient achieved full remission and discontinued all medications without any relapses. To our knowledge, this is the first case of baricitinib used in an infant with BP., (© 2024 Australasian College of Dermatologists.)

Disease Overview: The eosinophilias encompass a broad range of non-hematologic (secondary or reactive) and hematologic (primary or clonal) disorders with the potential for end-organ damage., Diagnosis: Hypereosinophilia (HE) has generally been defined as a peripheral blood eosinophil count greater than 1.5 × 10 9 /L, and may be associated with tissue damage. After the exclusion of secondary causes of eosinophilia, diagnostic evaluation of primary eosinophilias relies on a combination of various tests. They include morphologic review of the blood and marrow, standard cytogenetics, fluorescence in situ hybridization, molecular testing and flow immunophenotyping to detect histopathologic or clonal evidence for an acute or chronic hematolymphoid neoplasm., Risk Stratification: Disease prognosis relies on identifying the subtype of eosinophilia. After evaluation of secondary causes of eosinophilia, the 2022 World Health Organization and International Consensus Classification endorse a semi-molecular classification scheme of disease subtypes. This includes the major category "myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions" (MLN-eo-TK), and the MPN subtype, "chronic eosinophilic leukemia" (CEL). Lymphocyte-variant HE is an aberrant T-cell clone-driven reactive eosinophila, and idiopathic hypereosinophilic syndrome (HES) is a diagnosis of exclusion., Risk-Adapted Therapy: The goal of therapy is to mitigate eosinophil-mediated organ damage. For patients with milder forms of eosinophilia (e.g., <1.5 × 10 9 /L) without symptoms or signs of organ involvement, a watch and wait approach with close follow-up may be undertaken. Identification of rearranged PDGFRA or PDGFRB is critical because of the exquisite responsiveness of these diseases to imatinib. Pemigatinib was recently approved for patients with relapsed or refractory FGFR1-rearranged neoplasms. Corticosteroids are first-line therapy for patients with lymphocyte-variant HE and HES. Hydroxyurea and interferon-α have demonstrated efficacy as initial treatment and in steroid-refractory cases of HES. Mepolizumab, an interleukin-5 (IL-5) antagonist monoclonal antibody, is approved by the U.S Food and Drug Administration for patients with idiopathic HES. Cytotoxic chemotherapy agents, and hematopoietic stem cell transplantation have been used for aggressive forms of HES and CEL, with outcomes reported for limited numbers of patients. Targeted therapies such as the IL-5 receptor antibody benralizumab, IL-5 monoclonal antibody depemokimab, and various tyrosine kinase inhibitors for MLN-eo-TK, are under active investigation., (© 2024 Wiley Periodicals LLC.)

Background: Nasal epithelial cells are important regulators of barrier function and immune signaling; however, in allergic rhinitis (AR) these functions can be disrupted by inflammatory mediators. We aimed to better discern AR disease mechanisms using transcriptome data from nasal brushing samples from individuals with and without AR., Methods: Data were drawn from a feasibility study of individuals with and without AR to Timothy grass and from a clinical trial evaluating 16 weeks of treatment with the following: dupilumab, a monoclonal antibody that binds interleukin (IL)-4Rα and inhibits type 2 inflammation by blocking signaling of both IL-4/IL-13; subcutaneous immunotherapy with Timothy grass (SCIT), which inhibits allergic responses through pleiotropic effects; SCIT + dupilumab; or placebo. Using nasal brushing samples from these studies, we defined distinct gene signatures in nasal tissue of AR disease and after nasal allergen challenge (NAC) and assessed how these signatures were modulated by study drug(s)., Results: Treatment with dupilumab (normalized enrichment score [NES] = -1.73, p = .002) or SCIT + dupilumab (NES = -2.55, p < .001), but not SCIT alone (NES = +1.16, p = .107), significantly repressed the AR disease signature. Dupilumab (NES = -2.55, p < .001), SCIT (NES = -2.99, p < .001), and SCIT + dupilumab (NES = -3.15, p < .001) all repressed the NAC gene signature., Conclusion: These results demonstrate type 2 inflammation is an important contributor to the pathophysiology of AR disease and that inhibition of the type 2 pathway with dupilumab may normalize nasal tissue gene expression., (© 2024 Regeneron Pharmaceuticals Inc and The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)