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Objective: To investigate the clinicopathological features and differential diagnosis of eosinophilic vacuolated tumor (EVT). Methods: Seven cases of EVT with characteristic morphology and unequivocal diagnosis from the Affiliated Hospital of Qingdao University (6 cases), Qingdao, China and the 971 Hospital of PLA Navy (1 case), Qingdao, China between January 2010 and December 2021 were subject to morphological and immunohistochemical analyses. Additionally, whole exome sequencing (WES) was performed in two cases. Twenty-two cases of renal oncocytoma (RO) and 17 cases of eosinophilic chromophobe renal cell carcinoma (eChRCC) diagnosed at the same time were used as controls. Results: Four males and three females with a mean age of 42 years (range: 29-61 years) were included in the study. The tumors were nodular and well-circumscribed, with sizes ranging from 1.5 to 4.5 cm. On cross-section, they appeared gray-red or gray-white, solid, and soft. Tumor cells were arranged in nests, solid sheets, and acinar or small vesicular structures. These cells exhibited eosinophilic cytoplasm with large, prominent clear vacuoles and round nuclei with prominent nucleoli. Perinuclear halos were focally present in four cases, while small tumor cells with sparse cytoplasm and hyperchromatic nuclei were seen in one case. No necrosis or mitosis was noted. Edematous stroma was detected in three cases. All tumors were positive for CD117 and Cathepsin K, but negative for vimentin and CK7. CK20 was positive in scattered individual cells, and Ki-67 positivity ranged from 1% to 4%. Point mutations in MTOR were identified in both patients who were subject to the molecular analysis. Statistical differences in the expression of Cathepsin K, CD10, S-100A1, and Cyclin D1 between EVT and RO ( P <0.05) were significant, so were the differences in the expression of Cathepsin K, CD10, CK7 and claudin 7 between EVT and eChRCC ( P <0.001). Seven patients were followed up for 4 to 96 months (mean, 50 months), with no recurrences or metastases. Conclusions: EVT is a rare renal tumor that shares morphological and immunophenotypic features with RO and eChRCC, and it is closely linked to the TSC/MTOR pathway. The presence of large prominent transparent vacuoles in eosinophilic cytoplasm along with conspicuous nucleoli is its key morphological characteristics. The use of combined immunohistochemical stains greatly aids in its diagnosis. Typically, the tumor exhibits indolent biological behaviors with a favorable prognosis.

Immune activation status determines non-small cell lung cancer (NSCLC) prognosis, with reported positive/negative associations for T helper type 2 (TH2) responses, including allergen-specific IgE and eosinophils. Our study seeks to explore the potential impact of these comorbid immune responses on the survival rates of patients with NSCLC. Our retrospective study used data from the Data Warehouse of the German Center for Lung Research (DZL) and Lung Biobank at Thoraxklinik Heidelberg. We estimated the association of blood eosinophilia and neutrophilia on survival rates in an inflammatory cohort of 3143 patients with NSCLC. We also tested sensitization to food and inhalants and high-sensitivity C-reactive protein (hs-CRP) in a comorbidity cohort of 212 patients with NSCLC. Finally, we estimated the infiltration of immune-relevant cells including eosinophils, T-cells, and mast cells in a tissue inflammatory sub-cohort of 60 patients with NSCLC. Sensitization to at least one food or inhalant (sIgE) was higher in patients with adenocarcinoma (adeno-LC) than the non-adenocarcinoma (non-adeno-LC). Furthermore, hs-CRP was higher in non-adeno-LC compared with adeno-LC. Peripheral inflammation, particularly eosinophilia and neutrophilia, was associated with poor survival outcomes in NSCLC with a clear difference between histological subgroups. Finally, blood eosinophilia was paralleled by significant eosinophil infiltration into the peritumoral tissue in the lung. This study provides novel perspectives on the crucial role of peripheral inflammation, featuring eosinophilia and neutrophilia, with overall survival, underscoring distinctions between NSCLC subgroups (adeno-LC vs. non-adeno-LC). Peripheral eosinophilia enhances eosinophil infiltration into tumors. This sheds light on the complex interplay between inflammation, eosinophil infiltration, and NSCLC prognosis among various histological subtypes. Further studies are required to underscore the role of eosinophils in NSCLC among different histological subgroups and their role in shaping the tumor microenvironment.

Eosinophilic gastroenteritis poses a significant diagnostic challenge, particularly in developing countries, where the awareness of this condition may be limited. Here, the case of a patient in her early 30s, who presented with recurrent episodes of abdominal pain and diarrhea, is reported. Initial standard laboratory investigations revealed normal complete blood counts and elevated total serum immunoglobulin E levels. Upper and lower endoscopic evaluations with systemic biopsies did not reveal any significant abnormalities. However, computed tomography revealed a thickened small intestine wall, halo signs, and mild ascites. Analysis of the ascitic fluid confirmed eosinophilia. These findings prompted a diagnosis of eosinophilic gastroenteritis. The patient responded well to a targeted elimination diet, corticosteroids, and antileukotriene medication. The present case emphasizes the importance of considering eosinophilic gastroenteritis in the differential diagnosis of patients who present with abdominal pain and eosinophilic ascites., Competing Interests: Declaration of conflicting interestThe authors declare that there are no conflicts of interest.

Feline gastrointestinal eosinophilic sclerosing fibroplasia (FGESF) is a rare and poorly understood disease characterised by the infiltration of eosinophils and the development of fibrous tissue within the gastrointestinal tract of cats. A 2-year-old female neutered Ragdoll was presented for signs consistent with extrahepatic biliary tract obstruction (EHBO), including jaundice, hyporexia and lethargy. Marked progressive hyperbilirubinemia and mild anaemia were also present. Abdominal ultrasonography suggested a duodenal mass and pancreatitis as the cause of EHBO. Cytopathological results from fine needle aspirates detected mast cells and eosinophils in the duodenal mass and eosinophils in the spleen and the liver, suggestive of a possible mast cell tumour. A cholecystojejunostomy and a duodenotomy were performed to divert the biliary outflow and obtain biopsy samples, respectively. Eosinophilic sclerosing fibroplasia in the duodenal mass and fungal elements in an abdominal lymph node were reported on histopathological examination. A pan-fungal PCR targeting ITS2 performed on DNA extracted from an abdominal lymph node detected Candida albicans. This report adds to the growing body of evidence that FGESF can occur in association with fungal infections., (© 2024 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Background: Epithelial remodeling is a prominent feature of eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP), and infiltration of M2 macrophages plays a pivotal role in the pathogenesis of eCRSwNP, but the underlying mechanisms remain undefined., Objective: We sought to investigate the role of ALOX15 + M2 macrophages in the epithelial remodeling of eCRSwNP., Methods: Digital spatial transcriptomics and single-cell sequencing analyses were used to characterize the epithelial remodeling and cellular infiltrate in eCRSwNP. Hematoxylin and eosin staining, immunohistochemical staining, and immunofluorescence staining were used to explore the relationship between ALOX15 + M2 (CD68 + CD163 + ) macrophages and epithelial remodeling. A coculture system of primary human nasal epithelial cells (hNECs) and the macrophage cell line THP-1 was used to determine the underlying mechanisms., Results: Spatial transcriptomics analysis showed the upregulation of epithelial remodeling-related genes, such as Vimentin and matrix metalloproteinase 10, and enrichment of epithelial-mesenchymal transition (EMT)-related pathways, in the epithelial areas in eCRSwNP, with more abundance of epithelial basal, goblet, and glandular cells. Single-cell analysis identified that ALOX15 + , rather than ALOX15 - , M2 macrophages were specifically highly expressed in eCRSwNP. CRSwNP with high ALOX15 + M2 THP-1-IL-4+IL-13 macrophages had more obvious epithelial remodeling features and increased genes associated with epithelial remodeling and integrity of epithelial morphology versus that with low ALOX15 + M2 THP-1-IL-4+IL-13 macrophages. IL-4/IL-13-polarized M2 THP-1-IL-4+IL-13 macrophages upregulated expressions of EMT-related genes in hNECs, including Vimentin, TWIST1, Snail, and ZEB1. ALOX15 inhibition in M2 THP-1-IL-4+IL-13 macrophages resulted in reduction of the EMT-related transcripts in hNECs. Blocking chemokine (C-C motif) ligand 13 signaling inhibited M2 THP-1-IL-4+IL-13 macrophage-induced EMT alteration in hNECs., Conclusions: ALOX15 + M2 macrophages are specifically increased in eCRSwNP and may contribute to the pathogenesis of epithelial remodeling via production of chemokine (C-C motif) ligand 13., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

The large spectrum of etiologies, severities, and histologic appearances of eosinophilic myocarditis (EoM) poses challenges to its diagnosis and management. Endomyocardial biopsy is the current gold standard for diagnosis. However, cardiovascular magnetic resonance imaging is becoming more frequently used to diagnose acute myocarditis because of enhanced sensitivity when compared to histopathologic examination, and its less invasive nature. We report a complicated case of EoM in a male in his mid-thirties that led to fulminant cardiogenic shock that required immunosuppressive therapy on day 5 of admission and implantation of a left ventricular assist device (LVAD) on day 30. EoM was diagnosed on histopathologic examination of the resected fragment of the left ventricular myocardium. Nine months after the initial presentation, the patient ultimately required heart transplantation. The explanted heart showed minimal residual interstitial inflammation with evidence of mildly active intimal arteritis and patchy areas of interstitial fibrosis. In this report, we describe our patient's clinical features and correlate them with imaging and histopathologic findings to illustrate the difficulty in diagnosing EoM, particularly in this complicated patient that ultimately required heart transplantation. The diagnosis can be challenging due to the variable histopathologic features, clinical presentation, and utilization of therapeutic medications and devices., Competing Interests: Declaration of competing interest Declaration of competing interest: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The polymorphic presentation of annular dermatoses in the pediatric population renders them a diagnostic challenge to the clinician. They include various distinct disease entities that can be vaguely categorized according to the age of onset. Herein, we report on a young girl with clinical characteristics of Wells' syndrome, while histological findings favored the diagnosis of annular erythema of infancy (AEI). Although morphological and histological similarities do exist, AEI and eosinophilic annular erythema (EAE) of childhood are considered as distinct entities in the literature. Wells' syndrome (WS) is an eosinophilic dermatosis and histologically characterized by eosinophilic dermal infiltration with the hallmark feature of "flame figures." Based on this case, we discuss and review the differential diagnoses of annular dermatoses in children., (© 2023. The Author(s).)

Aim: Eosinophils are normal residents of the gastrointestinal tract (GIT). They are noted in small numbers with significant variation between anatomic locations. An idiopathic increase of eosinophils is known as eosinophilic gastrointestinal disease (EGID). EGIDs are a heterologous group of disorders that produce a range of enteric and colonic syndromes. Their incidence has been increasing worldwide. Our study aimed to quantify eosinophils in each segment of the GIT in surgical specimens with normal histology to facilitate the histological diagnosis of EGID. Similarly, we aimed to describe the effect of race and gender on gastrointestinal eosinophil numbers., Methods: A retrospective, quantitative comparative study was performed. We assessed 360 surgical specimens with normal histology from the lower gastrointestinal tract of African and Caucasian adults from the Free State Province, South Africa. The number of eosinophils per mm² was counted., Results: Overall, comparable eosinophil values were noted for both males and females, and African and Caucasian South Africans. However, Caucasians recorded a higher concentration of eosinophils in the appendix and the left colon. Eosinophils were most numerous in the lamina propria, with only small numbers present in the epithelium. Our results show that the South African population has similar eosinophil distribution trends to international studies. However, South Africans had far fewer eosinophils than Japanese and North American adults in each segment., Conclusions: Specific eosinophil reference ranges were formulated to quantify reference ranges of eosinophils in the lower GIT, allowing for the accurate diagnosis of EGIDs in our population in future., (©The Author(s) 2024. Open Access. This article is licensed under a Creative Commons CC-BY International License.)

Chromosomal rearrangements involving Janus kinase 2 (JAK2) are rare but recurrent findings in lymphoid or myeloid neoplasia. Detection of JAK2 fusion genes is important as patients with aberrantly activated JAK2 may benefit from treatment with tyrosine kinase inhibitors such as ruxolitinib. Here, we report a novel fusion gene between the transcriptional co-repressor-encoding gene transducin-like enhancer of split 3 (TLE3) and JAK2 in a patient initially diagnosed with chronic eosinophilic leukemia with additional mutations in PTPN11 and NRAS. The patient was successfully treated with the JAK2 inhibitor ruxolitinib for 8 months before additional somatic mutations were acquired and the disease progressed into an acute lymphoblastic T-cell leukemia/lymphoma. The present case shows similarities to previously reported cases with PCM1::JAK2 and BCR::JAK2 with regard to disease phenotype and response to ruxolitinib, and importantly, provides an example that also patients harboring other JAK2 fusion genes may benefit from treatment with JAK2 inhibitors., (© 2024 The Author(s). Genes, Chromosomes and Cancer published by Wiley Periodicals LLC.)

Objective: Eosinophilic solid and cystic renal cell carcinoma (ESC-RCC) is rare and difficult to diagnose. Therefore, we aim to investigate the imaging and pathologic features of ESC-RCC., Methods: Fifteen cases of ESC-RCC with pathologically confirmed diagnoses were retrospectively collected: CT was performed in 15 cases and MRI in 9 cases., Results: In these patients (6 males and 9 females) (age: mean, 53.3 ± 14.7 years; range, 27-72 years), all tumors were unilateral, renal, and solitary with no clinical symptoms and were classified into-type 1: cystic-solid component, with equal cystic and solid components, was the most common (8/15, 53.3%); type 2: predominantly cystic with a small solid component (4/15, 26.7%); and type 3: predominantly solid (3/15, 20%). The solid component showed equal/slightly higher density on the CT-plain-scan, equal/slightly high signal on the T1-weighted image (T1WI), and low signal on the T2-weighted image (T2WI). Ten cases showed progressive enhancement, while 5 showed a fast-wash-in and fast-wash-out enhancement. One patient experienced hemorrhage, while the others showed no signs of hemorrhage, necrosis, fat, or calcification. Pathologically, the tumor showed cystic solidity, with eosinophilic cytoplasm and granular basophilic-colored spots with focal or diffuse expression of CK20. Ten patients had componential nephrectomy and 5 had radical nephrectomy. No recurrence or metastasis was noted in any case at the follow-up (8-49 months)., Conclusion: This study describes the imaging and pathologic features of a rare type of renal cancer and proposes 3 imaging types to enhance physicians' diagnosis of this disease and guide clinical diagnosis and treatment., Competing Interests: Disclosure The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

ETV6::ACSL6 represents a rare genetic aberration in hematopoietic neoplasms and is often associated with severe eosinophilia, which confers an unfavorable prognosis requiring additional anti-inflammatory treatment. However, since the translocation is unlikely to produce a fusion protein, the mechanism of ETV6::ACSL6 action remains unclear. Here, we performed multi-omics analyses of primary leukemia cells and patient-derived xenografts from an acute lymphoblastic leukemia (ALL) patient with ETV6::ACSL6 translocation. We identified a super-enhancer located within the ETV6 gene locus, and revealed translocation and activation of the super-enhancer associated with the ETV6::ACSL6 fusion. The translocated super-enhancer exhibited intense interactions with genomic regions adjacent to and distal from the breakpoint at chromosomes 5 and 12, including genes coding inflammatory factors such as IL-3. This led to modulations in DNA methylation, histone modifications, and chromatin structures, triggering transcription of inflammatory factors leading to eosinophilia. Furthermore, the bromodomain and extraterminal domain (BET) inhibitor synergized with standard-of-care drugs for ALL, effectively reducing IL-3 expression and inhibiting ETV6::ACSL6 ALL growth in vitro and in vivo. Overall, our study revealed for the first time a cis-regulatory mechanism of super-enhancer translocation in ETV6::ACSL6ALL, leading to an ALL-accompanying clinical syndrome. These findings may stimulate novel treatment approaches for this challenging ALL subtype.

The protozoan parasite Dientamoeba fragilis is a frequently isolated stool organism and postulated cause of gastrointestinal symptoms. Peripheral blood eosinophilia has been described. This is the first study amongst the Australasian adult population to assess the relationship between organism detection and eosinophilia. A case-control study took place over 7 years at a single Sydney laboratory site, evaluating patients with D. fragilis identified on stool using real-time PCR with a recent full blood count, to control groups with Giardia spp. and sequential negatives with neither organism. A nested study compared those with microscopic evidence of D. fragilis as a marker of disease burden, to molecular diagnosis alone. Sixty-four D. fragilis, 30 Giardia spp., and 94 sequential controls were enrolled. Only 60.1% of samples were preserved in sodium acetate-acetic acid formalin (SAF) fixative, indication mostly not documented. The major co-organism detected amongst all participants was Blastocystis sp., particularly in the D. fragilis cohort (37.2%). The most common pathogen amongst sequential controls was Campylobacter spp. (7.4%). Patients with D. fragilis were more likely (12.5%) to have a clinically significant eosinophilia (>0.5×10 9 /L) compared to those with Giardia spp. (3.3%) or sequential controls (4.3%) (p=0.03). A significant difference was also noted in the overall median eosinophil count of those with D. fragilis versus all controls (0.2 vs 0.1×10 9 /L, p=0.01); however, this was within the reference interval (where up to >0.5×10 9 /L is accepted in healthy individuals within a typical population). No eosinophil difference was found between those with molecular versus additional microscopic detection of D. fragilis (0.1 vs 0.1×10 9 /L). These results support an association between the identification of clinically significant peripheral blood eosinophilia and D. fragilis presence, which may impact the diagnostic approach to the patient with unexplained eosinophilia. Further prospective trials may help assess any significance further and the implication of co-carriage with other enteric organisms. The importance of clinical indication and need for appropriate fixative media in diagnostic parasitology are also highlighted., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Chronic sinusitis with nasal polyps (CRSwNP) is a complex inflammatory condition characterized by recurring nasal polyps, often necessitating repeated interventions. Blood eosinophilia has emerged as a potential biomarker for predicting disease recurrence. The present study aims to assess the predictive significance of blood eosinophilia for the recurrence of nasal polyps. To accomplish this objective, we employed the appropriate search keywords to explore international databases such as Web of Science, PubMed, Embase, and Scopus. Through this process, we extracted scholarly articles that assessed the prognostic value of blood eosinophilia in the recurrence of nasal polyps. The statistical software STATA (version 15) was employed, along with random and fixed-effects models, to appraise the compiled data. Nine articles met inclusion criteria, with a total sample size of 1279 individuals (569 recurrent polyp individuals and 710 non-recurrent polyp individuals). Cumulative Odds ratio analysis revealed that CRSwNP is associated with high blood eosinophile percentage compared to the non-CRSwNP group (p=0.01, OR=1.26, 95%Cl (1.15,1.36). The cut-off value of blood eosinophil percentage (>0.78) had relatively good, and statistically significant predictive potential. No significant publication bias was observed for the included studies. Our findings indicate that the utilization of blood eosinophils holds significant predictive value and can serve as a valuable tool for detecting recurrence in patients with CRSwNP. Based on the outcomes of our comprehensive analysis, we propose a threshold of >0.78 as a reliable indicator for assessing the probability of recurrence in CRSwNP patients.

Eosinophil sombrero vesicles are large tubular carriers resident in the cytoplasm of human eosinophils, identifiable by transmission electron microscopy, and important for immune mediator transport. Increased formation of sombrero vesicles occurs in activated eosinophils in vitro and in vivo. In tissue sites of eosinophilic cytolytic inflammation, extracellular eosinophil sombrero vesicles are noted, but their frequency and significance in eosinophil-associated diseases remain unclear. Here, we performed comprehensive quantitative transmission electron microscopy analyses and electron tomography to investigate the numbers, density, integrity, and 3-dimensional structure of eosinophil sombrero vesicles in different biopsy tissues from 5 prototypic eosinophil-associated diseases (eosinophilic chronic rhinosinusitis/nasal sinuses, ulcerative colitis/intestines, hypereosinophilic syndrome/skin, dermatitis/skin, and schistosomiasis/rectum). The morphology of extracellular eosinophil sombrero vesicles was also compared with that of cytoplasmic eosinophil sombrero vesicles, isolated by subcellular fractionation from peripheral blood eosinophils. We demonstrated that (i) eosinophil cytolysis, releasing intact sombrero vesicles and membrane-bound granules, is a consistent event in all eosinophil-associated diseases; (ii) eosinophil sombrero vesicles persist intact even after complete disintegration of all cell organelles, except granules (late cytolysis); (iii) the eosinophil sombrero vesicle population, composed of elongated, curved, and typical sombreros, and the eosinophil sombrero vesicle 3-dimensional architecture, diameter, and density remain unchanged in the extracellular matrix; (iv) free eosinophil sombrero vesicles closely associate with extracellular granules; and (v) free eosinophil sombrero vesicles also associate with externalized chromatin during eosinophil ETosis. Remarkably, eosinophil sombrero vesicles appeared on the surface of other cells, such as plasma cells. Thus, eosinophil cytolysis/ETosis can secrete intact sombrero vesicles, alongside granules, in inflamed tissues of eosinophil-associated diseases, potentially serving as propagators of eosinophil immune responses after cell death., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology.)

Objective: To analyse the histopathological features of eosinophilic sialodochitis by using terminal duct biopsy., Methods: Sixty-five patients with suspected eosinophilic sialodochitis and four with chronic obstructive sialadenitis were prospectively enrolled. Clinical features, laboratory tests and sialograms were comparatively analysed. Terminal duct biopsy of the parotid or submandibular glands was performed concomitantly with endoscopy-assisted duct dilatation to determine the histopathological features of eosinophilic sialodochitis., Results: Based on eosinophil quantification, the samples of suspected patients were scored as 'definite', 'highly suspected' and 'negative' in 26 (40%), 15 (23.1%) and 24 (36.9%) cases, respectively. Gland types and peripheral blood eosinophil counts were significantly different among these three groups. The proportions of itching glands, mucus plug exudations and elevated immunoglobulin E levels were higher in the 'definite' group than in the other two groups; however, the intergroup differences were insignificant. The primary pathological features of eosinophilic sialodochitis were abundant eosinophils and lymphocytes infiltrated around the duct, degranulation of eosinophils, extensive fibrosis and scattered mastocytes. Periductal eosinophils were not found in cases of chronic obstructive sialadenitis., Conclusion: Our findings suggest that terminal duct biopsy is safe and valuable for the pathological confirmation of eosinophilic sialodochitis, and can be used simultaneously with endoscopy-assisted duct dilatation., (© 2023 Wiley Periodicals LLC.)

Introduction: The diagnosis of eosinophilic gastrointestinal diseases is largely based on mucosal eosinophil counts, but thresholds and normal ranges beyond the esophagus are debated, calling for much-needed methodological standardization. We aimed to develop a standardized workflow for duodenal cell quantification and estimate duodenal eosinophil and mast cell numbers in healthy controls., Methods: Software-based histological cell quantification using free-sized or fixed-sized regions was developed and applied to digitized hematoxylin and eosin (H&E)-stained slides from 58 individuals (healthy controls [HCs] and patients with functional dyspepsia). Intraclass correlation coefficients (ICCs) compared inter-rater reliability between software-based and microscopic quantification. Reproducibility of the software-based method was validated in an independent cohort of 37 control and functional dyspepsia subjects. Eosinophil identification on H&E staining was compared to immunohistochemistry (IHC). Normal eosinophil (H&E) and mast cell (cKit) ranges were determined in 70 adult HCs., Results: Eosinophil quantification on digitized slides demonstrated excellent (ICC = 0.909) and significantly improved reproducibility over microscopic evaluation (ICC = 0.796, P = 0.0014), validated in an independent cohort (ICC = 0.910). Duodenal eosinophils were more abundant around crypts than in villi ( P < 0.0001), while counts were similar on matched H&E- and IHC-stained slides ( P = 0.55). Mean ± SD (95th percentile) duodenal eosinophils and mast cells in HC were 228.8/mm 2 ± 94.7 (402.8/mm 2 ) and 419.5/mm 2 ± 132.2 (707.6/mm 2 ), respectively., Discussion: We developed and validated a standardized approach to duodenal histological cell quantification, generalizable to various mucosal cell types. Implementation of software-based quantification identified 400 eosinophils/mm 2 and 700 mast cells/mm 2 as thresholds for abnormal duodenal infiltration., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Allergic airway inflammation results from uncontrolled immune responses to environmental Ags. Although it is well established that allergic immune responses exhibit a high degree of diversity, driven by primary effector cell types such as eosinophils, neutrophils, or CD4 T cells with distinct effector signatures, the mechanisms responsible for such pathogenesis remain elusive. Foxp3+ regulatory T cells (Tregs) are essential immune regulators during chronic inflammation, including allergic airway inflammation. Emerging evidence suggests that Tregs infiltrating inflamed tissues exhibit distinct phenotypes dependent on the specific tissue sites and can display heterogeneity and tissue residency. Whether diverse allergic airway inflammatory responses influence infiltrating Treg heterogeneity or Treg lung residency has not been explored. We employed an unbiased single-cell RNA sequencing approach to investigate lung-infiltrating Tregs in models of eosinophilic and neutrophilic airway inflammation. We found that lung-infiltrating Tregs are highly heterogeneous, and that Tregs displaying lung-resident phenotypes are significantly different depending on the types of inflammation. Treg expression of ST2, a receptor for alarmin IL-33, was predominantly associated with eosinophilic inflammation and tissue residency. Nevertheless, Treg-specific ST2 deficiency did not affect the development of eosinophilic allergic inflammation or the generation of lung-resident Tregs. These results uncover a stark heterogeneity among Tregs infiltrating the lungs during allergic airway inflammation. The results indicate that varying types of inflammation may give rise to phenotypically distinct lung-resident Tregs, underscoring a (to our knowledge) novel mechanism by which inflammatory cues may shape the composition of infiltrating Tregs, allowing them to regulate inflammatory responses through tissue-adapted mechanisms., (Copyright © 2024 by The American Association of Immunologists, Inc.)

Background: SERPINB2, a biomarker of Type-2 (T2) inflammatory processes, has been described in the context of asthma. Chronic rhinosinusitis with nasal polyps (CRSwNP) is also correlated with T2 inflammation and elevated 15LO1 induced by IL-4/13 in nasal epithelial cells. The aim of this study was to evaluate the expression and location of SERPINB2 in nasal epithelial cells (NECs) and determine whether SERPINB2 regulates 15LO1 and downstream T2 markers in NECs via STAT6 signalling., Methods: SERPINB2 gene expression in bulk and single-cell RNAseq database was analysed by bioinformatics analysis. SERPINB2, 15LO1 and other T2 markers were evaluated from CRSwNP and HCs NECs. The colocalization of SERPINB2 and 15LO1 was evaluated by immunofluorescence. Fresh NECs were cultured at an air-liquid interface with or without IL-13, SERPINB2 Dicer-substrate short interfering RNAs (DsiRNAs) transfection, exogenous SERPINB2, 15-HETE recombinant protein and pSTAT6 inhibitors. 15LO1, 15-HETE and downstream T2 markers were analysed by qRT-PCR, western blot and ELISA., Results: SERPINB2 expression was increased in eosinophilic nasal polyps compared with that in noneosinophilic nasal polyps and control tissues and positively correlated with 15LO1 and other downstream T2 markers. SERPINB2 was predominantly expressed by epithelial cells in NP tissue and was colocalized with 15LO1. In primary NECs in vitro, SERPINB2 expression was induced by IL-13. Knockdown or overexpression SERPINB2 decreased or enhanced expression of 15LO1 and 15-HETE in NECs, respectively, in a STAT6-dependent manner. SERPINB2 siRNA also inhibited the expression of the 15LO1 downstream genes, such as CCL26, POSTN and NOS2. STAT6 inhibition similarly decreased SERPINB2-induced 15LO1., Conclusions: SERPINB2 is increased in NP epithelial cells of eosinophilic CRSwNP (eCRSwNP) and contributes to T2 inflammation via STAT6 signalling. SERPINB2 could be considered a novel therapeutic target for eCRSwNP., (© 2024 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)

Objective: Previous studies have acknowledged the presence of eosinophilic cytoplasm in clear cell renal cell carcinoma, yet the precise quantification method and potential molecular attributes in clear cell renal cell carcinoma remain elusive. This study endeavours to precisely quantify the eosinophilic attribute and probe into the molecular mechanisms governing its presence in clear cell renal cell carcinoma., Methods: Data from cohorts of clear cell renal cell carcinoma patients who underwent nephrectomy, comprising The Cancer Genome Atlas cohort (n = 475) and Sun Yat-sen University Cancer Center cohort (n = 480), were aggregated to assess the eosinophilic attribute. Additionally, Omics data from Clinical Proteomic Tumor Analysis Consortium (CPTAC) (n = 58) were leveraged to explore the potential molecular features associated with eosinophilic clear cell renal cell carcinoma. Employing receiver operating characteristic curve analysis, the proportion of tumour cells with eosinophilic cytoplasm was determined, leading to the classification of each cohort into distinct groups: a clear group (<5%) and an eosinophilic group (≥5%)., Results: In both cohorts, the eosinophilic feature consistently correlated with higher International Society of Urological Pathology (ISUP) grade, elevated tumor stage, and the presence of necrosis. Furthermore, the Kaplan-Meier method demonstrated that patients in the eosinophilic group exhibited shorter overall survival or disease-free survival compared with those in the clear group, a pattern reaffirmed in various stratified survival analyses. Intriguingly, within The Cancer Genome Atlas cohort, the pathological characterization of cell cytoplasm (eosinophilic vs. clear) emerged as an independent risk factor for overall survival (hazard ratio = 2.507 [95% confidence interval: 1.328-4.733], P = 0.005) or disease-free survival (hazard ratio = 1.730 [95% confidence interval: 1.062-2.818], P = 0.028) via Cox regression analysis. Moreover, multi-Omics data unveiled frequent BAP1 mutations and down-regulation of Erythroblast Transformation-Specific-Related Gene associated with the eosinophilic feature in clear cell renal cell carcinoma. Additionally, patients with low expression of Erythroblast Transformation-Specific-Related Gene showed worse overall survival (P < 0.001)., Conclusions: The quantification of the eosinophilic feature serves as a robust predictor of clinical prognosis in clear cell renal cell carcinoma. Furthermore, the manifestation of this feature may be linked to BAP1 mutations and the down-regulation of Erythroblast Transformation-Specific-Related Gene in clear cell renal cell carcinoma. Significantly, the expression levels of Erythroblast Transformation-Specific-Related Gene manifest as an exemplary prognostic marker, providing exceptional predictive accuracy for the clinical prognosis in clear cell renal cell carcinoma., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

STAT5B has been reported as a recurrent mutation in myeloid neoplasms with eosinophilia, but its overall frequency and importance across a spectrum of myeloid neoplasms are largely unknown. We conducted a multicenter study on a series of 82 myeloid neoplasms with STAT5B mutations detected by next-generation sequencing. The estimated frequency of STAT5B mutations in myeloid neoplasms was low, <0.5%, but mutations were detected in all categories of such neoplasms, including myelodysplastic syndrome (MDS, 28%), acute myeloid leukemia (AML, 26%), myelodysplastic/myeloproliferative neoplasm (MDS/MPN, 18%), Philadelphia chromosome-negative classic MPN (12%), systemic mastocytosis (1%), and, with a notably high frequency, chronic eosinophilic leukemia, not otherwise specified (CEL-NOS, 15%). STAT5B mutations occurred preferentially in the SH2 domain (95%), involved 12 different codons, with the N642H hotspot being the most common (78%). Co-mutations were present in all cases and clonal hierarchy analysis showed that STAT5B mutations tended to be subclonal in AML, MPN, and MDS, but frequently dominant/co-dominant in CEL-NOS (83%), followed by MDS/MPN (40%). Across the group, eosinophilia and/or basophilia were common (41%), frequently observed in cases in which STAT5B mutations were detected at initial diagnosis (P<0.0001), with a high variant allele frequency (median 42.5%, P=0.0001), as a dominant/ co-dominant clone (P<0.0001), involving the canonical N642H (P=0.0607), and associated with fewer co-mutations (P=0.0009). Our data show that the characteristics and importance of a STAT5B mutation differ among myeloid neoplasms, but if present as a dominant mutation and detected at initial diagnosis, it appears to be a driver mutation in a subgroup of chronic myeloid neoplasms, preferentially promoting a proliferation of eosinophils and basophils.

Background: The PI3K/Akt/mTOR pathway and autophagy are important physiological processes. But their roles in eCRSwNP remains controversial., Methods: In this study, we used the eCRSwNP mouse model, PI3K/Akt/mTOR pathway inhibitors, and autophagy inhibitors and activators to investigate the regulatory effects of the PI3K/Akt/mTOR pathway on autophagy, and their effects on eosinophilic inflammation, and tissue remodeling. The role of ILC2s in eCRSwNP was also studied, and the relationship between ILC2s and autophagy was preliminarily determined., Results: Our results show that eosinophilic inflammation in eCRSwNP mice could be inhibited by promoting the autophagy; otherwise, eosinophilic inflammation could be promoted. Meanwhile, inhibition of the PI3K/Akt/mTOR pathway can further promote autophagy and inhibit eosinophilic inflammation. Meanwhile, inhibiting the PI3K/Akt/mTOR pathway and promoting autophagy can reduce the number of ILC2s and the severity of tissue remodeling in the nasal polyps of eCRSwNP mice., Conclusions: We conclude that the PI3K/Akt/mTOR pathway plays roles in eosinophilic inflammation and tissue remodeling of eCRSwNP, in part by regulating the level of autophagy. The downregulation of autophagy is a pathogenesis of eCRSwNP; therefore, the recovery of normal autophagy levels might be a new target for eCRSwNP therapy. Furthermore, autophagy might inhibit eosinophilic inflammation and tissue remodeling, in part by reducing the number of ILC2s., (© 2024 The Author(s). Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Eosinophilic gastrointestinal diseases (EGIDs) are a group of diseases characterized by selective eosinophil infiltration of the gastrointestinal (GI) tract in the absence of other causes of eosinophilia. These diseases are generally driven by type 2 inflammation, often in response to food allergen exposure. Among all EGIDs, the clinical presentation often includes a history of atopic disease with a variety of GI symptoms. EGIDs are traditionally separated into eosinophilic esophagitis (EoE) and non-EoE EGIDs. EoE is relatively better understood and now associated with clinical guidelines and 2 US Food and Drug Administration-approved treatments, whereas non-EoE EGIDs are rarer and less well-understood diseases without US Food and Drug Administration-approved treatments. Non-EoE EGIDs are further subclassified by the area of the GI tract that is involved; they comprise eosinophilic gastritis, eosinophilic enteritis (including eosinophilic duodenitis), and eosinophilic colitis. As with other GI disorders, the disease presentations and mechanisms differ depending on the involved segment of the GI tract; however, the differences between EoE and non-EoE EGIDs extend beyond which GI tract segment is involved. The aim of this article is to summarize the commonalities and differences between the clinical presentations and disease mechanisms for EoE and non-EoE EGIDs., Competing Interests: Disclosure statement Supported by the National Institutes of Health (grant K99/R00 AI158660 [to T.S.] and grants R01 AI045898, R01 AI124355, and U19 AI070235 [to M.E.R.]); the Digestive Health Center (Pilot and Feasibility Program; grant P30 DK078392 [to T.S.]); Cincinnati Children's Trustee Award (to T.S.); the Campaign Urging Research for Eosinophilic Disease (CURED) (to M.E.R.); the Sunshine Charitable Foundation and its supporters Denise A. Bunning and David G. Bunning (to M.E.R.); and CEGIR (U54 AI117804 to M.E.R.), which is part of the Rare Diseases Clinical Research Network (RDCRN), an initiative of the Office of Rare Diseases Research (ORDR), NCATS, and is funded through collaboration between NIAID, NIDDK, NCATS. CEGIR is also supported by patient advocacy groups including the Campaign Urging Research for Eosinophilic Diseases (CURED), American Partnership for Eosinophilic Disorders (APFED), and Eosinophilic Family Coalition (EFC). As a member of the RDCRN, CEGIR is also supported by its Data Management and Coordinating Center (DMCC) (U2CTR002818). Funding support for the DMCC is provided by the National Center for Advancing Translational Sciences (NCATS) and the National Institute of Neurological Disorders and Stroke (NINDS). Disclosure of potential conflict of interest: M. E. Rothenberg is a consultant for Pulm One, Spoon Guru, ClostraBio, Serpin Pharm, Celldex, Uniquitybio, Santa Ana Bio, EnZen Therapeutics, Bristol Myers Squibb, AstraZeneca, Pfizer, GlaxoSmith Kline, Regeneron/Sanofi, and Guidepoint and has an equity interest in the first 8 listed plus Allakos and royalties from reslizumab (Teva Pharmaceuticals), PEESSv2 (Mapi Research Trust), and UpToDate. In addition, T. Shoda and M. E. Rothenberg are inventors of patents owned by Cincinnati Children’s Hospital. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Eosinophilic solid and cystic renal cell carcinoma (ESC-RCC) is a novel and uncommon type of renal cell carcinoma, which has been recently recognized and introduced as a distinct entity in the WHO 2022 kidney tumor classification. Previously known as "unclassified RCC", followed by "tuberous sclerosis complex (TSC)-associated RCC", ESC-RCC is now a distinct category of kidney tumor, with its own name, with specific clinical manifestations, and a unique morphological, immunohistochemical and molecular profile. Due to its recent introduction and the limited available data, the diagnosis of ESC-RCC is still a complex challenge, and it is probably frequently misdiagnosed. The secret of diagnosing this tumor lies in the pathologists' knowledge, and keeping it up to date through research, thereby limiting the use of outdated nomenclature. The aim of our case-based review is to provide a better understanding of this pathology and to enrich the literature with a new case report, which has some particularities compared to the existing cases.

Facioscapulohumeral muscular dystrophy (FSHD) is a progressive myopathy caused by the aberrant increased expression of the DUX4 retrogene in skeletal muscle cells. The DUX4 gene encodes a transcription factor that functions in zygotic genome activation and then is silenced in most adult somatic tissues. DUX4 expression in FSHD disrupts normal muscle cell function; however, the downstream pathogenic mechanisms are still unclear. Histologically, FSHD affected muscles show a characteristic dystrophic phenotype that is often accompanied by a pronounced immune cell infiltration, but the role of the immune system in FSHD is not understood. Previously, we used ACTA1;FLExDUX4 FSHD-like mouse models varying in severity as discovery tools to identify increased Interleukin 6 and microRNA-206 levels as serum biomarkers for FSHD disease severity. In this study, we use the ACTA1;FLExDUX4 chronic FSHD-like mouse model to provide insight into the immune response to DUX4 expression in skeletal muscles. We demonstrate that these FSHD-like muscles are enriched with the chemoattractant eotaxin and the cytotoxic eosinophil peroxidase, and exhibit muscle eosinophilia. We further identified muscle fibers with positive staining for eosinophil peroxidase in human FSHD muscle. Our data supports that skeletal muscle eosinophilia is a hallmark of FSHD pathology., (© The Author(s) 2024. Published by Oxford University Press.)

This manuscript represents a review of lymphoblastic leukemia/lymphoma (acute lymphoblastic leukemia/lymphoblastic lymphoma), acute leukemias of ambiguous lineage, mixed-phenotype acute leukemias, myeloid/lymphoid neoplasms with eosinophilia and defining gene rearrangements, histiocytic and dendritic neoplasms, and genetic tumor syndromes of the 5th edition of the World Health Organization Classification of Tumors of the Hematopoietic and Lymphoid Tissues. The diagnostic, clinicopathologic, cytogenetic, and molecular genetic features are discussed. The differences in comparison to the 4th revised edition of the World Health Organization classification of hematolymphoid neoplasms are highlighted., (Copyright © 2024. Published by Elsevier Inc.)

In the 2022, WHO and ICC classifications, myeloid/lymphoid neoplasms with eosinophilia (M/LN-eo) and tyrosine kinase gene fusions represent rare hematologic malignancies driven by rearrangements of PDGFRA, PDGFRB, FGFR1, JAK2, FLT3, and ETV6::ABL1 fusion. Eosinophilia is the most constant finding, whereas the clinicopathological features are quite heterogeneous, presenting as Chronic eosinophilic leukemia (CEL) NOS, myelodysplastic/myeloproliferative neoplasm (MDS/MPN), MDS, MPN, systemic mastocytosis (SM), T or B cell acute lymphoblastic leukemia/lymphoblastic lymphoma (ALL/LBL), acute myeloid leukemia (AML), blastic phase of MPN, or mixed phenotype acute leukemia (MPAL). Extramedullary involvement at diagnosis or during progression is common. Here, we report a very unusual case of myeloid/lymphoid neoplasm with ETV6::FLT3 fusion with a nodal presentation without associated eosinophilia. Our case draws attention to diagnostic pitfalls in these rare entities., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Abstract: Increased eosinophil counts are associated with cardiovascular disease and may be an independent predictor of major cardiovascular events. However, the causality and underlying mechanisms are poorly understood. Genome-wide association studies have shown an association of a common LNK variant (R262W, T allele) with eosinophilia and atherothrombotic disorders. LNK(TT) reduces LNK function, and Lnk-deficient mice display accelerated atherosclerosis and thrombosis. This study was undertaken to assess the role of eosinophils in arterial thrombosis in mice with hematopoietic Lnk deficiency. Hematopoietic Lnk deficiency increased circulating and activated eosinophils, JAK/STAT signaling in eosinophils, and carotid arterial thrombosis with increased eosinophil abundance and extracellular trap formation (EETosis) in thrombi. Depletion of eosinophils by anti-Siglec-F antibody or by the ΔdbIGata1 mutation eliminated eosinophils in thrombi and markedly reduced thrombosis in mice with hematopoietic Lnk deficiency but not in control mice. Eosinophil depletion reduced neutrophil abundance and NETosis in thrombi without altering circulating neutrophil counts. To assess the role of Lnk specifically in eosinophils, we crossed Lnkf/f mice with eoCre mice. LnkΔeos mice displayed isolated eosinophilia, increased eosinophil activation, and accelerated arterial thrombosis associated with increased EETosis and NETosis in thrombi. DNase I infusion abolished EETs and neutrophil extracellular traps (NETs) in thrombi and reversed the accelerated thrombosis. Human induced pluripotent stem cell-derived LNK(TT) eosinophils showed increased activation and EETosis relative to isogenic LNK(CC) eosinophils, demonstrating human relevance. These studies show a direct link between eosinophilia, EETosis, and atherothrombosis in hematopoietic Lnk deficiency and an essential role of eosinophil LNK in suppression of arterial thrombosis., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

The prevalence of diseases characterised by eosinophilia is on the rise, emphasising the importance of understanding the role of eosinophils in these conditions. Eosinophils are a subset of granulocytes that contribute to the body's defence against bacterial, viral, and parasitic infections, but they are also implicated in haemostatic processes, including immunoregulation and allergic reactions. They contain cytoplasmic granules which can be selectively mobilised and secrete specific proteins, including chemokines, cytokines, enzymes, extracellular matrix, and growth factors. There are multiple biological and emerging functions of these specialised immune cells, including cancer surveillance, tissue remodelling and development. Several oral diseases, including oral cancer, are associated with either tissue or blood eosinophilia; however, their exact mechanism of action in the pathogenesis of these diseases remains unclear. This review presents a comprehensive synopsis of the most recent literature for both clinicians and scientists in relation to eosinophils and oral diseases and reveals a significant knowledge gap in this area of research.

Eosinophilic fasciitis (EF) remains a diagnostic challenge due to its rarity and resemblance to scleroderma. This case report aims to provide a cohesive exploration of EF's clinical nuances, emphasizing the importance of accurate diagnosis and effective management. A 52-year-old male developed bilateral forearm and calf hardening, along with erythema, pruritus, and pain four months prior to the presentation in our Clinic. The symptoms initially debuted bilaterally in the forearms and progressed to involve the calves, distal arms, and thighs. Clinical examination revealed symmetrical plaques on forearms and calves, featuring erythematous, hyper, and hypopigmented elements extending proximally, a positive "groove sign" and a moderate difficulty in knee joint flexion. Despite these findings, the patient was generally in good condition, without any other notable clinical signs. Initial laboratory findings showed slightly increased percentual eosinophil levels, elevated C-reactive protein (CRP), normal erythrocyte sedimentation rate (ESR), and negative antinuclear and scleroderma specific antibodies. Magnetic resonance imaging (MRI) demonstrated enhanced fascial signal and thickening while the fascia-muscle biopsy revealed marked edema and inflammatory lymphoplasmacytic infiltrate, consistent with the diagnosis of EF. The patient showed a favorable response to systemic corticosteroids. EF predominantly affects males aged 30 to 60 and is characterized by a sudden onset and unclear etiological factors. Differential diagnosis requires careful exclusion of scleroderma and other mimicking conditions. Diagnostic modalities such as skin-muscle biopsy and MRI reveal characteristic findings like inflammatory infiltrate and fascial thickening. Accurate diagnosis and differentiation from scleroderma are crucial, with early intervention involving glucocorticoids and immunosuppressive agents improving long-term outcomes.

Objective: Eosinophilic chronic rhinosinusitis (eCRS) is a refractory subtype of CRS. This study aimed to compare the differences in clinical features and peripheral blood indices between eCRS and non-eCRS Chinese patients and identify the predictive factors for eCRS., Methods: In this study, a total of 1352 patients with CRS were enrolled and divided into eCRS and non-eCRS groups based on the degree of eosinophilic infiltration in histopathology, and their demographic and clinical characteristics, as well as peripheral blood indices, were compared. Logistic regression analysis was used to identify the factors associated with eCRS, and the optimal cut-off values of predictors were determined using subject working curves., Results: As compared to those in the non-eCRS group patients, the proportion of males, age, proportion of smokers, peripheral blood eosinophil count, and erythrocyte count were significantly higher, while the peripheral blood neutrophil count, platelet count, neutrophil/lymphocyte count ratio (NLR), platelet/lymphocyte count ratio (PLR), and neutrophil × platelet/lymphocyte count ratio (SII index) were significantly lower in the eCRS group patients. Logistic regression analysis showed that age, peripheral blood neutrophil count, eosinophil count, and platelet count were independent predictors of eCRS, and eosinophil count > 2.05 × 10 8 /L could be used as a diagnostic marker for eCRS with a sensitivity and specificity of 87.1% and 78.3%, respectively., Conclusions: There were significant differences in the clinical features of eCRS and non-eCRS patients. Peripheral blood eosinophil count could early and more accurately predict eCRS., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Traumatic Ulcerative Granuloma with Stromal Eosinophilia, commonly known as Eosinophilic Ulcer, is a reactive solitary and self-limiting benign lesion. It manifests as a punched-out ulcer with a distinct surrounding indurated border, often raising concerns about malignancy., Methods: A 44-year-old male presented with a painless, indurated tongue ulcer evolving over three months. Despite being asymptomatic, the patient underwent an incisional biopsy due to suspicions of oral squamous cell carcinoma., Results: Histological analysis revealed a disrupted epithelial lining, dense necrotic connective tissue, and a fibrino-purulent pseudomembrane. Proximal to the ulcer, a collar-like projection of reactive epithelial tissue hyperplasia was noted, accompanied by mononuclear cells and a predominantly histiocytic infiltrate in the submucosal layer surrounding skeletal muscle fibers. The final diagnosis was Traumatic Ulcerative Granuloma with Stromal Eosinophilia. Remarkably, the lesion spontaneously healed within 2 weeks post-biopsy, with no recurrence over 6 months., Conclusion: This case emphasizes considering this benign condition in the differential diagnosis of oral ulcers, highlighting the importance of accurate histopathological evaluation to rule out cancer., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Eosinophil-derived neurotoxin (EDN) is a viable marker of eosinophilic esophagitis (EoE) disease activity. We studied the utility of measuring EDN from esophageal epithelial brushings for diagnosing EoE, focusing on two scenarios: (1) cases of exclusive distal eosinophilia and (2) cases of discrepancy between endoscopy and histology., Methods: Records of patients who underwent esophagogastroduodenoscopy (EGD) with EDN measured via esophageal brushings at Arnold Palmer Hospital for Children in Orlando, Florida from January 2014 to October 2018 were retrospectively reviewed. Demographics, clinical, endoscopic, and histologic data were collected., Results: We reviewed 231 patient records (66.7% male, mean age 10.3 years, range 1-22 years). EDN values correlated with endoscopic reference score (EREFS) and peak eosinophil count (PEC) (Spearman's rho = 0.756 (p < 0.001) and 0.824 (p < 0.001) respectively). Average PEC, EREFS, and EDN concentrations were higher in patients with active EoE than in controls or patients with EoE in remission (inactive). When grouping patients based on esophageal eosinophilia distribution, EDN mirrored PEC, and EREFS. Patients with exclusive distal eosinophilia had lower EDN concentrations than those with eosinophilia in >1 level of the esophagus (23.8 ± 46.1 mcg/mL vs. 171.3 ± 205.8 mcg/mL respectively, p < 0.001). EDN values were more consistent with EREFS in cases of discrepancies between endoscopic findings and pathology (p < 0.001)., Conclusion: EDN measured in esophageal brushing samples reflects disease activity objectively and accurately. It also offers significant value in cases of exclusive distal esophageal eosinophilia and when discrepancies exist between endoscopy and histology., (© 2023 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objective: The purpose was to evaluate the relationship between peripheral eosinophilia, Japan Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) score, and olfactory dysfunction in chronic rhinosinusitis (CRS) patients and to explore the accuracy and specific cut points of the JESREC score in predicting olfactory dysfunction., Methods: In this cross-sectional, retrospective study, olfactory function was assessed by the Sniffin' Sticks 12-item test and multivariate logistic regression analyses were carried out. Receiver operating characteristic curves were plotted to derive accuracy and cutoff values for the JESREC scores of the olfactory dysfunction criterion., Results: A total of 354 patients [mean (SD) age, 50.0 (14.9) years; 41.8% women] were included in the final analysis. The prevalence of olfactory dysfunction was 46.3%. Individuals who had olfactory dysfunction were more likely to be male (64.6% vs. 52.6%), have eosinophilic chronic rhinosinusitis (ECRS) (39.0% vs. 7.9%), have a longer course of CRS (2.3 years vs. 1.5 years), have higher JESREC scores (8.5 vs. 4.5), and have higher proportions of nasal polyps (78.7% vs. 18.9%) and peripheral eosinophilia (3.3% vs. 1.4%). In logistic analysis, the percentage of eosinophils (1.25, 1.13-1.37), JESREC score (1.31, 1.22-1.40), bilateral lesion (2.06, 1.25-3.41), nasal polyps (15.83, 9.23-27.16), CT shadow (2.73, 1.69-4.43), and ECRS (6.86, 3.68-12.80) were associated with olfactory dysfunction in CRS patients after controlling for covariates, while peripheral neutrophils were not significant. In addition, the area under the curve was 0.778 and the cutoff value for JESREC score for olfactory dysfunction was defined as 5.5., Conclusions: Peripheral eosinophilia and high JESREC scores were significantly associated with the risk of olfactory dysfunction in CRS patients, and special attention should be paid to patients with a JESREC score ≥6., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Li, Wang, Wang, Wu, Guo, Li, Zhou, Xue and You.)

Background: Eosinophilic enterocolitis is a rare disorder characterized by abnormal eosinophilic infiltration of the small intestine and the colon., Case Presentation: We report a case of a 29-year-old White man, who presented with an acute bowel obstruction. He had a history of a 2 months non-bloody diarrhea. An abdominal computed tomography (CT) and a MR enterography showed a multifocal extensive ileitis. White blood cell and eosinophilic polynuclei count was elevated (700/mm 3 ). Ileo-colonoscopy showed normal ileum and segmental petechial colitis. Pathology showed a high eosinophilic infiltration in the colon. The patient was treated with steroids, with a clinical, biological and radiological recovery., Conclusion: Eosinophilic enterocolitis should be kept in mind as a rare differential diagnosis in patients presenting with small bowel obstruction., (© 2024. The Author(s).)

Asthma is the chronic pulmonary inflammatory response that could lead to respiratory failure when allergic reactions exacerbate. It is featured by type 2 immunity with eosinophilic inflammation, mucus, and IgE production, and Th2 cytokine secretion upon repeated challenge of allergens. The symptom severity of asthma displays an apparent circadian rhythm with aggravated airway resistance in the early morning in patients. Bmal1 is the core regulator of the circadian clock, while the regulatory role of Bmal1 in asthma remains unclear. Here, we investigate whether the myeloid Bmal1 is involved in the pathogenesis of house dust mite (HDM)-induced lung allergy. We found that knockdown of Bmal1 in macrophages suppressed the time-of-day variance of the eosinophil infiltration in the alveolar spaces in chronic asthmatic mice. This was accompanied by decreased bronchial mucus production, collagen deposition, and HDM-specific IgE production. However, the suppression effects of myeloid Bmal1 deletion did not alter the allergic responses in short-term exposure to HDM. The transcriptome profile of alveolar macrophages (AMs) showed that Bmal1-deficient AMs have enhanced phagocytosis and reduced production of allergy-mediating prostanoids thromboxane A2 and prostaglandin F2α synthesis. The attenuated thromboxane A2 and prostaglandin F2α may lead to less induction of the eosinophil chemokine Ccl11 expression in bronchial epithelial cells. In summary, our study demonstrates that Bmal1 ablation in macrophages attenuates eosinophilic inflammation in HDM-induced chronic lung allergy, which involves enhanced phagocytosis and reduced prostanoid secretion., Competing Interests: Conflict of interest statement. The authors declare no conflict of interest. None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Leukocyte Biology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Two recent articles by the same research group documented that patients with severe eosinophilic asthma exhibit an increased proportion of a subtype of eosinophils, namely CD62L low inflammatory eosinophils (iEos) and identified an intriguing correlation between such iEos and asthma control scores. Moreover, CD62L low iEos were reduced after treatment with the anti-IL-5 monoclonal antibody mepolizumab. In the future, we believe that eosinophil subtypes could represent a useful biomarker in severe eosinophilic asthma, helping clinicians characterize patient endotypes and monitoring the response to biological drugs.