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Background: Rituximab (RTX) is a monoclonal antibody that has been increasingly used in the treatment of myasthenia gravis (MG). In most studies, the therapeutic protocol of RTX has been similar to that adopted for B cell lymphoma, with an increasing number of studies aimed at exploring the efficacy of low-dose RTX in MG. However, the beneficial effects of low-dose RTX in MG remain a subject of critical debate. Methods: This study was conducted following the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidelines. Two reviewers (Xishuai Yang and Bingxia Li) independently conducted searches across multiple databases, including PubMed, MEDLINE, EMBASE, Web of Science, Cochrane Library, and China National Knowledge Infrastructure (CNKI). A meta-analysis, utilizing representative forest plots, was performed to assess "Improved clinical status" and changes in the Quantitative Myasthenia Gravis (QMG) score before and after treatment. Results: A total of 17 studies involving 292 patients were included in the meta-analysis. A noticeable improvement in clinical status was observed in 91% of patients at the final follow-up after therapy (95% CI: 84–96%, P < 0.001). The QMG score showed a significant reduction following the treatment, with a standardized mean difference (SMD) of −1.69 (95% CI: −2.21 to −1.16, Z = 6.29, P < 0.001). In the acetylcholine receptor antibody-positive myasthenia gravis (AChR-MG) group, 90% of patients achieved improved clinical status (95% CI: 80–97%, P < 0.001) and the QMG score significantly decreased after low-dose RTX treatment, with an SMD of −1.51 (95% CI: −0.80 to −2.21, Z = 4.50, P < 0.001). In the muscle-specific kinase antibody-positive myasthenia gravis (MuSK-MG) group, 97% of patients achieved improved clinical status (95% CI: 89–100%, P < 0.001). The QMG score also significantly decreased following low-dose RTX treatment, with an SMD of −2.31 (95% CI: −2.99 to −1.62, Z = 6.60, P < 0.001). Adverse effects were reported in 29 out of 207 patients (14%, including infusion reactions in 22 patients (10.1%), infections in three patients (1.45%), cytopenia in two patients (0.96%), eosinophilia in one patient (0.48%), and hemiplegia in one patient (0.48%). Additionally, one patient (0.48%) succumbed to complications from invasive thymoma. Conclusion: Our meta-analysis shows that low-dose RTX is both effective and safe for treating MG. Systematic Review Registration: PROSPERO, identifier: CRD42024509951. [ABSTRACT FROM AUTHOR]

Fumarate hydratase (FH) mutated papillary renal cell carcinoma is an aggressive variant of kidney cancer that poorly responds to conventional targeted therapies and immunotherapy. Here, we present the 10-year follow-up of a heavily pre-treated patient with several lines of therapy, achieving a remarkable complete response to anti-PD-1 rechallenge. In addition, we highlight a common immune-related adverse event of anti-PD-1, eosinophilia, as a possible biomarker of response and using TCGA data analysis, provide proof-of-concept for tumor expression of the eosinophil-related gene SIGLEC8, as a promising powerful predictor of prognosis for papillary renal cell carcinoma patients. [ABSTRACT FROM AUTHOR]

Background: Asthma, a complex respiratory disease, presents with inflammatory symptoms in the lungs, blood, and other tissues. We investigated the relationship between DNA methylation and 35 clinical markers of asthma. Methods: The Illumina Infinium EPIC v1 methylation array was used to evaluate 742,442 CpGs in whole blood from 319 participants from 94 families. They were part of the Netherlands Twin Register from families with at least one member suffering from severe asthma. Repeat blood samples were taken after 10 years from 182 individuals. Principal component analysis on the clinical asthma markers yielded ten principal components (PCs) that explained 92.8% of the total variance. We performed epigenome-wide association studies (EWAS) for each of the ten PCs correcting for familial structure and other covariates. Results: 221 unique CpGs reached genome-wide significance at timepoint 1 after Bonferroni correction. PC7, which correlated with loadings of eosinophil counts and immunoglobulin levels, accounted for the majority of associations (204). Enrichment analysis via the EWAS Atlas identified 190 of these CpGs to be previously identified in EWASs of asthma and asthma-related traits. Proximity assessment to previously identified SNPs associated with asthma identified 17 unique SNPs within 1 MB of two of the 221 CpGs. EWAS in 182 individuals with epigenetic data at a second timepoint identified 49 significant CpGs. EWAS Atlas enrichment analysis indicated that 4 of the 49 were previously associated with asthma or asthma-related traits. Comparing the estimates of all the significant associations identified across the two time points yielded a correlation of 0.81. Conclusion: We identified 270 unique CpGs that were associated with PC scores generated from 35 clinical markers of asthma, either cross-sectionally or 10 years later. A strong correlation was present between effect sizes at the 2 timepoints. Most associations were identified for PC7, which captured blood eosinophil counts and immunoglobulin levels and many of these CpGs have previous associations in earlier studies of asthma and asthma-related traits. The results point to a robust DNA methylation profile as a new, stable biomarker for asthma. [ABSTRACT FROM AUTHOR]

Eosinophils are often encountered in the stroma and peritumoral microenvironment of squamous cell carcinomas. Because eosinophils are readily identified on routine hematoxylin and eosin stained sections, researchers have explored multiple ways in which identifying the extent of eosinophil infiltration on routine biopsy and excisional specimens might provide diagnostic and prognostic information. We review the literature on this evolving topic. [ABSTRACT FROM AUTHOR]

Simple Summary: Siglec-8 has been identified as a promising target to treat eosinophilic and mast cell disorders. However, there are currently few Siglec-8 antibodies available, and therapeutic efforts have so far primarily focused on unconjugated antibodies, which may be insufficiently effective in many patients. To address these limitations, we raised a diverse panel of fully human Siglec-8 antibodies as the basis for novel therapeutics. They were all efficiently internalized, suggesting their potential to deliver cytotoxic payloads. T cell-engaging bispecific antibodies and chimeric antigen receptor (CAR)-modified natural killer (NK) cells built from these Siglec-8 antibodies were highly potent against Siglec-8-positive cells even in cases of very low target antigen abundance. Importantly, mechanistic studies with target cells expressing either full-length Siglec-8 or an artificial smaller Siglec-8 variant demonstrated that T cell-engaging bispecific antibodies and CAR-modified NK cells were substantially more effective if they bound Siglec-8 closer to the cell membrane, indicating targeting membrane-proximal epitopes enhances effector functions of Siglec-8 antibody-based therapeutics. Indeed, tool therapeutics that bind one of the membrane-proximal C2-set domains of Siglec-8 were very effective against Siglec-8-positive target cells. Together, these data demonstrate Siglec-8-directed immunotherapies can be highly potent, supporting their further development for eosinophilic and mast cell disorders. Background/Objective: Current treatments for eosinophilic and mast cell disorders are often ineffective. One promising target to improve outcomes is sialic acid-binding immunoglobulin-like lectin-8 (Siglec-8). As limitations, there are few Siglec-8 monoclonal antibodies (mAbs) available to date, and Siglec-8-directed treatments have so far primarily focused on unconjugated mAbs, which may be inadequate, especially against mast cells. Methods: Here, we used transgenic mice to raise a diverse panel of fully human mAbs that either recognize the V-set domain, membrane-distal C2-set domain, or membrane-proximal C2-set domain of full-length Siglec-8 as a basis for novel therapeutics. Results: All mAbs were efficiently internalized into Siglec-8-expressing cells, suggesting their potential to deliver cytotoxic payloads. Tool T cell-engaging bispecific antibodies (BiAbs) and chimeric antigen receptor (CAR)-modified natural killer (NK) cells using single-chain variable fragments from Siglec-8 mAbs showed highly potent cytolytic activity against Siglec-8-positive cells even in cases of very low target antigen abundance, whereas they elicited no cytolytic activity against Siglec-8-negative target cells. Siglec-8V-set-directed T cell-engaging BiAbs and Siglec-8V-set-directed CAR-modified NK cells induced substantially greater cytotoxicity against cells expressing an artificial smaller Siglec-8 variant containing only the V-set domain than cells expressing full-length Siglec-8, consistent with the notion that targeting membrane-proximal epitopes enhances effector functions of Siglec-8 antibody-based therapeutics. Indeed, unconjugated Siglec-8C2-set mAbs, Siglec-8C2-set-directed T cell-engaging BiAbs, and Siglec-8C2-set-directed CAR-modified NK cells showed high antigen-specific cytolytic activity against Siglec-8-positive human cell lines and primary patient eosinophils. Conclusions: Together, these data demonstrate Siglec-8-directed immunotherapies can be highly potent, supporting their further development for eosinophilic and mast cell disorders. [ABSTRACT FROM AUTHOR]

Background: Rituximab (RTX) is a monoclonal antibody that has been increasingly used in the treatment of myasthenia gravis (MG). In most studies, the therapeutic protocol of RTX has been similar to that adopted for B cell lymphoma, with an increasing number of studies aimed at exploring the efficacy of low-dose RTX in MG. However, the beneficial effects of low-dose RTX in MG remain a subject of critical debate. Methods: This study was conducted following the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidelines. Two reviewers (Xishuai Yang and Bingxia Li) independently conducted searches across multiple databases, including PubMed, MEDLINE, EMBASE, Web of Science, Cochrane Library, and China National Knowledge Infrastructure (CNKI). A meta-analysis, utilizing representative forest plots, was performed to assess "Improved clinical status" and changes in the Quantitative Myasthenia Gravis (QMG) score before and after treatment. Results: A total of 17 studies involving 292 patients were included in the meta-analysis. A noticeable improvement in clinical status was observed in 91% of patients at the final follow-up after therapy (95% CI: 84-96%, P < 0.001). The QMG score showed a significant reduction following the treatment, with a standardized mean difference (SMD) of -1.69 (95% CI: -2.21 to -1.16, Z = 6.29, P < 0.001). In the acetylcholine receptor antibody-positive myasthenia gravis (AChR-MG) group, 90% of patients achieved improved clinical status (95% CI: 80-97%, P < 0.001) and the QMG score significantly decreased after low-dose RTX treatment, with an SMD of -1.51 (95% CI: -0.80 to -2.21, Z = 4.50, P < 0.001). In themuscle-specific kinase antibody-positivemyasthenia gravis (MuSK-MG) group, 97% of patients achieved improved clinical status (95% CI: 89-100%, P < 0.001). The QMG score also significantly decreased following low-dose RTX treatment, with an SMD of -2.31 (95% CI: -2.99 to -1.62, Z = 6.60, P < 0.001). Adverse effects were reported in 29 out of 207 patients (14%, including infusion reactions in 22 patients (10.1%), infections in three patients (1.45%), cytopenia in two patients (0.96%), eosinophilia in one patient (0.48%), and hemiplegia in one patient (0.48%). Additionally, one patient (0.48%) succumbed to complications from invasive thymoma. Conclusion: Our meta-analysis shows that low-dose RTX is both effective and safe for treating MG. [ABSTRACT FROM AUTHOR]

Objective: Asthma is linked to atherosclerosis, yet the underlying mediators remain elusive. Eosinophils may contribute to both asthmatic and atherosclerotic inflammation. Hence, this study aimed to explore the potential associations of eosinophils with artery changes among patients with asthma. Methods: We assessed strain values of the common carotid arteries (CCAs) via vascular speckle tracking and compared asthma patients with low (< 300/µl) and high (≥ 300/µl) blood eosinophil counts (BEC). Results: We enrolled 100 patients, 42 with a BEC of < 300 and 58 with a BEC of ≥ 300 n/µl. Patients with high BEC exhibited more severe disease, characterized, e.g., by a higher frequency of acute exacerbations (1.3 ± 2.1 vs. 2.6 ± 2.4 n/year, p = 0.005). Both groups presented similar profiles in terms of conventional cardiovascular risk. The high BEC group demonstrated elevated arterial stiffness, reflected by reduced radial strain (mean radial strain of the right CCA: 2.7 ± 1.4% for BEC ≥ 300 n/µl vs. 3.5 ± 1.7% for BEC < 300 n/µl, p = 0.008; left CCA: 2.6 ± 1.4% vs. 4.1 ± 2.2%, p < 0.001). A weak yet statistically significant negative correlation was observed between BEC and radial strain for the right CCA (R2 = 0.131, b=-0.001, p = 0.001) and left CCA (R2 = 0.086, b=-0.001, p = 0.015). However, the prevalence of cerebrovascular disease was similar in both groups (31,0% vs. 50,0%, p = 0.057). Conclusion: We identified a correlation between BEC and vascular stiffness, which supports the hypothesis that eosinophils may promote atherosclerosis. Clinical trial number: Due to the exploratory and predominantly retrospective nature of the study, trial registration was not conducted. The only prospective procedure conducted was the angiological sonography to evaluate the current state. No ensuing health-related interventions were performed specifically for this study. [ABSTRACT FROM AUTHOR]

Background: The association between blood eosinophils and COPD exacerbation has been controversial. This study aims to investigate whether high blood eosinophils predict the risk of COPD exacerbation across different thresholds and subgroups. Methods: PubMed, Embase and Web of science were searched for randomized controlled trial (RCT) and observational studies regarding the relationship between blood eosinophils and COPD exacerbation. Pooled risk ratio (RR) for COPD exacerbation was calculated using the Mantel-Haenszel method with a random-effects model. Results: A total of 21 studies (1 RCT and 20 observational studies) with 79868 participants were included. Thresholds of high blood eosinophils including absolute counts (200, 300 and 400 cell/μL) and percentages (2%, 3% and 4%) were analyzed respectively. Pooled analyses suggested that high blood eosinophils were significantly associated with increased risk of COPD exacerbation when using the thresholds of 300 cells/μL (RR 1.21, 95%CI 1.12–1.30, P <0.001, 16 studies), 400 cells/μL (RR 1.79, 95%CI 1.41–2.28, P <0.001, 3 studies), 2% (RR 1.26, 95%CI 1.02–1.55, P = 0.030, 10 studies) and 4% (RR 1.44, 95%CI 1.05–1.96, P = 0.022, 4 studies), but not 200 cells/μL and 3% (P>0.05). Moreover, high blood eosinophils contributed to moderate-severe exacerbation of COPD by the cutoffs of 300 cells/μL (RR 1.30, 95%CI 1.16–1.45, P<0.001, 11 studies) and 2% (RR 1.33, 95%CI 1.02–1.76, P = 0.037, 8 studies). In subgroup analyses, the pooled results further showed a significant association between high blood eosinophils (especially over 300 cells/μL) and risk of COPD exacerbation among patients from Europe and Asia, and whether with stable or exacerbation phase at baseline, and regardless of the follow-up time (≤ or > 1year). Conclusions: This study demonstrates that high blood eosinophils (over 300 cells/μL or 2%) could predict the risk of moderate-severe exacerbation of COPD in specific subgroups. However, large sample-sized, prospective, and well-designed studies are required to validate the present findings. [ABSTRACT FROM AUTHOR]

Context.--Eosinophilic solid and cystic renal cell carcinoma is now defined in the 5th edition of the 2022 World Health Organization classification of urogenital tumors. Objective.--To perform morphologic, immunohistochemical, and preliminary genetic studies about this new entity in China for the purpose of understanding it better. Design.--The study includes 18 patients from a regional tertiary oncology center in northern China (Tianjin, China). We investigated the clinical and immunohistochemical features of these cases. Results.--The mean age of patients was 49.6 years, and the male to female ratio was 11:7. Macroscopically, 1 case had the classic cystic and solid appearance, whereas the others appeared purely solid. Microscopically, all 18 tumors shared a similar solid and focal macrocystic or microcystic growth pattern, and the cells were characterized by voluminous and eosinophilic cytoplasm, along with coarse ampho-philic stippling. Immunohistochemically, most of the tumors had a predominant cytokeratin (CK) 20-positive feature, ranging from focal cytoplasmic staining to diffuse membranous accentuation. Initially, we separated these cases into different immunohistochemical phenotypes. Group 1 (7 of 18; 38.5%) was characterized by positive phospho-4EBP1 and phospho-S6, which can imply hyperactive mechanistic target of rapamycin complex 1 (mTORC1) signaling. Group 2 (4 of 18; 23%) was negative for NF2, probably implying a germ-line mutation of NF2. Group 3 (7 of 18; 38.5%) consisted of the remaining cases. One case had metastatic spread and exhibited an aggressive clinical course, and we detected cyclin-dependent kinase inhibitor 2A (CDKN2A) mutation in this case; other patients were alive and without disease progression. Conclusions.--Our research proposes that eosinophilic solid and cystic renal cell carcinoma exhibits prototypical pathologic features with CK20 positivity and has aggressive potential. [ABSTRACT FROM AUTHOR]

Simple Summary: Insect bite hypersensitivity (IBH) is a common skin allergic condition in horses caused by insect bites, mainly of Culiocides species. Affected horses develop severe itchy lesions, up to traumatic skin injuries. Eosinophils are known to play a crucial role in the pathogenesis of IBH. Recently, we described two subsets of eosinophils: inflammatory eosinophils (iEos) dominant in blood of IBH-affected horses, and resident eosinophils (rEos) present in blood of healthy horses. iEos and rEos were distinguishable by size, granularity, and proteins present on their cell surface. Interleukin (IL)-5, the main activator and regulator of eosinophils, is our vaccine target. Vaccinated horses showed a significant reduction of total eosinophils, in particular iEos, where the very few remaining eosinophils still showed iEos phenotype. In the present study, we followed the phenotype of eosinophil subsets in the 2nd year of vaccination in IBH-affected horses. Our results showed comparably lower levels of iEos and a significant increase of rEos in 2nd compared to 1st year vaccinated and unvaccinated horses. This suggests a shift from iEos to the rEos phenotype, the dominant eosinophil type of healthy horses. The change in size, granularity and migration properties suggests a benefit of long term vaccination of IBH-affected horses. Eosinophils play a key role in allergic diseases such as insect bite hypersensitivity (IBH). Together with Th2 cells, they shape the course of inflammation in associated type I/IVb allergies. Therefore, a virus-like particle (VLP)-based vaccine targeting equine interleukin-5 (eIL-5), eIL-5-CuMV-TT, was developed to interfere with the IL-5 dependency of eosinophils by inducing the production of anti-self-IL-5 antibodies and alleviating clinical signs in IBH-affected horses. A previous study highlighted the presence of two eosinophil subsets, steady-state resident eosinophils (rEos) and inflammatory eosinophils (iEos), circulating in the blood of healthy and IBH-affected horses, distinguishable by the expression of integrin CD49f. Furthermore, eIL-5-CuMV-TT 1st year vaccination showed a significant decrease of total eosinophils and, in particular, iEos. Nevertheless, the very few remaining eosinophils still shared an iEos phenotype, reflected by bigger size and higher granularity. The aim of this study was to follow up on the phenotype of eosinophils in the 2nd year of vaccination of IBH-affected horses with eIL-5-CuMV-TT. Using flow cytometry analysis of the blood of healthy, IBH, IBH-placebo, and IBH-vaccinated horses, the percentage and count of cells were compared between groups with a focus on pair analysis of eosinophils in 1st and 2nd year vaccinated horses. Our data showed comparably low levels of iEos and a significant increase of rEos in 2nd year compared to 1st year vaccinated horses, suggesting a phenotypic shift toward a resident-like eosinophil population, primarily associated with the phenotype of healthy horses. The reduction of size, granularity, and expression of integrin CD49f in the 2nd year suggests a benefit of long-term treatment with the eIL-5-CuMV-TT vaccine. [ABSTRACT FROM AUTHOR]

Estrogens regulate eosinophilia in asthma and other inflammatory diseases. Further, peripheral eosinophilia and tumor-associated tissue eosinophilia (TATE) predicts a better response to immune checkpoint blockade (ICB) in breast cancer. However, how and if estrogens affect eosinophil biology in tumors and how this influences ICB efficacy has not been determined. Here, we report that estrogens decrease the number of peripheral eosinophils and TATE, and this contributes to increased tumor growth in validated murine models of breast cancer and melanoma. Moreover, estrogen signaling in healthy female mice also suppressed peripheral eosinophil prevalence by decreasing the proliferation and survival of maturing eosinophils. Inhibiting estrogen receptor (ER) signaling decreased tumor growth in an eosinophil-dependent manner. Further, the efficacy of ICBs was increased when administered in combination with anti-estrogens. These findings highlight the importance of ER signaling as a regulator of eosinophil biology and TATE and highlight the potential near-term clinical application of ER modulators to increase ICB efficacy in multiple tumor types. [ABSTRACT FROM AUTHOR]

Background: The potential link between alopecia areata (AA) and eosinophilia is unclear, as well as its clinical manifestations in these patients' subsets. Methods: This is a monocentric retrospective observational study in which clinical and laboratory data were summarized and evaluated the AA subset with concurrent eosinophilia. Results: In a sample of 205 AA patients, 38 (18.5%) were classified as AA with eosinophilia. Interestingly, this subset of patients had a statistically higher prevalence of atopia and nail abnormalities (p < 0.05) than AA without eosinophilia. AA patients with eosinophilia had a 3.70 higher odds of more severe hair loss versus age‐ and gender‐matched AA without eosinophilia. Conclusions: AA patients with eosinophilia had distinctive clinical and laboratory characteristics, so future studies may potentially explore the use of IL‐5 inhibitors. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions The aim of this study was to explore the clinical characteristics and risk factors for hypersensitivity reactions induced by antituberculosis drugs.A retrospective analysis was conducted on the medical records of patients with active tuberculosis (TB) treated in the TB ward at West China Hospital, Sichuan University, from November 2010 to April 2020.Out of 7106 patients with active tuberculosis, 205 experienced hypersensitivity reactions to antituberculosis drugs; the incidence of hypersensitivity was 2.9%. The predominant clinical manifestation was a rash, observed in 57.1% (117/205) of these cases. Additionally, 19.0% (39/205) of patients presented with concurrent liver injury. The laboratory parameters white blood cell count, total lymphocyte count, monocyte count, eosinophil count, basophil count, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase were significantly elevated in patients with hypersensitivity compared to those without. In 38 patients who tested positive for oral antituberculosis drug provocation, 14 (36.8%) were allergic to more than two antituberculosis drugs. Significant risk factors included being female (odds ratio [OR] = 1.387, 95% confidence intervals [CI]: 1.016–1.894), under 65 years of age (OR = 1.826, 95% CI: 1.145–2.913), existing liver disease (OR = 2.464, 95% CI: 1.822–3.333) and a history of allergic diseases (OR = 6.633, 95% CI: 2.681–16.406) and were significantly correlated with hypersensitivity to antituberculosis drugs.Hypersensitivity reactions to antituberculosis drugs primarily affect the skin, with significant associations observed with liver injury. Females, individuals younger than 65 years, those with pre‐existing liver disease and patients with a history of allergic diseases are at elevated risk for hypersensitivity. [ABSTRACT FROM AUTHOR]

This study reported a woman with drug reaction with eosinophilia and systemic symptom (DRESS) syndrome induced by phloroglucinol who developed fulminant type 1 diabetes as sequelae. The literature review emphasized the necessity of at least seven months of follow‐up for better management of DRESS syndrome. [ABSTRACT FROM AUTHOR]

Kimura's disease (KD) is a rare, chronic inflammatory disorder characterized by angiolymphoid hyperplasia, peripheral eosinophilia, and elevated serum immunoglobulin E levels. It primarily affects young Asian males and typically involves the head and neck region, especially near the mandible and postauricular regions. Orbital involvement is unusual and extraocular muscle (EOM) involvement is exceedingly rare, with only a few cases reported in the literature. The present report describes a case of surgically confirmed KD in a 16-yearold male, involving the bilateral EOM, lacrimal gland, and left parotid gland. [ABSTRACT FROM AUTHOR]

Background: Our aim is to investigate cardiovascular risk factors, chronic graft-versus-host disease (CGvHD), and vitamin D metabolism in very long-term survivors of adult allogeneic stem cell transplantation (alloSCT). Methods: This study is a prospective unicentric, non-interventional trial. The detailed study protocol is available via the WHO Clinical Trial Registry. Results: We were able to include 33 patients with a mean age of 60.5 years (SD 11.1). Acute myeloid leukemia (AML) was the most frequent underlying disease (n = 12; 36.4%). The median survival time was 9.0 years (IQR 8.5–13.0). Relevant cardiovascular risk factors in the study population are the body mass index, cholesterol, LDL cholesterol, and lipoprotein(a). Cardiovascular risk factors have no significant impact on HRQoL. CGvHD of the skin as a limited disease was present in six patients (18.2%), and it has no impact on HRQoL. CGvHD was significantly associated with eosinophilia in peripheral blood (p = 0.003). Three patients (9.1%) had a shortage of calcitriol, and one patient (3.0%) took calcium substitution. The shortage is significantly associated with increased infection rates (p = 0.038). Conclusions: Cardiovascular risk factors and CGvHD need to be closely monitored. Eosinophilia might be a good and convenient monitoring parameter for CGvHD. [ABSTRACT FROM AUTHOR]

Background: Studies involving chronic rhinosinusitis with nasal polyps (CRSwNP) have mostly focused on bilateral cases, making unilateral CRSwNP inadequately recognized. This study examined the differences in clinical characteristics, outcomes, and risk factors for poor outcomes between unilateral and bilateral CRSwNP to facilitate a better assessment in the two groups. Methods: Demographic information, tissue and blood cells, endoscopic scores, Lund‐Mackay scores, recurrence rates, and disease control conditions were compared between 310 unilateral and 596 bilateral CRSwNP patients. Furthermore, the stepwise regression multivariate Cox proportional hazard models were performed to generate risk factors for poor outcomes in the two groups. Results: Bilateral cases exhibited higher rates of smoking, AR, and asthma comorbidities, along with higher numbers of tissue eosinophils and blood inflammatory cells when compared to unilateral patients. Endoscopic nasal polyp score, total computed tomography (CT) score (with scores for each sinus cavity), and adjusted CT scores were significantly higher in the bilateral group, except for a markedly higher adjusted maxillary score in the unilateral group. Furthermore, significantly higher proportions of bilateral patients experienced nasal polyp recurrence, uncontrolled status, and most disease control‐related symptoms at follow‐up. The primary risk factors for poor outcomes were asthma, tissue eosinophils, and total CT score in the bilateral group and blood basophils in the unilateral group. Conclusions: Bilateral CRSwNP patients experience worse disease severity and outcomes than their unilateral counterparts. Primarily, asthma, tissue eosinophils, and total CT score were risk factors for poor outcomes in bilateral CRSwNP patients, with blood basophils in unilateral cases. [ABSTRACT FROM AUTHOR]

Background/Aim. The cause of eosinophilia often remains unelucidated. The aim of the study was to analyze causes and treatment approaches in children with eosinophilia in pediatric tertiary care hospital. Methods. The medical records of children investigated for eosinophilia (based on the International Classification of Diseases code D72.1) were retrospectively reviewed in the University Children's Hospital, Belgrade, Serbia, from December 2011 to December 2022. A total of 105 children (62 boys; male:female ratio was 1:4) aged one month to 16.5 years (median 7.7 years) were diagnosed with eosinophilia. After excluding 15 of them due to incorrectly assigned diagnosis based on relative eosinophil number only, the remaining 90 children were grouped according to the severity of eosinophilia (mild, moderate or severe). Results. Serological analysis confirmed toxocariasis in six (6.7%) patients, while two (2.2%) had a confirmed nematode infestation (Ascaris lumbricoides and Enterobius vermicularis, respectively). Thirty-two (35.6%) children with eosinophilia and three with no true eosinophilia were diagnosed with helminthiasis ex juvantibus. Eosinophilia was ultimately explained by allergic/atopic conditions [19 (21.1%)], drug reactions [four (4.4%)], bacterial infections [nine (8.9%)], hematological problems [five (5.5%)], autoimmune disorders [three (3.3%)], unrelated congenital disorders (one), or as an isolated finding [seven (7.8%)]. In addition, one of the children without an increased absolute eosinophil number was diagnosed with eosinophilic esophagitis. A total of 56 (53.3%) children received anthelminthic treatment: 9 (90.0%) with severe eosinophilia, 19 (51.4%) with moderate, 23 (53.5%) with mild, and 5 (33.3%) children with no true eosinophilia. Most (42) of the children were given mebendazole only, while the remaining 14 (eight with severe, three with moderate, and three with mild) were also initially treated with mebendazole but subsequently shifted to albendazole due to the persistence of eosinophilia. In all treated children, eosinophilia and other relevant findings (if any) subsided in a matter of a few days to a few weeks after initializing treatment. Conclusion. Our results support the recommendation that unexplained eosinophilia of all levels of severity requires a standardized diagnostic approach. The results also provide some support for a potential rational basis for ex juvantibus administration of anthelminthic drugs in a fraction of children with eosinophilia without an obvious etiological explanation. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICI) are increasingly utilized as first‐line treatment for many solid tumour malignancies. One downside of ICI therapy is autoimmune‐mediated organ inflammation, or immune‐related adverse events (irAE). ICI‐related pneumonitis, or non‐infectious inflammation of the lung, is a well‐described irAE. While guidelines surrounding ICI‐related pneumonitis are well established, other ICI‐related pulmonary toxicities, including reactive airways disease, are rarely described in the literature. Here, we present a series of patients without pre‐existing COPD or asthma who developed reactive airways disease with peripheral eosinophilia after ICI therapy and without radiographic evidence of pneumonitis. The patients were treated with typical therapies for reactive airways disease, including– inhaled steroids, bronchodilators, systemic steroids, and in one instance, dupilumab. All experienced symptomatic improvement with these therapies, enabling some of the patients to continue receiving ICI therapy. [ABSTRACT FROM AUTHOR]

Few reports have described the treatment of eosinophilic pneumonia (EP) complicated by refractory pneumothorax. A 62‐year‐old man with a medical history of ulcerative colitis who was undergoing maintenance treatment presented with fever, cough, and diffuse bilateral consolidation on chest radiography. Laboratory findings showed peripheral eosinophilia, and he was hospitalized with a diagnosis of drug‐induced EP and started on corticosteroid therapy. During the course, he developed refractory pneumothorax, and it was difficult to control the air leakage. As it was necessary to control the eosinophilic inflammation and air leakage, mepolizumab, a humanized anti‐interleukin‐5 monoclonal antibody, and an endobronchial Watanabe spigot (EWS), were introduced. After EWS insertion, the leakage of the refractory pneumothorax disappeared. The patient continued to have no recurrence of EP or pneumothorax after the removal of the EWS. The combination of mepolizumab and an EWS may be effective in cases of EP complicated by refractory pneumothorax. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The authors present the case of a 39-year-old male with an initial diagnosis of de novo acute myeloid leukemia who, despite complete remission without measurable residual disease after conventional induction chemotherapy, presented with persistent splenomegaly and eosinophilia. As reactive eosinophilia was excluded and CBFB::MYH11 and RUNX1::RUNX1T1 gene fusions were not identified in additional molecular studies, we decided to test for other causes of clonal eosinophilia. Cytogenetic and molecular testing identified FIP1L1::PDGFRA gene fusion and prompted the introduction of imatinib. The initial diagnosis of de novo acute myeloid leukemia was changed to myeloid/lymphoid neoplasm with eosinophilia and FIP1L1::PDGFRA in the blast phase as myeloid blast count in the bone marrow at the diagnosis was >20%. The patient has maintained a complete molecular response with imatinib at a dose of 100 mg for more than two years. [ABSTRACT FROM AUTHOR]

Background Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare disease caused by small- to medium-sized vessel vasculitis which can also impact the heart. Because of its rarity and diverse clinical manifestations, diagnosis can be challenging. Here, we present a unique case of EGPA causing perimyocarditis in a young female patient. Case summary A 37-year-old woman with hypertension, asthma, and sickle cell trait presented with palpitations, dyspnoea, and sharp chest pain. White blood cell was elevated to 16 300/μL with peripheral eosinophilia at 5216/μL. Electrocardiogram revealed sinus tachycardia with frequent non-sustained ventricular tachycardia. Echocardiogram showed an ejection fraction of 20–25% with severe diffuse hypokinesis and dilated cardiac chambers. Coronary angiogram was normal. Cardiac magnetic resonance imaging revealed focal subendocardial late gadolinium enhancement (LGE) of the septum and subepicardial LGE of the basal anterolateral wall of the left ventricle. Further work-up showed elevated Immunoglobulin E level, left antrochoanal polyp, and ground glass opacities in the left upper lobe. Endomyocardial biopsy showed interstitial infiltrates of eosinophils with sporadic necrosis, confirming the diagnosis of EGPA perimyocarditis. The patient was treated with prednisone, colchicine, and guideline-directed medical therapy. Discussion This case report describes an unusual cause of perimyocarditis. Keeping a broad differential is important as diagnosis is challenging, and cardiac involvement in EGPA is associated with higher morbidity and mortality. Recognizing the typical manifestations of EGPA, implementing multidisciplinary approach, and promptly initiating appropriate treatment are crucial for the optimal management of EGPA perimyocarditis. [ABSTRACT FROM AUTHOR]

Abstract Background Eosinophilic gastroenteritis is a rare disease characterized by eosinophilic infiltration into one or more layers of the gastrointestinal tract. It commonly affects children more than adults. The clinical features depend on the site of gut involvement, but the most common symptoms include abdominal pain and diarrhea. The most common cause reported in the literature is hypersensitivity, as many patients have a history of seasonal allergies, atopy, asthma, food allergies, and so on. However, drugs can be a rare triggering factor. In the literature review, we found multiple case reports of eosinophilic gastroenteritis; however, only one other case of carbimazole-induced eosinophilic gastritis has been reported. Case presentation We report herein the case of a 36-year-old female from the Philippines who developed eosinophilic gastroenteritis localized to the esophagus and ileum 12 months following treatment with carbimazole for hyperthyroidism. In our facility, she was extensively investigated for malignancy, autoimmune pathologies and infectious etiologies. As the symptoms coincided with carbimazole exposure and other causes were ruled out, we labeled her as carbimazole-induced eosinophilic gastroenteritis. On subsequent follow-up after discharge, her symptoms and eosinophilia resolved when carbimazole was discontinued, suggesting a causative role. This is the first case of eosinophilic gastroenteritis secondary to carbimazole encountered in our region. Conclusion Diagnosis of eosinophilic gastroenteritis requires three criteria, namely (1) presence of gastrointestinal symptoms, (2) histologic evidence of eosinophilic infiltration in one or more areas of the gastrointestinal tract, and (3) exclusion of other causes of tissue eosinophilia. Our patient fulfilled all the criteria; additionally, she had a positive history of atopic tendencies and drug exposure. The diagnosis of hyperthyroidism was established a year ago and in another facility, so we were not sure of the underlying etiology of hyperthyroidism. Upon subsequent follow-up, her thyroid function remained stable. The case highlights the need for a collaborative multidisciplinary approach toward managing rare conditions.

Loeffler first described “fibroplastic parietal endocarditis with blood eosinophilia” in 1936. This we now know refers to the most common cardiac manifestation of an uncommon condition, the so-called hypereosinophilic syndromes. This condition typically results in a restrictive cardiomyopathy affecting the left heart, but here, we present an unusual case of a 65-year-old woman with chronic hypereosinophilia of at least 2 years, who presented with right heart failure as a result of eosinophilic endomyocardial infiltration of her right ventricle. We explore the diagnostic pathway and look at the literature on management.

Abstract Objective Asthma is linked to atherosclerosis, yet the underlying mediators remain elusive. Eosinophils may contribute to both asthmatic and atherosclerotic inflammation. Hence, this study aimed to explore the potential associations of eosinophils with artery changes among patients with asthma. Methods We assessed strain values of the common carotid arteries (CCAs) via vascular speckle tracking and compared asthma patients with low (

Background Patients with chronic obstructive pulmonary disease (COPD) expressing eosinophilia experience slightly fewer episodes of community-acquired pneumonia (CAP), than those without eosinophilia. However, the severity and burden of hospitalized pneumonia patients with COPD involving eosinophilia have not been assessed. Methods We evaluated the differences in clinical characteristics between patients with CAP and COPD with or without eosinophilia by a post hoc analysis of a prospective, multi-center, cohort study data. Results Of 349 CAP patients with COPD, 45 (12.9%) had eosinophilia (blood eosinophil ≥300 cells/μL). Patients with eosinophilia had a lower sputum culture percentile (8.1% vs. 23.4%, p

Background and objectives: Asthma is a chronic airway inflammatory disease. Viola odorata has been traditionally used to treat inflammatory diseases. This study was conducted to explore the anti-inflammatory effects of V. odorata aqueous extract on a murine model of asthma. Methods: Forty-eight Balb/c female mice were divided into six groups of eight animals. The healthy controls received distilled water and other groups became asthmatic using ovalbumin. Then, one group received dexamethasone, and the extract (100, 200, and 400 mg/kg) was administered to three groups for a week. Subsequently, the number of eosinophils, and the levels of interleukins 4, 5, and 13 were measured in bronchoalveolar lavage fluid (BALF) samples. Histopathological changes were analyzed in lung tissues. Results: Eosinophils count and the levels of interleukins 4, 5, and 13 in BALF specimens significantly reduced. Hyperplasia of goblet cells, lymphoid tissue hyperplasia, and peribronchial and perivascular inflammations decreased in the extract-treated mice. The effects of V. odorata aqueous extract on all parameters were comparable with dexamethasone. Conclusion: The present study is the first report of anti-inflammatory activities of V. odorata aqueous extract in a mouse model of allergic asthma. Therefore, these data may suggest V. odorata as a promising drug to treat asthma-induced inflammation.

A 3-year-old male pit bull terrier was presented for a 4-day history of progressive tetraparesis and cervical pain. Magnetic resonance imaging confirmed an extradural mass within the left lateral vertebral canal extending from caudal C5 to mid-T2. Lumbar cerebrospinal fluid (CSF) demonstrated marked (90%) eosinophilic inflammation. A C6-7 dorsal laminectomy and C7-T2 left hemilaminectomy were done, with gross disease remaining. Histopathology revealed a large T cell lymphoma with marked eosinophilic infiltration. The dog underwent CHOP-based chemotherapy with resolution of clinical signs, with a similar course of therapy performed at recurrence 37 months after initial presentation. The dog was euthanized 39 months after presentation for multiorgan failure secondary to neutropenic sepsis and aspiration pneumonia. This represents a positive long-term response to multimodal treatment of extradural T-cell lymphoma within the vertebral canal associated with a marked CSF eosinophilia.