Search Results (1,887)

Proton therapy spares normal tissues better than photon therapy, potentially reducing toxicity while maintaining tumor control. However, challenges remain due to variations in proton dose distribution, particularly at the distal edge of the spread-out Bragg peak (SOBP); for organs at risk, such variation is crucial. We evaluated the biological effects by comparing two positions of the proton profile, the entrance plateau (EP) and SOBP, in a murine model and investigated distinct metabolomic and proteomic signatures. Mice exposed to the EP beam segment (LET_d = 0.8 keV/µm) exhibited less weight reduction than their SOBP-irradiated counterparts (LET_d = 2.6 keV/µm). Two hours post-irradiation,the SOBP caused more severe DNA damage in the hippocampus and thalamus. Hematoxylin and eosin staining revealed eosinophil aggregation in both groups, with more surviving neurons in the EP group. Metabolomic profiles differed more between the EP and SOBP groups at 2 h than at 3 days post-irradiation. Relative to EP, SOBP irradiation at 2 h increased fructose-1,6-bisphosphate (FBP), dihydroxyacetone phosphate (DHAP), and inosine but decreased prostaglandin F2α; subsequently, proteomic analysis at day 3 showed that calcium signaling, NF-κB, and endocytosis pathways were enriched in the SOBP group. Combined multi-omics analysis further demonstrated that SOBP irradiation significantly activated the pentose phosphate pathway, purine metabolism, and phospholipase D signaling, while concurrently suppressing arachidonic acid metabolism. Our findings underscore the need for early detection of proton-induced brain toxicity and demonstrate that the higher-LET SOBP segment causes more severe damage than the EP. Targeting these dysregulated multi-omics pathways may offer a promising strategy for mitigating radiation-induced brain injury during proton therapy. Full article

Background/Objectives: Atopic dermatitis (AD) and food allergy (FA) frequently coexist in the concept of atopic march; however, their combined associations with psychological problems remain poorly understood. This study aimed to investigate the associations of AD and FA with psychological outcomes at age 7 and evaluate whether respiratory allergies account for part of these associations. Methods: We enrolled 1577 children aged 7 years from the Panel Study of Korean Children. The Korean version of the Child Behavior Checklist was used to assess psychological and behavioral problems. Multivariable regression and parallel mediation analyses were used to evaluate independent and interactive associations. Results: AD and FA were associated with psychological and behavioral problems, most consistently with somatic problems on the Diagnostic and Statistical Manual of Mental Disorders (DSM)-oriented scale. These associations were more pronounced in children with comorbid AD and FA than in those with single allergies. Among the 9 children with concurrent AD and FA, an interaction between the two conditions on somatic problems was observed (P for interaction = 0.033). The comorbid group showed higher eosinophil counts and total IgE levels, but no differences in SCORAD indices or C-reactive protein levels. Mediation analysis identified a direct association of AD with somatic problems (B = 1.062; 95% CI, 0.601–1.562), with a portion accounted for by allergic rhinitis (AR) (B = 0.656; 95% CI, 0.306–1.241). Conclusions: Comorbid AD and FA were associated with higher odds of somatic problems than either condition alone in 7-year-old children, with a portion of the AD association accounted for by AR. Because exposures and outcomes were assessed concurrently, these associations are exploratory and hypothesis-generating rather than causal. Clinical attention may be warranted for children with both AD and FA. Full article

Background: Eosinophilic jejuno-duodenitis is a rare inflammatory disorder characterized by eosinophilic infiltration of the gastrointestinal tract, with highly variable clinical presentations. Mucosal eosinophilic duodenitis and jejunitis associated with ascites is uncommon and may mimic inflammatory or neoplastic conditions. Case Presentation: A 26-year-old male presented with persistent left-sided abdominal pain without bowel habit changes. Laboratory investigations revealed only slight inflammatory syndrome and peripheral eosinophilia. Contrast-enhanced abdominopelvic computed tomography demonstrated minimal ascites and circumferential wall thickening with contrast enhancement of duodenal and jejunal loops in the left flank. Given the nonspecific imaging findings, differential diagnoses included Crohn’s disease, intestinal lymphoma, and infectious enteritis. Endoscopic evaluation with histopathological analysis confirmed dense eosinophilic infiltration of the duodenal and jejunal mucosa, establishing the diagnosis of eosinophilic jejuno-duodenitis after exclusion of secondary causes. Management and Outcome: The patient was treated with budesonide, with rapid clinical improvement and resolution of inflammatory markers. Follow-up magnetic resonance enterography performed three months after initiation of treatment demonstrated complete resolution of bowel wall thickening and disappearance of the minimal ascites. Conclusions: Eosinophilic jejuno-duodenitis should be considered in young patients presenting with small bowel thickening, ascites, and peripheral eosinophilia. Awareness of this entity is essential to avoid misdiagnosis and unnecessary invasive procedures. Full article

Objective: The aim of this study was to investigate the prevalence of exercise-induced bronchoconstriction and associated clinical risk factors in children in the early phase of subcutaneous allergen immunotherapy for moderate-to-severe persistent allergic rhinitis. Methods: This cross-sectional observational study included 62 children aged 6–18 years who were in the early phase of subcutaneous allergen immunotherapy for moderate-to-severe persistent allergic rhinitis. Patients with a diagnosis of asthma or asthma symptoms were excluded from the study. All participants underwent an exercise provocation test with spirometry in accordance with the recommendations of the American Thoracic Society and the European Respiratory Society. A decrease of ≥10% in FEV₁ from baseline at any time point following exercise was defined as exercise-induced bronchoconstriction. Demographic characteristics, concomitant atopic diseases, laboratory parameters, nasal symptom scores and respiratory function tests were evaluated. Results: The median age of the patients was 14 (9–18) years, and 71% were male. Exercise-induced bronchoconstriction was detected in 21 (33.9%) patients following the exercise provocation test. Exercise-induced bronchoconstriction positivity was most frequently observed at the 15th minute post-exercise. A family history of asthma was significantly higher in the exercise-induced bronchoconstriction-positive group (23.8% versus 2.4%, p = 0.014). Furthermore, the baseline Visual Analogue Scale and Total Nasal Symptom Score were significantly higher in exercise-induced bronchoconstriction positive patients (p = 0.035 and p = 0.016, respectively). No significant differences were observed between the groups in terms of total IgE levels, peripheral eosinophil counts, multiple aeroallergen sensitization, and baseline spirometric parameters. Conclusions: The prevalence of latent exercise-induced bronchoconstriction was 33.9% among children with moderate-to-severe persistent allergic rhinitis without asthma symptoms who had initiated subcutaneous allergen immunotherapy. In particular, including an exercise provocation test in the assessment process for patients with a family history of asthma and a high nasal symptom score may contribute to the early diagnosis of subclinical lower airway involvement. Full article

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory disease with a complex pathogenesis that significantly affects patients’ quality of life. Type 2 inflammation plays a dominant role in its course and is associated with the activation of immune pathways involving interleukins IL-4, IL-5 and IL-13, eosinophils, and immunoglobulin E. Standard treatment methods, including corticosteroids and surgical interventions, despite their proven efficacy, often fail to provide sustained disease control and are associated with a high rate of recurrence. The aim of this review is not only to summarize the available evidence on biological therapies in CRSwNP, but also to critically evaluate their current position within treatment algorithms, with particular emphasis on patient selection, integration with endoscopic sinus surgery, comparison of available biologic mechanisms, and remaining challenges in personalized treatment strategies. The paper discusses available monoclonal antibodies, such as dupilumab, omalizumab, mepolizumab, and benralizumab, which act by selectively inhibiting key mediators of type 2 inflammation. Analysis of clinical trial results indicates that biological therapies lead to a significant reduction in nasal polyp size, improvement in nasal patency, restoration of olfactory function, and enhancement of quality of life as measured by the SNOT-22 scale. Furthermore, they demonstrate a favourable safety profile and may represent an effective therapeutic option for patients with severe, treatment-resistant disease, particularly in cases with coexisting eosinophilic asthma. Biological therapies represent a breakthrough in the treatment of CRSwNP and align with the concept of personalised medicine. Their role in clinical practice continues to expand; however, further research is required to optimise patient selection and assess long-term treatment outcomes. Full article

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory disease in which identifying simple biomarkers reflecting disease severity remains challenging. This study aimed to evaluate the relationship between systemic inflammatory indices and radiological disease severity assessed by the Lund–Mackay (LM) score. This retrospective study included 90 adult patients with CRSwNP who underwent endoscopic sinus surgery. Preoperative computed tomography findings were scored using the LM system, and systemic inflammatory indices, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), eosinophil-to-lymphocyte ratio (ELR), neutrophil-to-monocyte ratio (NMR), systemic immune-inflammatory index (SII), systemic inflammation response index (SIRI), and eosinophil/leukocyte ratio, were calculated from complete blood count parameters. Spearman correlation and univariate logistic regression analyses were performed. ELR (r = 0.49, p < 0.001) and eosinophil/leukocyte ratio (r = 0.46, p < 0.001) showed moderate positive correlations with LM score, whereas other indices were not significantly associated. In logistic regression analysis, both ELR (OR = 5.44 × 10⁴, p < 0.001) and eosinophil/leukocyte ratio (OR = 4.99 × 10¹², p = 0.001) were significantly associated with high disease burden (LM ≥ 15). These findings suggest that eosinophil-based inflammatory indices may better reflect radiological disease severity in CRSwNP compared to traditional systemic inflammatory markers. Full article

The therapeutic goals related to chronic airway diseases are evolving from short-term symptom control toward sustained suppression of disease activity and prevention of future risk. In severe asthma, this shift has been captured by the concept of clinical remission, generally defined by absence of exacerbations, no need for oral corticosteroids, symptom control, and stable or improved lung function. In chronic obstructive pulmonary disease (COPD), the analogous concept has more often been described as disease stability. Although remission in asthma and stability in COPD have developed within different biological and clinical frameworks, they may reflect disease-specific expressions of the same therapeutic ambition. Recent studies support COPD stability as a measurable and clinically meaningful state, associated with reduced exacerbation risk and mortality. Evidence from optimized inhaled triple therapy, particularly with fluticasone furoate/umeclidinium/vilanterol, indicates that multidimensional stability can be achieved and maintained in a proportion of patients, while real-world studies reinforce its applicability beyond randomized trials. The emergence of biologic therapies for selected patients with eosinophilic or type 2 COPD further strengthens the rationale for considering stability as an ambitious treatment target. In this narrative review, informed by a structured literature search, we discuss the conceptual relationship between asthma remission and COPD stability, and summarize the evidence supporting disease stability as an attainable and prognostically relevant outcome. In addition, we propose a pragmatic multidimensional definition based on symptom stability, absence of moderate or severe exacerbations, no systemic corticosteroid use, and maintained lung function over 12 months. COPD stability should not be viewed as a weaker goal than asthma remission, but rather as the most appropriate COPD-specific expression of sustained low disease activity. Full article

Existing diagnostic markers of sepsis indicate already developed inflammatory complications, whereas predictors enable preoperative identification of high-risk patients for preventive measures. This study aimed to evaluate the prognostic value of preoperative inflammatory biomarkers for postoperative complications in cardiac surgery patients. Preoperatively, we assessed age, body mass index, EuroSCORE II (European System for Cardiac Operative Risk Evaluation II), complete blood count with hematological indices including neutrophil-to-lymphocyte ratio (NLR), serum cytokines, HIF1A (hypoxia-inducible factor 1-alpha), and EPAS1 (endothelial PAS domain protein 1) expression in peripheral blood leukocytes. During surgery, cardiopulmonary bypass time, myocardial ischemia time, and blood loss were recorded. Postoperatively, complications, intensive care unit (ICU) stay, and total hospitalization were documented. No differences were found in non-modifiable risk factors or perioperative parameters between groups, except for longer ICU stay in the complications group. Preoperatively, absolute neutrophil count and NLR were higher in patients without complications, while eosinophil count, HIF1A expression, and HIF1A/EPAS1 ratio were higher in those with it. The HIF1A/EPAS1 ratio demonstrated the best diagnostic characteristics. Thus, preoperative predictors of postoperative inflammatory complications include low neutrophil count and NLR, as well as high HIF1A expression and HIF1A/EPAS1 ratio. These markers may facilitate early risk stratification and preventive strategies before surgery. Full article

An 8-year-old, 3.3 kg spayed female Korean Shorthair cat presented with chronic vomiting, waxing and waning hyporexia, and weight loss. Ultrasonography revealed a 1.5 × 1.6 cm ileocecocolic junction (ICCJ) mass and multiple colonic nodules. Fine-needle aspiration biopsy yielded predominantly oval cells with loosely cohesive clustering, and an intestinal neuroendocrine tumor (NET) was favored. Segmental resection of the distal ileum, ICCJ, and proximal colon with stapled side-to-side ileocolic anastomosis was performed. Histopathology also favored NET because the lesion consisted of relatively monomorphic round-to-polygonal cells with eosinophilic to chromophobic granular cytoplasm. Neoplastic cells showed strong CD20 immunoreactivity and nuclear PAX5 labeling but lacked CD3 immunoreactivity, with CD3-positive lymphocytes mainly peripheral to the neoplastic population. Labeling for chromogranin A, synaptophysin, and NSE was absent. These findings led to reclassification as B-cell lymphoma with NET-like morphology, most consistent with an intermediate-cell type. Postoperatively, vomiting improved and resolved after cyclophosphamide, doxorubicin, vincristine, and prednisolone-based chemotherapy was initiated. At approximately 6 months after surgery, body weight remained stable, no postoperative complications were identified, and no discrete recurrent mass was detected. This case demonstrates that feline enteric B-cell lymphoma may rarely exhibit NET-like morphology and be misclassified on cytology and routine histopathology without immunophenotypic confirmation. Full article

Background: Specific learning disorder (SLD), termed “specific learning disability” in the Human Phenotype Ontology (HP:0001328), is a heterogeneous neurodevelopmental disorder, and the association between peripheral biological changes and cognitive function remains not well understood. Peripheral hematological and immune-endocrine biomarkers and their relationships with neuropsychological evaluations were evaluated in children with SLD. Methods: In this retrospective case–control study, we evaluated the peripheral biomarkers of a complete blood count and biochemical panel in 103 children with SLD and 102 well-child outpatient controls. Within the SLD group, we examined the association of systemic inflammatory indices with cognitive domains as assessed by the Wechsler Intelligence Scale for Children—Revised. Results: Group comparisons revealed modest peripheral changes, including reduced mean platelet volume (MPV) and increased eosinophil counts, that persisted after false discovery rate correction. Both differences remained significant after adjustment for age and sex. Inflammatory indices from complete blood count showed poor discriminative validity and were not strongly related to the global intelligence quotient. Exploratory analyses revealed only nominal, domain-specific associations between systemic inflammation indices and particular Wechsler subtests for verbal abstraction and visuospatial organization that did not survive multiple-comparison correction. Conclusions: The findings indicate a selective peripheral hematological pattern in SLD rather than evidence of generalized systemic inflammation. The evaluated indices showed limited discriminative utility and were not independently associated with global cognitive performance after multiple-testing correction. They should not be considered screening or diagnostic biomarkers for SLD. The selective pattern of lower MPV and higher eosinophil count observed in children with SLD appears to be novel but should be considered preliminary and requires independent confirmation in larger, prospectively recruited groups. Full article

Staphylococcus aureus frequently colonizes the skin and upper airways and produces a broad repertoire of immunomodulatory molecules. In asthma, the most consistent evidence concerns staphylococcal enterotoxins (SEs), which can act both as superantigens and as allergens, and IgE sensitization to SEs (SE-sIgE). SE-sIgE is associated with severe asthma, type 2 inflammation, chronic rhinosinusitis with nasal polyps (CRSwNP), exacerbations, and, in some longitudinal studies, persistent airflow obstruction. However, this relationship is not necessarily causal: SE-sIgE may reflect exposure, an immune response, or a biologically active endotype, whereas colonization, local toxin production, and systemic sensitization are not equivalent. SEs simultaneously bind class II MHC molecules and Vbeta regions of the T-cell receptor, activating large fractions of T lymphocytes; they also promote IL-4, IL-5, and IL-13 production, polyclonal B-cell activation, local IgE synthesis, mast-cell degranulation, eosinophilia, and IL-8/neutrophil circuits. Alpha-toxin (Hla) and SEB can damage the epithelial barrier, facilitating allergen penetration and alarmin signalling. These observations support an interaction model in which dysbiosis, barrier dysfunction, and type 2 immunity mutually reinforce one another along the nasobronchial axis. Corticosteroids and antibiotics may modify selected nodes in this circuit, but current evidence is insufficient to recommend decolonization or antitoxin therapy in stable asthma. Biologics interrupt downstream pathways potentially fuelled by toxins: omalizumab neutralizes free IgE; mepolizumab and benralizumab reduce the eosinophilic axis; dupilumab blocks IL-4/IL-13 signalling; and tezepelumab acts upstream on TSLP. Nevertheless, randomized trials stratified by SE-sIgE are lacking, and no evidence demonstrates that these treatments eliminate colonization or toxin production. SE-sIgE therefore appears to be a promising biomarker, particularly in severe asthma with CRSwNP, but it is not yet an autonomous criterion for biologic selection. A broader barrier-organ analysis also identifies nasal, cutaneous, and intestinal colonization as distinct ecological states; atopic dermatitis as a complementary model of toxin-amplified type 2 inflammation; and biofilms and extracellular vesicles as candidate mechanisms of persistent toxin delivery. These data increase biological plausibility but remain indirect for asthma. Full article

Tylosin (TYL), a macrolide antibiotic, is commonly used to treat respiratory infections in weaned piglets. Despite its utility, TYL administration is associated with adverse side effects, including immune dysregulation and gut microbiota imbalance. This study evaluated whether methyl gallate (MG), a natural polyphenolic compound with antimicrobial and immunomodulatory properties, could mitigate these side effects of TYL. Forty weaned piglets were randomly assigned to a saline control group, a TYL (10 mg/kg) group, an MG (10 mg/kg) group, and a TYL + MG (10 mg/kg each) group. Changes in body weight, hematological parameters, plasma cytokines, culturable fecal bacterial populations, and 16S rRNA-based gut microbiota composition were evaluated in all weaned piglets. There were no significant differences (p > 0.05) in ADG, ADFI, or FE among the treatment groups. Hematological analysis revealed significant changes in neutrophil and eosinophil counts, showing significant fluctuations in the MG-treated group compared with the control. TYL administration significantly decreased TNF-α and IL-1β levels while increasing IL-10 and IL-1ra concentrations, indicating immunomodulatory effects. In contrast, MG significantly increased adaptive immune-associated cytokines, including IL-2, IL-4, IL-6, and IL-12. Culture-based fecal microbiological analysis revealed that TYL reduced Lactobacillus abundance and lowered the culture-based Lactobacillus/Enterobacteriaceae ratio, suggesting acute dysbiosis. Co-administration of MG partially attenuated these microbiota-associated alterations and promoted the recovery of bacterial populations. Moreover, 16S rRNA sequencing demonstrated that similar relative abundances of Proteobacteria were observed in the TYL and TYL + MG groups. Therefore, no clear reduction in relative abundance of Proteobacteria was demonstrated under the present experimental conditions. These findings support the possibility that MG may partially attenuate selected TYL-associated immunological and gut microbiota-related changes under the conditions of the present exploratory study. A graphical summary of the study design and the principal findings is presented in the Graphical Abstract. Full article

Fine particulate matter (PM2.5) is an air pollutant that significantly impacts environmental and health outcomes. In Chiang Mai province, Thailand, residents face recurring PM2.5 pollution from November to May each year, primarily due to open biomass burning and transboundary emissions. The long-term health impacts of PM2.5 in Chiang Mai remain inadequately documented. This study aims to investigate leukocyte distribution and IgE level in response to long-term PM2.5 exposure. Participants residing in San Patong district, Chiang Mai, were recruited. Leukocyte distribution was investigated by the complete blood count and flow cytometry. IgE levels were measured by sandwich enzyme-linked immunosorbent assay. Long-term PM2.5 exposure is associated with significant changes in leukocyte distribution, including WBC count, neutrophil, monocyte, and basophil absolute count, while lymphocyte and eosinophil counts were not significantly affected. In the present study, flow cytometric immunophenotyping was performed during the late PM2.5 season to evaluate the distributions of major leukocyte populations and the expression of activation and inhibitory markers on lymphocyte subsets. Interestingly, IgE levels showed a decreasing trend. These findings highlight the immunological effects of repeated PM2.5 exposure and underscore the need for further research to clarify its mechanisms and health implications. Full article

Respiratory medicine is transitioning from symptom-driven, standardized care to a more precise, patient-specific approach guided by molecular profiling. This evolution is being enabled by advances in liquid biopsy, multiomics, and artificial intelligence (AI) analytics. Fractional exhaled nitric oxide (FeNO) and blood eosinophils, the two commonly used markers in asthma, are now being joined by more precise airway markers such as galectin-10, which could aid clinicians in making more informed decisions for biological treatments. In chronic obstructive pulmonary disease (COPD) similar progress is underway, with treatment now emphasizing inflammation endotypes, especially eosinophilic patterns, to direct therapeutic choices. Alongside these developments, routine blood-based ratios (e.g., platelet-to-lymphocyte and neutrophil-to-lymphocyte) are being explored as predictors of exacerbation risk, and forced oscillation testing (FOT) is proving useful for picking up early disease shifts. In more severe conditions, biomarkers are linked to an early and better prognosis, enabling timely intervention. Markers like Matrix metalloproteinase-7 (MMP-7) and CC chemokine ligand 18 (CCL18) have proven to be reliable indicators of mortality and disease progression in idiopathic pulmonary fibrosis. Meanwhile, in lung cancer, liquid biopsies, especially those measuring circulating tumor DNA and micro-RNA (miRNA) panels, are enhancing screening accuracy while helping to cut down on the high false-positive rates seen with low-dose computerised tomography (CT). Other respiratory conditions such as bronchiectasis, pulmonary embolism, pneumonia, and acute respiratory distress syndrome (ARDS) are also benefiting from biomarker advances. At the same time there is a growing push to standardize how these biomarkers are measured. AI-based clinical decision support systems are also playing an increasingly important role in the translation of all these complicated data into actionable clinical insights. Together these developments pave the way for improved respiratory care that is precise and responsive to individual patient needs. Full article

Kingella kingae is now recognised as the leading cause of osteoarticular infections (OAIs) in young children. Because these infections typically produce mild symptoms and a weak inflammatory response, early diagnosis remains challenging. Complete blood count-derived immune-inflammatory biomarkers (IIBs) have recently gained interest as accessible, low-cost indicators of systemic inflammation, with potential diagnostic value in several fields, including oncology, rheumatology, cardiology, and infectious diseases. This study therefore aimed to assess whether IIBs could support the screening of K. kingae OAIs. We retrospectively reviewed the medical records of 209 children admitted to our hospital between 2007 and 2025 with confirmed or highly suspected K. kingae OAIs. Complete blood counts were analysed for each patient, including leukocyte subtypes such as neutrophils, lymphocytes, monocytes, eosinophils, and basophils. We then calculated biomarkers (NLR, MLR, PLR, SII, SIRI, and PIV) and interpreted them using age-adjusted reference values. As expected, most children were younger than 48 months, and septic arthritis was the predominant clinical presentation. Classical acute-phase reactants (WBC, CRP, and ESR) were frequently normal or only mildly elevated. Likewise, most IIBs remained within or near reference ranges; the platelet-to-lymphocyte ratio was the most commonly abnormal marker, exceeding the threshold in only 59.3% of patients. These results indicate that, like conventional inflammatory markers, CBC-derived IIBs have limited standalone screening utility for K. kingae OAIs. Further studies are needed to determine whether systemic IIBs can help distinguish OAIs caused by K. kingae from those caused by pyogenic bacteria. Full article