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Bioactive fibrous microwell platforms induce m1 macrophage clusters that enhance anti-tumor activity and T cell polarization☆

2026-06-01T00:00:00Z

Title: Bioactive fibrous microwell platforms induce m1 macrophage clusters that enhance anti-tumor activity and T cell polarization☆ Authors: Choi, Juhwan; Hong, Yongpyo; Heo, Chungmo; Yeom, Eunji; Kim, Taehyeon; Moon, In Seok; Koh, Won-Gun Abstract: Engineering immune-regulatory microenvironments that direct macrophage function is central to advancing immunotherapies for solid tumors. Here, we present a bioactive fibrous microwell platform that integrates electrospun polycaprolactone/polyvinylpyrrolidone (PCL/PVP) nanofibers with photopatterned threedimensional confinement and sustained lipopolysaccharide (LPS) delivery, enabling the formation of stable M1-polarized macrophage clusters beyond conventional transient stimulation. The hybrid microenvironment guided macrophages into compact clusters while providing continuous pro-inflammatory cues. As a result, macrophages exhibited pronounced M1-like characteristics, including elevated inflammatory cytokine production, cytoskeletal and metabolic remodeling, and enhanced tumoricidal activity against breast and melanoma tumor models. Proteomic analyses revealed coordinated regulation of cytoskeletal, stress-response, metabolic, and translational pathways underlying this phenotype. Importantly, the macrophage-derived pro-inflammatory secretomes promoted cytokine-driven polarization of na & iuml;ve CD4+ and CD8+ T cells toward Th1-, Th17-, and effector-like phenotypes, forming a functional innate-adaptive immune cascade that contributed to robust tumor cell apoptosis. Together, these results establish the fibrous microwell platform as a versatile immunomodulatory system that couples macrophage programming with T cell polarization for enhanced anti-tumor immunity.

Oral Corticosteroids and Adverse Events in Chronic Rhinosinusitis With Nasal Polyps

2026-06-01T00:00:00Z

Title: Oral Corticosteroids and Adverse Events in Chronic Rhinosinusitis With Nasal Polyps Authors: Moon, Seojin; Lee, Myeongjee; Jung, Inkyung; Rha, Min-Seok Abstract: Importance Oral corticosteroids are commonly used in the management of chronic rhinosinusitis with nasal polyps to control inflammation. However, evidence on the long-term safety of repeated or high-dose oral corticosteroid exposure in this population remains limited. Objective To investigate the association between oral corticosteroid exposure and systemic adverse events in patients with chronic rhinosinusitis with nasal polyps. Design, Setting, and Participants A retrospective, nationwide, nested case-control study included adult patients (>= 20 years) with incident chronic rhinosinusitis with nasal polyps, excluding those with prior immune-mediated diseases or outcome diagnoses, using the Korean Health Insurance Review and Assessment Service database (2010-2023). Data analysis was conducted from March 2025 to April 2026. Patients who developed adverse events (case patients) were matched 1:10 with controls by age, sex, and diagnosis date. Exposures Oral corticosteroid exposure was quantified using 3 metrics: exposure intensity (annual duration: low [<= 30 days], moderate [31-90 days], or high [>90 days]), cumulative dose (<0.5 g, 0.5-1.0 g, or >= 1.0 g prednisolone-equivalents per year), and prescription frequency. Main Outcomes and Measures First occurrence of systemic adverse events. Adjusted odds ratios and 95% CIs were estimated using multivariable conditional logistic regression. Results A total of 165 361 patients with chronic rhinosinusitis with nasal polyps who were prescribed at least 1 oral corticosteroid were identified. The matched cohort included 523 316 patients (51 647 case patients and 472 369 controls; mean [SD] midpoint approximated age, 47.1 [13.9] years; 39.7% women). High exposure intensity (>90 days per year) was associated with a significantly increased risk of avascular bone necrosis, osteoporosis, and pneumonia. A cumulative dose greater than 1.0 g per year was associated with a 23% higher overall adverse event risk (adjusted odds ratio, 1.23; 95% CI, 1.11-1.36) and increased risks of avascular bone necrosis, pneumonia, dyslipidemia, heart failure, hypertension, and type 2 diabetes. Prescription frequency was not independently associated with adverse event risk. Conclusions and Relevance In this nested case-control study within a nationwide cohort of patients with chronic rhinosinusitis with nasal polyps, higher oral corticosteroid exposure, in terms of annual duration and cumulative dose, was associated with an increased risk of systemic adverse events, particularly musculoskeletal and infection-related complications. These findings underscore the need for steroid-sparing treatment strategies for long-term management of chronic rhinosinusitis with nasal polyps.

Murine Eosinophilic and Neutrophilic Chronic Rhinosinusitis Models Reveal Phenotype-Specific Steroid Responses

2026-06-01T00:00:00Z

Title: Murine Eosinophilic and Neutrophilic Chronic Rhinosinusitis Models Reveal Phenotype-Specific Steroid Responses Authors: Kang, Miran; Kim, Dachan; Seo, Juhee; Kim, Yosep; Kim, Subin; Rha, Min-Seok; Kim, Chang-Hoon; Cho, Hyung-Ju Abstract: Background Chronic rhinosinusitis (CRS) comprises heterogeneous eosinophilic (type-2) and neutrophilic (type-1/3) endotypes, yet existing murine models rarely distinguish them or compare their therapeutic responsiveness.Methods Seven-week-old female C57BL/6N mice received intranasal instillations three times weekly for 4 or 12 weeks with either (1) a clinically relevant airborne allergen cocktail (house dust mite [HDM], Aspergillus fumigatus, Alternaria alternata, and Staphylococcus aureus protease) to induce eosinophilic CRS (ECRS) or (2) an innate stimulus mixture (lipopolysaccharide, beta-1,3-glucan, and S. aureus protease) to induce neutrophilic CRS (NCRS). A parallel cohort received weekly dexamethasone administration (2 mg/kg). Endpoints included flow cytometry, enzyme-linked immunosorbent assays, quantitative PCR, histology, and immunofluorescence assays.Results Four-week allergen exposure produced a pure ECRS phenotype characterized by robust tissue eosinophilia, type-2 cytokines, and marked responsiveness to dexamethasone. Extending allergen delivery to 12 weeks generated mixed CRS with superimposed neutrophilia, upregulation of Il1b/Tgfb1, mucus hypersecretion, and attenuated steroid efficacy. Innate stimulus treatment yielded a steroid-resistant NCRS phenotype dominated by neutrophils, elevated Ifng/Il17a expression, and minimal type-2 biomarkers. Systemic eotaxin and HDM-specific immunoglobulin E mirrored those found in local eosinophilia, whereas circulating granulocytes remained unchanged across groups.Conclusions By adjusting the stimulus type and duration, we established tunable murine models that recapitulate pure ECRS, mixed CRS, and steroid-resistant NCRS within a single genetic background. These paired models provide a versatile platform for dissecting endotype-specific mechanisms and evaluating tailored interventions, highlighting the potential importance of early, phenotype-directed CRS therapy.

Analysis of skull base reconstruction methods in huge cranial-nasal communication defect: Bilateral reverse temporalis muscle flap and free flap

2026-05-01T00:00:00Z

Title: Analysis of skull base reconstruction methods in huge cranial-nasal communication defect: Bilateral reverse temporalis muscle flap and free flap Authors: Nuch, Kong Srey; Hong, Jong Won; Lee, Won Jai; Chang, Jong Hee; Kim, Chang Hoon Abstract: Background: Effective skull base reconstruction for huge cranial-nasal defects is critical to restoring function and esthetics and preventing complications, such as cerebrospinal fluid (CSF) leakage and ascending infection. We introduced and evaluated two advanced surgical methods of reconstruction: bilateral reverse temporalis muscle flaps and free flaps. Methods: A retrospective review of 16 patients (11 males and 5 females) who underwent skull base reconstruction from January 2017 to December 2024 was conducted. Bilateral reverse temporalis muscle flaps or free flaps, predominantly anterolateral thigh flaps and one rectus myocutaneous flap, were used. Data included patient demographics, defect origins, pathological lesions, reconstruction methods, and postoperative outcomes. Results: Huge cranial-nasal defects resulted from benign tumors (n=3), malignant tumors (n=10), or mucocele/infection (n=3). The defect originated from the nasal cavity (n=12), and the cranium (n=4), with an average defect size of 23.8 +/- 9.3 cm2. Reconstruction was performed using bilateral reverse temporalis muscle flaps (n=6) or free flaps (n=10). Both reconstruction methods effectively prevented CSF leakage and ensured primary healing. Complication rates were comparable, with free flap reconstructions associated with fewer postoperative issues. There were no significant differences in operation times or hospital stays between the two techniques. Conclusion: Bilateral reverse temporalis muscle and free flaps were both effective for skull base reconstruction in patients with huge cranial-nasal communication defects. Bilateral reverse temporalis flaps provide reliable vascularization without microsurgery, and free flaps offer customizable volume. The reconstruction approach should be tailored to the defect size, donor site condition, and surgeon's expertise. (c) 2026 Published by Elsevier Ltd on behalf of British Association of Plastic, Reconstructive and Aesthetic Surgeons.