Mycosis fungoides (MF), the most common subtype of cutaneous T cell lymphoma (CTCL), has a poor prognosis in advanced stages. Brentuximab vedotin (BV), a CD30-targeting antigen-drug conjugate approved for CD30+ MF following prior systemic treatment, still exhibits resistance with unclarified mechanisms. With single-cell RNA analysis on 13 paired tumor samples from 6 CD30+ MF patients, we revealed that BV-induced immunogenic cell death (ICD) in both CD30+ and CD30- malignant T cells while specifically enhanced interferon-α (IFNα) and IFNγ responses in CD30- subsets. BV also directly targeted CD30+ tumor-infiltrating regulatory T cells (TI-Tregs), and activated anti-tumor immunity mediated by dendritic cells and CD8+ T cells. The treatment responses and mechanistic insights were validated using seven CTCL cell lines. Resistance arose from upregulated drug efflux transporters and impaired endosomal processing in CD30+ malignant T cells, while CD30- tumor cells showed blunted IFNα and IFNγ responses. Anti-apoptotic BCL2 was upregulated in all tumor cells from nonresponsive lesions, especially in CD30- subsets. We further confirmed a potent synergy between BV and BCL2 inhibitors in tumor cell lines, indicating a promising strategy to overcome resistance in CTCL.

PURPOSE:Brain metastasis is a frequent site of metastasis in extensive-stage small cell lung cancer (ES-SCLC). We investigated the incidence, risk factors, and the impact of immunotherapy on brain metastasis development in patients without initial brain involvement. MATERIALS AND METHODS:A prospective cohort of 371 ES-SCLC patients without baseline brain metastasis from January 2012 to December 2023 were included in this study. Competing risk models were used to estimate the cumulative incidence of brain metastasis. Multivariate competing risk regression identified risk factors of brain metastasis. RESULTS:Among 371 patients (chemoimmunotherapy [CIT]: n = 147; chemotherapy alone: n = 224), 25.88% (96/371) developed brain metastasis over a median follow-up of 37.73 months. Brain metastasis was the first site of progression in 17.79% patients (66/371), with 11.32% (42/371) experiencing isolated brain metastasis. The 1-year cumulative incidence did not differ significantly between CIT and chemotherapy-alone groups (26.37% v 19.93%; P = .133). Prophylactic cranial irradiation (PCI) was independently associated with a lower risk of brain metastasis (adjusted subdistribution hazard ratio, 0.431 [95% CI, 0.195 to 0.955]; P = .038). CONCLUSION:Adding immunotherapy to chemotherapy did not significantly reduce brain metastasis incidence in ES-SCLC patients without baseline brain involvement. PCI remained the sole evidence-based strategy for brain metastasis prevention in this population, underscoring the need for novel CNS-directed approaches.

BACKGROUND:Accurate assessment of lymph node (LN) involvement is crucial in cutaneous T-cell lymphoma (CTCL), but biopsy-based evaluation carries risks, limiting its use. This study aims to evaluate ultrasound effectiveness in detecting malignant LN involvement and identify optimal ultrasound parameters for prediction. PATIENTS AND METHODS:A retrospective cohort study was conducted with 250 CTCL patients who underwent LN ultrasound evaluations between 2018 and 2024. Ultrasound parameters were compared with histopathological results, and receiver operating characteristic (ROC) analysis was performed to assess diagnostic accuracy. RESULTS:Ultrasound improves the detection rate of LN enlargement, from 21.6% to 57.6%. Lymphadenopathy on ultrasound was associated with higher disease staging and lower progression-free survival rates in mycosis fungoides. Key parameters, including increased short-axis diameter (p = 0.004) and loss of the echogenic hilum (p = 0.04), were significant indicators of malignant LN involvement. The combination of these two parameters in predicting malignant lymphadenopathy achieved an accuracy of 76.2%, with a sensitivity of 68.4% and a specificity of 82.6%, demonstrating superior diagnostic performance and providing valuable prognostic insights. CONCLUSIONS:Ultrasound is a reliable method for detecting malignant lymphadenopathy in CTCL, aiding clinicians in deciding whether an invasive biopsy is necessary.

Evidence links severe atopic dermatitis (AD) to increased mycosis fungoides (MF) risk, yet the relationship remains debated due to overlapping clinical features, chronic Th2) inflammation and reports of dupilumab-associated cases of MF. By integrated analysis of single-cell RNA sequencing data from 47 skin lesions and multiplex immunofluorescence validation, we identified a distinct CD4+ T-cell subset in AD and MF, persisting after dupilumab treatment, and characterized by proliferative programmes and an IL-13-independent Th2-polarized phenotype with autonomous OX40-OX40L signalling. These results reveal a molecular continuum between AD and MF, offering mechanistic insights into their association and highlighting OX40/OX40L as potential targets in lymphomagenesis.

OBJECTIVE:This study aims to compare the real-world efficacy of abrocitinib versus upadacitinib in patients with atopic dermatitis (AD). METHODS:We conducted a retrospective analysis of multicenter data from the CORNERSTONE database. Patients with AD treated with abrocitinib or upadacitinib were included. Propensity score matching (PSM) was performed to balance baseline characteristics between groups. RESULTS:After PSM, 282 patients were included in each cohort for outcome comparisons. No between-group differences in EASI-75 and EASI-90 responses were observed from week 2 through week 12. The proportion of patients achieving PP-NRS4 response was higher in the upadacitinib group than in the abrocitinib group at week 2 (p < 0.001). When stratified by body sites, the two medications showed comparable efficacy in skin lesion clearance across all body sites. However, patients receiving upadacitinib and abrocitinib exhibited lower EASI-75 response rates in the head and neck region than in other body regions at week 12. CONCLUSION:This study demonstrated that upadacitinib provided greater pruritus relief at early treatment phase compared with abrocitinib in AD patients. Additionally, selective JAK inhibitors showed a lower response rate in the head and neck region than in other body regions.

Eine bakterielle Kolonisation, insbesondere durch Staphylococcus aureus (SA), ist auf der Haut von Patienten mit primärem kutanen T‐Zell‐Lymphom (CTCL) prävalent. Die vorliegende Studie hatte das Ziel, Risikofaktoren für kutane bakterielle und SA‐Besiedelungen sowie deren Einfluss auf die Prognose von Patienten mit CTCL zusammen mit der Einnahme systemischer Antibiotika zu untersuchen. Diese retrospektive Studie umfasste 113 Patienten mit CTCL, bei denen zwischen 2010 und 2024 am Peking University First Hospital ein Hautabstrich durchgeführt wurde. Fünfundachtzig Patienten (75,2%) wurden positiv auf bakterielle Kolonisationen der Haut getestet (SA, 60,2%). Ulzerierte Läsionen erhöhten die Wahrscheinlichkeit positiver Ergebnisse bei bakteriellen/SA‐Hautkulturen signifikant (multivariate Analyse). Außerdem waren fortgeschrittene Stadien, Tumoren, Erythrodermie, Lymphopenie und Eosinophilie mit erhöhtem Risiko für positive Hautkulturen verbunden (univariate Analyse). Die Cox‐Regressionsanalyse zeigte, dass die bakterielle/SA‐Kolonisation der Haut und die antibiotische Intervention nicht mit dem Gesamtüberleben korrelierten ( p > 0,05). Diese retrospektive Studie berichtet Daten zur Prävalenz bakterieller Kolonisationen der Haut asiatischer Patienten mit CTCL. Ulzerierte Läsionen erwiesen sich als wichtigster Risikofaktor für kutane bakterielle/SA‐Besiedelungen. Bei den asiatischen Patienten mit CTCL war weder die bakterielle Besiedelung der Haut noch eine solche mit Staphylococcus aureus mit einer schlechteren Prognose assoziiert, noch verbesserte eine kurzzeitige systemische Antibiotikatherapie die Ergebnisse.

AIM:To investigate whether the hypoxia-inducible factor-1alpha (HIF-1α)/heme oxygenase-1 (HO-1) axis mediates ferroptosis in periodontal ligament tissues and contributes to impaired periodontal tissue repair in periodontitis. MATERIALS AND METHODS:RNA sequencing was performed to identify ferroptosis-related pathways in ligature-induced periodontitis (LIP) model. In vivo, LIP and ligature-removal recovery models were treated with the ferroptosis inhibitor Ferrostatin-1 (Fer-1). Alveolar bone changes were assessed by micro-computed tomography. Osteoclast activity and periodontal ligament-associated repair were evaluated by TRAP staining and Periostin immunohistochemistry. Ferroptosis-related alterations were assessed by immunohistochemistry of HIF-1α, HO-1, GPX4, SLC7A11, 4-HNE and Perls staining. In vitro, an HIF-1α-activated hPDLSC model was established. Ferroptosis-related changes were evaluated by ROS, MDA, Fe2+ levels, C11-BODIPY staining and expression of ferroptosis-associated molecules. The HIF-1α/HO-1 regulatory relationship was examined by ChIP-qPCR and dual-luciferase reporter assays. RESULTS:RNA sequencing revealed enrichment of ferroptosis-related pathways and identified HIF-1α and HO-1 as central regulators in inflamed periodontal ligament tissues. In vivo, Fer-1 attenuated alveolar bone loss, osteoclast activity and inflammatory cell infiltration. These changes were accompanied by decreased HO-1 expression, iron deposition and 4-HNE levels, along with increased GPX4 and SLC7A11 expression. In the recovery model, Fer-1 further reduced oxidative stress, suppressed osteoclast activity and increased Periostin expression, indicating improved periodontal tissue repair. In vitro, HIF-1α activation was associated with increased Fe2+ accumulation, ROS production and ferroptosis-related molecular alterations. Mechanistically, HIF-1α directly transactivated HO-1, which contributed to iron accumulation and downstream ferroptosis-associated changes. CONCLUSIONS:The HIF-1α/HO-1 signalling axis is associated with ferroptosis-related alterations in the PDL, which constitute periodontal tissue damage and impaired repair in periodontitis.

Background Atopic dermatitis (AD) is burdensome. AD with head, face and neck (HFN) involvement seems more strongly associated with quality-of-life impairment than other locations. Aim To investigate how HFN involvement affects the psychological and economic burden of AD in elderly population. Methods We evaluated elderly patients with AD using the eczema area and severity index (EASI), patient-oriented eczema measure (POEM), worst itch numerical rating scale (WI-NRS), dermatology life quality index (DLQI), and hospital anxiety and depression scale. Additionally, we collected data on annual direct medical costs to assess economic burden. Results A total of 3,066 elderly patients with AD were included in the study and 1375 (44.85%) patients had HFN involvement. Compared to patients without HFN involvement, patients with HFN involvement showed a greater proportion of hand, foot, breast and perianal/genital areas involvement and exhibited a higher prevalence of severe AD signs, severe AD symptoms, severe itching, moderate to severe anxiety, and moderate to severe depression, as well as annual direct medical cost. Limitations This study has several limitations; there is potential for selection and recall bias due to its reliance on data from tertiary hospitals and patient-reported outcomes, and statistical bias from using binary logistic regression rather than ordinal regression methods. Conclusion In this real-world study, HFN involvement had significant effects on clinical presentation and disease burden among elderly patients with AD. These findings could guide clinicians in formulating tailored treatment strategies and evaluating disease prognosis in elderly patients with AD.

IntroductionChromoblastomycosis (CBM) is a chronic, neglected tropical fungal infection. Its immunopathogenesis, particularly the mechanism underlying its chronicity, remains poorly understood.MethodsWe performed single-cell RNA sequencing (scRNA-seq) on lesional skin from a CBM patient, followed by comprehensive bioinformatics analyses. We then used multiplex immunofluorescence (mIF) to validate CD4+ T cell exhaustion in CBM patient lesions and the mouse model of Fonsecaea pedrosoi infection.ResultsWe identified a significantly expanded population of exhausted CD4+ T cells within the patient’s lesions, which exhibited high co-expression of inhibitory receptors (PD-1, TIM-3, LAG-3) and functional impairment. Trajectory inference suggested a differentiation path from naive towards exhaustion within the chronic inflammatory environment. Cell-cell communication analysis implicated monocytes/macrophages (MoMacs) as key drivers of this process via persistent antigen presentation and ligand-receptor interactions such as CTLA4-CD80/86 and LGALS9-CD44. The accumulation of exhausted CD4+ T cells was confirmed in human CBM lesions by multiplex immunofluorescence (mIF), and the progressive development of exhaustion was recapitulated in the mouse model of Fonsecaea pedrosoi infection.DiscussionOur findings establish CD4+ T cell exhaustion as an important mechanism underlying the chronicity of chromoblastomycosis, revealing a new immunopathological perspective for this neglected disease.

BACKGROUND:Mycosis fungoides (MF), the most prevalent variant of cutaneous T-cell lymphoma (CTCL), is characterized by the clonal proliferation of skin-homing CD4+ T lymphocytes. Forkhead box M1 (FOXM1) plays significant roles in the progression of various solid tumors. Its expression has been reported to diminish following treatment with Neosetophomone B in CTCL cells in vitro. However, the role of FOXM1 in the pathogenesis of MF remains unclear. OBJECTIVES:To evaluate the expression pattern and underlying mechanism of FOXM1 in MF. METHODS:FOXM1 expression in lesional skin samples was accessed via immunohistochemistry analyses. Inhibition of FOXM1 was performed through lenti-virus shRNA vector mediated gene knockdown and treatment with specific FOXM1 inhibitors (RCM1 and FDI-6). Furthermore, animal experiments were conducted to evaluate the effects of FOXM1 knockdown or treatment with FOXM1 inhibitors on tumor growth in vivo. RESULTS:Overexpression of FOXM1 was observed in MF with a stage-dependent pattern and poor prognosis. Inhibition of FOXM1 via either shRNA or specific inhibitors, significantly impaired MF cell proliferation by inducing cell cycle arrest and apoptosis, while also suppressing tumorigenicity in vitro and in vivo. Transcriptomic analysis revealed that FOXM1 suppression led to the downregulation of genes involved in cell cycle regulation, including CCNB2, CDK1, and E2F1. CONCLUSIONS:The overexpression of FOXM1 contributes significantly to the progression of MF primarily by regulating the cell cycle. Furthermore, FOXM1 may serve as a reliable prognostic biomarker and a promising therapeutic target for MF.

We show a woman who developed generalized skin laxity after receiving chemotherapy for a year to treat mycosis fungoides. A diagnosis of GSS was made on the characteristic clinical and pathological features. GSS affecting the whole body is extremely rare and this condition is difficult to treat.