Acute appendicitis is an exceptionally rare complication of autologous hematopoietic stem cell transplantation (HSCT) and represents a diagnostic challenge, since its presentation overlaps with conditioning-related gastrointestinal toxicity and neutropenic enterocolitis. Published data are limited to isolated case reports, and its occurrence during autologous stem cell transplantation (ASCT) for human immunodeficiency virus (HIV)-associated lymphoma has not previously been described. We report the case of a 39-year-old man with HIV-associated diffuse large B-cell lymphoma (DLBCL), non-germinal center subtype, Ann Arbor stage IV with gastric involvement, and a high-risk age-adjusted International Prognostic Index (score three). After failure of first-line rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with a Deauville score of four on interim positron emission tomography-computed tomography, complete metabolic remission was achieved with two cycles of second-line rituximab, dexamethasone, cytarabine, and carboplatin (R-DHAC). The patient then proceeded to carmustine, etoposide, cytarabine, and melphalan (BEAM)-conditioned ASCT under controlled HIV viral load and persistent CD4 lymphopenia. On the day of stem cell infusion (day zero), he developed right lower quadrant tenderness associated with elevated inflammatory markers; abdominopelvic computed tomography demonstrated acute appendicitis. Emergency laparoscopic appendectomy revealed ulcerative appendicitis without tumor infiltration on histopathology. The postoperative course during aplasia was complicated by septic shock due to multidrug-resistant Pseudomonas aeruginosa bacteremia, with a favorable evolution to broad-spectrum antibiotic therapy and vasopressor support. Neutrophil engraftment occurred on day +14, and the patient was discharged on day +20, with no further complications and a complete remission maintained at six months of follow-up. This case illustrates that acute appendicitis may occur as early as the day of stem cell infusion. Its presentation may be initially indistinguishable from melphalan-induced gastrointestinal toxicity, which makes early abdominopelvic CT indispensable for an early diagnosis. It also shows that, even when surgical source control is timely, profound aplasia and the HIV-related CD4 lymphopenia predispose to severe infectious complications. This justifies anticipatory broad-spectrum coverage adapted to local multidrug-resistant epidemiology and close multidisciplinary monitoring throughout the aplastic phase.

In this study, density functional theory (DFT) calculations and molecular dynamics (MD) simulations were combined to investigate the interaction mechanism and drug-loading performance of chitosan (CS) as a carrier for carmustine (BCNU). DFT results indicate that adsorption of BCNU onto the CS surface is an exothermic process, with adsorption energies ranging from -8.69 to -26.41 kcal·mol[-1]. The complexes are primarily stabilized by hydrogen bonding and van der Waals (vdW) interactions. Among them, complex D exhibits the most negative adsorption energy and the greatest structural stability. FMO analyses show that the HOMO is mainly localized on CS, whereas the LUMO is localized on BCNU. The complexes exhibit a smaller Eg than isolated BCNU and show enhanced electrophilicity relative to isolated CS, which is beneficial for the chemical reactivity of the drug. QTAIM and NCI analyses confirm that medium strength hydrogen bonds and vdW forces dominate the non-covalent interactions between CS and BCNU. MD simulations reveal the assembly behavior and stability of the complexes at different drug loading ratios. Among the studied systems, the 8BCNU@8CS complex with a drug loading of 14.08 wt% exhibits the lowest mean square displacement and solvent accessible surface area, suggesting a more compact and stable encapsulation structure, which may be conducive to achieving sustained release based on simulation conditions. This work elucidates the atomic-scale interaction mechanisms between CS and BCNU and provides a theoretical basis for designing efficient, stable CS-based nanocarriers for BCNU delivery.

The European Group for Blood and Bone Marrow transplantation Practice Harmonization and Guidelines Committee together with the Lymphoma Working Party convened 23 experts in Hodgkin lymphoma, transplantation, and radiation oncology, to develop consensus recommendations on the use of autologous and allogeneic haematopoietic cell transplantation (HCT) in relapsed or refractory Hodgkin lymphoma. Through a structured literature review and a 2-day workshop in Berlin, Germany, on Sept 29 and 30, 2025, the panel established guidance across major clinical decision points. The outcome of this review and workshop include the following recommendations. Salvage therapy should include brentuximab vedotin or checkpoint inhibitors, or both, with metabolic complete response preferred before autologous HCT. BEAM (carmustine, etoposide, cytarabine and melphalan) remains the most commonly used conditioning regimen, and autologous HCT continues to be the standard for chemosensitive relapse. Peri-transplantation radiotherapy could be considered for PET-positive or residual disease. Brentuximab vedotin consolidation is recommended for patients at high-risk. Allogeneic HCT is advised for eligible patients who relapse after autologous HCT, ideally with reduced intensity conditioning and post-transplantation cyclophosphamide as graft-versus-host disease prophylaxis. Routine maintenance after allogeneic HCT is not recommended; relapse management should be tailored and can involve donor lymphocyte infusion, brentuximab vedotin, checkpoint inhibitors, chemotherapy, radiotherapy, or clinical trial enrolment.

Purpose The aim of this retrospective single-center study was to evaluate the safety and efficacy of palliative intra-arterial chemoperfusion (IAC) for patients diagnosed with recurrent or post-therapeutic progressive symptomatic lung cancer brain metastases (LCBM). Materials and methods A total of 10 patients (five women and five men; median age: 56 years (range: 40-80 years)) with recurrent or post-therapeutic LCBM were included. Chemotherapy consisted of either carmustine or a combination of mitomycin C, gemcitabine, and cisplatin. The radiological follow-up was performed using magnetic resonance imaging (MRI) according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The overall survival (OS) was calculated using the Kaplan-Meier method. Results All patients were treated with prior systemic therapy, and seven patients additionally received radiation therapy. A total of 37 sessions of IAC (3.7/patient) were performed. No major complications occurred. The mean sum of the longest diameter (SLD) was 4.5±1.2 cm for all patients prior to treatment. The mean SLD for patients with radiological follow-up was 3.9±2.1 cm after treatment. Four patients (4/8) developed progressive disease. Three patients (3/8) achieved stable disease, and one patient (1/8) showed complete response. None of the patients had partial response. Two patients (2/10) were not assessable due to loss of radiological imaging post-interventional. The mean OS time was 9.7 months (95% CI: 2.4-17.0). Conclusion Although IAC seems to be a safe approach for palliative patients with recurrent or post-therapeutic progressive symptomatic LCBM, further studies with a larger patient population are needed to confirm its efficacy.

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) remains a key consolidation strategy for patients with relapsed/refractory (R/R) lymphoma. The BEAM regimen (carmustine, etoposide, cytarabine, melphalan) is the standard conditioning therapy, but clinical carmustine supply shortages have necessitated the search for alternatives. This study compared the toxicity and transplant outcomes of four carmustine-substituted conditioning regimens. We retrospectively analyzed 80 lymphoma patients who underwent ASCT between January 2018 and December 2023. Patients received one of four regimens: BeEAM (bendamustine, etoposide, cytarabine, melphalan; n = 16), CBV (cyclophosphamide, oral semustine, etoposide; n = 12), CEAC (oral semustine, etoposide, cytarabine, cyclophosphamide; n = 16), or SEAM (oral semustine, etoposide, cytarabine, melphalan; n = 36). The primary endpoint was severe toxicity. Secondary endpoints included progression-free survival (PFS), overall survival (OS), complete response rate (CRR) and non-relapse mortality. The SEAM regimen was associated with a significantly higher rate of BNP elevation (61.1%, p = 0.040). All patients in the BeEAM group developed febrile neutropenia (p = 0.004), and this regimen also led to more platelet transfusions (median 6.5 units, p = 0.001) and longer hospital stays (median 28.5 days, p = 0.012). The CBV group had the highest rate of cardiovascular adverse events (25.0%, p = 0.081), while the CEAC group showed the highest incidence of hypoproteinemia (100.0%, p = 0.006) and a notably high rate of intestinal infection (81.3%, p = 0.069). No significant intergroup differences were observed in PFS, OS, day + 100 CRR, or non-relapse mortality. Multivariate Cox analysis identified pre-transplant partial remission as an independent adverse prognostic factor for PFS (HR: 4.864; 95% CI: 1.094-21.634, p = 0.038). Although the four carmustine-substituted conditioning regimens demonstrated similar efficacy outcomes for ASCT in lymphoma patients, their distinct toxicity profiles highlight the need for personalized regimen selection, particularly in the context of carmustine shortages.

The management of glioblastoma multiforme (GBM) remains challenging due to its poor prognosis and extremely high postoperative recurrence rate. Although the Gliadel wafer locally delivers carmustine, its clinical application is limited by suboptimal therapeutic efficacy and poor conformability to irregular resection cavities. To overcome these limitations, we developed a novel drug delivery system based on thermosensitive injectable chitosan-β-glycerol phosphate hydrogel containing doxorubicin-loaded mesoporous silica nanoparticles encapsulated within tumor-derived exosomes (Exo-DMSNs@CS). In an orthotopic mouse GBM relapse model recapitulating clinical tumor resection, the liquid Exo-DMSNs@CS formulation was injected into the surgical cavity and subsequently gelated in situ, achieving seamless adhesion to the irregular resection margins of the cavity. The exosome-coated nanoparticles (Exo-DMSNs), released gradually from chitosan hydrogel, exhibited enhanced tumor-targeting capability via exosome-mediated tumor-homing performance, thereby substantially promoting drug internalization. Compared to non-exosomal controls (DMSNs@CS), Exo-DMSNs@CS markedly suppressed tumor recurrence and prolonged survival. Our findings demonstrate that this Trojan-horse-inspired delivery strategy-leveraging tumor-derived exosomes to encapsulate drug-loaded nanoparticles-enables a localized and precise tumor-targeted drug delivery system, representing a promising therapeutic paradigm for GBM treatment.

Focal cortical dysplasia (FCD) is a leading cause of pharmacoresistant epilepsy in pediatric populations, yet its role in epileptogenesis remains incompletely understood. Recent findings suggest that hyperexcitability may originate in non-dysplastic peripheral areas rather than the malformation itself. However, given the significant variability across FCD cases, clarifying whether cytoarchitectural disorganization drives activity changes remains challenging. Using the carmustine-induced animal model, we investigated how varying degrees of cortical malformation influence neural dynamics. Local field potentials were recorded via multielectrode arrays during spontaneous activity and external perturbation. We introduced a novel metric to quantify spatial heterogeneity in signal organization and assessed its association with excitation-inhibition balance. Results show that alterations in signal structure correlate with the extent and distribution of cortical abnormalities, highlighting the functional relevance of cytoarchitectural variability. This work advances understanding of FCD-related network dysfunction and offers analytical tools with potential translational value for pre-surgical evaluation.

Objective To examine the expression patterns,prognostic relevance,and immune regulatory functions of thymine DNA glycosylase (TDG) across a spectrum of cancer types,with a particular emphasis on its role in lung adenocarcinoma. Methods A comprehensive analysis was conducted using multiple bioinformatics databases to assess TDG expression levels in pan-cancer contexts,as well as its associations with prognosis and immune regulation.The expression and clinical relevance of TDG in lung adenocarcinoma were examined through online platforms such as UALCAN and BEST.Additionally,small interfering RNA targeting TDG was developed,and cell biological function assays were performed to determine the impact of TDG on cell functionality in lung adenocarcinoma.The LinkedOmics database was used to analyze the genes related to TDG and target kinases in lung adenocarcinoma,and their correlations with tumor status.The PRISM database was utilized to examine the correlation between TDG expression and clinical treatment response in lung adenocarcinoma. Results TDG was markedly overexpressed in a variety of cancers,including lung adenocarcinoma,papillary renal cell carcinoma,and gastric cancer (all P<0.001).It held potential as a prognostic biomarker for hepatocellular carcinoma,lung adenocarcinoma,and papillary renal cell carcinoma.The expression of TDG was intricately linked to immune cell infiltration and tumor heterogeneity.In the context of lung adenocarcinoma,the analysis using the TIMER algorithm revealed negative correlations between TDG expression and the infiltration levels of CD4+ T cells,dendritic cells,and B cells (all P<0.001).Furthermore,CIBERSORT analysis demonstrated that TDG expression was positively correlated with activated CD4+ memory T cells (P<0.001),neutrophils (P<0.001),resting NK cells (P<0.001),resting mast cells (P<0.001),M1 macrophages (P<0.001),M0 macrophages (P=0.014),and naive B cells (P<0.001),while it was negatively correlated with regulatory T cells (P<0.001),monocytes (P<0.001),activated mast cells (P<0.001),and memory B cells (P<0.001). Additionally,TDG expression was positively associated with tumor mutational burden (P<0.001),microsatellite instability (P=0.045),mutant-allele tumor heterogeneity (P=0.001),and tumor neoantigens (P<0.001) in lung adenocarcinoma.In lung adenocarcinoma,the expression of TDG was notably elevated in the tumor tissue compared with that in adjacent normal tissue (P<0.001).Male patients exhibited higher levels of TDG expression than female patients (P=0.002),and smokers demonstrated higher TDG expression than non-smokers (P<0.001).Furthermore,TDG expression was correlated with smoking cessation duration (P=0.014).Positive correlations were observed for TDG expression with both clinical T stage (P=0.003) and distant metastasis (P=0.012),while a negative correlation was found with patient prognosis (P=0.030).Furthermore,TDG emerged as an independent prognostic factor for lung adenocarcinoma.In vitro experiments revealed that silencing TDG inhibited the proliferation and migration of lung adenocarcinoma cells (both P<0.05).A correlation analysis between TDG-related genes and target kinases revealed that in lung adenocarcinoma,genes encoding aurora kinase A,cyclin-dependent kinase 2 and other enzymes exhibited positive correlations with TDG expression (all P<0.001).Furthermore,TDG expression demonstrated positive correlations with functional states including the cell cycle,DNA damage,and DNA repair processes (all P<0.001).In addition,the expression of TDG was correlated with the efficacy of treatment in the first course in clinical patients (P=0.007).Specifically,TDG expression levels were higher in the progressive disease group than in the stable disease group (P=0.016),and lower in the complete remission group than in the progressive disease group (P<0.001).Additionally,elevated TDG expression was associated with enhanced resistance to oxaliplatin (P<0.001),carmustine (P<0.001),and olaparib (P=0.004). Conclusion TDG serves as a potential prognostic biomarker,an immunotherapeutic target,and a oncogene in pan-cancer,with particular significance in lung adenocarcinoma.