Nitro-oleic acid (NO₂-OA), a nitric oxide (NO)- and nitrite (NO₂⁻)-derived electrophilic fatty acid metabolite, displays anti-inflammatory and anti-fibrotic signaling actions and therapeutic benefit in murine models of ischemia-reperfusion, atrial fibrillation, and pulmonary hypertension. Muscle LIM protein-deficient mice (Mlp^−/−) develop dilated cardiomyopathy (DCM), characterized by impaired left ventricular function and increased ventricular fibrosis at the age of 8 weeks. This study investigated the effects of NO₂-OA on cardiac function in Mlp^−/− mice both in vivo and in vitro. Mlp^−/− mice were treated with NO₂-OA or vehicle for 4 weeks via subcutaneous osmotic minipumps. Wildtype (WT) littermates treated with vehicle served as controls. Mlp^−/− mice exhibited enhanced TGFβ signalling, fibrosis and severely reduced left ventricular systolic function. NO₂-OA treatment attenuated interstitial myocardial fibrosis and substantially improved left ventricular systolic function in Mlp^−/− mice. In vitro studies of TGFβ-stimulated primary cardiac fibroblasts further revealed that the anti-fibrotic effects of NO₂-OA rely on its capability to attenuate fibroblast to myofibroblast transdifferentiation by inhibiting phosphorylation of TGFβ downstream targets. In conclusion, we demonstrate a substantial therapeutic benefit of NO₂-OA in a murine model of DCM, mediated by interfering with endogenously activated TGFβ signaling.

BK polyomavirus–associated nephropathy is a significant therapeutic challenge in kidney transplant recipients, often leading to allograft dysfunction. We report on a 12-year-old male kidney transplant recipient with severe, biopsy-proven BK polyomavirus–associated nephropathy and concurrent JC polyomavirus (JCPyV)–associated neurological symptoms. Due to failure of standard therapy, adoptive transfer of partially HLA-matched, BK polyomavirus–specific T cells from the kidney donor was administered as rescue therapy. The intervention induced a rapid decline in both BK polyomavirus (BKPyV) and JCPyV viral loads. This virological response was accompanied by the resolution of neurological symptoms and stabilization of allograft function. This case indicates that donor-derived BK polyomavirus–specific T cells represent a viable therapeutic modality for severe, refractory polyomavirus disease.

Purpose: Neuroblastoma, a common cancer in children, is characterized by striking clinical heterogeneity, ranging from spontaneous regression to fatal disease. Precise risk classification is therefore essential for appropriate treatment stratification. Given that genotoxic chemotherapy constitutes the mainstay of neuroblastoma treatment, it is particularly important to avoid overtreatment in patients with biologically favorable disease, notably in the heterogeneous group of current non–high-risk patients. Here, we tested the hypothesis that telomere maintenance mechanisms (TMM), which have been proposed as key hallmark of high-risk neuroblastoma, may improve neuroblastoma risk classification over current standard of care. Methods: We examined the prognostic accuracy of TMM in comparison with current standard-of-care prognostic variables in 366 patients with neuroblastoma, including 259 non–high-risk patients (test set, n = 116; validation set, n = 143). Patient event-free survival (EFS) and overall survival (OS) were determined according to TMM and currently used molecular classification by chromosomal copy-number alterations or gene expression profiles. The prognostic impact of the three molecular classifications was compared pairwise and with standard-of-care prognostic variables in multivariable analyses. Results: TMM-based and gene expression-based classification accurately distinguished non–high-risk patients with excellent and adverse EFS and OS in both the test and validation sets. On multivariable analyses of standard-of-care prognostic factors, TMM-based classification remained the only risk factor in the final models (EFS, hazard ratio [HR], 6.4 [95% CI, 3.9 to 10.6], P < .001; OS, HR, 29.4 [95% CI, 9.6 to 90.0], P < .001), in contrast to the two other molecular classifiers. In pairwise comparisons, TMM-based classification outperformed the two other molecular classifications in models built on both EFS and OS ( P < .001 each). Conclusion: TMM-based classification improves risk assessment in neuroblastoma, providing a rationale for clinical implementation as a new standard for risk stratification of patients with neuroblastoma.