Background/Objectives: Non-covalent nanocarrier-based systems have become a promising platform as they offer a strategy to improve the efficacy-safety profile of doxorubicin (DOX) without altering its chemical structure. Praised for biocompatibility and rich surface chemistry, nanodiamonds (NDs) have launched as nanocarriers of choice for advanced cancer therapy. By investigating DOX-ND physicochemical interactions, this work advances the structural understanding of a non-covalent potential anticancer system, which has not been quantitatively experimentally explored so far. Methods: To our knowledge, this is among the first studies combining ultraviolet-visible (UV-VIS) spectroscopy with spectral deconvolution to reveal the redistribution of different DOX species in the presence of NDs. Centrifugation-assisted analysis enabled differentiation between hypothetical labile and stable ND/DOX fractions. Adsorption kinetics was studied, and dynamic light scattering (DLS) measured particle size and zeta potential. In vitro screening was performed in non-malignant fibroblasts (MRC-5) and malignant melanoma (HS294T), glioblastoma (U251), and breast cancer (MCF-7) cells to evaluate ND/DOX combinations. Results: Centrifugation analysis revealed heterogeneous ND-DOX binding. Kinetic experiments showed fast multi-stage adsorption kinetics, best described by a bi-exponential decay function and the Weber-Morris model. DLS suggested stable systems with a particle size within 10-80 nm, predominantly around 20 nm, and positive zeta potential. Comparative in vitro screening demonstrated differential cellular responses across cell types, highlighting the relevance of ND/DOX interactions. Conclusions: The findings contribute to elucidating ND-DOX interactions relevant for the design and optimization of drug delivery systems, emphasizing the importance of spectroscopic insights for the design of nanodiamond-based drug delivery systems.
Accurate cardiovascular risk assessment is essential in type 1 diabetes (T1D), but agreement between disease-specific prediction models remains insufficiently characterized. This retrospective, single-center, cross-sectional study compared 10-year cardiovascular risk estimates from the Steno Type 1 Risk Engine (ST1RE) and the Scottish/Swedish risk prediction model in 100 adults aged 20–35 years with T1D and no previous atherosclerotic cardiovascular disease or major cardiovascular event. Continuous and categorical agreement were assessed using Bland–Altman analysis and linearly weighted Cohen’s κ, respectively, with identical thresholds applied for risk classification. Risk estimates were strongly correlated (Spearman’s ρ = 0.849, p < 0.001), with no significant paired difference on the Wilcoxon signed-rank test (p = 0.893). However, categorical agreement was fair, with a weighted κ of 0.334 and a 95% confidence interval (CI) of 0.078–0.590. The mean difference (ST1RE − Scottish/Swedish) was −1.46 percentage points (95% CI: −2.48 to −0.44), with 95% limits of agreement from −11.54 to 8.62 percentage points. Significant proportional bias indicated progressively higher Scottish/Swedish estimates as mean predicted risk increased (β = 0.91, p < 0.001). Despite strong correlation, individual-level discrepancies and proportional bias suggest limited interchangeability of these models in this cohort. Larger prospective studies assessing cardiovascular outcomes are needed to establish their comparative predictive accuracy and clinical utility.
Hashimoto thyroiditis (HT) coexists with differentiated thyroid carcinoma (DTC), particularly papillary thyroid carcinoma, in approximately 25% of cases. However, the impact of this association on DTC outcomes remains controversial. The aim of this study was to analyze the influence of Hashimoto thyroiditis on disease-specific survival (DSS) and recurrence-free survival (RFS) in DTC patients. Methods: A retrospective study conducted at our institution between 2007 and 2020 analyzed 707 DTC patients treated with surgery and/or I-131 therapy. Cox proportional hazards regression was used to identify independent predictors, including sex, age, tumor histology, HT status, and initial TNM stage. Results: Among 707 DTC patients, 628 (88.8%) had papillary cancer, 582 (82.3%) were female, 395 (55.9%) were <55 years old; HT coexisted in 137 (19.4%) patients. During follow-up, 23 (3.25%) developed recurrent disease; at last follow-up, 638 (90.2%) were alive. Initial distant metastases (p < 0.001) and higher T stage (p = 0.002) independently predicted worse DSS. For RFS, male sex (p = 0.015), higher T stage (p = 0.018), and lymph node involvement (p = 0.023) independently predicted an increased risk of recurrence. HT was not an independent predictor of DSS (HR 0.97, 95% CI 0.21-4.52; p = 0.964) or recurrence (HR 0.36, 95% CI 0.05-2.73; p = 0.322). Conclusions: Although Hashimoto thyroiditis was associated with favorable clinicopathological features, it was not independently associated with disease-specific or recurrence-free survival. Conventional staging parameters, particularly tumor stage, remain the principal determinants of prognosis in differentiated thyroid cancer.
