Diseases

Acute myeloid leukemia (AML) is a genetically and biologically heterogeneous hematologic neoplasm that arises from the clonal transformation of hematopoietic progenitor cells. AML cells undergo extensive metabolic reprogramming to sustain proliferation, survival, and adaptation to therapeutic stress. Among these alterations, cholesterol metabolism has emerged as a critical determinant of leukemic cell fitness. AML cells enhance cholesterol biosynthesis, uptake, trafficking, and storage, generating a dynamic network that supports membrane organization, mitochondrial function, oncogenic signaling, and resistance to therapy. Beyond these tumor-intrinsic roles, accumulating evidence indicates that cholesterol and its metabolites actively shape communication between leukemic and immune cells, influencing immune checkpoint expression, inflammatory signaling, and antitumor immune responses within the bone marrow microenvironment. This narrative review examines the mechanisms underlying cholesterol reprogramming in AML and discusses how alterations in cholesterol homeostasis integrate metabolic adaptation with immune regulation. Particular emphasis is placed on the interplay between cholesterol metabolism, leukemic stem cell persistence, therapeutic resistance, and immune dysfunction. Emerging therapeutic strategies targeting cholesterol-related pathways are also considered. Collectively, these findings position cholesterol metabolism as a central interface between tumor-intrinsic biology and immune crosstalk, highlighting its potential as a therapeutic vulnerability in AML.

Background: Vitamin D is a key regulator of skeletal homeostasis, and hypovitaminosis D is highly prevalent among postmenopausal women, who are at increased risk of osteoporosis, sarcopenia, and related complications. Accurate assessment of serum 25-hydroxyvitamin D [25(OH)D] is therefore essential. However, substantial variability exists among analytical methods, particularly between automated chemiluminescent immunoassays (CLIA) and liquid chromatography–tandem mass spectrometry (LC-MS/MS), the latter considered the reference technique. This study aimed to compare four analytical methods, three CLIA platforms, and LC-MS/MS for measuring circulating 25(OH)D levels in a cohort of menopausal and postmenopausal women. Methods: A total of 425 serum samples from menopausal and postmenopausal women representing the real-world distribution of vitamin D levels in this population were analyzed using three automated CLIA systems and LC-MS/MS. Method comparison, agreement, precision through quality control assessment, total error, and sigma were evaluated. Results: The evaluated CLIA platforms (Abbott, Snibe, and Siemens) showed strong correlation with LC-MS/MS, with r = 0.919, r = 0.978, and r = 0.879. Furthermore, all assays showed excellent precision (CV < 5%), with good-to-acceptable total error (TE) and Sigma-metric performance. Conclusions: In conclusion, these findings demonstrate that while CLIA platforms offer a reliable and precise alternative for routine clinical use, these findings underscore the importance of method selection and result interpretation in the clinical assessment of vitamin D status in postmenopausal women. Furthermore, it highlights the ongoing need to minimize inter-assay variability and ensure consistent vitamin D assessment.

Background: Traditional cardiovascular risk models often overlook “residual risk” driven by psychopathological factors. This study investigates the exploratory prognostic baseline associations of Type D personality (TDP) and specific symptomatic dimensions with long-term all-cause mortality in patients with coronary artery disease (CAD). Methods: We conducted a retrospective case study based on hospital records evaluating 221 patients with confirmed CAD. Anatomical complexity was quantified via the SYNTAX Score (SS). Psychological profiling utilized the DS14 scale for TDP and the SCL-90 for granular symptoms (depression, anxiety, and hostility). Mortality was analyzed over a mean follow-up of 1026 days using multivariate Cox proportional hazards models. Results: Over a mean follow-up of 1026 days, the overall all-cause mortality rate was 33.0% ($n=73$). TDP prevalence was 19.0% ($n=42$) and significantly correlated with higher anatomical complexity (SS: 26.21 vs. 15.49; $p<0.001$). In the adjusted psychological model, baseline anxiety symptom severity presented an exploratory, borderline relationship with survival (HR = 0.941; $p=0.049$), with the 95% confidence interval upper bound reaching the null threshold (1.000), suggesting a potential, hypothesis-generating “Anxiety Paradox”. The psychological model demonstrated variations in descriptive validation indices (C-index = 0.624) compared to a baseline model integrating trait metrics and anatomical severity (C-index = 0.527). Significant correlations were confirmed between SS and psychological distress ($r=0.493$). Conclusions: TDP components and granular psychological tracks show significant baseline associations with coronary anatomical distributions, while anxiety dimensions present an exploratory relationship with long-term survival. Given the lack of adjustment for major clinical determinants of mortality (such as age, comorbidities, or ventricular function), these findings must be interpreted strictly as hypothesis-generating and exploratory.