Breast cancer remains a major global health burden, indicating the need for less invasive methods and more accurate biomarkers for diagnosis, prognosis, and treatment monitoring. Circulating microRNAs (miRNAs) are promising liquid biopsy biomarkers that can be detected in peripheral blood and may reflect tumor-associated molecular changes. This integrative literature review assessed recent evidence on circulating miRNAs in breast cancer, with emphasis on blood, plasma, and serum samples and their applications in diagnosis, prognosis, and treatment-related monitoring. The search was conducted for original studies published between 2024 and 2026. After screening and eligibility assessment, 44 studies were included. Serum was the most commonly analyzed sample, followed by plasma; RT-qPCR was the dominant detection method. Diagnostic applications were the most frequently reported, with miR-21 and miR-155 among the most consistently investigated biomarkers. Multi-miRNA panels and computational signatures generally showed higher diagnostic performance than individual miRNAs. Circulating miRNAs were also associated with disease stage, metastasis, recurrence, survival, and response to neoadjuvant chemotherapy, endocrine therapy, trastuzumab, and CDK4/6 inhibitors. Nonetheless, despite these promising findings, methodological heterogeneity, small sample sizes, inconsistent normalization strategies, and limited external validation remain barriers to clinical applications. Standardization and prospective multicenter validation are needed to establish clinical utility.
Variants of uncertain significance (VUS) complicate the genetic diagnosis and clinical interpretation of congenital heart disease (CHD). Human induced pluripotent stem cells (iPSCs) can model patient-specific genetic backgrounds, relevant cardiac cell types, and developmental processes, providing an opportunity to investigate variant effects in biologically relevant human systems. However, the observation of a cellular or molecular phenotype alone does not establish functional evidence for pathogenicity or benignity. Interpreting such phenotypes requires careful consideration of genetic background, experimental variability, developmental stage, cardiac lineage, and the biological relevance of the selected model and assay endpoint. Isogenic controls, independent iPSC clones, and reproducible phenotyping strategies can help distinguish variant-specific effects from background or assay-related variation. This review proposes a question-first framework for model selection, isogenic testing, prespecified phenotyping, replication, and calibration assay with emphasis on matching the experimental system to the established disease mechanism. Collectively, this framework defines when iPSC-based findings are sufficiently robust, reproducible, and disease-relevant to contribute to ACMG/AMP PS3 or BS3 evidence and support the functional interpretation of CHD-associated VUS.
Background: Whether plasma α-Klotho carries prognostic value in patients with acute coronary syndrome (ACS) who undergo percutaneous coronary intervention (PCI) is still unclear. Objectives: We set out to examine the links between plasma α-Klotho levels, routine clinical and laboratory findings, the occurrence of acute kidney injury (AKI), and cardiovascular mortality after PCI. Methods: Eighty-six patients with ACS treated by PCI were enrolled in this prospective study. Plasma α-Klotho was measured within 48 h of the procedure. Relationships were assessed by correlation analysis and logistic regression; cardiovascular mortality was tracked for 12 months. Results: Acute kidney injury developed in 30 patients (34.9%), and nine cardiovascular deaths (10.5%) occurred during the year of follow-up. α-Klotho showed positive correlations with platelet count, triglycerides and total protein, and inverse correlations with FIB-4, aspartate aminotransferase, creatinine, GRACE score, contrast volume and international normalized ratio. No significant link was found between α-Klotho and AKI (p = 0.882). Erythrocyte sedimentation rate (OR = 1.090; p < 0.001) and contrast volume (OR = 1.014; p = 0.007) remained independently associated with AKI. In univariable analysis higher α-Klotho levels were linked to lower cardiovascular mortality (OR = 0.648; p = 0.009). Conclusions: Higher plasma α-Klotho concentrations were associated with reduced odds of cardiovascular death in the univariable model. No association with AKI was detected. The mortality results should be regarded as exploratory and do not demonstrate an independent prognostic role.
Heritable thoracic aortic disease (HTAD) comprises genetic disorders that predispose to thoracic aortic aneurysm and dissection. Several also affect arteries beyond the aorta. This narrative review examines the burden, distribution, mechanisms, and screening implications of extra-aortic vascular disease in vascular Ehlers–Danlos syndrome (vEDS), Loeys–Dietz syndrome (LDS), Marfan syndrome (MFS), and nonsyndromic HTAD, alongside the related systemic arteriopathies spontaneous coronary artery dissection (SCAD) and fibromuscular dysplasia (FMD). Disease- and genotype-specific patterns emerge, although estimates differ with referral patterns, imaging coverage, and outcome definitions. In the Montalcino Aortic Consortium (MAC), COL3A1 carriers had the highest proportion of extra-aortic clinical arterial events, with prominent abdominopelvic and cervical involvement. LDS showed widespread arterial disease and head and neck involvement. MFS had fewer clinical arterial events, but imaging studies identified branch aneurysms, particularly in patients with advanced aortic disease. SCAD and FMD frequently involved additional vascular territories. Findings from broader nonsyndromic thoracic aortic disease cohorts should be distinguished from genetically confirmed HTAD. Imaging-detected aneurysm prevalence and clinical event proportions are not interchangeable. Guidelines and consensus support disease-specific vascular assessment, but anatomical coverage, surveillance intervals, and evidence strength vary. Comprehensive baseline imaging is supported in LDS, FMD, and SCAD; European guidance also recommends peripheral surveillance in vEDS and MFS. Additional assessment in nonsyndromic HTAD and cervical artery dissection depends on genotype and clinical features. We outline a practical framework integrating the presenting vascular lesion, molecular diagnosis, prior events, family history, and imaging-related burden, and discuss when an extra-aortic presentation should prompt aortic evaluation. Prospective studies are needed to establish whether increased detection and changes in management improve patient-important outcomes.
