Search Results (1,784)

Exposure to blast waves without kinetic, penetrating, thermal, or toxic components causes a distinct form of traumatic brain injury, termed primary blast-induced TBI (pbTBI). Clinical manifestations of pbTBI span a wide spectrum, ranging from life-threatening intracranial hemorrhage, hyperemia, and delayed cerebral edema to mild and transient neurological symptoms without detectable structural abnormalities on routine imaging. At the mild end of the spectrum, symptoms after a single exposure may resolve quickly, yet repeated exposures—even at very low levels, termed “subconcussive”—can develop into post-concussive syndrome (PCS) or persistent post-concussive symptoms (PPCS) in a subset of individuals. Despite extensive studies, the molecular pathobiology linking primary blast exposure to delayed and sometimes chronic neurobehavioral deficits remains incompletely understood. A mechanistic framework connecting blast-wave physics to biomechanics to biological vulnerability may therefore help define exposure hazards, interpret clinical symptomatology, and guide diagnostic and therapeutic development. This review summarizes the physics of primary blast waves, the resulting biomechanical responses, and candidate biological substrates, emphasizing structures and interfaces with distinct acoustic impedances across anatomical, tissue, cellular, and molecular scales. We synthesize evidence supporting the hypothesis that the cerebral vasculature and endothelial cells represent critically vulnerable substrates of primary blast-wave injury, in part because the vascular tree constitutes the brain’s largest and most widely distributed interface between compartments with different acoustic impedances. Across experimental and human studies, endothelial stress, vascular injury, and downstream neuroinflammation emerge as convergent molecular responses to primary blast exposure. Temporal dynamics are central to understanding pbTBI because many blast-induced processes unfold in sequential phases. These observations support conceptualizing pbTBI as a condition characterized by prominent cerebrovascular injury of varying severity with secondary consequences for neuronal signaling, network function, and behavior. Within this framework, cerebrovascular and neurovascular unit (NVU) dysfunction provides a parsimonious bridge between primary blast-wave exposure and chronic symptom trajectories, where vascular pathology may offer more accessible therapeutic targets than neuronal injury. Key knowledge gaps include identifying which physical component(s) of the blast are most injurious, establishing biologically meaningful dose–response relationships at molecular and physiological levels, and defining windows of vulnerability during recovery that are relevant to repeated exposures. Addressing these gaps is essential for refining safety protocols, improving diagnostic specificity through mechanism-informed biomarkers, and developing evidence-based molecular and vascular therapeutic targets for pbTBI-associated conditions. Progress will require integrating waveform-aware dosimetry with longitudinal physiological and molecular monitoring across both preclinical and human cohorts. Such integration offers a practical path toward translating blast physics into actionable medical guidance for prevention, triage, and recovery management. Full article

Progesterone (P4) exerts important vascular and immunomodulatory effects that influence platelet (PLT) activation and serotonin (5-HT) handling across mammalian species; nevertheless, its role in modulating PLT physiology during diestrus in mares remains poorly defined. This study hypothesized that physiological variations in luteal activity during diestrus are associated with changes in PLT activation and 5-HT-related parameters. The first objective was to determine whether changes in circulating P4 during diestrus are associated with alterations in PLT aggregation, circulating 5-HT, and PLT morphological indices in healthy mares; the second objective was to identify a diestrus day providing consistent physiological conditions for assessing PLT-related biomarkers. Twenty clinically healthy Spanish Purebred mares aged 4–9 years old were monitored. Blood samples were collected on days 5, 14, and 16 post-ovulation, with luteal status confirmed by ultrasonography. P4 concentrations were determined using a solid-phase I-125 radioimmunoassay (RIA), 5-HT concentrations were quantified using a competitive enzyme immunoassay, and PLT indices were measured using an ADVIA 2120i hematology analyzer. Data were compared using appropriate parametric or non-parametric tests after assessing distribution, and correlations were analyzed using rank-based correlation analysis, using Pearson or Spearman coefficients according to variable distribution. P4 concentrations were higher on days 14 and 16 compared with day 5 (p < 0.05), with no significant differences between days 14 and 16. Platelet aggregates (AGREG) showed the greatest variation, with significantly higher values on day 14 compared with day 5 (p < 0.05). In contrast, circulating 5-HT and all PLT morphological indices (PLT count, PCT, MPV, PLCR, PDW, PCDW, MPM, and PMDW) remained unchanged across diestrus. PLT aggregation showed a strong positive association with circulating P4 concentrations (r = 0.88, p < 0.05), whereas no meaningful correlations were observed between 5-HT and AGREG or between 5-HT and PLT morphological parameters. Internal correlations among PLT indices followed expected biological patterns, confirming the stability of structural PLT traits over short physiological intervals. These findings demonstrate that during diestrus, PLT activation—but not PLT morphology or circulating 5-HT—varies in parallel with P4 in mares. Day 14, corresponding to mid-diestrus, characterized by high luteal activity, represents an informative time point for assessing PLT activation and related biomarkers, providing a framework for standardizing sampling protocols for PLT-derived products in equine reproductive medicine. Full article

Objective: This study aimed to evaluate the prognostic value of inflammatory biomarkers and their interaction with nutritional status for risk stratification in patients with chronic limb-threatening ischemia (CTLI). Material and Methods: This was a prospective, single-center observational cohort study including adult patients admitted with CTLI. Clinical outcomes included major amputation, major vascular events (MACE), and all-cause mortality. Multivariate logistic regression analyses were performed using two separate models, one including IL-6 and another including hsCRP, to avoid potential collinearity between biomarkers. Model discrimination was assessed using ROC curves, and Kaplan–Meier survival analyses were performed. Results: A total of 170 patients were included (mean age 72 ± 12 years; 74% male), with high cardiovascular risk and frequent malnutrition and sarcopenia. At 6 months, major amputations occurred in 35.3% of patients, MACE in 35%, and all-cause mortality in 32%. In multivariable analyses, malnutrition was the strongest independent predictor of the composite endpoint. IL-6 (OR 2.90, 95% CI 1.45–5.81; p = 0.003) and hsCRP values above the median (OR 4.22, 95% CI 2.04–8.72; p < 0.001) remained independently associated with adverse outcomes, together with age > 72 years. The hsCRP-based model showed slightly higher discriminative performance than the IL-6 model (AUC = 0.77 VS AUC = 0.75). Kaplan–Meier analyses demonstrated significantly reduced event-free survival in patients with elevated inflammatory biomarkers. Conclusions: In CTLI, systemic inflammation and nutritional status jointly identify patients at extremely high risk of adverse outcomes. hsCRP, given its availability, may be a practical tool for clinical risk stratification. Full article

Cell membranes exhibit specific structural and chirality properties influencing their biological behavior and functionality. Artemia salina endothelial-like cell membranes, structurally simpler, provide insights into fundamental cellular structures, whereas human endothelial cell membranes represent complex, specialized tissues essential for understanding advanced vascular functions. This study aims to compare the structural and chiral properties of Artemia salina endothelial-like cell membranes and human endothelial cell membranes through computational molecular-level modeling, evaluating potential histological and biological implications. Membrane models for Artemia salina and human endothelial cells were developed using Protein Data Bank (PDB) structures. Computational descriptors, including radius of gyration (Rg), solvent-accessible surface area (SASA), geometric asymmetry index (GAI), chiral moment (CM), fractal dimension (FD), and additional chirality indices (SOC, HCI, ACI, CAI, ME, RDF) were calculated to assess membrane complexity, structural asymmetry, and chirality. Significant structural divergences between Artemia salina and human endothelial membranes were identified. Artemia membranes exhibited lower values of Rg, SASA, and chirality metrics, indicating simpler, more symmetrical structures. In contrast, human endothelial membranes displayed elevated structural complexity, pronounced asymmetry, higher chirality indices, and more significant structural heterogeneity, consistent with their specialized physiological functions. Principal Component Analysis (PCA) further highlighted clear structural clustering distinctions between the two models. The comparative analysis underscores fundamental structural and functional divergences between Artemia salina and human endothelial cell membranes. Artemia membranes represent simplified, uniform cellular arrangements optimized for fundamental physiological roles, while human endothelial membranes exhibit complex architectures, structural specialization, and significant chirality essential for dynamic vascular functionalities. These computational descriptors offer potential diagnostic biomarkers for evaluating endothelial functionality and pathological states. Full article

Blood disorders encompass a wide range of diseases including anemia, hemophilia, thrombotic disorders, platelet dysfunction, and hematological cancers, making blood disorders a major global health concern. These conditions can impair processes vital to human physiology including oxygenation, coagulation, and immune defense. Hematologic malignancies, both chronic and acute, require timely diagnosis and ongoing disease monitoring for effective clinical management. Microfluidic technologies have emerged as promising alternatives to benchtop techniques for diagnosing and monitoring hematological disorders. For example, microfluidic assays can be used for the isolation and characterization of liquid biopsy markers such as rare cells, extracellular vesicles, and cell-free molecules to support disease management in a minimally invasive manner while the process automation afforded by microfluidics decentralizes healthcare, making it more accessible. Advances in lab-on-a-chip technologies, including large-scale fabrication methods and novel design strategies, will provide tools for the clinical validation of biomarkers and the translation of these technologies from the laboratory bench to the patient bedside. In this review, we will show that microfluidic devices enable disease monitoring via high-throughput analysis of liquid biopsy samples for the detection of rare disease-specific biomarkers found in blood, plasma, urine, etc., providing an alternative to standard benchtop testing using specimens secured via invasive bone marrow procedures, typically used for managing blood-based diseases. A key advantage of microfluidics is their ability to manipulate blood components at scales that closely mimic the body’s microvascular environment. Not surprisingly, microfluidic vascular models have been developed to replicate physiological rheology enabling quantitative assessment of blood cell deformability, aggregation, or clot formation. We provide a critical perspective on the use of the microfluidic “organ-on-chip” designed for blood disorders’ modeling and employed to recapitulate the blood cancer microenvironment. A summary of advances in microfluidic strategies for detection, diagnosis, drug screening, and mechanistic investigations of blood disorders, and future directions for precision testing, will be presented. Full article

Background: Gliomas are characterized by a high degree of molecular heterogeneity, which impairs the reproducibility of predictive biomarkers derived from bulk-based molecular profiling due to immune/stromal contamination of tumors and the high prevalence of the IDH mutation signature. Methods: In this study, we used MOFA+ to derive intrinsic molecular signatures from transcriptional, methylation, and genomic profiles of a cohort of 667 diffuse gliomas in the Cancer Genome Atlas database. Thereafter, factor scores were derived for two separate Chinese Glioma Genome Atlas batches (Batch 1, n = 325; Batch 2, n = 693) without any retraining on the model. The prognostic independence of identified molecular signatures was assessed using multivariable Cox regression adjusted for IDH mutation status and tumor purity; purity-residualized survival analyses; IDH-stratified Cox regression in each cohort; validation by concordance index against established molecular signatures; and survival extreme profiling. To characterize the biological significance of factor signatures, we projected gene set signatures corresponding to each factor signature onto a single-cell RNA-seq dataset of GBM (GSE131928). Results: MOFA+ identified 12 latent factors, of which a vascular–extracellular matrix (ECM) remodeling axis (Factor 1) explained the highest multi-omics variance (24.9%) and was the strongest independent prognostic factor. In multivariable Cox regression adjusting for IDH status and tumor purity, Factor 1 remained independently prognostic (HR = 1.67, 95% CI 1.27–2.20, p = 0.0002); in a fully-adjusted model additionally including age, WHO grade, MGMT methylation, and 1p/19q codeletion (plus radiotherapy and chemotherapy status in the CGGA cohorts), Factor 1 remained prognostic in both CGGA cohorts (CGGA1: HR = 1.50, p = 3.8 × 10⁻⁵; CGGA2: HR = 1.18, p = 0.003) but lost significance in TCGA (HR = 1.04, p = 0.83), consistent with the cohort-dependent magnitude reported in the IDH-stratified and meta-regression analyses below. Purity-residualized survival analysis showed negligible attenuation of the Factor 1 signal (raw HR = 3.57 vs. residualized HR = 3.72; concordance 96.5%). Within IDH-wildtype gliomas, Factor 1 was significant in both external validation cohorts (CGGA1: HR = 1.64, FDR = 4.6 × 10⁻⁶; CGGA2: HR = 1.20, FDR = 0.02), though the TCGA IDH-wildtype subgroup showed a trend that did not survive FDR correction (FDR = 0.060). All validation was performed without model retraining. Within IDH-mutant gliomas, Factor 1 was strongly prognostic in both CGGA cohorts but was not significant in TCGA (HR = 1.17, FDR = 0.33). These findings should therefore be interpreted as consistent in directionality across cohorts but not uniformly replicated at the FDR-adjusted significance threshold in the TCGA discovery dataset. Concordance index benchmarking on a matched subset (n = 503) showed Factor 1 achieved discrimination comparable to the Mesenchymal signature (C = 0.797 vs. 0.801; ΔC = −0.004) while outperforming four other established classifiers. Factor 1 consistently separated patients with extreme survival phenotypes (OS < 6 vs. >15 months) across all three cohorts (all log-rank p < 0.001). Projection onto a single-cell GBM atlas (GSE131928), supported by inferCNV-based malignant-cell classification, localized the Vascular–ECM program to malignant cells and the Immune–ECM axis to myeloid compartments. Conclusions: The Vascular–ECM axis is a consistent, prognostic program robust to purity adjustment for diffuse gliomas that remains relevant across IDH-defined subgroups in three independent datasets comprising 1685 patients. The Vascular–ECM axis is a reproducible, purity-robust prognostic program in diffuse glioma, with directionally consistent adverse effects across TCGA, CGGA Batch 1, and CGGA Batch 2 (pooled n = 1685). Given the strong co-loading of endothelial, ECM, and myeloid genes observed in the single-cell projection, Factor 1 is best interpreted as a vascular/ECM-associated tumor–microenvironment ecosystem program rather than a malignant-cell-autonomous signature. Its FDR-adjusted significance within IDH-stratified subgroups is cohort-dependent and robust in both CGGA cohorts but attenuated in the TCGA IDH-wildtype (FDR = 0.060) and TCGA IDH-mutant (FDR = 0.33) strata. The pooled signal should therefore be interpreted as evidence of a generalizable biological program rather than a uniformly replicated subgroup-specific biomarker. It is possible to calculate factor scores based on RNA sequencing alone using fixed loadings (Z = XWᵀ), which may have implications for future translational applications. All findings are correlative; a causal role for the Vascular–ECM program in glioma progression, invasion, or therapy resistance remains to be established through functional perturbation experiments. Full article

Background/Objectives: Non-alcoholic steatohepatitis (NASH) represents a worldwide health challenge with limited currently available effective treatment. The present analysis was designed to examine possible therapeutic advances of Ambrisentan (AMB) targeting multiple features of hepatic damage in dexamethasone (DEXA)-provoked nonalcoholic steatohepatitis (NASH) in rats. Methods: Rats were randomly divided into four groups: a control group; a DEXA group; and two AMB-treated groups that received AMB (5 or 10 mg/kg/day orally for a week) before and concomitantly with DEXA (8 mg/kg/day, i.p.) for 6 days. After completion of the experiment, serum markers of liver function and lipid profile were assessed, and hepatic histopathological alterations were examined. Results: AMB (mainly at 10 mg/kg/day) markedly ameliorated liver-function parameters, the lipid profile, and hepatic histopathological characteristics in DEXA-treated rats. MDA was reduced, whereas GSH, GPX4 and Nrf2 were heightened, indicating elevated oxidative damage. Moreover, AMB efficiently reinstated iron homeostasis and aggravated iron overload by altering serum iron, hepatic ferritin, transferrin and hepcidin. AMB decreased serum calcium and hepatic calcineurin A levels, followed by a reduction in hepatic autophagy biomarker Beclin-1. AMB downregulated pro-inflammatory biomarkers NF-κB, IL-6 and TGF-β1. Moreover, it notably repressed the hepatic gene expression of ferritinophagy biomarker NCOA4, with elevated FTH1 hepatic gene expression. Moreover, AMB ameliorated DEXA-induced changes in endothelial and vascular function by increasing hepatic PGI2 and cGMP and lowering ET-1 and iNOS. Conclusions: AMB improved DEXA-induced NASH, primarily through its action on endothelin pathways, with associated reductions in inflammation and the downstream processes of ferroptosis, ferritinophagy, lipophagy, and autophagy. Full article

Background: Hypertension is one of the most prevalent comorbidities in patients with COVID-19 and a major contributor to chronic kidney disease (CKD). Traditional kidney injury markers, including creatinine, estimated glomerular filtration rate (eGFR) and microalbuminuria, reflect renal injury only after substantial nephron loss has already occurred. Urinary podocyte proteins, such as nephrin (nephrinuria), have been suggested as early markers of glomerular barrier dysfunction; however, their clinical behavior and diagnostic value in hypertensive patients with previous SARS-CoV-2 infection are unknown. Aim: To assess urinary nephrinuria, microalbuminuria, transforming growth factor β1 (TGF-β1), aldosterone, vascular endothelial growth factor A (VEGF-A) and renal hemodynamics across different stages of hypertension in patients with and without a history of COVID-19 and to assess the response to conventional antihypertensive and nephroprotective treatment. Methods: In a prospective comparative cohort study, 120 patients (aged 30–60 years) with stage I–III essential hypertension were stratified by COVID-19 history into a post-COVID-19 group (n = 60) and a non-COVID-19 group (n = 60); within each group, 20 patients were assigned to each hypertension stage. Comparisons were performed between the post-COVID-19 and non-COVID-19 subgroups at the same hypertension stage. Serum creatinine, cystatin-C, aldosterone, TGF-β1 and VEGF-A, urinary microalbumin and nephrin and intrarenal Doppler hemodynamics were measured at baseline and after six months of guideline-based treatment. Results: Nephrinuria was markedly increased in post-COVID-19 patients in all stages of hypertension, including stage I, where serum creatinine, cystatin-C and eGFR were within the normal range (126.5 ± 9.1 vs. 91.9 ± 8.3 pg/mL, p < 0.01). Nephrinuria was strongly correlated with renal functional reserve (r = −0.824, p < 0.001), eGFR (r = −0.797, p < 0.001), microalbuminuria (r = 0.758, p < 0.001), aldosterone (r = 0.613, p < 0.001) and VEGF-A (r = 0.589, p < 0.001). Antihypertensive and nephroprotective treatment for six months decreased nephrinuria, blood pressure and TGF-β1, with more limited effects in stage III disease. Conclusions: Nephrinuria was found to be an early marker of renal involvement in COVID-19, occurring before microalbuminuria and conventional functional markers and with a greater relative difference than these markers in stage I disease, suggesting podocyte injury as an early and potentially reversible mechanism of post-COVID renal involvement in hypertensive patients. Nephrinuria seems to be a potential biomarker for early renal surveillance in this population and its prognostic role for incident CKD needs to be validated in longitudinal outcome studies. Full article

Background and Objectives: Pericoronary adipose tissue (PCAT) attenuation measured on coronary CT angiography is a promising imaging biomarker of coronary inflammation; however, absolute values may be influenced by technical and inter-individual variability, and a standardized methodology for measurement has not been established. Our study aimed to evaluate the association between PCAT attenuation and CAC burden while comparing absolute attenuation values with normalized values to minimize these sources of variability. Materials and Methods: Two hundred patients undergoing cardiac CT were included and stratified into four CAC categories (0, 1–99, 100–299, ≥300). PCAT attenuation was measured at multiple locations on two main levels: aortic root level and four-chamber view level. Relative PCAT attenuation was calculated by subtracting subcutaneous fat attenuation from raw PCAT values. Group comparisons were performed using ANOVA or Kruskal–Wallis tests, and multivariable linear regression models were adjusted for age, sex, and body mass index. Results: In univariate analysis, relative PCAT attenuation differed significantly across CAC categories at the aortic-level right coronary artery (RCA) site (p = 0.007). In multivariable analysis, higher CAC categories were associated with increased relative PCAT attenuation at the aortic RCA (β = 8.56, p = 0.015 for CAC 100–299; β = 10.68, p = 0.005 for CAC ≥300), while associations at the left main coronary artery (LMCA) showed significance in low and moderate CAC categories (β = 6.91, p = 0.047 for CAC 1–99 and β = 8.57, p = 0.016 for CAC 100–299). No significant associations were observed between CAC and raw PCAT attenuation at the aortic level, while isolated and inconsistent findings were observed in other territories. Conclusions: Relative PCAT attenuation is independently associated with CAC severity and normalized values may reduce technical and biological variability, potentially enhancing the sensitivity and robustness of this CT-based biomarker. Full article

Atherosclerosis (AS) is a chronic inflammatory disease of large arteries. It underlies many cardiovascular disorders, including coronary artery disease, myocardial infarction, stroke, and peripheral arterial disease. Current therapies have improved outcomes, especially lipid-lowering, antithrombotic, and anti-inflammatory treatments. Yet residual cardiovascular risk remains, and new molecular targets are still needed. Leucine-rich α-2-glycoprotein 1 (LRG1) is an inflammation-inducible secreted glycoprotein. It has drawn attention because it is linked to pathological angiogenesis, vascular dysfunction, tissue remodeling, and fibrosis. Recent studies indicate that LRG1 is related to AS at several levels. These include circulating clinical associations, plaque localization, and experimental models. In AS, LRG1 may not simply act as a biomarker. It may promote macrophage pro-inflammatory polarization, disturb endothelial homeostasis, support abnormal angiogenesis, and influence extracellular matrix remodeling and plaque structural change. This review examines the biological features of LRG1 and the current evidence connecting it with AS. It also discusses possible mechanisms, therapeutic feasibility, and current limitations. Overall, LRG1 appears to be a promising but still incompletely validated candidate target in AS. Full article

Long-term survival after solid organ transplantation remains limited by chronic remodeling, fibrosis, vascular complications, and malignancy despite advances in immunosuppressive therapy. Current monitoring strategies primarily rely on functional and immunological parameters that often identify complications only after irreversible injury has occurred. There is a critical need for earlier, mechanistically informative biomarkers that can predict survival outcomes. Many platelet-associated growth factors (PDGF, TGF-β, VEGF, EGF, and IGF-1) are stored in platelet α-granules but can also originate from immune, endothelial, and stromal cells, regulate angiogenesis, extracellular matrix deposition, immune modulation, and tissue repair—processes central to graft adaptation and chronic injury. In this review, we propose the growth factor signaling network as a conceptual framework that potentially links platelet biology, ischemia-reperfusion injury, alloimmune responses, and chronic immunosuppression to sustained growth factor signaling and maladaptive graft remodeling. This framework should be interpreted as a biologically plausible integrative model rather than a fully validated mechanistic pathway in transplant recipients. Importantly, direct clinical evidence linking platelet activation markers (e.g., P-selectin, PF4, β-thromboglobulin) with circulating growth factor levels and long-term transplant outcomes remains limited, highlighting a critical gap in current biomarker research. Emerging clinical evidence suggests their potential prognostic relevance in transplant outcomes. Elevated TGF-β levels have been associated with increased risk of opportunistic infections, while early postoperative IGF-1 concentrations predict short-term survival. Increased VEGF-A levels correlate with primary graft dysfunction and cardiac allograft vasculopathy, while PDGF isoforms contribute to fibrotic and vascular progression across transplanted organs. However, their clinical applicability is limited by methodological variability and lack of large-scale validation. Rather than serving solely as markers of rejection, platelet-associated growth factors may reflect dynamic processes involved in transplant remodeling and mortality risk. Incorporating growth factor profiling into multiparametric survival prediction models may improve early risk stratification and support precision post-transplant management strategies. Full article

Background: Major cardiac surgery with cardiopulmonary bypass (CPB) induces a systemic inflammatory response that contributes to postoperative organ dysfunction and hemodynamic instability. While C-reactive protein (CRP) is a well-established downstream marker of postoperative inflammation, the upstream determinants of interindividual variability in inflammatory burden are not fully understood. Platelet-activating factor (PAF) is a potent inflammatory mediator implicated in platelet activation, endothelial dysfunction, and vascular dysregulation, but its role in modulating postoperative inflammation and clinical outcomes after cardiac surgery has not been fully characterized. Methods: We conducted a retrospective observational study of 87 patients undergoing major cardiac surgery with CPB. Preoperative plasma PAF levels and postoperative CRP concentrations were measured, and patients were stratified according to postoperative CRP severity. Associations between PAF, inflammatory response, postoperative vasoactive–inotropic requirements, recovery parameters, acute kidney injury, and mortality were assessed using correlation analyses, multivariable regression models, and receiver operating characteristic curve analyses. Results: Preoperative PAF levels increased progressively across postoperative CRP strata (p < 0.001) and were strongly associated with postoperative CRP concentrations in both univariate and multivariable analyses. Specifically, each 1000 pg/mL increase in preoperative PAF was associated with an adjusted increase of 36.0 mg/L in postoperative CRP (β = 36.0; p < 0.001). Each 1000 pg/mL increase in preoperative PAF was associated with an adjusted increase of approximately 36 mg/L in postoperative CRP. Elevated PAF was also associated with increased intermediate postoperative vasoactive–inotropic requirements and a modest increase in hospital length of stay (r = 0.25, p = 0.023). However, neither PAF nor CRP independently predicted AKI or mortality after adjustment for clinical variables. Discriminative performance for mortality was modest for both biomarkers. Conclusions: Preoperative platelet-activating factor was strongly associated with postoperative inflammatory burden and early hemodynamic instability following major cardiac surgery. Although PAF and CRP were not independent predictors of adverse outcomes, they may help identify a biologically vulnerable phenotype characterized by exaggerated inflammatory and vascular responses to surgical stress. These findings support further investigation of platelet-mediated inflammatory pathways as targets for perioperative risk stratification and mechanistic research. Full article

Background: Peripheral artery disease (PAD) impacts more than 200 million individuals globally. Despite its prevalence, management remains suboptimal, partly due to the lack of reliable blood-based biomarkers. The ankle–brachial index (ABI), the current gold-standard test for PAD, is limited by inter-operator variability, misinterpretation, and reduced accuracy in patients with diabetes. Fatty acid binding protein 3 (FABP3) has emerged as a potential biomarker for PAD; however, its prognostic performance relative to ABI remains unclear. This study compared FABP3 and ABI for predicting PAD outcomes using statistical and machine learning approaches. Methods: A total of 1001 participants were prospectively recruited, including 644 patients with PAD and 357 without PAD. The primary outcome was 2-year major adverse limb event (MALE), defined as a composite of vascular intervention, major amputation, or acute limb ischemia. At enrollment, plasma FABP3 was quantified using a validated multiplex immunoassay. Kaplan–Meier analysis of MALE-free survival was performed across pre-specified FABP3 tertiles (high [>3.55 ng/mL], moderate [1.55–3.55 ng/mL], and low [<1.55 ng/mL]) and ABI tertiles (severe [<0.40], moderate [0.40–<0.70], and mild [0.70–0.90]), with curve separation assessed using log-rank tests. Multivariable Cox proportional hazards modelling was used to evaluate the independent relationships of FABP3 and ABI with 2-year MALE after adjustment for baseline demographic and clinical covariates. To assess predictive performance for 2-year MALE, an extreme gradient boosting (XGBoost) classification model incorporating 10-fold cross-validation was trained using a combination of clinical covariates, plasma FABP3 levels, and ABI. Discriminatory performance was assessed using the area under the receiver operating characteristic curve (AUC). Results: The average participant age was 68 years (SD 12), and 34% (n = 340) were women. Mean ABI was 0.75 ± 0.25 and mean FABP3 concentration was 2.97 ± 2.06 ng/mL. Among the 644 participants with PAD, 558 (86.6%) had complete time-to-event data for MALE status, FABP3, and ABI. Over the median follow-up period of 2 years, 140 (25.1%) participants with PAD experienced MALE. Kaplan–Meier analyses demonstrated significant separation in MALE-free survival across FABP3 tertiles (log-rank p < 0.001). At 24 months, MALE-free survival was 100.0% in the FABP3 < 1.55 group, compared with 71.1% in the FABP3 1.55–3.55 group and 67.7% in the FABP3 > 3.55 group. In contrast, ABI severity groups showed less pronounced separation, with 24-month MALE-free survival rates of 80.3% for mild ABI, 73.2% for moderate ABI, and 71.3% for severe ABI, without a statistically significant overall difference (p = 0.170). In adjusted Cox proportional hazards models, FABP3 demonstrated strong prognostic performance for 2-year MALE. A 1 SD increase in log-transformed FABP3 was independently associated with a higher risk of 2-year MALE (HR 1.90, 95% CI 1.60–2.25; p < 0.001), with minimal change after additional adjustment for ABI (HR 1.90, 95% CI 1.60–2.24; p < 0.001). Machine learning analyses similarly favored FABP3 over ABI, with the FABP3-based model achieving an AUC of 0.773 compared to 0.686 for the ABI-based model. Adding ABI to the FABP3 model did not improve discrimination. Conclusions: Circulating plasma levels of FABP3 are strongly associated with PAD outcomes. Specifically, FABP3 demonstrated a stronger and more robust association with 2-year MALE compared to ABI. This study validates the prognostic value of FABP3 for PAD outcomes in comparison to ABI. Full article

Coronary artery bypass grafting (CABG) using the autologous saphenous vein (SV) remains widely performed for obstructive atherosclerosis; however, vein graft disease drives recurrent ischaemia through early thrombosis and progressive intimal hyperplasia, and accelerated atherosclerosis developing within the grafts. Extracellular vesicles (EVs) are membrane-bound particles that transfer proteins, lipids, and microRNAs between cells. They modulate endothelial dysfunction, vascular smooth muscle cell phenotypic switching, inflammation, and coagulation, which are core processes in vein graft remodelling. Arterialisation exposes the vein to abrupt rises in shear stress, cyclic stretch, and intraluminal pressure. These forces increase EV release and reshape EV cargo in experimental systems, suggesting a potential mechanism for amplifying early graft injury which warrants direct investigation in vein tissue. This review synthesises current evidence for cell-specific EV contributions from ECs, vascular smooth muscle cells, platelets, and macrophages, and appraises EV-associated microRNAs with biomarker potential relevant to graft failure pathways. We also review therapeutic strategies that may modulate EV signalling including antiplatelet therapy, statins, KCa3.1 inhibition, and pro-reparative mesenchymal stromal cell-derived EVs. No published clinical studies evaluate EV-based biomarkers specifically for saphenous vein graft patency, and none prospectively predict saphenous graft failure. CABG provides a well-defined time zero event that enables longitudinal sampling and risk stratification. Prospective studies linking EV phenotypes and miRNA signatures to imaging-defined graft outcomes are needed to support clinical translation. Full article

Background: The aim of this study was to assess the macular vasculature and retinal thickness using optical coherence tomography angiography (OCTA) in patients with migraine with aura (MA) and migraine without aura (MO) compared with healthy controls (HCs). Methods: A prospective cohort study included 37 MO patients, 34 MA patients, and 34 HCs. Vessel density (VD) in the superficial and deep retinal plexuses, radial peripapillary capillaries (RPC), optic nerve head (ONH), and foveal avascular zone (FAZ) was measured. The retinal thickness, retinal nerve fiber layer (RNFL) thickness, visual field parameters, and body mass index (BMI) were also evaluated. Results: Significantly lower macular superficial VD in the whole image was observed in the MA group compared with both the MO and HCs. MO patients showed higher RPC VD in the inferior quadrant compared with HCs. No significant differences were found in the RNFL thickness, deep plexus, FAZ area, non-flow area, or visual field parameters. In the MA group, the FAZ area showed a significant inverse correlation with the BMI, and a higher incidence of comorbidities was observed, particularly of Hashimoto’s thyroiditis. Conclusions: These findings suggest that migraine subtypes are associated with distinct retinal microvascular patterns detectable via OCTA. Reduced macular perfusion in MA and increased peripapillary perfusion in MO may reflect subtype-specific vascular dysregulation. OCTA may therefore serve as a noninvasive biomarker for detecting early microvascular alterations in migraine. Full article