Search Results (146)

Background/Objectives: Risk stratification of patients presenting to the emergency department (ED) with suspected infection is essential. Soluble urokinase plasminogen activator receptor (suPAR) has emerged as a promising biomarker of immune activation and outcome prediction, but its role in febrile ED patients remains to be fully defined. The aim of this study was to evaluate the prognostic value of suPAR and its potential clinical application in the ED. Methods: A single-center retrospective study including 125 patients was performed. Plasma suPAR levels were measured together with C-reactive protein (CRP) and procalcitonin (PCT), and their association with 28-day mortality using Cox regression and ROC curve analyses was assessed. Results: SuPAR was independently associated with the risk of 28-day mortality, showing a very high negative predictive value. Higher suPAR levels were associated with an increased risk of death. Conclusions: SuPAR may represent a valuable tool to support early patient assessment and risk stratification in the ED, potentially improving resource utilization and patient prioritization. Full article

Background: The growing use of Emergency Departments (EDs) by older adults highlights the need for early and accurate identification of clinical deterioration. Early Warning Scores (EWSs) are widely implemented tools based on standardized vital sign thresholds; however, their performance in elderly patients is inconsistent, likely reflecting the biological heterogeneity, multimorbidity, and reduced physiological reserve typical of this population. Objectives: This narrative review aims to summarize current evidence on the use of EWSs in adults aged ≥ 65 years presenting to the ED, with a specific focus on mortality and intensive care unit (ICU) admission, and to discuss their role within the evolving framework of personalized medicine. Sources: A narrative review of 36 clinical studies published between 2014 and 2025 was conducted. Content: Traditional scores such as National Early Warning Score (NEWS), National Early Warning Score 2 (NEWS2), Modified Early Warning Score (MEWS), VitalPAC Early Warning Score (ViEWS), Rapid Acute Physiology Score (RAPS) and Rapid Emergency Medicine Score (REMS) show variable and often reduced prognostic accuracy in older and frail patients. Evidence consistently suggests that applying uniform cut-off values fails to capture individual vulnerability in elderly patients. The integration of age, frailty, comorbidities, and baseline physiological status improves risk stratification. Second-generation tools—including Copeptin-NEWS, NEWS-L, suPAR-NEWS, OPERA, and RISE UP—as well as artificial intelligence-based models, represent emerging personalized approaches to clinical deterioration prediction. Implications: No single score currently provides reliable early risk prediction for all elderly ED patients. Moving beyond “one-size-fits-all” EWSs toward adaptive, person-centered models may better reflect the complexity of geriatric emergency care and improve prognostic accuracy. Full article

Background/Objectives: Postoperative organ complications following open thoracoabdominal aortic aneurysm (TAAA) repair pose significant challenges during the early postoperative period, where prompt detection is crucial for improving patient outcomes. Sepsis is often a central factor in these complications. This study investigates the perioperative dynamics of soluble urokinase plasminogen activator receptor (suPAR) plasma levels in TAAA patients undergoing elective surgical repair and evaluates its diagnostic potential for early detection of postoperative sepsis. Methods: In this retrospective, single-center study, 28 patients (mean age 52.6 ± 13.4 years; 67.9% male) underwent elective open TAAA repair between 2022 and 2024. Blood samples were collected at five perioperative time points, and suPAR levels were measured using ELISA. The primary endpoint was the onset of postoperative sepsis, with secondary endpoints including other organ complications. The predictive performance of suPAR levels was evaluated using Receiver Operator Characteristics (ROC) analysis. Results: Postoperative sepsis developed in 7 of 28 patients (25%), with the diagnostic criteria met at a mean of 9.7 ± 6.9 days. Baseline suPAR levels did not differ between groups; however, from 12 h after surgery, the sepsis group exhibited significantly higher serum concentrations (14.43 ng/mL vs. 7.23 ng/mL; p = 0.004), a difference that persisted throughout the first 24 h. At 24 h, suPAR had the highest predictive accuracy for sepsis, with an AUC of 0.90, 90% sensitivity, and 86% specificity at a 9 ng/mL cut-off (p < 0.001). Conclusions: Elevated suPAR levels in the early postoperative period are strongly associated with the later onset of sepsis. Early monitoring may enable timely intervention, potentially improving outcomes in this high-risk patient population. Full article

The deterioration of high-penetration asphalt pavements due to oxidative aging presents a significant challenge in highway maintenance. This study investigates the rejuvenation effect of three bio-oils, namely palm oil, soybean oil, and sunflower oil, on aged PEN 90 asphalt through an integrated approach combining experimental characterization and molecular dynamics (MD) simulations. Laboratory evaluations, including penetration, softening point, dynamic shear rheology (DSR), and Fourier Transform Infrared (FTIR) spectroscopy, were conducted to quantify the recovery of the physical, rheological, and chemical properties of aged high-penetration asphalt. MD simulations were conducted to provide insights into diffusion behavior and intermolecular interactions between bio-oil molecules and aged asphalt components. Experimental results show that bio-oils effectively restore the lost viscoelastic performance after long-term aging. An 8% dosage was determined as optimal, with rejuvenation efficiency decreasing in the order of SSO, SO, and PO. MD simulations clarify mechanisms by showing that soybean and palm oils have higher diffusion efficiency than sunflower oil, thus promoting the dispersion of asphaltene and resin. RDF shows that bio-oils enhance asphalt molecules’ short-range order via hydrogen bonds and van der Waals forces, which improves compatibility. Full article

Background: Early stratification of patients at emergency department (ED) admission is crucial. The soluble urokinase plasminogen activator receptor (suPAR) has emerged as a promising biomarker to identify the worsening of different clinical conditions. We aimed at evaluating whether baseline suPAR values predict 28-day and 90-day mortality in patients presenting to the ED with different conditions. Methods: In this prospective observational study, we enrolled patients with dyspnoea (D), chest pain (CP), and abdominal pain (AP). suPAR levels, together with clinical and laboratory data, were recorded at ED admission. The data collected included 28-day and 90-day mortality data, as well as 28-day and 90-day hospital readmission; and their correlation with suPAR values was assessed. Results: We enrolled 298 consecutive patients (CP 23.8%, D 31.9%, AP 44.3%). suPAR was significantly higher in patients with dyspnoea, compared to both patients with chest and abdominal pain (5.50 [3.50–8.60], 3.20 [2.30–4.10], 3.20 [2.33–4.48] ng/mL, respectively; p < 0.001). suPAR plasmatic levels were also higher in patients admitted to semi-intensive or intensive care units compared to other patients (4.10 [3.15–8.05] vs. 3.50 [2.55–5.50] ng/mL, respectively; p = 0.049). suPAR levels were significantly higher in patients dead at 28 days than in survivors (12.65 [9.83–18.53] vs. 3.60 [2.60–5.48] ng/mL, respectively; p < 0.001). Using the stepwise logistic regression analysis, only suPAR emerged as an independent predictor of 28-day mortality with an odds ratio of 1.31 (95% CI 1.10–1.56). Conclusions: Baseline suPAR levels are an independent predictor of mortality in ED patients with chest pain, dyspnoea, or abdominal pain. Full article

Sepsis-associated acute kidney injury (SA-AKI) is a prevalent and life-threatening complication in critically ill children, contributing to high mortality rates (up to 30%) and long-term renal dysfunction in pediatric intensive care units. This review synthesizes recent advances in the signalling pathways underlying SA-AKI, emphasizing pediatric-specific mechanisms, biomarkers, and therapeutic targets. This review covers inflammatory cascades via TLR/NF-κB leading to cytokine storms (IL-6, TNF-α); apoptosis and necrosis involving mitochondrial Bcl-2 dysregulation and OLFM4; and emerging processes like pyroptosis (NF-κB-mediated), metabolic reprogramming (choline deficiency and Nrf2-mitophagy), and novel routes such as cGAS-STING and TGF-β signalling. Biomarkers like urinary OLFM4, DKK3, NGAL, and serum suPAR, alanine, and Penkid enable early diagnosis and risk stratification, with models like PERSEVERE-II enhancing prognostic accuracy. Therapeutic strategies include fluid optimization, renal replacement therapies (CRRT, SLED-f), and pathway-targeted interventions such as choline supplementation, oXiris for cytokine removal, Humanin for immunomodulation, and investigational cGAS-STING inhibitors. Despite progress, challenges persist in translating animal models to pediatric trials and addressing heterogeneity. Integrating multi-omics and precision medicine holds promise for improving outcomes, underscoring the need for multicenter studies in children. Full article

The urokinase-type plasminogen activator receptor (uPAR) plays a pivotal role in regulating extracellular proteolysis, cell migration, immune responses, and tissue remodeling across diverse physiological and pathological contexts. This review provides detailed insights into the structure of uPAR, ligand interactions, and signaling mechanisms, emphasizing its central function in cancer progression, including tumor invasion, metastasis, angiogenesis, and modulation of the tumor microenvironment. We also summarize the involvement of uPAR as a key player in cardiovascular, infectious, and neurological diseases, where it contributes to inflammation, tissue damage, and disease progression. However, translational gaps remain, most notably inconsistent assay harmonization (especially for suPAR), uncertain context-specific cut-offs and patient-selection criteria and limited multicenter validation for uPAR-targeted imaging and therapeutics. This review addresses these gaps by synthesizing cross-disease evidence to clarify clinical use cases and outline practical selection frameworks. Furthermore, we discuss the clinical potential of uPAR as a diagnostic and prognostic biomarker in diverse disease contexts, along with recent advances in therapeutic strategies targeting uPAR. Full article

Background: Chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment of relapsed/refractory large B-cell lymphoma (LBCL), but its administration is often complicated by cytokine release syndrome (CRS). Interleukin-6 (IL-6) is widely used to monitor CRS, though its clinical value diminishes after tocilizumab administration. We aimed to evaluate serum amyloid A (SAA), a dynamic acute-phase reactant, as a treatment-independent biomarker of inflammation and toxicity in CAR-T recipients. Methods: This retrospective study included 43 adults with LBCL treated with axicabtagene ciloleucel. SAA and other inflammatory markers were assessed from lymphodepletion through day +11 post-infusion. CRS and ICANS were graded per ASTCT criteria. Statistical analyses included Mann–Whitney U tests, Spearman’s correlation, and ROC curve analysis to evaluate predictive performance. Results: SAA levels peaked at day +4 and normalized by day +11, displaying wave-like kinetics. Levels were significantly higher in patients with any-grade CRS at early timepoints but showed no association with ICANS. SAA correlated strongly with CRP, suPAR, sST2, fibrinogen, ferritin, procalcitonin, and IL-6. Compared to IL-6, SAA was more predictive of CRS at day +2 and +4, and unaffected by tocilizumab. Baseline SAA also correlated with the mEASIX score, suggesting linkage to endothelial stress. Non-responders at 3-month PET had higher baseline SAA than responders (196.0 vs. 17.7 mg/L, p = 0.036), with ROC analysis yielding an AUC of 0.74 and an optimal threshold of 79.8 mg/L. Conclusions: SAA is a robust and dynamic marker of systemic inflammation, with potential utility in both toxicity monitoring and response prediction in the CAR-T setting. Its independence from IL-6 modulation positions it as a promising biomarker for future integration into clinical algorithms. Full article

Primary podocytopathies, including minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS), are caused by a circulating factor or factors injurious to the podocyte. An immunologic origin seems likely based on responsiveness to corticosteroids or other immunosuppressive agents, including calcineurin inhibitors targeting T-cells and rituximab targeting B-cells. Potential non-antibody-mediated circulating factors have been identified, including cardiotrophin-like cytokine 1, soluble urokinase plasminogen activator receptor, and angiopoietin-like 4, among others. More recent research supports a primary antibody pathogenesis, with anti-nephrin antibodies found in a significant percentage of cases. Such antibodies also predict recurrence after transplantation. Other potential antigenic targets besides nephrin include annexin, the proteosome, podocin, and CD40. Additionally, high-resolution confocal microscopy has identified punctate immunoglobulin deposits along the slit diaphragm and podocyte cell body that may or may not colocalize with abnormal punctate nephrin staining and may correlate with detectable circulating antibodies. The success of rituximab in observational studies in both native kidneys and transplants supports a primary role for autoantibodies. We discuss in detail the data supporting putative non-antibody circulating factors, as well as the recent data supporting antibody pathogenesis, which may provide some clues on treating the individual patient. Full article

Systemic sclerosis (SSc) is an autoimmune disease associated with a high burden of morbidity and mortality due to organ complications. Pulmonary arterial hypertension (PAH) and cardiac involvement, characterized by chronic right ventricular (RV) pressure overload with consequent RV dysfunction and ultimately right heart failure (HF), are among these. A common comorbidity in SSc is chronic kidney disease (CKD). CKD is often present at the time of PAH diagnosis or a decline in renal function may occur during the course of the disease. CKD is strongly and independently associated with mortality in patients with PAH and HF. The cardiovascular and renal systems are closely interconnected, and disruption of this balance may result in cardiorenal syndrome (CRS). Type 2 CRS refers to CKD as a consequence of chronic HF. In clinical practice, non-specific markers such as troponin, B-type natriuretic peptide (BNP), N-terminal pro-BNP (NT-proBNP), and serum creatinine aid in CRS diagnosis. More specific biomarkers, including cystatin C (CysC), neutrophil gelatinase-associated lipocalin (NGAL), galectin-3, and soluble urokinase plasminogen activator receptor (suPAR), have shown value for diagnosis and prognosis in CRS. This study aimed to evaluate comprehensively heart/kidney damage markers related to CRS in SSc patients compared with healthy controls (HC) and to examine their association with renal and cardiac ultrasound parameters. SSc patients showed significantly higher CRS markers than HC (p < 0.001). SSc patients with clinically diagnosed CRS had significantly elevated galectin-3, suPAR, sNGAL, and uNGAL levels (p < 0.05) than SSc patients without CRS. Positive correlations were found between renal resistive index (RRI) and NT-proBNP (r = 0.335, p < 0.05), and between RRI and suPAR (r = 0.331, p < 0.05). NT-proBNP, suPAR, galectin-3, sNGAL, and uNGAL emerge as promising biomarkers for the early detection of cardiac and renal involvement in SSc patients. Full article

Background: Despite improvements in medical therapy, heart failure with reduced ejection fraction (HFrEF) is a major burden on the healthcare system and remains a leading cause of death with a 5-year mortality rate of more than 60%. Novel therapeutic agents such as angiotensin-receptor-neprilysin-inhibitors (ARNIs) lead to significant improvement in clinical outcomes. Optimal therapy monitoring under these novel drugs is crucial for improving the outcome. In this trial, the diagnostic potential of four novel cardiovascular biomarkers—GDF-15, sST2, H-FABP, and suPAR—was evaluated during follow-up in patients with HFrEF. Methods: In this prospective cohort pilot study, 70 patients with HFrEF with ischemic (n = 34) and non-ischemic (n = 36) origin were included. All included patients were on a stable treatment regimen and in a non-decompensated state. The clinical parameters NYHA class, LVEF, MPI/Tei index and ESC Score 2 and the laboratory parameters sST2 (remodeling, inflammation), GDF-15 (remodeling, inflammation), H-FABP (subclinical ischemia and ischemia), suPAR (remodeling, inflammation) and NT-proBNP were assessed before ARNI therapy initiation and at 3 to 6 months at follow-up. Before starting ARNI therapy with sacubitril/valsartan patients had stable and well-established heart failure therapy. Results: There was a sufficient response to therapy with significant improvement in ejection fraction from 29.9% to 38.5% (p < 0.001) and a significant decrease in NT-proBNP from 1402 pg/mL to 572.0 pg/mL (p = 0.003). Interestingly, along with that, a significant increase in sST2 levels from 9602 pg/mL to 12,001 pg/mL (p = 0.039) but no significant change in H-FABP (p = 0.397), GDF-15 (p = 0.382) or suPAR (p = 0.328) were observed. Furthermore, the baseline sST2 level correlated with the risk of cardiovascular events calculated with the ESC Score 2 and the GDF15 level at follow-up correlated with the right ventricular global function, assessed with the MPI/Tei index and this correlation persisted after correction for confounders (r = 0.323, p = 0.039; r = 0.504, p = 0.011). Conclusions: The novel biomarker sST2 but not H-FABP, GDF-15 and suPAR was significantly affected by medical therapy with ARNIs. Monitoring sST2 might offer new opportunities for therapy guidance and disease management. However, these results are hypothesis generating and should be interpreted with caution, given the pilot nature of this study. Full article

Background: Minimized extracorporeal circulation (miECC) was developed to mitigate the adverse effects of cardiopulmonary bypass (CPB), yet its impact on soluble urokinase plasminogen activator receptor (suPAR) is unclear. SuPAR has been linked to adverse outcomes, including acute kidney injury (AKI). This study investigated perioperative suPAR kinetics in patients undergoing cardiac surgery with miECC or conventional CPB (cCPB) and explored its association with AKI, postoperative delirium (POD), and infections. Methods: This study is a secondary analysis of an observational cohort of 79 cardiac surgical patients. It evaluates perioperative suPAR levels and their association with the type of CPB used (miECC vs. cCPB) and postoperative adverse outcomes, including POD, AKI, and infections. Statistical analyses included repeated measures ANOVA, Wilcoxon tests, logistic regression, and ROC curve analysis to assess the predictive value of suPAR for these outcomes. Results: During surgery, suPAR significantly increased to higher levels with the use of cCPB compared to miECC (p = 0.027; odds ratio of 0.69 [0.57–0.84], p < 0.001). The use of miECC was an independent influencing factor on suPAR (−0.41 ± 0.1; p < 0.001). Regardless of the type of CPB, suPAR levels differed significantly between patients with and without kidney damage (n = 25; no AKI: 1.6 [1.1–2.0], AKI: 1.7 [1.3–2.4], p < 0.001). Multivariate regression analysis showed that AKI was an independent influencing factor on suPAR (−0.49 ± 0.1; p < 0.001). SuPAR demonstrated only low predictive value for AKI and could not predict POD. Conclusions: This study provides evidence that miECC is associated with lower intraoperative suPAR levels, suggesting a reduced inflammatory response compared to cCPB. While suPAR levels were significantly higher in patients with AKI, their predictive value for AKI remains limited. Furthermore, suPAR did not predict POD but was elevated in patients with pneumonia. Full article

Background/Objectives: Pulmonary hypertension (PH) is a progressive disorder with high morbidity and mortality, partly driven by chronic inflammation. Soluble urokinase plasminogen activator receptor (suPAR) reflects immune activation. We evaluated whether suPAR is altered in Group 1 and Group 4 PH and its association with clinical, echocardiographic, and laboratory parameters. Methods: We enrolled 44 PH patients (36 in Group 1, 8 in Group 4) and 45 healthy controls. All underwent clinical and echocardiographic assessments; right heart catheterization was performed in the PH patients. Serum suPAR was measured by ELISA. N-terminal pro B-type natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) were also assessed. Results: The suPAR plasma levels in the PH group were between 23.91 and 960.8 pg/mL (median: 73.14 p25: 62.77, p75: 167.13). suPAR was significantly higher in PH versus controls (73.14 [62.77–167.13] vs. 65.52 [53.06–80.91] pg/mL; p = 0.012). In logistic regression, systolic blood pressure, erythrocyte sedimentation rate, NT-proBNP, and suPAR independently predicted PH. suPAR correlated negatively with six-minute walk distance (r = −0.310) and tricuspid annular plane systolic excursion (r = −0.295) but positively with systolic pulmonary artery pressure (r = 0.241). On multivariate analysis, six-minute walk distance was the only independent correlate of suPAR (p = 0.004). suPAR levels did not differ between Group 1 and Group 4 PH. Conclusions: suPAR is elevated in Group 1 and Group 4 PH and correlates with functional and echocardiographic indices of disease severity. Larger prospective studies are needed to determine suPAR’s role in diagnosis, risk stratification, and therapeutic decision-making. Full article

The Bayan Obo deposit, located on the northern margin of the North China Plate (NCP), is the world’s largest comprehensive Fe-REE-Nb deposit. After its formation, this deposit was affected by multiple tectonic thermal events, but the ages of these geological events are controversial. To determine the evolutionary history of the Bayan Obo deposit, we conducted a detailed study of the macroscopic and microscopic deformation characteristics of the ore district and selected representative minerals, such as riebeckite and biotite, which are widely present in the banded rocks of the deposit, for an ⁴⁰Ar-³⁹Ar isotopic analysis. The results show that a large number of deformation structures have developed in the carbonatite and surrounding rocks, including mineral bands, boudins, tight folds, and rotated porphyroclasts, suggesting that the region has undergone intense compression and shearing and that the deformation temperature can reach ~550 °C. ⁴⁰Ar-³⁹Ar plateau ages of 414.9 ± 1.4 Ma and 264.5 ± 2.5 Ma were obtained for the riebeckite and biotite, respectively. Using these results in conjunction with regional geological data and considering the closure temperature of the mineral isotope system, it was inferred that these two ages corresponded to two distinct reworking events experienced by the deposit during the Early Paleozoic and Late Paleozoic following its initial formation. These events corresponded to the collision between the Bainaomiao Arc and the NCP and the magmatic activity induced by a continental–continental collision during the closure of the Paleo-Asian Ocean (PAO), respectively. Full article

Patients on standard hemodialysis (HD) show insufficient clearance of medium-molecular-weight uremic toxins, resulting in long-term complications. In this study we investigated the effectiveness of expanded HD (xHD) in the clearance of medium-molecular-weight uremic substances. This prospective study included patients on standard thrice-weekly HD. Participants were treated with xHD for 4 weeks, and the clearance of urea and β2-microglobulin was measured at the beginning and at the end of the study and compared with standard HD (sHD). Moreover, we investigated the clearance of Su-PAR, MCP-1, and activin, comparing sHD, xHD, and online hemodiafiltration (HDF). xHD had the same efficiency in the removal of low-molecular-weight substances compared to sHD but led to a significant decrease in β2-microglobulin levels from the first application of the method (sHD: from 36.9 ± 10.6 to 39.7 ± 18.9 mg/dL, p = 0.595 vs. 1st xHD: from 40 (36.5, 41.8) to 11 (9.8, 13.2) mg/dL, p = 0.008 vs. after 4 weeks on xHD: from 31.5 (28.5, 34.5) to 8.7 (8.2, 9.0) mg/dL, p = 0.008). Moreover, pre-session β2-microglobulin levels significantly decreased after 4 weeks on xHD. Su-PAR, MCP-1, and activin during xHD were also significantly reduced. xHD leads to a significant and cumulative reduction in medium-molecular-weight uremic toxins compared to standard HD. Full article