Search Results (177)

One of the main targets for snake venoms in animal and human organisms is the circulatory system. Mechanisms of circulatory system injury within the victim’s body include, among others, the direct effect of snake toxins on structures in blood vessel walls. The interaction of a toxin with cells and the extracellular matrix of the vessel wall may manifest as cytotoxicity, leading to cell death by necrosis or apoptosis, and damage to vascular wall structures. Such interactions may increase capillary permeability, promoting hemorrhage or edema, and may also induce alterations in vascular tone, resulting in changes in blood pressure. Snake toxins may also affect the growth, function, and regenerative ability of the endothelium, thus modulating angiogenesis; some toxins exert protective or anti-atherosclerotic effects. Toxins interacting with the vasculature may be classified as enzymes (phospholipases A₂, metalloproteinases, L-amino acid oxidases, and hyaluronidases), proteins without enzymatic activity (vascular endothelial growth factors, disintegrins, C-type lectins and snaclecs, three-finger toxins, etc.), peptides (bradykinin-potentiating peptides, natriuretic peptides, sarafotoxins), and low-molecular-weight substances. This review summarizes the data on the vascular effects, particularly on the blood vessel wall, exhibited by various classes and groups of snake toxins. Full article

Background and Objectives: Diastolic dysfunction (DD) is a frequent complication following percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS), potentially contributing to adverse outcomes. This study aimed to investigate the association between post-procedural inflammatory markers and the severity of DD and to propose a preliminary risk score for early prediction. Materials and Methods: We retrospectively analyzed 181 ACS patients undergoing PCI, assessing C-reactive protein (CRP), leukocyte, neutrophil counts, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) measured 24–48 h post-PCI. Echocardiographic DD grading was performed according to ASE/EACVI guidelines. Spearman correlation, ordinal regression, and decision-curve analysis were used to evaluate predictive performance. Results: CRP correlated with DD severity (ρ = 0.232, p = 0.002) and showed a borderline independent association (OR 1.004, 95% CI 0.999–1.009, p = 0.081). NT-proBNP correlated positively with both CRP and DD severity, while leukocyte and neutrophil counts were not significant. A three-parameter risk score (CRP > 10 mg/L, NT-proBNP > 125 pg/mL, age ≥ 65 years) identified patients at higher risk of moderate-to-severe DD (score ≥ 2: sensitivity 62%, specificity 71%). Decision-curve analysis demonstrated clinical utility in guiding post-PCI monitoring. Conclusions: A simple 0–3 point score combining age, CRP, and NT-proBNP showed potential for early identification of patients at risk of moderate-to-severe diastolic dysfunction after PCI. While the model demonstrated acceptable discrimination and calibration, its single-center design, limited sample size, and timing of biomarker assessment warrant cautious interpretation. External validation in larger, multicenter cohorts is required before clinical application. Full article

Introduction: In renal transplant recipients (RTRs), kidney graft failure and cardiovascular (CV) disease are prevalent and associated with mortality. Objectives: The objective of the study was to evaluate biomarkers, (cardiac troponin T (cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP)), to identify RTRs who are at greater risk of death, CV event, and graft renal survival. Patients and methods: A total of 342 stable RTRs were enrolled in this study, with a median follow-up time of 54 months. The probability of death, CV event, and renal graft survival were calculated using Kaplan–Meier analysis for the group defined by cTnT and NT-proBNP levels above the cutoff values. Results: The probability of death for troponin T level above the cut-off was 23% and for NT-proBNP 29%. For CV events the probability for troponin T was 20% and for NT-proBNP it was 21%. Troponin T concentrations above the cutoff point suggested a 25% probability of death-censored graft survival. For NT-proBNP, it was 26%. The probability of overall graft survival was 38% for patients with higher troponin T levels, and 40% for NT proBNP. Conclusions: These data suggest that cTnT and NT-proBNP could potentially identify patients at high risk for death, CV event, and graft survival. 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/Objectives: Fulminant myocarditis (FM) is an uncommon but potentially reversible form of myocardial inflammation that can rapidly progress to cardiogenic shock (CS). In patients who are refractory to conventional treatment, venoarterial extracorporeal membrane oxygenation (VA-ECMO) represents an effective life support strategy. However, the factors that determine functional recovery remain uncertain. The primary objective of this study was to characterize patients who recover ventricular function. Secondary objectives included analyzing VA-ECMO-related complications and overall patient survival. Methods: This was a retrospective, single-center, observational study including all consecutive patients diagnosed with FM between 2008 and 2025 who were supported with VA-ECMO (n = 22). Clinical, biochemical, echocardiographic, and imaging variables were collected. Patients were classified based on their outcomes as either recovery or death/transplantation. Differential factors potentially affecting myocardial recovery, survival, and complications were analyzed. Results: The mean age was 49.7 ± 11 years, with 36% being male. Severe cardiogenic shock was the most common initial presentation (86%), and the average time from symptom onset to hospital admission was 5.7 days. Regarding mechanical support, the non-recovery group required longer ECMO support (328 ± 225 h vs. 188 ± 103 h; p = 0.03). The presence of fibrosis on cardiac magnetic resonance imaging (MRI) was associated with a lower probability of recovery (100% vs. 44.4%; p = 0.03). Renal failure and vascular complications were more frequent in the non-recovery group, with a significantly higher rate of surgical reintervention (50% vs. 10%; p = 0.04). Echocardiography performed before discharge (recovery group) vs. before death/transplant (non-recovery group) showed significant differences in left ventricular ejection fraction (51.1% vs. 29.5%; p = 0.04), along with better levels of creatinine, N-terminal pro-B-type natriuretic peptide (NT-proBNP), leukocytes, and C-reactive protein (CRP) in the recovery group. In-hospital survival for the entire cohort was 63.6%, significantly higher in the recovery group (100% vs. 33.3%; p < 0.01). One-year survival was 59%, which was also greater among those who recovered (90% vs. 33.3%; p = 0.02). Conclusions: FM is associated with an acceptable in-hospital survival rate. The presence of myocardial fibrosis on MRI and longer ECMO support duration were observed to be associated with a lower likelihood of cardiac recovery. Patients who recovered showed better ventricular function at discharge, as well as reduced systemic inflammation and renal dysfunction. These findings highlight the importance of early identification of predictors of myocardial recovery to optimize management and therapeutic decision making in this high-risk population. Full article

Background: Cardiac glycosides such as digoxin have been commonly used for patients with heart failure; however, their toxicity remains a main concern. 17βH-neriifolin (SNA209), a cardiac glycoside compound, has been recently isolated from Ceberra odollum Gaertn and was shown to improve the heart’s pumping ability in failing hearts ex vivo. Thus, this study aimed to investigate the potential use of SNA209 as a treatment for isoprenaline (ISO)-induced heart failure in rats. Methods: Forty male Wistar rats were randomly divided into five groups. Heart failure was induced by isoprenaline (ISO, 10 mg/kg/s.c) for 14 days daily, followed by SNA209 treatment (5 mg/kg; p.o) for another 14 days daily. Control rats were given saline as a vehicle for ISO and DMSO as a vehicle for SNA209. Results: Systolic and diastolic blood pressure (SBP and DBP) in all ISO-treated groups were significantly increased compared to the control group (p < 0.05), and SNA209 treatment managed to reduce the SBP and DBP. Additionally, SNA209 treatment significantly increased the heart rate and normalized the ECG parameters in ISO-treated rats. Pro-B-type natriuretic peptide and troponin T level, a cardiac injury markers, was remarkably reduced by SNA209 in the ISO-treated group. Cardiac hypertrophy was evident in increased cardiomyocyte size in ISO groups; however, SNA reduced the cardiomyocyte size. The left ventricular developed pressure (LVDP) in ISO treated with SNA209 was significantly raised, indicating a chronotropic effect. Cardiac Na⁺/K⁺-ATPase expression of the α1 subunit, sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase 2a (SERCA2a), and sodium–calcium exchanger subunit were significantly increased in the SNA treatment groups. Conclusions: The SNA 209 treatment improved cardiac function and structure, likely via modulating intracellular calcium management, so underscoring its potential as an adjuvant therapy for heart failure. Full article

Background: Atrial fibrillation (AF) is common complication of heart failure with preserved ejection fraction (HFpEF) that sufficiently intervenes in the prognosis. The aim of the study is a) to investigate the possible discriminative value of adropin for newly onset AF in patients with HFpEF without a previous history of AF and who are being treated in accordance with conventional guideline and b) to compare it with predictive potencies of conventionally used predictors. Methods: A total of 953 patients with HFpEF who had sinus rhythm on ECG were enrolled in the study. The course of the observation was 3 years. Echocardiography and assessment of conventional hematological, biochemical parameters and biomarker assay including N-terminal brain natriuretic pro-peptide (NT-proBNP), high-sensitivity cardiac troponin T, tumor necrosis factor-alpha, high-sensitivity C-reactive protein (hs-CRP), galectin-3, interleukin-6, soluble suppressor tumorigenisity-2 (sST2) and adropin, were performed at baseline. Results: Incident atrial fibrillation was found in 172 patients with HFpEF, whereas 781 had sinus rhythm. In unadjusted rough Cox regression model, age ≥ 75 years, type 2 diabetes mellitus, chronic kidney disease (CKD) stages 1–3, left atrial volume index (LAVI) ≥ 40 mL/m², NT-proBNP ≥ 1440 pmol/mL, hs-CRP ≥ 5.40 mg/L, adropin ≤ 2.95 ng/mL, sST2 ≥ 15.5 ng/mL were identified as the predictors for new onset AF in HFpEF patients. After adjusting for age ≥ 75 years, a presence of type 2 diabetes mellitus and CKD stages 1–3, the levels of NT-proBNP ≥ 1440 pmol/mL and adropin ≤ 2.95 ng/mL were independent predictors of new onset AF in patients HFpEF. We also found that discriminative value of adropin was superior to NT-proBNP, while adding adropin to NT-proBNP did not improve predictive information of adropin alone. Conclusions: adropin ≤ 2.95 ng/mL presented more predictive information than NT-proBNP ≥ 1440 pmol/mL alone for new cases of AF in symptomatic patients with HFpEF, whereas the combination of both biomarkers did not improve the predictive ability of adropin alone. Full article

Background: This study presents an innovative approach to cardiovascular disease (CVD) risk prediction based on a comprehensive analysis of clinical, immunological and biochemical markers using mathematical modelling and machine learning methods. Baseline data include indices of humoral and cellular immunity (CD59, CD16, IL-10, CD14, CD19, CD8, CD4, etc.), cytokines and markers of cardiovascular disease, inflammatory markers (TNF, GM-CSF, CRP), growth and angiogenesis factors (VEGF, PGF), proteins involved in apoptosis and cytotoxicity (perforin, CD95), as well as indices of liver function, kidney function, oxidative stress and heart failure (albumin, cystatin C, N-terminal pro B-type natriuretic peptide (NT-proBNP), superoxide dismutase (SOD), C-reactive protein (CRP), cholinesterase (ChE), cholesterol, and glomerular filtration rate (GFR)). Clinical and behavioural risk factors were also considered: arterial hypertension (AH), previous myocardial infarction (PICS), aortocoronary bypass surgery (CABG) and/or stenting, coronary heart disease (CHD), atrial fibrillation (AF), atrioventricular block (AB block), and diabetes mellitus (DM), as well as lifestyle (smoking, alcohol consumption, physical activity level), education, and body mass index (BMI). Methods: The study included 52 patients aged 65 years and older. Based on the clinical, biochemical and immunological data obtained, a model for predicting the risk of premature cardiovascular aging was developed using mathematical modelling and machine learning methods. The aim of the study was to develop a predictive model allowing for the early detection of predisposition to the development of CVDs and their complications. Numerical methods of mathematical modelling, including Runge–Kutta, Adams–Bashforth and backward-directed Euler methods, were used to solve the prediction problem, which made it possible to describe the dynamics of changes in biomarkers and patients’ condition over time with high accuracy. Results: HLA-DR (50%), CD14 (41%) and CD16 (38%) showed the highest association with aging processes. BMI was correlated with placental growth factor (37%). The glomerular filtration rate was positively associated with physical activity (47%), whereas SOD activity was negatively correlated with it (48%), reflecting a decline in antioxidant defence. Conclusions: The obtained results allow for improving the accuracy of cardiovascular risk prediction, and form personalised recommendations for the prevention and correction of its development. Full article

This study included 221 patients with COVID-19 who were admitted to the emergency department of Avicenne Hospital in Rabat between August 2020 and August 2021. Patients were divided into three groups according to their D-dimer levels (<1, 1–2, and >2 µg/mL). Adjusted and unadjusted logistic regression analyses were performed to assess the association between elevated D-dimer levels and in-hospital mortality. Pearson’s correlation analysis was performed to explore the relationship between D-dimer levels and various biological and clinical parameters. The results revealed a statistically significant difference in the mean (SD) age among the three groups (p = 0.006). Analysis showed a statistically significant difference in the means (SD) of oxygen saturation, duration of hospital stay, and breathing rate among the three independent groups of COVID-19 patients. Patients with elevated D-dimer levels (greater than 2 µg/mL) experienced worse outcomes than those in the other groups, with severity, transfer to intensive care, and in-hospital mortality of 55 (40.7%), 35 (16%), and 24 (11%) patients, respectively, with p-values of 0.048, 0.002, and 0.002, respectively. Patients in the D-dimer > 2 µg/mL group had significantly higher C-reactive protein (CRP), lactate dehydrogenase, urea, cardiac troponin, B-type natriuretic peptide, and ferritin levels than those in the other two groups. The p-value was significant among the three groups (p = 0.044, p = 0.001, and p < 0.001). Age and elevated D-dimer levels (greater than 2 µg/mL) were associated with mortality in patients diagnosed with COVID-19. Correlation analysis indicated that D-dimer in COVID-19 patients is associated with worsening respiratory, hepatic, cardiac, and coagulation parameters, suggesting their utility as an integrative marker of disease severity. D-dimer levels > 2 µg/mL were identified as an independent risk factor for COVID-19 in-hospital mortality. Measuring and monitoring D-dimer levels can assist clinicians in taking timely actions and predicting the prognosis of patients with COVID-19. Full article

Post-acute sequelae of COVID-19 have been associated with an elevated risk of thromboembolism and adverse cardiovascular events (CVEs). We aim to evaluate whether alterations in poorly studied hemostatic and endothelial proteins are associated with CVEs in patients previously admitted to the ICU and evaluated one year post-discharge. We carried out a cross-sectional study involving 63 COVID-19 patients previously admitted to the ICU one year post-discharge. Plasma levels of factor IX (coagulation factor), protein C, protein S (natural anticoagulant), and von Willebrand factor (VWF, an endothelial marker) were measured using a Luminex 200™ analyzer. Generalized linear models (GLMs) were used to assess the association of these coagulation proteins with CVEs and N-terminal pro-B-type natriuretic peptide (NT-proBNP). We found that lower levels of factor IX (p = 0.011), protein C (p = 0.028), and protein S (p = 0.008) were associated with CVEs one year after ICU discharge. Additionally, at the one-year follow-up, we found lower levels of factor IX (p = 0.002) and higher levels of VWF (p = 0.006) associated with higher levels of NT-proBNP, underscoring the involvement of both hemostatic imbalance and persistent endothelial dysfunction. Our findings revealed a gender-specific pattern of associations with NT-proBNP levels. These findings highlight the significant role of persistent hemostatic imbalance and endothelial dysfunction in the development of cardiovascular abnormalities among COVID-19 survivors discharged from the ICU. 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

In vitro maturation (IVM) of oocytes retrieved from ovum pick-up (OPU) or ovarian tissue (OT) is a standard approach for patients with specific conditions where prior hormonal stimulation is contraindicated. However, the developmental competence of oocytes matured in vitro is still inferior to that of oocytes matured in vivo. Capacitation IVM (CAPA-IVM) includes an extra step of pre-maturation culture (PMC) with c-type natriuretic peptide (CNP) as a meiotic arrestor to better synchronize cytoplasmic and nuclear maturity in oocytes by allowing the cytoplasm additional time to acquire essential components critical for optimal competency. This study aims to evaluate the effect of CAPA-IVM on equine oocyte quality and developmental competence. Immature cumulus–oocyte complexes (COCs) were retrieved from slaughterhouse ovaries and matured in vitro either in CAPA-IVM (short 6 h, long 24 h pre-maturation) or standard IVM. Mature oocytes from each group were analyzed for calcium-releasing potential (n = 52) and single-oocyte proteomics (n = 44), and embryo development (n = 229) was assessed after fertilization with piezo-drilled intracytoplasmic sperm injection (ICSI). Genetic analysis of developed blastocysts (n = 41) was performed to detect chromosomal aberrations. Our findings demonstrate that CAPA-IVM of equine COCs yields significantly higher maturation rates than controls. Moreover, short CAPA-IVM with six hours pre-maturation culture showed substantially higher embryo development potential than the control group (20/69 vs. 9/63, respectively). Genetic analysis revealed a high euploidy rate in equine blastocysts regardless of the maturation conditions. Live calcium imaging of the fertilized oocytes demonstrated that the majority of oocytes displayed non-continuous calcium oscillation patterns, irrespective of maturation conditions. Single-oocyte proteomics reveals a comparable proteomic landscape between mature oocytes subjected to short CAPA-IVM and standard IVM. However, we identified four enriched gene sets with positive enrichment scores after short CAPA-IVM, related to cytoskeleton regulation, ribosomal function, and cytosolic components. Our findings indicate that CAPA-IVM holds the potential to improve oocyte quality and competence in horses. However, further fine-tuning of culture conditions would benefit the effective use of these IVM systems. Moreover, given that the mare serves as an excellent model for human reproduction, the molecular trends identified in this study could provide valuable insights for advancing human artificial reproductive technologies. Full article

Background/Objectives: Malnutrition, muscle wasting, and fluid overload are highly prevalent in patients undergoing maintenance hemodialysis (HD) and may contribute to increased mortality risk. However, the combined impact of these factors has not been fully elucidated. Methods: In this multicenter prospective cohort study, we enrolled 368 patients in maintenance HD at four dialysis facilities in Japan. Malnutrition was defined as moderate or higher nutritional risk using the nutritional risk index for Japanese hemodialysis patients (NRI-JH). Low muscle mass was assessed using the skeletal muscle mass index (SMI) according to the Asian Working Group for Sarcopenia 2019 (AWGS 2019), and elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) was defined as values in the top quartile (≥7650 pg/mL). Mortality risk was analyzed using Cox proportional hazards models. Associations with inflammation, assessed by C-reactive protein (CRP), were also explored. Results: Over a three-year follow-up period, 52 deaths occurred. Malnutrition, low muscle mass, and elevated NT-proBNP were each independently associated with increased all-cause mortality (HR: 4.98, 3.25, and 5.45, respectively). Patients with multiple concurrent risk factors had significantly worse survival. Although CRP was positively associated with these risk factors, it was not an independent predictor of mortality. Conclusions: Malnutrition, low muscle mass, and elevated NT-proBNP are independent and additive risk factors for mortality in HD patients. These findings highlight the need for integrated assessment and management strategies to improve prognoses in this high-risk population. Full article

Brugada syndrome (BrS) is a cardiac disease associated with characteristic ECG abnormalities and a heightened risk of sudden cardiac death, especially in young individuals with structurally normal hearts. The primary aim of this study was to highlight, for the first time, the potential of using droplet digital PCR (ddPCR), a highly sensitive method, to detect C-type natriuretic peptide (CNP) and its receptors, NPR-B and NPR-C, expression in BrS. Whole-blood samples from 12 subjects with type 1 BrS and 12 controls were analyzed. CNP expression was detectable and lower in BrS patients than in the controls, although not significantly. NPR-B and NPR-C expression was significantly reduced in the same patients (p ≤ 0.05). Strong correlations were observed between CNP and NPR-B (p = 0.01) and NPR-C (p < 0.0001), as well as between NPR-B and NPR-C (p = 0.0002). Body weight correlated with CNP (p = 0.02), NPR-B (p = 0.03), and NPR-C (p = 0.02); meanwhile, NPR-B expression was related to height (p = 0.05). This study is the first to analyze CNP expression and its specific receptors using ddPCR technology, showing for the first time their presence and activation in individuals with BrS. Although further research is needed to clarify CNP-related mechanisms, these findings offer a valuable starting point for exploring its role in BrS. Full article

Mucopolysaccharidosis type IVA (MPS IVA, Morquio A syndrome) is a rare inherited disorder characterized by skeletal dysplasia due to deficient N-acetylgalactosamine-6-sulfate sulfatase activity, resulting in glycosaminoglycan (GAG) accumulation. Identifying accurate biomarkers reflecting clinical severity and therapeutic response remains challenging. This study evaluated potential surrogate biomarkers, including N-terminal pro-C-type natriuretic peptide (NT-proCNP), collagen types I and II, mono-sulfated keratan sulfate (KS), di-sulfated KS, and chondroitin-6-sulfate (C6S), in blood and urine samples from 60 patients ranging from 1 to 62 years of age. NT-proCNP levels were significantly elevated in patients of all ages and negatively correlated with growth impairment, especially after 8 years of age. Collagen type I levels significantly increased in adult patients, whereas collagen type II showed age-dependent elevations. Urinary KS, in mono- and di-sulfated forms, demonstrated moderate negative correlations with growth impairment. Moreover, NT-proCNP, mono- and di-sulfated KS in plasma, and urinary di-sulfated KS were not affected by enzyme replacement therapy in patients younger than 12 years, unlike urinary mono-sulfated KS. In conclusion, NT-proCNP has emerged as a promising independent biomarker reflecting the severity of skeletal dysplasia and possibly the near-future growth rate. These findings highlight the potential role of NT-proCNP in clinical assessment and monitoring therapeutic efficacy, addressing current unmet needs in MPS IVA management. Full article