N-Terminal Pro-Brain Type Natriuretic Peptide Predicts Cardiovascular Events Independently of Arterial Stiffness, Assessed By Carotid-to-Femoral Pulse Wave Velocity, in Apparently Healthy Subjects.

AIM: This study aimed to evaluate whether N-terminal pro-brain natriuretic peptide (NT-proBNP) and carotid-to-femoral pulse wave velocity (PWV) carried independent prognostic value in predicting cardiovascular events in apparently healthy individuals beyond traditional risk factors. METHODS: A total of 1,872 participants aged 41, 51, 61, or 71 years from the MONItoring of trends and determinants in CArdiovascular disease (MONICA) study were included. Traditional risk factors were assessed, including: smoking status; mean systolic and diastolic blood pressure; body mass index; fasting plasma glucose; serum triglycerides; total, high-density, and low-density lipoprotein cholesterol; NT-proBNP; and PWV. The principal endpoint that was assessed during 16 years of follow-up was a composite of major adverse cardiovascular events (MACE). The secondary endpoints were cardiovascular mortality (CVM), hospitalisation for coronary artery disease (CAD), and a composite of hospitalisation for heart failure (HF) or atrial fibrillation (AF). RESULTS: At baseline, NT-proBNP was associated with PWV (ß=0.14; p<0.001), but not after adjustment for traditional risk factors (ß=-0.01; p=0.67). In models including traditional risk factors and PWV, NT-proBNP was associated with all four outcomes (HRMACE=1.33, 95% CI 1.16-1.52; HRCVM=2.02, 95% CI 1.65-2.48; HRCAD=1.29, 95% CI 1.07-1.55; and HRHF or AF=1.79, 95% CI 1.40-2.28). In the same model, PWV was only associated with CVM (HRCVM=1.20, 95% CI 1.01-1.41). No interactions between NT-proBNP and PWV were found. N-terminal pro-brain natriuretic peptide significantly improved net reclassification (NRI) for MACE (NRI=0.12; p=0.03), CVM (NRI=0.33; p<0.001), and HF or AF (NRI=0.33; p<0.001) beyond traditional risk factors, while PWV did not aid in net reclassification improvement for any endpoint. CONCLUSIONS: In apparently healthy individuals, NT-proBNP and PWV predicted cardiovascular events independently. N-terminal pro-brain natriuretic peptide improved reclassification for the prediction of MACE, CVM, and hospitalisation for HF or AF beyond traditional risk factors, while PWV did not.

The beneficial effect of Batroxobin on blood loss reduction in spinal fusion surgery: a prospective, randomized, double-blind, placebo-controlled study.

OBJECTIVE: Our objective was to evaluate the efficacy and safety of Batroxobin on blood loss during spinal operations. METHODS: After obtaining approval from the ethics committee at the hospital along with informed written consent, we performed a double-blind, randomized, placebo-controlled study with 100 patients who were randomized equally into 2 groups (Batroxobin and placebo). Patients received either 2 ku IV 15 min before surgery and followed 1 ku IM of Batroxobin following surgery, or an equivalent volume of placebo (normal saline). Cost of Batroxobin treatment is amounted to 84.75 euros. The primary outcomes were intraoperative, 24 h postoperative, and total perioperative blood loss. Secondary outcomes were hemoglobin (Hb), red blood cell count (RBC), the volume of blood/fluid transfusion intraoperatively, and 24 h postoperatively. Safety evaluation parameters were the incidence of venous thrombosis in the lower extremities, active partial thromboplastin time, prothrombin time, thrombin time, and fibrinogen. The data were analyzed using the Statistical Package for the Social Science Version 12.0. The results were presented as mean ± SEM. The Mann-Whitney test and Independent Student t test, when appropriate, were used to compare the 2 groups, and differences were considered significant if the P value was <0.05. RESULTS: 88 patients were included in the analysis while 12 patients were withdrawn from the study due to extended surgical duration, change of surgical procedure, or after the patients' request. The total perioperative blood loss was approximately 31% lower in patients given Batroxobin versus placebo (700.5 ± 45.81 vs 485.7 ± 30.01 mL, P = 0.001). The Batroxobin group had significantly less intraoperative blood loss (326.1 ± 24.16) compared to the placebo group (556.0 ± 43.58), but there was no difference in the amount of blood/fluid transfused, postoperatively Hb, or RBC between the two groups. After the operation, coagulation parameters were not significantly different between the 2 groups at the days 1 or 3 postoperatively. No adverse events related to the use of Batroxobin were recorded. There were no cases of superficial wound infection. None of the subjects died during the study. CONCLUSIONS: In this study, prophylactic use of Batroxobin provided an effective and cheap method for reducing blood loss without coagulopathy during or after operations. The use of Batroxobin for patients undergoing one-level PLIF surgery safely and effectively reduced the total amount of perioperative blood loss.

Circulating biomarkers for long-term cardiovascular risk stratification in apparently healthy individuals from the MONICA 10 cohort.

AIMS: The aim of this study was to examine whether high-sensitivity C-reactive protein (hs-CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP), and soluble urokinase plasminogen activator receptor (suPAR) carried incremental prognostic value in predicting cardiovascular morbidity and mortality beyond traditional risk factors in apparently healthy individuals. METHODS AND RESULTS: This was a prospective population-based cohort study comprising 1951 subjects included in the 10-year follow-up of the MONItoring of trends and determinants in CArdiovascular disease (MONICA) study, between 1993 and 1994. The principal endpoint was death from cardiovascular causes. Secondary endpoints were death from any cause, coronary artery disease, heart failure, and cerebrovascular disease. Predictive capabilities of each of the three biomarkers were tested using Cox proportional-hazards regression, Harrell's concordance index (C-index), and net reclassification improvement (NRI). Study participants were aged 41, 51, 61, or 71 years, and equally distributed between the two sexes. During a median follow-up of 18.5 years (interquartile range: 18.1-19.0), 177 (9.1%) subjects died from a cardiovascular cause. Hs-CRP (adjusted standardized hazard ratio (HR): 1.37, 95% confidence interval (CI): 1.17-1.60), NT-proBNP (HR: 1.90, 95% CI: 1.58-2.29), and suPAR (HR: 1.35, 95% CI: 1.17-1.57) were all significantly associated with cardiovascular deaths after adjustment for age, sex, smoking status, systolic blood pressure, and total cholesterol (p < 0.001 for all). Furthermore, all three biomarkers were significantly associated with significant NRI. However, only NT-proBNP significantly raised the C-index in predicting death from cardiovascular causes when added to the risk factors (C-index 0.860 versus 0.847; p = 0.02). CONCLUSIONS: Hs-CRP, suPAR, and particularly NT-proBNP predicted cardiovascular death and may enhance prognostication beyond traditional risk factors in apparently healthy individuals.

Inhibiting actin depolymerization enhances osteoblast differentiation and bone formation in human stromal stem cells.

Remodeling of the actin cytoskeleton through actin dynamics is involved in a number of biological processes, but its role in human stromal (skeletal) stem cells (hMSCs) differentiation is poorly understood. In the present study, we demonstrated that stabilizing actin filaments by inhibiting gene expression of the two main actin depolymerizing factors (ADFs): Cofilin 1 (CFL1) and Destrin (DSTN) in hMSCs, enhanced cell viability and differentiation into osteoblastic cells (OB) in vitro, as well as heterotopic bone formation in vivo. Similarly, treating hMSC with Phalloidin, which is known to stabilize polymerized actin filaments, increased hMSCs viability and OB differentiation. Conversely, Cytocholasin D, an inhibitor of actin polymerization, reduced cell viability and inhibited OB differentiation of hMSC. At a molecular level, preventing Cofilin phosphorylation through inhibition of LIM domain kinase 1 (LIMK1) decreased cell viability and impaired OB differentiation of hMSCs. Moreover, depolymerizing actin reduced FAK, p38 and JNK activation during OB differentiation of hMSCs, while polymerizing actin enhanced these signaling pathways. Our results demonstrate that the actin dynamic reassembly and Cofilin phosphorylation loop is involved in the control of hMSC proliferation and osteoblasts differentiation.