Plasma Levels Of Factor Research Articles

Gyrification patterns in first-episode, drug-naïve major depression: Associations with plasma levels of brain-derived neurotrophic factor and psychiatric symptoms.

Cortical structural changes in major depressive disorder (MDD) are usually studied using a voxel-based morphometry approach to delineate the cortical gray matter volume. Among cortical structures, gyrification patterns are considered a relatively stable indicator. In this study, we investigated differences in gyrification patterns between MDD patients and healthy controls (HCs) and explored the association of gyrification patterns with plasma brain-derived neurotrophic factor (BDNF) levels and depressive symptoms in MDD patients. We evaluated 79 MDD patients and 94 HCs and assessed depression severity in the patients using the 17-item Hamilton Depression Rating Scale (HAM-D). Blood samples of both groups were collected to measure plasma BDNF levels. Magnetic resonance imaging (MRI) data were obtained using three-dimensional fast-spoiled gradient-recalled acquisition. Differences in plasma BDNF levels between groups were examined using the Mann-Whitney U test. Principal component analysis and orthogonal partial least squares discriminant analysis (OPLS-DA) were conducted to investigate the gyrification patterns which were significantly different between the groups, i.e., those with variable importance in projection (VIP) scores of >1.5 and p-value < 0.05 in multiple regression analyses adjusted for age and sex. Finally, multiple regression analysis was performed on the selected gyrification patterns to examine their association with BDNF levels in the two groups and HAM-D in the patients. There were no significant differences in plasma BDNF levels between the groups. We found that 108 (71.0%) of 152 total local gyrification indices were MDD < HC. We identified 10 disease-differentiating factors based on critical gyrification features (VIP > 1.5 and p-value adjusted for age and sex < 0.05). However, we found no significant correlations between the 10 gyrification patterns and plasma BDNF levels and no interaction with group. Moreover, no significant correlations were observed between the local gyrification indices and HAM-D total scores. These results suggest that abnormal early cortical neurodevelopment may mediate vulnerability to MDD, independent of plasma BDNF levels and depressive symptoms.

Increase of ALCAM and VCAM-1 in the plasma predicts the Alzheimer's disease.

Cell adhesion molecules (CAM) are crucial in several pathological inflammation processes in Alzheimer's disease (AD). However, their potential for clinical diagnostics remains unknown. The present investigation evaluated the clinical significance of ALCAM, VCAM-1, NCAM, and ICAM-1 levels in the plasma of participants with cognitive impairment (44 patients with mild cognitive impairment, 71 patients with Alzheimer's dementia, and 18 patients with other dementia) and 28 controls with normal cognitive ability. We also detected plasma levels of multiple inflammatory factors (IFN-gamma, IL-18, IL-1beta, IL-13, IL-8, IL-7, CCL11, MCP-1, TSLP, IL-10, BDNF, IL-17, IL-5, TREM-1) using Multiplex liquid chip and plasma levels of Abeta1-42 and Abeta1-40 using liquid-phase flow cytometry (FCM). Our findings demonstrated a correlation of ALCAM and VCAM-1 with age, the severity of cognitive decline, and MTA, but no significant difference between groups for NCAM and ICAM-1. ALCAM and VCAM-1 both demonstrated a positive correlation with the degree of atrophy in the medial temporal lobe structure. Further analysis revealed no significant correlation in plasma between VCAM-1, ALCAM and Abeta1-40, Abeta1-42. Nevertheless, there was a significant correlation between VCAM-1, ALCAM and many inflammatory factors. Furthermore, the predictive value of ALCAM and VCAM-1 for AD was assessed using a multi-parameter regression model. ALCAM and VCAM-1 in combination with ApoE4, education, age, and MMSE could predict AD with high precision (AUC=0.891; AIC=146.9) without imaging diagnosis. ALCAM and VCAM-1 combination improved the predictive accuracy significantly. In a nutshell, these findings revealed ALCAM and VCAM-1 as reliable indicators of Alzheimer's disease.

Evaluation Of International Society On Thrombosis and Haemostasis-Bleeding Assessment Tool (ISTH-BAT) Scores In Hemophilia Patients: Single Center Experience

Objective: We aimed to examine the relationship between the clinical bleeding severity classification based on the factor levels and the ISTH-BAT score (calculated numerically over +/- or 10), to evaluate the usability of the ISTH-BAT score in Hemophilia A and B. Materials and Methods: In this retrospective study, the data of Hemophilia A and B patients who were administered a face-to-face ISTH-BAT survey upon admission to the outpatient clinic were evaluated. In addition to the positivity rate of the ISTH BAT score of patients with hemophilia, the relationship between this score and the patient's age, hemophilia type and factor level was also evaluated. Results: The study included 158 male patients(n:125 hemophilia A, n:33 hemophilia B). ISTH-BAT positivity was detected in 45.6% of hemophilia A patients and 57.6% of hemophilia B patients. There were no significant differences between hemophilia A and hemophilia B patients in terms of ISTH-BAT scores (p=0.43). Scores were higher in severe hemophilics, as expected, but there was no statistically significant correlation between factor levels and ISTH-BAT scores in hemophilia A (p=0.56), or hemophilia B (p=0.54). Conclusion: The ISTH-BAT can help recognize individuals with a bleeding history without a diagnosis. However, it does not correlate with factor level in patients with hemophilia and is not effective in determining bleeding susceptibility. Plasma factor levels are the most predictive data for bleeding frequency and severity.

PS-B13-7: AMELIORATIVE EFFECT OF VERNONIA AMYGDALINA LEAVES AND PERSEA AMERICANA LEAVES AND SEEDS ON VASCULAR INFLAMMATION GENERATED IN PREECLAMPSIA

Objective: this study was conducted to examine the ameliorative effect of Vernonia amygdalina (Bitter Leaves), Persea americana (Avogado) Leaves and Seeds on vascular inflammation generated in preeclampsia. Design and method: Female Rats after mated with male rats and confirmed pregnant were randomly grouped into nine and induced with Lipopolysaccharide (0.1 ml per Kg body weight) at gestational day 14 except for group one which served as the normal control. Other groups were treated with low and high doses of V. amygdalina, P. americana (Leaves and Seeds) except group two that were not treated (negative control) and group three that were treated with standard drug; Aldoment (positive control). Inducement, which was stopped after four days were done concurrently with treatment. Blood pressure and urinalysis were carried out before, during and after inducement and treatment. Biomarkers of vascular inflammation: Vascular Endothelial Growth Factor (VEGF), Tumour Necrosis Factor (TNF), Uric Acid, Total Cholesterol, Total Protein and Albumin were determined in plasma while histological analysis was done on the harvested organ (kidney). Data were analysed using Graph pad at significant less than 0.05. Results: In preeclamptic animals, there was a significant increase in the plasma level of Vascular Endothelial Growth Factor (VEGF), Tumour Necrosis Factor (TNF), Uric Acid, Total Cholesterol and decrease in the plasma level of Total Protein and Albumin compared with normal control. In addition, histopathological evaluation of renal tissues showed evidence of glomerular nephritis with picnotic changes in the tubular cells compared with normal glomerular and tubular component in the control animals. However, treatment with Vernonia Amygdalin, Persea Americana Leaves and Seeds ethanoic extract at high doses (200 mL per Kg body weight) significantly reverse this alterations at almost the same level with the standard drug. Conclusions: The present study suggest that preeclampsia is associated with vascular inflammation which is evidence in excess of Vascular Endothelial Growth Factor, Tumour Necrosis Factor, Uric Acid, Total Cholesterol and inadequate of Total Protein and Albumin as well as glomerular nephritis and this is ameliorated with supplementation of Vernonia Amygdalina, Persea Americana Leaves and Seeds. This effect is dose dependent.

Demonstration of ameliorating effect of papaverine in sepsis-induced acute lung injury on rat model through radiology and histology.

Our target was to show the role of high mobility group box-1/receptor for (HMGB1/RAGE) interaction in feces intraperitoneal injection procedure (FIP)-induced acute lung injury (ALI) pathophysiology, to investigate the effect of papaverine on RAGE associated NF-κB pathway by determining the level of soluble RAGE (sRAGE) and HMGB1, and to support this hypothesis by evaluating inflammatory biochemical, oxidative stress markers, Hounsfield unit (HU) value in computed tomography (CT), and histo-pathological results. FIP was performed on 37 Wistar rats for creating a sepsis-induced ALI model. The animals were assigned into four groups as follows: Normal control (no treatment), placebo (FIP and saline), and receiving 20 mg/kg and 40 mg/kg per day papaverine. Twenty h after FIP, CT examination was performed for all animals, and HU value of the lung parenchyma was measured. The plasma levels of tumor necrosis factor (TNF)-α, HMGB1, sRAGE, C-reactive protein (CRP) and malondialdehyde (MDA), and lactic acid (LA) were determined and PaO2 and PaCO2 were measured from arterial blood sample. Lung damage was assessed by histopathological. TNF-, IL-6, CRP, HMGB1, MDA, LA levels, histopathologic scores, and HU values of CT were significantly increased and sRAGE levels were decreased in the saline-treated group against normal group (all P<0.05). Papaverine significantly reversed all results regardless of the dose (all P<0.05) and demonstrated inhibition of HMGB1/RAGE interaction through increasing sRAGE levels and suppresses the pro-inflammatory cytokines. We concluded that papaverine has ameliorating effects in rat model of ALI.

Thrombosis in hereditary hemorrhagic telangiectasia

Thrombosis in hereditary hemorrhagic telangiectasia

Reduced Angiopoietin Factor 2 Levels Are Correlated with Better Cardiac Function and Prognosis in Valvular Heart Disease.

There are few circulating biomarkers for valvular heart disease. Angiopoietin (Ang) 1, Ang2, and vascular endothelial growth factor are important inflammation-associated cytokines. The aim of this study was to investigate the clinical significance and association of Ang1, Ang2, and vascular endothelial growth factor in valvular heart disease. This is a retrospective study; a total of 62 individuals (valvular heart disease patients [n=42] and healthy controls [n=20]) were included. Plasma levels of Ang1, Ang2, and vascular endothelial growth factor were detected by enzyme-linked immunosorbent assays. We retrospectively collected the baseline characteristics and short-term outcomes; logistic regression was performed to identify predictor for short-term mortality. Ang2 was significantly decreased in the valvular heart disease group compared with the healthy control group (P=0.023), while no significant difference was observed in the Ang1 and vascular endothelial growth factor levels. The Ang2 level of New York Heart Association (NYHA) I/II patients - but not NYHA III/IV patients - was significantly decreased compared with that of healthy control individuals (NYHA I/II: P=0.017; NYHA III/IV: P=0.485). Univariable logistic regression analysis indicated that Ang2 was a significant independent predictor for short-term mortality (odds ratio 18.75, P=0.033, 95% confidence interval 8.08-102.33). Ang1 was negatively correlated with Ang2 (P=0.032, Pearson's correlation coefficient =-0.317) and was positively correlated with vascular endothelial growth factor (P=0.019, Pearson's correlation coefficient = 0.359). Ang2 might serve as a therapeutic and prognostic target for valvular heart disease.

Alteration of faecal microbiota balance related to long-term deep meditation

BackgroundAdvancements in research have confirmed that gut microbiota can influence health through the microbiota–gut–brain axis. Meditation, as an inner mental exercise, can positively impact the regulation of an individual’s physical...

The influence of lower-leg injury and knee arthroscopy on natural anticoagulants and fibrinolysis

BackgroundPatients with lower-leg injuries and those undergoing knee arthroscopy are at increased risk of developing venous thromboembolism. The mechanism is unknown, including the influence of lower-leg injury and knee arthroscopy on natural anticoagulant factors and fibrinolysis. ObjectivesTo study the effect of lower-leg injury and knee arthroscopy on plasma levels of anticoagulant and fibrinolytic factors. MethodsWe applied the following 2 designs to investigate this effect: a cross-sectional study for lower-leg trauma and a before-and-after study for knee arthroscopy. Plasma samples of POT-CAST– and POT-KAST–randomized clinical trial participants (collected shortly after lower-leg trauma or before or after arthroscopy) were analyzed for clot lysis time and levels of antithrombin, tissue factor pathway inhibitor, protein C, free protein S, plasminogen, tissue plasminogen activator, plasminogen activator inhibitor 1, antiplasmin, thrombin activatable fibrinolysis inhibitor, plasmin-antiplasmin, and D-dimer. For the effect of lower-leg injury, samples of 289 patients were compared with preoperative samples of 293 arthroscopy patients, acting as controls using linear regression and adjusting for age, sex, body mass index, comorbidities, and diurnal variation. For the effect of knee arthroscopy, mean changes were calculated for 277 patients using linear mixed models adjusted for diurnal variation. Parameters other than CLT and D-dimer were measured in smaller subsets. ResultsIn lower-leg injury patients, most parameters were stable, whereas D-dimer increased. After arthroscopy, most parameters decreased (especially clot lysis time, D-dimer, plasminogen, and anticoagulant factors), whereas tissue plasminogen activator and thrombin activatable fibrinolysis inhibitor slightly increased. ConclusionIn contrast to lower-leg injury, knee arthroscopy was associated with decreased natural anticoagulant factor levels. Neither lower-leg injury nor knee arthroscopy affected in vivo fibrinolysis.

The modulation of Plasma Levels of Dopamine, Serotonin, and Brain-derived neurotrophic factor in response to variation in iron availability.

In the context of iron deficiency anemia, central dopamine, serotonin, and brain-derived neurotrophic factor (BDNF) are intensively investigated. However, peripheral isoforms are poorly investigated. This study aimed to investigate the modulation of plasma levels of dopamine, serotonin, and BDNF among children with iron deficiency anemia. A total of seventy-three iron-deficient (n=38) and iron-sufficient (n=35) children were included in the study. Twenty-nine subjects were showing clinical presentations and were diagnosed with iron deficiency anemia and forty-four were asymptomatic normal children. Plasma levels of dopamine, serotonin, and brain-derived neurotrophic factor were determined by enzyme-linked immunosorbent assay. As compared to corresponding levels among control subjects, Anemic subjects were having significantly higher plasma dopamine and lower plasma brain-derived neurotrophic factor levels. A significant linear and monotonic association of plasma dopamine and brain-derived neurotrophic factor with hemoglobin concentration (r=-0.520, P < 0.001 and ρ = 0.411, P = 0.001), respectively. Furthermore, there were significantly higher plasma serotonin levels among iron-deficient subjects with a significant inverse linear association with serum ferritin levels (r = -0.337, P = 0.005). Iron deficiency anemia is associated with the modulation of peripheral dopamine, serotonin, and brain-derived neurotrophic factor. Upregulation of dopamine and downregulation of brain-derived neurotrophic factor are correlated to the anemic status. The upregulation of plasma serotonin levels is iron-dependent and, probably, is attributed to the impairment of its metabolic fate. Further investigation is required to explore the pathophysiological and clinical association of these peripheral biomolecules in the context of iron deficiency anemia. (www.actabiomedica.it).

Defibrotide improved the outcome of monocrotaline induced rat hepatic sinusoidal obstruction syndrome

Background and aimPyrrolizidine alkaloids (PA) induced hepatic sinusoidal obstruction syndrome (HSOS) occurred worldwide and the mortality rate remained high because there were no specific therapies. Defibrotide was effective for HSOS following hematopoietic stem cell transplantation. But the pathogenesis of the two types of HSOS were not equivalent. The purpose of this study was to see if defibrotide was also effective in PA induced rat HSOS.MethodsFirst we improved rat HSOS model by using higher dose (230 mg/kg) of monocrotaline (a kind of PA) as the dose of median lethal dose. So drug effectiveness could be assessed by survival time. Next, male SD rats were divided into 5 groups. They were control group, model group, low dose low molecular weight heparin (LMWH) treatment group, high dose LMWH treatment group and defibrotide treatment group. Rats’ survival time, liver function, white blood cell count and cytokines were compared among the groups. The DeLeve score was used to assess the severity of liver pathology.ResultsThe model group exhibited typical liver pathology of HSOS, such as hepatic sinus dilation, congestion, endothelial injury of central lobular vein, coagulative necrosis of hepatocytes and fibrin deposition in the subendothelial. The pathologic characteristics indicated that the model was built up successfully. The survival rate was significantly higher in defibrotide group (81.8%) than model group (43.7%), while the survival rates were similar in the two LMWH groups (62.5% and 75%) and model group. The survival time only be prolonged by defibrotide (P=0.028) but not LMWH (P>0.05). DeLeve score was improved most in the defibrotide group than the two LMWH groups (both P<0.01). Changes in DeLeve score, liver function, plasma level of tumor necrosis factor α and plasminogen activator inhibitor-1 exhibited the same trends.ConclusionDefibrotide could improve the outcome of monocrotaline-induced rat HSOS indicating that defibrotide might be a better choice than LMWH in clinical practice.

Regulators of angiogenesis in chemotherapy-induced peripheral neuropathy

Background: Chemotherapy-induced peripheral polyneuropathy is a major neurotoxicity of treatment for acute lymphoblastic leukemia (ALL) in children. Pathophysiological mechanisms of the injury of peripheral neural system are not fully investigated; however, some studies have shown the involvement of vascular endothelial growth factors.&#x0D; Aim: To evaluate plasma levels of angiogenic growth factors in children with ALL and to identify their association with the development of vincristine-induced peripheral polyneuropathy.&#x0D; Materials and methods: This single center prospective study included 41 patients with ALL aged 3 to 17 years. All patients were given the ALL-MB 2015 chemotherapy regimen. Depending on the vincristine-induced peripheral polyneuropathy, the patients were divided into two groups: the main group (n = 22) comprised of the patients with neurological signs and symptoms of peripheral neuropathy and the control group (n = 19), those without clinical signs of the peripheral nervous system involvement. The levels of angiogenic growth factors (VEGF-A, VEGF-D, PlGF-1, and PDGF-BB) were measured in plasma by multiparameter immunofluorescent analysis.&#x0D; Results: During 3 months of the follow up the chemotherapy-induced signs of peripheral polyneuropathy developed in 53.6% (n = 22) of the children. In 72.7% (n = 16) of the patients the chemotherapy-induced peripheral polyneuropathy was characterized by a combination of neurologic abnormalities with prevailing motor symptoms. The comparative analysis of plasma angiogenic growth factors in children with ALL depending on the presence or absence of the vincristine-induced peripheral polyneuropathy showed that there was a significant decrease of the VEGF-A in those with chemotherapy-induced peripheral polyneuropathy, compared to those without (Me [Q1; Q3]: 178.20 [138.40; 228.45] and 558.50 [160.10; 650.0], respectively, p 0.017). This parameter had diagnostic sensitivity of 77.7% and specificity of 76.9%.&#x0D; Conclusion: We have shown a high clinical value of plasma vascular endothelial growth factor (VEGF-A) level, which makes it possible to consider it as a significant biological marker of neurotoxicity in vincristine-induced peripheral polyneuropathy.

Plasma Level of Apelin as a Promising Factor for Retinopathy of Prematurity

Introduction: The aim of this study was to investigate the relevance of plasma levels of apelin and other risk factors in infants with retinopathy of prematurity (ROP). Methods: This was a single-center cross-sectional study. Fifty preterm infants with ROP and 50 preterm infants without ROP were enrolled. The analysis included evaluation of gestational age (GA), birth weight (BW), and measurement of plasma concentrations of apelin, vascular endothelial growth factor (VEGF), erythropoietin (EPO), and insulin-like growth factor (IGF-1) using enzyme-linked immunosorbent assay. Results: The mean BW and GA of babies with ROP were considerably lower than those without ROP (p < 0.001, p = 0.003, respectively). Plasma levels of VEGF, EPO, and IGF-1 were all lower in babies with ROP (all p < 0.001), while plasma apelin levels were greater (p < 0.001). We compared the sensitivity and selected the best cut-offs while keeping the specificity constant (80.0%). Among all the criteria, plasma apelin levels had the best sensitivity (72%), with the cut-off of 21.08 pg/mL. Multivariable logistic regression analyses showed that the plasma level of apelin was the only parameter associated with ROP (p = 0.02, OR = 16, 95% CI: 1.54–166.53). The area under the curve of the multivariable regression model that comprised GA, BW alone was 0.67, while that of the model that included apelin was 0.90. Conclusions: Plasma apelin level demonstrated good sensitivity and specificity with regard to the association of ROP; the inclusion of apelin may be a promising factor to include in screening criteria.

The search for systemic biomarkers for monitoring degenerative lumbar spinal disorders

ObjectivesIn our previous study, we reported that low back pain (LBP) severity and disability significantly correlate with body composition and several blood biochemical factors. Herein, we tested the hypothesis that these covariates are associated with anatomical deformations of the lumbar spine, in particular, radiographic facet joint osteoarthritis (FJOA) and lumbar disc degeneration (LDD) features important contributors to LBP. MethodsCT and MRI images of the lumbar spine were obtained from 200 individuals suffering from LBP-sciatica. We examined the FJOA and total LDD score - the sum of the scores of the three radiographic features (intervertebral disc herniation, osteophythosis and spondylolisthesis) at the L1 - S1 vertebral levels. By implementing a bioelectrical impedance analysis, we assessed the participants for body composition, specifically, extracellular water (ECW). Plasma levels of growth and differentiation factor 15 (GDF-15) and visceral adipose tissue-derived serine protease inhibitor (vaspin), were detected by ELISA. ResultsBy conducting a series of multivariable regression analyses, we report that the circulating levels of GDF-15, vaspin, and ECW are significantly and independently associated with FJOA scores [βGDF15 ​= ​0.38 ​± ​0.08, p ​= ​0.0001; βVASPIN ​= ​0.36 ​± ​0.07, p ​= ​0.000004; βECW ​= ​0.24 ​± ​0.07, p ​= ​0.002]. The levels of GDF-15 (β ​= ​0.30 ​± ​0.10, p ​= ​0.007) and ECW (β ​= ​0.20 ​± ​0.09, p ​= ​0.03) were also found significantly associated with the LDD scores. ConclusionThe obtained new data suggest that GDF-15, vaspin and ECW may serve as biomarkers for FJOA and LDD phenotypes.

Models including preoperative plasma levels of angiogenic factors, leptin and IL-8 as potential biomarkers of endometrial cancer.

The diversity of endometrial cancer (EC) dictates the need for precise early diagnosis and pre-operative stratification to select treatment options appropriately. Non-invasive biomarkers invaluably assist clinicians in managing patients in daily clinical practice. Currently, there are no validated diagnostic or prognostic biomarkers for EC that could accurately predict the presence and extent of the disease. Our study analyzed 202 patients, of whom 91 were diagnosed with EC and 111 were control patients with the benign gynecological disease. Using Luminex xMAP™ multiplexing technology, we measured the pre-operative plasma concentrations of six previously selected angiogenic factors - leptin, IL-8, sTie-2, follistatin, neuropilin-1, and G-CSF. Besides basic statistical methods, we used a machine-learning algorithm to create a robust diagnostic model based on the plasma concentration of tested angiogenic factors. The plasma levels of leptin were significantly higher in EC patients than in control patients. Leptin was higher in type 1 EC patients versus control patients, and IL-8 was higher in type 2 EC versus control patients, particularly in poorly differentiated endometrioid EC grade 3. IL-8 plasma levels were significantly higher in EC patients with lymphovascular or myometrial invasion. Among univariate models, the model based on leptin reached the best results on both training and test datasets. A combination of age, IL-8, leptin and G-CSF was determined as the most important feature for the multivariate model, with ROC AUC 0.94 on training and 0.81 on the test dataset. The model utilizing a combination of all six AFs, BMI and age reached a ROC AUC of 0.89 on both the training and test dataset, strongly indicating the capability for predicting the risk of EC even on unseen data. According to our results, measuring plasma concentrations of angiogenic factors could, provided they are confirmed in a multicentre validation study, represent an important supplementary diagnostic tool for early detection and prognostic characterization of EC, which could guide the decision-making regarding the extent of treatment.

Baseline severity and soluble vascular cell adhesion molecule 1 (sVCAM-1) as biomarker predictors of short-term mortality in acute ischemic stroke.

The aim was to investigate the association between plasma levels of cellular adhesion molecules (CAMs) and risk factors, subtypes, severity and short-term mortality of acute ischemic stroke (IS), and to identify a panel of biomarkers to predict short-term mortality after IS. The prospective study evaluated 132 IS patients within 24h of their hospital admission. The baseline IS severity was assessed using the National Institutes Health Stroke Scale (NIHSS) and categorized as mild (NIHSS < 5), moderate (NIHSS 5-14) and severe (NIHSS ≥ 15). After three-month follow-up, the disability was assessed using the modified Rankin Scale (mRS); moreover, the patients were classified as survivors and non-survivors. Baseline inflammatory and anti-inflammatory cytokines and soluble CAMs were evaluated. Twenty-nine (21.9%) IS patients were non-survivors and showed higher NIHSS and soluble vascular cellular adhesion molecule 1 (sVCAM-1) than the survivors. The sVCAM-1 levels positively correlated with age, homocysteine, severity, and disability. The model #3 combining sVCAM-1 and NIHSS showed better results to predict short-term mortality with an area under the curve receiving operating characteristics (AUC/ROC) of 0.8841 [95% confidence interval (CI): 0.795-0.941] than the models with sVCAM-1 and NIHSS alone, with positive predictive value of 68.0%, negative predictive value of 91.3%, and accuracy of 86.5%. In conclusion, the combined model with baseline severity of IS and sVCAM-1 levels can early predict the prognosis of IS patients who may benefit with therapeutic measures of personalized therapy that taken into account these biomarkers. Moreover, this result suggests that VCAM-1 might be a potential target for the therapeutic strategies in IS.

Profile of Perioperative Coagulation in Major Liver Resection for Cancer: A Prospective Observational Study

Background: The liver plays a key role in the complex and dynamic process of blood coagulation. Consequently, after liver resection the equilibrium between procoagulant and anticoagulant activity is often deranged. Major hepatectomies have been associated with excessive intraoperative blood loss, hemodynamic instability, massive fluid shifts, and coagulopathy. Alterations of the coagulation profile are always present post-operatively even in case of normal pre-operative coagulation function. Cumulative evidence supports the superiority of global coagulation analysis compared with conventional coagulation for clinical decision-making. Aim: The purpose of this study was to assess the perioperative coagulation status of patients undergoing major hepatectomies for primary or metastatic hepatic malignancy. Conventional coagulation tests, plasma levels of coagulation factors, and TGA measurements were used for longitudinal documentation of the coagulation activity. Methods: Patients included in the study were referred for major liver resection which was defined as a resection of three or more liver segments, and were followed up to the 10th post-operative day by serial measurements of conventional coagulation tests, plasma levels of coagulation factors, and thrombin generation assay parameters. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) were determined by STA Neoplastin R, and STA-Cephascreen, Fibrinogen by STA-Liquid Fib, D-dimer STA Liatest D-DI Plus, all from Diagnostica Stago, France. Coagulation factor activity for FII, FV, FVII, FVIII, FIX, FX, was measured by clotting assay using coagulation factor deficient plasma, vWFAg , and vWFAc by vWFAg and Innovance vWFAc, from Siemens Healthcare Diagnostics, Germany. Thrombin generation (TG) was assessed in samples of PPP with the TF 5 pM PPP-Reagent on Calibrated Automated Thrombogram (Stago, France). Results: Changes over time for FII, FV, FVII and FX were statistically significant (p <0.05). Factor VIII level was above normal values at baseline. A steady rise was observed for fibrinogen, FVIII, and vWF antigen throughout the study period, but only vWF antigen exhibited statistically significant changes over time. Levels of coagulation inhibitors, AT, PC and PS, decreased significantly during the first postoperative day and then increased reaching baseline values by POD5 for protein C and S, but AT, remained low by POD10. INR increased after surgery, reaching a peak on the first post-operative day and decreasing toward baseline levels from then on (p <0.001). The aPTT remained within normal range throughout the study period (Table 1). TG conducted at baseline, on POD1, POD5, and POD10 showed elevated of Lag time and time to peak at baseline, whereas the rest thrombin generation parameters were within reference range. ETP decreased significantly over time, reaching lower values by POD5 and sustaining those low values by POD10. Peak height fluctuated in a similar manner, but changes over time did not bear any statistical significance. Lag-time, which was prolonged at baseline, exhibited a steady rise throughout the study period, bearing borderline statistical significance (Table 2) . A statistically significant positive correlation was detected between AT and time to Peak (ttPeak) at baseline, however any other significant difference between coagulation factors, natural coagulation inhibitors, and TGA parameters was observed. Conclusion: This study shows that patients with hepatic malignancy have systematic endothelial activation and hyper-coagulability as indicated by increased FVIII levels and lag time prolongation in thrombin generation. These patients are in a hyper-coagulable state in the early post-operative period, as shown by increased vWF, FVIII, D-dimer, fibrinogen and decreased levels of natural coagulation inhibitors AT, PC, and PS. Measurements of INR, PT, aPTT are not useful in this setting and could be misleading. Global coagulation analysis may be more appropriate for clinical guidance. To the best of our knowledge this is the first report in literature documenting the pre-existing coagulation disturbances in patients with hepatic carcinoma and their impact on the coagulation status after major hepatectomy. However, the clinical implications of our findings deserve further investigation. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Elevated Plasma Levels of Von Willebrand Factor and Syndecan-1 Predict 60-Day Mortality in Patients with Severe and Critical COVID-19

Introduction: Endotheliopathy is common pathologic findings in acute and long COVID-19, which is associated with the disease severity and predisposes to long-term complications. Previous studies have demonstrated that plasma levels of von Willebrand factor (VWF) and proteoglycan syndecan-1 are significantly elevated in patients with severe COVID-19. However, the role of these endothelial biomarkers for predicting a long-term outcome is still lacking. Patients and Methods:151 consecutive hospitalized patients between January and March 2022 at the University of Kansas Hospital with a confirmed SARS-CoV-2 infection by polymerase chain reaction were prospectively enrolled for the study. Whole blood anticoagulated with EDTA or sodium citrate was collected at least 3 times on admission (T1), 4-5 days following treatment (T2), and a few days prior to discharge or death (T3). Plasma levels of VWF antigen, ADAMTS13 antigen/activity, and syndecan-1 were determined using immunoassays or a functional assay. Kaplan-Meier survival analysis was performed to determine the predictive value of each biomarker for 60-day mortality. Results. Of 151 patients with a positive PCR test for SARS-CoV2, 124 patients were studied and analyzed. These patients were categorized into an asymptomatic control, a moderate, a severe, and a critical group according to an updated World Health Organization (WHO) guidance. The admission plasma levels (median, IQR) of VWF in patients of critical (334%,164.7-526.2%) (p=0.0049) and severe (255%, 143.1-410.9%) (p=0.0088) groups were significantly higher than in those of moderate (153%, 186.3-240.1%) (Fig. 1A). Interestingly, no statistically significant difference in the admission plasma levels of ADAMTS13 antigen among all groups (p>0.05) (Fig. 1B) despite a significantly lower plasma ADAMTS13 activity (median, IQR) in patients with severe (39.8%, 30.0-49.3%) (p=0.0067) and critical (38.6%, 26.9-51.5%) (p=0.047) COVID-19 than in those with a asymptomatic disease (49.2%, 37.5-103.4%) (Fig. 1C). Furthermore, plasma levels of syndecan-1 on admission were not different among all groups (p>0.05) (Fig. 1D). Longitudinal analysis demonstrated that plasma levels of VWF antigen and syndecan-1 were persistently elevated from baseline in patients who died but not in those who survived (Fig. 2A-D). Kaplan-Meier survival analysis revealed that an elevated level of plasma VWF (> 320%) on T2 (p<0.0001) (Fig. 2E) or an elevated level of plasma syndecan-1 on admission (T1) (> 260 ng/mL) (p=0.0002) (Fig. 2F), but not 4-5 days following therapy (T2) or before being discharged home or death (T3) predicted the 60-day mortality rate. Conclusions: Our results demonstrate significantly elevated plasma VWF antigen and reduced ADAMTS13 activity on admission in patients with severe and critical COVID-19. The dynamic change in plasma VWF or the initial plasma levels of syndecan-1 on admission predict the 60-day survival. The findings suggest that the additional therapeutic strategies may be needed to alleviate endothelial activation and damage to improve survival and long-term complications in patients with severe and critical COVID-19. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Early Experiences in the Von Willebrand Factor in Pregnancy (VIP) Study

Background: Plasma levels of von Willebrand factor (VWF) and factor VIII (FVIII) increase dramatically during healthy pregnancy. These increases are markedly less pronounced in pregnancies affected by von Willebrand disease (VWD). Individuals who have VWD have high rates of primary and secondary postpartum hemorrhage (PPH), despite treatment. In 2021, guidance was published on the prophylactic use of tranexamic acid postpartum and target VWF levels for neuraxial anesthesia. Guidance is still lacking on VWF target levels for delivery and on the duration of treatment postpartum due to a lack of evidence. Aims: To improve our understanding of bleeding during and after childbirth in individuals with VWD whose VWF levels are maintained >100%. Methods: The VIP Study (NCT04146376) is an investigator-initiated, prospective, open-label, multicenter cohort study in the US designed to document the rate of PPH in VWD when VWF levels are maintained >100% during and after childbirth (Fig. 1). Pregnant patients ≥18 years of age and diagnosed with VWD type 1 (VWF ≤30%), type 2, or type 3 are eligible for enrollment. Patients whose third trimester VWF levels do not reach 100% are termed "non-correctors", while patients with third trimester VWF levels >100% are termed "correctors". Non-correctors will receive VWF/FVIII replacement therapy (wilate®) targeting VWF levels of 100-150% for delivery. VWF replacement will continue postpartum, targeting VWF levels of 100-150% through postpartum Day 3 and VWF levels of 50-100% thereafter until postpartum Day 5-10. All patients (non-correctors and correctors) will receive antifibrinolytic therapy (tranexamic acid) postpartum for 14 days. Target enrollment is completion of 65 non-correctors and up to 30 correctors. The primary outcome is the rate of PPH within the first 24 hours postpartum. Secondary outcomes include PPH from 24 hours to 6 weeks postpartum, laboratory assessment of coagulation, and safety, including adverse drug reactions and thrombotic events. Results: As of March 2022, 11 sites across the US have been initiated and 9 patients have been enrolled. Conclusion: The VIP study aims to address the knowledge gap regarding bleeding during and after childbirth in VWD. The data obtained will provide important information to help guide future steps to study and reduce PPH in VWD and to develop evidence-based management for these patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Xuebijing Administration Alleviates Pulmonary Endothelial Inflammation and Coagulation Dysregulation in the Early Phase of Sepsis in Rats.

Xuebijing injection is a Chinese herbal-derived drug composed of radix paeoniaerubra, rhizomachuanxiong, Salvia miltiorrhiza, floscarthami, and Angelica sinensis. This study aimed to investigate the effects of Xuebijing administration on pulmonary endothelial injury and coagulation dysfunction in a cecal ligation and puncture (CLP)-induced sepsis rat model. A CLP-induced sepsis rat model was established. The CLP rats were treated with a vehicle or Xuebijing via intravenous infusion and sacrificed at 2, 4, 6, 8, or 12 h after CLP for lung tissue and blood sample collection. The mean arterial pressure (MAP) was monitored. Transmission microscopy examination and H&E staining were performed to observe pulmonary structural alterations. Enzyme linked immunosorbent assay (ELISA) was performed to measure the plasma levels of epithelial markers, proinflammatory cytokines, and coagulation-related proteins. Compared with vehicle treatment, Xuebijing administration maintained the MAP in the normal range until 11 h after CLP. Transmission microscopy and H&E staining revealed that Xuebijing administration alleviated alveolar-capillary barrier impairments and lung inflammation in CLP rats. ELISA showed that Xuebijing administration effectively reversed CLP-induced elevations in the plasma levels of epithelial markers endothelin-1 and von Willebrand factor, starting 6 and 8 h after CLP, respectively. Xuebijing administration also significantly abolished CLP-induced rises in circulating proinflammatory cytokines interleukin 6 (IL-6) at 6 h after CLP, IL-1β at 2 and 12 h after CLP, and TNF-α at 2, 4, 6, 8, and 12 h after CLP. In addition, Xuebijing administration strongly reversed CLP-induced alterations in circulating active protein C and tissue-type plasminogen activator, starting 4 h and 2 h after CLP, respectively. Xuebijing ameliorates pulmonary endothelial injury, systemic inflammation, and coagulation dysfunction in early sepsis.