Higher Fibrinogen Research Articles

Fibrinogen to albumin ratio as a powerful predictor of the exaggerated morning blood pressure surge in newly diagnosed treatment-naive hypertensive patients

ABSTRACT Background The exaggerated morning blood pressure surge (MS) is a risk factor for cardiovascular diseases. Inflammation is associated with the pathogenesis of hypertension. We aimed to investigate the association between fibrinogen, albumin, fibrinogen to albumin ratio (FAR), and exaggerated MS, and which of those variables is a better predictor for identifying an exaggerated MS in newly diagnosed treatment-naive hypertensive patients. Material and Methods The study included 249 treatment-naive patients who were newly diagnosed with hypertension in both clinical and ambulatory blood pressure (BP) monitoring measurements. Morning BP was defined as the mean of BPs measured during the first 2 hours after wake-up. The lowest BP was defined as the mean of 3 BP measurements focused on the lowest nighttime computations. The MS was calculated as the morning systolic BP minus the lowest systolic BP. Fibrinogen and albumin levels were measured from venous blood. FAR was obtained by dividing the fibrinogen to the albumin. Results Patients with higher-value MS had a higher fibrinogen, FAR, and a lower albumin than those with low-value MS. MS was positively correlated with fibrinogen and FAR, and negatively correlated with albumin (for all, p < .001). Fibrinogen, albumin, and FAR were independent predictors of exaggerated MS. FAR was a more powerful predictor than fibrinogen (p < .001) and albumin (p = .02) in determining exaggerated MS. Conclusion Patients with exaggerated MS had a higher fibrinogen and FAR, and a lower albumin level than those without exaggerated MS. FAR may be a better predictor than fibrinogen and albumin for determining exaggerated MS.

Clinicopathological Profile of Disseminated Intravascular Coagulopathy (DIC) in Natural Course of Moderate COVID-19 Patients

Background: Timely and accurately identification of thrombotic complications seems to become an important issue in patients suffering from coronavirus disease 2019 (COVID-19). Preliminary reports on critical ill COVID-19 patients include thrombocytopenia, abnormal coagulation tests, and disseminated intravascular coagulation. While the COVID-19 pandemic is spreading worldwide, the progression of DIC in the natural course of COVID-19 remains unpredictable and enigmatic. Methods: Out of a total of 694 COVID-19 inpatients, we selected 332 adults (≥18 - <65 years old) without any comorbidities from twelve hospitals (Wenzhou, China). The patients were divided into mild, moderate and severe groups, depending on the degree of disease severity. According to patient’s onset time of the first symptoms before admission, the natural course of COVID-19 was categorized at 3-day intervals for analysis, as follows: 1-3 days (D1-3), D4-6, D7-9 and D10-14. Demographic, clinical, treatment, and laboratory data were extracted from electronic medical records and compared between groups at different stages of COVID-19 course. Findings: The nature course of COVID-19 can be classified into two or four stages depending on patients with or without pneumonia. Mild patients without pneumonia showed two stages: virus infection stage (day 1-3) and recovery stage (day 4-6). In contrast, moderate and severe patients with pneumonia had four stages: virus infection stage (day 1-3); inflammation stage (day 4-6) characterized by c-reactive protein (CRP) >10 mg/L and fibrinogen >4 g/L; early stage of DIC (day 7-9) characterized by high fibrinogen levels and d-dimer >500 µg/L; and the stage of overt DIC (day 10-14) characterized by platelet >300×109, high fibrinogen and high d-dimer levels. These data showed that natural course of COVID-19 closely linked with the occurrence and progression of DIC might be one of the major causes for the progression of the disease and the occurrence of events. Interpretation: To elucidate the natural course of COVID-19 accompanying the DIC progression can help clinicians quickly and accurately identify the stage of the disease, make the correct diagnosis and treatment, promote patient recovery and survival. Funding Statement: This work was supported by the National Natural Science Foundation of China (grant 81670336) , the Wenzhou Grant for Scientific Talents, Wenzhou Science and Technology Bureau (RX2016003); the Key Research and Development Program of Zhejiang Province (2019C03011); and Special Project for Significant New Drug Research and Development in the Major National Science and Technology Projects of China (2020ZX09201002);Wenzhou Science and Technology Key problem program (ZY2020001); The Key Research and Development Program of Zhejiang Province (2019C03011). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The Ethics Committee of the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University waived the need for a written informed consent.

MON-LB108 Measurement Of Carotid Intima,hepatic Steatosis And Inflammatory Markers In Obese Children

Measurement of carotid intima,hepatic steatosis and inflammatory markers in obese children. Elevated levels of inflammatory factors and increased mean intimal carotid thickness (IMT) would increase the risk of atherothrombotic events and contribute to the progression of cardiovascular disease in obese children. Objectives: Evaluate inflammatory factors, metabolic syndrome and non-alcoholic liver steatosis and carotid IMT as an early cardiovascular risk marker. Patients and methods: Descriptive cross-sectional exploratory study. Consider 41 obese children both sexes between 6- 12 years old. Evaluated: anthropometry and determinations of lipid and liver profile, blood glucose, insulin, HOMA, ultrasensitive CRP, fibrinogen. Hepatic ultrasound and measurement of carotid IMT with ESAOTE Mylab 50 Exdicion equipment. . Results: From 41 studied patients, 57% were female. 51% presented MS and 68% elevated triglycerides. CRP> 1 was found in 71% of cases. Hepatic steatosis was observed in 60%, which only 10% had altered transaminases. 12% presented high fibrinogen. Patients with MS had a significant positive difference in the IMTCC (X = 0.41 ± 0.12; p 0.024), HDL (X 37.89 ± 1.72; p 0.004) triglycerides (X 149.42 ± 10.69; p 0.002) in relation to patients without MS. Conclusion: CRP is an inflammatory risk factor associated with elevated BMI and MS. There was a higher prevalence of MS in our study. The increase in the average intimal thickness is significantly related to the presence of MS and RCP>1. The determination of marker molecules of an inflammatory state and measurement of carotid IMT would contribute to the implementation of strategies to prevent cardiovascular, hepatic and metabolic risk since childhood.

Assessment of the reliability and validity of a novel point-of-care fibrinogen (F-Point) device against an industry standard at fibrinogen levels >2 g/L in non-haemorrhage scenarios

IntroductionA diagnostic accuracy study assessing the reliability and validity of a novel plasma fibrinogen point-of-care (F-Point) device compared with the von Clauss method of assay. MethodsForty-one women presenting for elective caesarean delivery and 43 non-pregnant female patients presenting for elective gynaecological surgery were recruited to assess agreement at normal fibrinogen levels (elective gynaecological cohort) and high fibrinogen levels (elective caesarean section cohort). Validity was assessed by comparing the F-Point results with the gold standard of von Clauss fibrinogen assay performed on the ACL Top 500. Reliability (test–retest) and validity were assessed using the intraclass correlation to control for operator variance (two-way random absolute agreement method), presented as intra class correlation coefficients (ICCs) and 95% confidence interval, and Bland-Altman analysis, presented as mean bias and 95% limits of agreement and coefficient of variation (COV). ResultsThe results demonstrated a high test–retest reliability demonstrated in the paired F-Point measurements with an intraclass correlation coefficient (ICC) of 0.95, a bias of 0 (-00.69 to 0.69) and a COV of 9%. Similarly, there was acceptable agreement demonstrated between F-Point and von Clauss assay with an ICC of 0.91, a bias of −0.1 (−0.96 to 0.75) and a COV of 11%. ConclusionsOur novel plasma fibrinogen point-of-care device has been shown to be reliable and valid when testing fibrinogen levels as low as 2 g/L. Future studies investigating the correlation at lower fibrinogen levels, for example during haemorrhage and in patients with coagulopathies, are required.

Coagulation test changes associated with acute normovolemic hemodilution in cardiac surgery.

Patients undergoing cardiac surgery requiring cardiopulmonary bypass (CPB) are at risk for coagulopathy and bleeding requiring blood product transfusion. Acute normovolemic hemodilution (ANH) is a blood conservation technique shown to reduce transfusion and bleeding associated with cardiac surgery. Despite numerous advantages, little is known about the effect of ANH on coagulation testing. Prospective observational study, 80 patients (40 controls, 40 ANH) undergoing cardiac surgery requiring CPB. Blood for coagulation testing (hemoglobin, platelet count, prothrombin time/International Normalized Ratio [PT/INR], activated partial thromboplastin time [aPTT], fibrinogen, and kaolin thromboelastography [TEG]) was collected 5 minutes after protamine (Time 1), and following ANH reinfusion (or 30 minutes after Time 1) in controls (Time 2). Patients undergoing ANH had a significantly lower aPTT (-1.4 seconds 95% CI [-2.7, 0.0]; P = .044) and higher fibrinogen (+13 mg/dL [+1, +26]; P = .040) between Time 1 and Time 2 compared to controls. Additionally, the change in hemoglobin between Time 1 and Time 2 was significantly increased in the ANH group (+0.4 [+0.1, +0.8]; P = .024). The study also demonstrated a normalization of the platelet count, PT/INR, aPTT, and TEG values between Time 1 and Time 2 in control patients. In patients undergoing cardiac surgery requiring CPB, ANH results in significant improvements of aPTT, fibrinogen and hemoglobin values; however, the true clinical significance is questionable. In the absence of ongoing surgical bleeding, there appears to be normalization of coagulation tests (excluding fibrinogen) following CPB.

The factor XIII‐A Val34Leu polymorphism decreases whole blood clot mass at high fibrinogen concentrations

BackgroundFactor XIII (FXIII) promotes fibrin crosslinking and red blood cell (RBC) retention in clots. The FXIII‐A polymorphism, Val34Leu, is associated with protection against venous thrombosis. This effect is hypothesized to result from fibrinogen concentration‐dependent changes in fibrin structure. Effects of the FXIII‐A Val34Leu polymorphism in whole blood clots have not been investigated. AimCharacterize effects of FXIII‐A Val34Leu polymorphism and fibrinogen on whole blood clots. MethodsWe isolated platelet‐poor plasmas from human donors (FXIIIVal/Val, FXIIIVal/Leu, FXIIILeu/Leu), reconstituted plasmas with platelets and RBCs, and triggered clotting. We assessed contributions of gender, age, clotting times, thrombin generation, FXIII activity, FXIII‐A Val34Leu polymorphism, and fibrinogen to clot mass. We also reconstituted FXIII‐depleted plasma with platelets, RBCs, and purified FXIIIVal/Val or FXIIILeu/Leu, varied fibrinogen, and characterized effects on clot mass. ResultsClot mass was associated with age, fibrinogen, prothrombin time, and thrombin generation. Clots reconstituted with plasmas from individuals with FXIII‐AVal/Val and FXIII‐AVal/Leu did not differ in mass from clots with FXIII‐ALeu/Leu. However, clots containing a 34Val allele demonstrated a fibrinogen concentration‐dependent increase in mass, whereas clots with homozygous 34Leu did not. In plasmas with high fibrinogen, mass was higher for clots with 34Val alleles compared with clots with homozygous 34Leu. In clots reconstituted with purified FXIII, increasing fibrinogen enhanced clot mass in the presence of 34Val, but decreased mass in the presence of 34Leu. ConclusionsFXIII 34Leu mitigates the effect of elevated fibrinogen on whole blood clot mass. The Val34Leu polymorphism may protect against venous thrombosis by reducing clot mass.

Abnormal left ventricular global strain during exercise-test in young healthy smokers

Background. It is unknown how much precociously the cigarette smoking (CS) may compromise the integrity of the cardiovascular (CV) system. Myocardial function can be routinely assessed by conventional echocardiography, but abnormalities are only detected when somewhat a remodelling has already occurred. These limitations could be overcome by strain imaging. Methods. We evaluated whether young smokers with normal left ventricular (LV) geometry, wall motion and ejection fraction may present abnormalities in myocardial deformation, both at rest and during physical effort. We selected 50 young smokers with no additional CV risk factors, and 60 non-smokers to undergo a standardized exercise-test. Consistently, we evaluated the CV adaptation to exercise by both conventional echocardiography and speckle-tracking analysis (2D-STE). Results. We found no difference between smokers and controls regarding baseline characteristics; as expected, smokers presented with lower HDL-cholesterol (p < 0.005), and higher fibrinogen, C-reactive protein (CRP), and interleukin-6 (p < 0.001). Conventional echocardiography parameters were not different between groups, while we detected a different behaviour of global longitudinal strain (GLS), global circumferential strain (GCS) and twist by 2D-STE during exercise-test. Indeed, GLS, GCS and twist behaved differently during exercise test in smokers with respect to controls. We found an association between CS, inflammation and LV mechanics changes uncovered by physical effort, and regression analysis confirmed that the intensity of the exposure to cigarette smoking, together with the inflammatory status (CRP, fibrinogen and Il-6) plasma levels, drive this impairment. Conclusions. We confirm strain imaging (2D-STE) as a very useful tool to identify early changes in cardiac mechanics, as adaptation to exercise; our findings may reflect a very precocious functional abnormality in active smokers, likely long before structural damage occurs.

The Incidence of Venous Thromboembolism and Impact on Survival in Hodgkin Lymphoma

BackgroundThrombosis increase the acute and long-term morbidity and mortality in malignancy patients. We analyzed venous thromboembolism (VTE) in patients with Hodgkin lymphoma, the impact of VTE on survival, predisposing factors for VTE, and predicting value of Khorana and ThroLy score models. Patients and MethodsWe included 150 adult patients with Hodgkin lymphoma between January 2010 and 2018 at our university hospital. ResultsVTE was observed in 31 patients (20.7%). The types of VTE were 18 upper and 3 lower extremity deep vein thrombosis and 10 pulmonary embolism (1 with lower extremity deep vein thrombosis). Twenty-nine patients developed VTE during the treatment with a median time of episode as 5 months. In logistic regression analysis, a body mass index of >32 kg/m2, high fibrinogen levels, initial thrombocytosis and leukocytosis, splenic and extranodal involvement, presence of a central venous line, advanced stage, line of treatment status of thromboprophylaxis, VTE timing, and better Eastern Cooperative Oncology Group performance scores were observed to be related with VTE. Kaplan Meier survival analysis showed a negative impact of VTE on survival. Khorana and ThroLy risk assessment models were found predictive for VTE (P = .000 and P = .003, respectively), although only ThroLy score was associated with the survival. ConclusionThromboprophylaxis and precautions for VTE in patients with Hodgkin lymphoma according to validated risk assessment models can improve prognosis and quality of life owing to the impact of VTE on survival in the study.

Abstract P456: The Association Between Clonal Hematopoiesis Of Indeterminate Potential And Inflammatory Biomarkers Among Chronic Kidney Disease Patients

Introduction: Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related disorder associated with increased risk of atherosclerotic cardiovascular disease (ASCVD). Mechanistic studies of CHIP implicate inflammatory pathways underlying this relationship. Although inflammation is a well-established component of chronic kidney disease (CKD), linked to both CKD progression and ASCVD in CKD patients, CHIP has not been investigated in a CKD setting. Objective: To estimate the prevalence of CHIP in patients with CKD and to examine the cross-sectional associations between CHIP and biomarkers that were previously related to CKD progression and ASCVD among CKD patients. Methods: The current study was conducted among 598 Chronic Renal Insufficiency Cohort (CRIC) study participants with whole-exome sequencing data and baseline measures of fibrinogen, interleukin (IL)-6, serum albumin, and tumor necrosis factor-α. CHIP was detected from sequencing data using MuTect2. CHIP was defined as the presence of a somatic hematologic malignancy-associated mutation with a variant allele frequency (VAF) of at least 2%. CHIP was also categorized ordinally by clone size as no CHIP, small CHIP clone (VAF&lt;10%), and large CHIP clone (VAF ≥10%). Ordinal logistic regression was used to test associations of CHIP with each biomarker in age- and multivariable-adjusted models. Multivariable models adjusted for age, sex, ancestry, body mass index, estimated glomerular filtration rate, systolic blood pressure, low-density lipoprotein cholesterol, fasting plasma glucose, and blood pressure, lipid, and glucose lowering medications. Results: CHIP was detected in a total of 28 individuals from the WES study (4.7%). Among those 70 years of age and older, we detected a CHIP prevalence of nearly 16%. As expected, participants with CHIP were older than those without CHIP (mean age: 67 and 58 years, respectively; P&lt;0.0001). Other demographic and clinical variables were similar between groups . Age-adjusted models showed strong associations between CHIP and both fibrinogen and IL-6 with odds ratios of 2.49 (95% CI: 1.09, 5.71) and 2.45 (95% CI: 1.05, 5.72), respectively. After multivariable adjustment, only fibrinogen remained associated with CHIP with an odds ratio of 4.70 (95% CI: 1.69, 13.0). Consistent with these findings, there was a strong dose-dependent association between CHIP clone size and fibrinogen in multivariable adjusted analyses (P for linear trend=0.009). Compared to those without CHIP, odds ratios for higher fibrinogen tertile were 3.0 (95% CI: 0.84, 11.3) and 4.7 (95% CI: 1.29, 16.7) among those with small and large CHIP clone sizes, respectively. Conclusions: CHIP prevalence was higher among CKD patients in the current study compared to previous estimates from the general population. Furthermore, a strong, dose-dependent association between CHIP and fibrinogen was identified.

Combination of Preoperative Plasma Fibrinogen and Neutrophil-to-Lymphocyte Ratio (the F-NLR Score) as a Prognostic Marker of Locally Advanced Rectal Cancer Following Preoperative Chemoradiotherapy.

Coagulation and inflammation play important roles in tumor progression. This study aimed to explore the prognostic impact of combined analysis of fibrinogen and neutrophil-to-lymphocyte (NLR) ratio (F-NLR score) in locally advanced rectal cancer (LARC) receiving preoperative chemoradiotherapy (pCRT) and radical surgery. Totally 317 patients were included. X-tile analysis was used to determine the optimal cutoff values of preoperative fibrinogen and NLR. F-NLR scores were defined as 2 (both high fibrinogen and NLR), 1 (one of these abnormalities), or 0 (neither abnormality). Time-dependent ROC analysis was used to evaluate the predictive accuracy of fibrinogen, NLR, and F-NLR score. Cox regression analysis was performed to evaluate the prognostic impact of the F-NLR score. A predictive nomogram for disease-free survival (DFS) was developed and validated internally. One hundred and seventeen (36.9%), 156 (49.2%), and 44 (13.9%) patients had F-NLR score of 0, 1, and 2, respectively. Higher F-NLR score was associated with poorly differentiated tumors, deeper tumor invasion, lymph node metastasis, and more advanced pTNM stage (all P < 0.05). The 5-year OS rates in the F-NLR 0, 1, and 2 groups were 93.6%, 87.3%, and 68.4%, respectively (P < 0.001), while the 5-year DFS rates were 91.8%, 76.8%, and 56.1%, respectively (P < 0.001). Cox regression analysis demonstrated that F-NLR score (F-NLR 1, HR = 2.021, P = 0.046; F-NLR 2, HR = 3.356, P = 0.002), pTNM stage III (HR = 3.109, P = 0.009), and circumferential resection margin (CRM) involvement (HR = 3.120, P = 0.021) were independently associated with DFS. A nomogram for DFS was developed (C-index 0.708). F-NLR score is a promising predictor for disease recurrence in LARC patients after pCRT.

Fibrinogen and Low-Density Lipoprotein (LDL) Cholesterol Levels with the Occurrence of Acute Myocardial Infarction: Is it Correlated?

Fibrinogen is considered as a risk factor associated with cardiovascular disease, especially acute myocardial infarction (AMI). The role of increasing levels of fibrinogen in the thrombosis shows that there is an effect that causes the pathway to form a thrombosis. Increased plasma high-density lipoprotein (LDL) cholesterol can also induce the development of atherosclerosis and is associated with AMI events. This study was an observational analytic study using a cross-sectional approach, carried out from August-November 2015 in Dr. Soetomo Hospital Surabaya. Samples were 67 subjects who fulfilled inclusion and exclusion criteria. A total of 67 subjects were assessed, 47 (70.15%) were males, and 20 (29.85%) were females. The mean age was 5.07 ± 11.02 years old, ranging from 30 to 85 years. AMI was diagnosed in 49 patients (26.87%). Management of AMI patients consisted of conservative medical therapy (42.86%), thrombolytic therapy (18.37%) and PPCI (38.77%). The statistical analysis revealed significant differences in plasma fibrinogen and LDL cholesterol levels between the AMI patient group and the control group. There was a significant correlation between fibrinogen levels and LDL cholesterol levels. Fibrinogen and LDL cholesterol levels are correlated with AMI risk factors. In subjects with AMI, there were higher fibrinogen and LDL cholesterol levels compared to non-AMI subjects.

Abstract TP128: Determinants of Hemorrhagic Transformation After Emergent Extracranial Internal Carotid Artery Stenting for Tandem Occlusions

Background and Purpose: Extracranial internal carotid artery (ICA) lesion in the setting of tandem occlusions is a therapeutic challenge, and hemorrhagic transformation (HT) is one of the leading causes of poor clinical outcome. We aimed to determine determinants of HT for tandem occlusions undergoing emergent extracranial ICA stenting during endovascular treatment (EVT). Methods: We performed a prospective, observational cohort study of consecutive patients with non-cardioembolic ischemic stroke due to tandem occlusion who underwent EVT with extracranial ICA stent placement during the procedure from April 2013 to June 2019 in a single stroke center. We compared clinical (vascular risk factors, previous antiplatelet treatment, and IV rtPA), radiological (ASPECTS at admission and in-stent thrombosis at 24 hours) and serological (platelet count, fibrinogen, total cholesterol, HDL-cholesterol, and LDL-cholesterol) parameters according to the presence of HT in 24 hours CT-scan. Results: One-hundred and eight patients were included: 78.7% were men, mean age 68.5±14.3 years, median time from symptoms onset to treatment was 220 (150-337.5) minutes, median ASPECTS at admission was 9 (8-10). Eighty-six (79.6%) patients presented an extracranial ICA occlusion, and 22 (20.4%) a high-grade (&gt;50%) stenosis. In 88 (81.5%) patients the etiology of extracranial ICA lesion was ateroma, and in 20 (18.5%) was a dissection. Intravenous rtPA was administered in 47 (43.5%) patients. Successful recanalization (mTICI ≥2b) was achieved in 83 (76.9%) patients, and extracranial ICA recanalization in 108 (100%) patients. Type 2 diabetes (OR 1.5, 95% CI 1.1-3.5), higher fibrinogen levels (OR 4.6, 95% CI 1.6-12.9), and ASPECTS &lt;7 at admission (OR 2.1, 95% IC 1.1-5.1) were found as independent predictors of HT in multiple logistic regression analysis. Conclusions: Patients with a non-cardioembolic ischemic stroke due to tandem occlusion who present type 2 diabetes, higher fibrinogen levels, or ASPECTS &lt;7 at admission are at high risk of HT. In these particular cases, it might be useful to stent with a stent that does not need double antiplatelet treatment immediately after the procedure.

Long-term lipoprotein apheresis in the treatment of severe familial hypercholesterolemia refractory to high intensity statin therapy: Three year experience at a lipoprotein apheresis centre.

Severe familial hypercholesterolemia (FH) individuals, refractory to conventional lipidlowering medications are at exceptionally high risk of cardiovascular events. The established therapeutic option of last choice is lipoprotein apheresis (LA). Herein, it was sought to investigate the clinical usefulness of LA in a highly selected group of severe heterozygous FH (HeFH), as recently described by the International Atherosclerosis Society (IAS), for their efficacy in lipid reduction and safety. Efficacy and safety of LA were investigated in 318 sessions of 7 severe HeFH females with cardiovascular disease, over a mean period of 26.9 ± 6.5 months. Relative reduction of low density lipoprotein cholesterol (LDL-C) ≥ 60%, clinical complications and vascular access problems were evaluated and compared between the direct adsorption of lipoproteins (DALI) and lipoprotein filtration (Membrane Filtration Optimized Novel Extracorporeal Treatment [MONET]). Additionally, lipoprotein (a) [Lp(a)], total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), triglycerides (TG) and fibrinogen concentrations were investigated. The relative reduction of LDL-C, TC, TG and Lp(a) were 69.4 ± 12.9%, 59.7 ± 9.1, 51.5 ± ± 14.2% and 71.3 ± 14.4%, respectively. A similar efficacy was found in both systems in LDL-C removal. DALI system led to larger depletions of Lp(a) (80.0 [76-83]% vs. 73.0 [64.7-78.8]%; p < 0.001). The frequency of clinical side effects and vascular access problems were low (8.5%). Long-term LA in severe HeFH individuals is safe and efficiently reduces LDL-C and Lp(a). Higher efficacy of the DALI system than MONET in Lp(a) removal may indicate the need for individualized application of the LA system in severe HeFH individuals.

High Preoperative Plasma Fibrinogen Independently Predicts a Poor Prognosis in Patients with Nonmetastatic RCC.

Background: This study aims to determine the relationship between preoperative plasma fibrinogen levels and the prognosis of patients with nonmetastatic renal cell carcinoma (RCC), including overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS).Methods: We retrospectively analysed the clinical data and prognostic information of 1194 nonmetastatic RCC patients who received radical nephrectomy or nephron-sparing surgery between 2005 and 2015 at our institution. Serum was collected for fibrinogen detection in the week prior to curative operation, and prognostic information was regularly collected by specially trained personnel. The cut-off value of the preoperative plasma fibrinogen level was defined by receiver operating characteristic (ROC) analysis. The chi-square test was used to analyse the association between preoperative fibrinogen level and clinical characteristics. Kaplan-Meier analysis was used to calculate survival curves, and significant differences were determined by the log-rank test. Other significant prognostic factors were evaluated by the Cox multivariate proportional hazard model.Results: The median follow-up period after radical or partial nephrectomy was 42.4 months (ranging from 0.433 to 146.37 months). The optimal preoperative plasma fibrinogen concentration was 3.975 g/L. The preoperative fibrinogen level was significantly associated with age, pathological T stage, sarcomatoid differentiation, necrosis and vein tumour thrombus (all p<0.05). High plasma fibrinogen levels were related to poor prognosis in terms of OS (p<0.001), CSS (p<0.001) and PFS (p<0.001). Multivariate analysis showed that the preoperative fibrinogen level remained an independent prognostic factor for OS (HR: 3.22, 95%CI: 1.87-5.55, p<0.001), CSS (HR: 4.12, 95%: 2.15-7.89, p<0.001) and PFS (HR: 3.137, 95%CI: 2.17-4.53, p<0.001).Conclusions: High preoperative plasma fibrinogen level is an independent negative prognostic factor for OS, CSS and PFS in patients with non-metastatic RCC. Preoperative plasma fibrinogen could be an ideal indicator for evaluating the outcomes of postoperative patients with nonmetastatic RCC.

Socioeconomic status and cardiovascular risk factors in young adults: a cross-sectional analysis of a Brazilian birth cohort.

In high-income countries, persons of high socioeconomic status (SES) have a lower cardiovascular risk. However, in middle and low-income countries, the results are controversial. To evaluate the association between family income and cardiovascular risk factors in young adults. A total of 2,063 individuals of a birth cohort initiated in 1978/79 in the city of Ribeirão Preto, Brazil, were evaluated at age of 23/25 years. Cardiovascular risk factors (hypertension, sedentary lifestyle, smoking, low high-density lipoprotein (HDL)-cholesterol, high low-density lipoprotein (LDL)-cholesterol, high fibrinogen, insulin resistance, diabetes, abdominal and total obesity, and metabolic syndrome) were evaluated according to family income. Income was assessed in multiples of the minimum wage. Simple Poisson regression models were used to estimate the prevalence ratios (PR) with robust estimation of the variance. High-income women showed lower prevalences of low HDL-cholesterol (PR = 0.47), total obesity (PR = 0.22), abdominal obesity (PR = 0.28), high blood pressure (PR = 0.28), insulin resistance (PR = 0.57), sedentary lifestyle (PR = 0.47), metabolic syndrome (PR = 0.24), and high caloric intake (PR = 0.71) (p < 0.05). High-income men showed lower prevalences of low HDL-cholesterol (PR = 0.73) and sedentarism (PR = 0.81) (p < 0.05). These results may be explained by the fact that high-income women pay more attention to healthy habits and those with the lowest family income are least likely to access health services resources and treatments. Women were in the final phase of the epidemiologic transition, whereas men were in the middle phase.

Contribution of Streptokinase-Domains from Groups G and A (SK2a) Streptococci in Amidolytic/Proteolytic Activities and Fibrin-Dependent Plasminogen Activation: A Domain-Exchange Study

Background:SK, a heterogeneous PA protein from groups A, C, and G streptococci (GAS, GCS, GGS, respectively) contains three structural domains (SKα, SKβ, and SK). Based on the variable region of SKβ, GAS-SK (ska) are clustered as SK1 and SK2 (including SK2a/SK2b), which show low and high FG-dependent Plg activation properties, respectively. Despite being co-clustered as SK2a, GCS/GGS-SK (skcg) variants display properties similar to SK1. Herein, by SKβ exchange between GGS (G88) and GAS-SK2a (STAB902) variants, the potential roles of SK domains in amidolytic/proteolytic activity and FG-bound-Plg activation are represented. Methods:Two parental SKG88 and SKSTAB902 genes were cloned into the NdeI/XhoI site of pET26b expression vector. The two chimeric SKβ-exchanged constructs (SKC1: αG88-βSTAB-γG88 and SKC2; αSTAB-βG88-γSTAB) were constructed by BstEII/BsiWI digestion/cross-ligation in parental plasmids. SK were expressed in E. coli and purified by Ni-NTA chromatography. PA potencies of SK were measured by colorimetric assay. Results:SDS-PAGE and Western-blot analyses confirmed the proper expression of 47-kDa SK. Analyses indicated that the catalytic efficiency (Kcat/Km) for amidolytic and proteolytic activity were less and moderately dependent on SKβ, respectively. The increase of FG-bound-Plg activation for SKSTAB902/SKC1 containing SK2aβ was around six times, whereas for SKG88/SKC2 containing skcgβ, it was four times. Conclusion:Although SKβ has noticeable contribution in FG-bound-Plg activation activity, it had minor contribution in fibrin-independent, amidolytic activity. These data might be of interest for engineering fibrin-specific versions of SK.

Effect of tranexamic acid on symptomatic venous thromboembolism in patients undergoing primary total knee arthroplasty

IntroductionThis study aimed to investigate the effect of tranexamic acid (TXA) with sequential routine anticoagulation on postoperative symptomatic venous thromboembolism (VTE) in patients undergoing primary total knee arthroplasty (TKA).Material and methodsThis was a prospective study with randomized trials. From January 2013 to May 2015, 1880 patients undergoing primary TKA were enrolled in this study. Seven hundred and twenty patients who received TXA injection were included in the TXA group while 1160 patients who received placebo injection were included in the control group. Patients in the TXA group were treated with intravenous TXA or topical intravenous TXA, and all received sequential routine anticoagulation 12 h after the operation. We extracted data of patients’ sex, age, primary diagnoses, and comorbidities that could potentially affect the prevalence rate of VTE. To discuss the risk factors of symbolic VTE, comparisons were made within the TXA group between patients with symbolic VTE and non-symbolic VTE. Logistic regression analysis was performed to analyze the concurrent effects of various factors on the prevalence rate of postoperative VTE.ResultsThigh perimeter was not closely associated with TXA injection. Within the TXA group, 24 (3.3%) patients had perioperative symptomatic VTE, 16 (2.2%) deep vein thrombosis (DVT) and 8 (1.1%) pulmonary embolism. High body mass index (BMI), low fibrinogen (Fbg) and simultaneous bilateral TKA were significant risk factors in both univariate analysis and multivariate analysis.ConclusionsIncreased BMI, low Fbg, and simultaneous bilateral TKA could act as risk factors for postoperative symptomatic VTE treated with TXA.

Demographic, clinic, and genetic characteristics in 149 children diagnosed with familial mediterranean fever

Familial Mediterranean fever (FMF) is a hereditary disease characterized by recurrent attacks of fever, peritonitis, pleuritis and/or synovitis. In this study, we retrospectively evaluated demographic, clinical findings, and genetic features in 149 children (63 male/86 female) with FMF. The mean age of the patients at the time of diagnosis was 6.44 ± 3.21 years. A positive family history for FMF was present in 26%, and 8% of the patients had consanguinity between the parents. The frequency of family history of FMF was found to be higher in patients diagnosed under 10 years of age (p=0.038). Frequencies of the most frequent symptoms observed in cases during episodes were abdominal pain (95%), fever (68%), and arthralgia/arthritis (23%). Genetic analysis revealed that 16% of the patients had homozygous mutations, 32% had heterozygous mutations, and 38% had compound heterozygous mutations, while no mutations were detected in 21 (14%). There were mutant genes in 218 alleles, the most frequently observed were R202Q (48%), M694V (24%), and E148Q (17%). Patients with non-R202Q compound heterozygous mutation had higher frequency of high fever, CRP (C-reactive protein) levels, and fibrinogen levels during the episodes (p=0.006, p=0.001, and p=0.042, respectively). Thus, our study showed that R202Q mutation appeared to have no significant disease-causing and clinical effects, while mutations at exon 10 were associated with increased severity of symptoms as well as elevated levels of acute phase reactants. Further studies with larger FMF populations may shed more light on the role of these mutations in the pathogenesis of FMF.

Enhanced pro-inflammatory response and higher mortality rates in geriatric trauma patients.

Age has been associated with increased morbidity and mortality after traumatic injury. Disregarding trauma-related factors, this may be caused by the diminished ability to cope with stressors due to limited reserve, the so-called frailty. Inflammation is assumed to promote frailty, and thus, pro-inflammatory markers may constitute as being predictive factors in geriatric trauma patients (TP). Here, we analyzed the influence of age on systemic inflammatory markers and outcome parameters in TP. 204 TP with injury severity score (ISS) ≥ 16 were included and grouped to younger vs. geriatric, defining an age of 65 as cut-off. ISS, vital signs, physiological parameters, stay at the intensive-care unit (ICU) or in-hospital, and outcome parameters were analyzed. Systemic fibrinogen, interleukin (IL)-6, and IL-10 levels were determined upon admission. A p value < 0.05 was considered statistically significant. 43 geriatric and 161 younger TP were included. ISS (24.19 ± 9.59 vs. 26.93 ± 9.68) was comparable between both groups. Abbreviated Injury Scale (AIS) ≥ 3 of head trauma was more prevalent in geriatric TP (74.42 vs. 64.59%). In both groups, there were significantly more male than female patients; however, this disparity was significantly more distinct in younger TP. Geriatric group showed significantly lower shock indices, higher fibrinogen, and lower IL-10 levels (all p < 0.05). A significant spearman´s rank correlation with age was found for fibrinogen (positive correlation, r = 0.364, p < 0.05), and for IL-10 (negative correlation, r = - 0.168, p < 0.05). In-hospital mortality was significantly increased in geriatric TP. An enhanced inflammatory response is associated with higher mortality rates in geriatric trauma patients.

Combination of preoperative fibrinogen and neutrophil to lymphocyte ratio is a predictive prognostic factor in esophageal squamous cell carcinoma systematic review

Objective To explored the clinical value of preoperative fibrinogen and neutrophil to lymphocyte ratio (NLR) in patients with esophageal squamous cell carcinoma (ESCC) in this study. Methods 327 patients undergoing ESCC radical surgery was performed to evaluate prognostic factors for overall survival (OS) by univariate and multivariate COX regression analyses. The optimal cut-off values for fibrinogen and NLR were 3.09 g/L and 1.89, respectively. The fibrinogen and NLR (F-NLR) scoring criteria were defined according to the cut-off criteria. High fibrinogen (≥3.09 g/L) and high NLR (≥1.89) were defined as 2 points, patients with high fibrinogen or high NLR were defined as 1 point, and neither hyperfibrinogen or high NLR scored 0 points. Results The OS of patients with high fibrinogen ESCC was significantly poor than patients with low fibrinogen (31.4% vs. 63.3%, P<0.01), while the OS of patients with elevated NLR was also significantly poor than patients with low NLR (40.4% vs. 50.3%). The F-NLR score was significantly correlated with tumor size (P<0.01) and pathological stage (P<0.01). The 5-year OS rates for F-NLR score groups 0, 1, and 2 were 69.1%, 42.6%, and 31.9%, respectively, there were significant differences between subgroups (P<0.01). Multivariate analysis showed that tumor size (P<0.01), pathological stage (P<0.01), and F-NLR (P<0.01) were independent prognostic factors for OS. Conclusion Preoperative F-NLR score can be used as an independent prognostic indicator for ESCC patients. Key words: Esophageal squamous cell carcinoma; Fibrinogen; Platelet to lymphocyte ratio; Prognostic indicator