Clinical Hemorheology and Microcirculation - Volume 78, issue 4

Authors: Hodis, Howard N. | Mack, Wendy J. | Meiselman, Herbert J. | Kalra, Vijay | Liebman, Howard | Hwang-Levine, Juliana | Dustin, Laurie | Kono, Naoko | Mert, Melissa | Wenby, Rosalinda B. | Huesca, Emiliano | Rochanda, Leanne | Li, Yanjie | Yan, Mingzhu | St. John, Jan A. | Whitfield, Lora

Article Type: Research Article

Abstract: BACKGROUND: Described to be antithrombotic and antihypertensive, nattokinase is consumed for putative cardiovascular benefit. However, no large-scale, long-term cardiovascular study has been conducted with nattokinase supplementation. OBJECTIVE: To determine the effect of nattokinase on subclinical atherosclerosis progression and atherothrombotic biomarkers. METHODS: In this double-blinded trial, 265 individuals of median age 65.3 years, without clinical evidence of cardiovascular disease (CVD) were randomized to oral nattokinase 2,000 fibrinolytic units or matching placebo. Primary outcome was rate of change in subclinical atherosclerosis measured by serial carotid ultrasound every 6 months as carotid artery intima-media thickness (CIMT) and carotid arterial …stiffness (CAS). Additional outcomes determined at least every 6 months were clinical parameters including blood pressure and laboratory measures including metabolic factors, blood rheology parameters, blood coagulation and fibrinolysis factors, inflammatory markers and monocyte/macrophage cellular activation markers. RESULTS: After median 3 years of randomized treatment, annualized rate of change in CIMT and CAS did not significantly differ between nattokinase supplementation and placebo. Additionally, there was no significant effect of nattokinase supplementation on blood pressure or any laboratory determination. CONCLUSIONS: Results of this trial show that nattokinase supplementation has a null effect on subclinical atherosclerosis progression in healthy individuals at low risk for CVD. Show more

Keywords: Nattokinase, natto, fermented soy, soybeans, fibrinolysis, atherosclerosis, cardiovascular disease, carotid artery intima-media thickness, blood pressure, thrombosis, blood rheology

DOI: 10.3233/CH-211147

Citation: Clinical Hemorheology and Microcirculation, vol. 78, no. 4, pp. 339-353, 2021

Authors: Zhao, Wei | Lu, Ruigang | Yin, Li | Guo, Ruijun

Article Type: Research Article

Abstract: PURPOSE: To explore the application value of SMI scoring assignment method combined with 2017 American College of Radiology (ACR) Thyroid Imaging, Reporting and Data System (TI-RADS) in differentiating benign and malignant thyroid nodules. METHODS: According to the 2017 ACR TI-RADS classification, the enrolled nodules were divided into 3 points group, 4 points group, 5 points group, 6 points group and≥7 points group. The nodules were assigned scores according to the echocity of the nodules and the microvessels detected by SMI and their distribution patterns based on ACR TI-RADS. Accompany with the scores increased or decreased after assignment, the …thyroid nodules were re-grouped. RESULTS: The AUC after the scores assignment is better than before (Z = 3.881, P  < 0.001). The specificity, positive predictive value and accuracy after score assigned are better than those of before (Z = 8.323, P  < 0.001; Z = 8.619, P  < 0.001; Z = 5.345, P  < 0.001), there is no statistical difference in sensitivity before and after score assigned (Z = –0.513, P = 0.60), and the negative predictive value before assigned score is better than that of after (Z = –3.826, P  < 0.001). CONCLUSION: The diagnostic efficacy after scoring was better than that of before. Show more

Keywords: Superb microvascular imaging (SMI), thyroid nodules, ultrasonography, Thyroid Imaging, Reporting and Data System (TI-RADS)

DOI: 10.3233/CH-211235

Citation: Clinical Hemorheology and Microcirculation, vol. 78, no. 4, pp. 355-363, 2021

Authors: Cao, Jiaying | Dong, Yi | Fan, Peili | Mao, Feng | Chen, Kailing | Chen, Rongxin | Huang, Beijian | Cheng, Yaqing | Wang, Wen-Ping

Article Type: Research Article

Abstract: BACKGROUND: Dynamic three-dimensional contrast-enhanced ultrasound (3D-CEUS) with quantitative analysis is available in recent years. It can reduce the quantitative sampling error caused by the inconsistency of different sections in order to evaluate local treatment response of hepatocellular carcinoma (HCC) accurately. OBJECTIVE: To investigate the value of dynamic 3D-CEUS in evaluating the early response to transarterial chemoembolization (TACE) treatment in patients with advanced HCC lesions. METHODS: In this prospective study, both two-dimensional (2D) CEUS and dynamic 3D-CEUS were performed on 40 HCC patients who scheduled for TACE at baseline (T0) and 1–3 days (T1) after treatment. Tumor …microvascular perfusion changes were assessed by CEUS time-intensity curve (TIC) and quantitative parameters. According to contrast-enhanced computed tomography (CT) and magnetic resonance (MR) imaging 1 month after treatment results, patients were divided into responders and non-responders groups. The changes of perfusion parameters of both 2D-CEUS and 3D-CEUS were compared between responders and non-responders groups before and after TACE treatment. RESULTS: Before and after TACE treatment, no significant difference in maximum diameter of HCC lesions between the two groups could be found. There were more significant differences and ratios of perfusion parameters in 3D-CEUS quantitative analysis than in 2D-CEUS. The mutual significant differences and ratios of 2D-CEUS and 3D-CEUS included peak intensity (PI) difference, PI ratio, ratio of area under the curve (A), ratio of area under the wash-out part (AWO) and slope (S) difference. The former 4 corresponding parameters were better on 3D-CEUS than on 2D-CEUS. CONCLUSION: Dynamic 3D-CEUS can be used as a potential imaging method to evaluate early treatment response to TACE in advanced HCC patients. Show more

Keywords: Contrast-enhanced ultrasound, advanced, hepatocellular carcinoma, three-dimensional, treatment response

DOI: 10.3233/CH-201086

Citation: Clinical Hemorheology and Microcirculation, vol. 78, no. 4, pp. 365-377, 2021

Authors: Natrus, Larysa | Ryzhko, Irina | Blazquez-Navarro, Arturo | Panova, Tatyana | Zaychenko, Ganna | Klymenko, Olena | Bondur, Vitalii | Babel, Nina | Gayova, Ludmila

Article Type: Research Article

Abstract: AIM: The aim of this study was to correlate the content of cells with regulatory molecules associated with angiogenesis in wound healing in a rat model of hyperglycemia. We hypothesize that blood neutrophils are the main VEGF source and can stimulate FLT-1 receptor expression, which is the perquisite for efficient neoangiogenesis. MATERIALS AND METHODS: Kinetic studies of the healing dynamics (3, 7, 14, 21 days) of burn wounds on the skin were conducted in white adult male rats. The content of nuclear factor kappa B (NF-κB), vascular endothelial growth factor (VEGF), its receptor (Flt-1) in the regenerated tissue …was analyzed by western blot. Numbers of cells associated with the regenerative process and from peripheral blood (PB) were determined. Additionally a bone marrow (BM) myelogram was conducted. RESULTS: The relative number of peripheral blood (PB) neutrophils was found to be associated with the level of VEGF (R  = 0.708) and Flt-1 (R  = 0.472). The relative number of fibroblasts was also associated with VEGF (R  = 0.562), but not with Flt-1. A negative association was found between the number of neutrophils in the regenerated tissue with VEGF (R  = –0.454) and FLT-1 (R  = –0.665). This confirms our hypothesis, that blood neutrophils are the main VEGF producer that stimulate the expression of the FLT-1 receptor subsequently inducing neoangiogenesis. Furthermore, that under hyperglycemic conditions fibroblasts were highly associated with VEGF (R  = 0.800), while negatively associated with FLT-1 (R  = –0.506). There was a high association between PB neutrophils and newly generated tissue cells: neutrophils (R  = 0.717) and macrophages (R  = 0.622), as well as the association between neutrophils and macrophages (R  = 0.798). This is an indication of chronic inflammation and increased transmigration of blood cells to the burned tissue. CONCLUSION: Blood neutrophils are the main producer of VEGF and stimulate the expression of the FLT-1 receptor. In the context of hyperglycemia the imbalance of receptor and ligand associated with angiogenesis indicates for chronic inflammation: VEGF and FLT-1, which facilitates hypoxia, prevents the physiological course of burn wound healing and may be an important factor in impaired tissue regeneration in diabetes. Show more

Keywords: Angiogenesis, granulocytes, neutrophils, macrophages, connective tissue, burn wound

DOI: 10.3233/CH-201077

Citation: Clinical Hemorheology and Microcirculation, vol. 78, no. 4, pp. 379-390, 2021

Authors: Li, Jia-Xin | Zhang, Hui-Li | Xu, Hui-Xiong | Yu, Song-Yuan

Article Type: Case Report

Abstract: Endometriosis is one of the most common diseases that happen in reproductive women. The main symptoms include ovarian endometrial cyst, pelvic pain, and so on. We report a case of a 23-year-old woman with a refractory long-course ovarian endometrial cyst (OEC). The patient was previously identified to have a hypoechoic mass sized 9.7 cm in diameter on ultrasound (US) in the right ovary and was tentatively diagnosed as OEC in another tertiary hospital, who was then subjected to US-guided cyst sclerotherapy while the procedure was failed since only a very small amount of viscous and sticky fluid can be aspirated. The …patient was then referred to our hospital for further treatment. Pretreat contrast-enhanced ultrasound (CEUS) showed non-enhancement of the mass with a thin cyst wall and a cyst-in-cyst pattern was observed. The possibility of ovarian malignancy was ruled out and the initial diagnosis of OEC was confirmed. The patient was then subjected to US-guided cyst sclerotherapy with lauromacrogol. The interventional procedure was eventful that no fluid was aspirated as what happened in the previous hospital. Thus urokinase was used to dissolve the old, viscious and sticky blood and finally, all the fluid was aspirated. The total consumption of urokinase was 60,000 U. Then lauromacrogol as a sclerosant was injected into the cyst cavity and the cyst wall was flushed repeatedly with lauromacrogol until the aspirated fluid became light red. Finally, 20 mL lauromacrogol was reserved in the cyst and the interventional procedure cost 2 hours. The post-procedure course was uneventful without any discomfort, and the volume reduction rate of the cyst was 54%at 3-month follow-up. The visual analogue scale for the pain decreased from 4 before treatment to 1 after treatment, indicating a successful and effective outcome for the refractory long-course OEC. Show more

Keywords: Contrast-enhanced ultrasound, ovarian endometrial cyst, lauromacrogol, sclerotherapy

DOI: 10.3233/CH-211134

Citation: Clinical Hemorheology and Microcirculation, vol. 78, no. 4, pp. 391-400, 2021

Authors: Caimi, Gregorio | Hopps, Eugenia | Montana, Maria | Urso, Caterina | Carollo, Caterina | Canino, Baldassare | Lo Presti, Rosalia

Article Type: Research Article

Abstract: The goal of this research was to evaluate the plasma concentration of MMP-9 and its tissue inhibitor (TIMP-1) in different clinical conditions. It included several groups of subjects: 31 overweight subjects; 91 obese adults divided into two subgroups according to the BMI value (BMI 30–35 Kg/m2 and BMI > 35 Kg/m2 ); 90 subjects with metabolic syndrome (MS) divided into two subgroups (with and without diabetes mellitus); 100 subjects with preclinical carotid atherosclerosis (PCA) divided according to the number of cardiovascular risk factors and to the insulin resistance degree; 48 subjects with obstructive sleep apnoea syndrome (OSAS) divided according to the apnoea/hypopnea index (AHI); …27 subjects with chronic kidney disease (CKD) on conservative management; 31 subjects with CKD on regular haemodialysis treatment. We have found a significant increase of MMP-9 and TIMP-1 in overweight subjects, in obese adult and in MS subjects. In obese adults, the behaviour of these two parameters was not influenced by the degree of obesity, while in the group of MS subjects both these parameters were clearly influenced by the presence of diabetes mellitus. In subjects with PCA, we observed an increase of MMP-9 associated with a significant decrease of TIMP-1; the same trend was found by subdividing the entire group in accordance with the number of cardiovascular risk factors and with the insulin resistance degree. In subjects with OSAS, we noted an increase in MMP-9 and TIMP-1; this increase was more evident in subjects with OSAS having AHI > 30. In individuals with CKD on conservative and haemodialysis treatment we have found, at baseline, a marked increase in MMP-9 and a significant decrease of TIMP-1. In dialyzed subjects, after a standard dialysis session was noted, a significant increase in MMP-9 was associated with a further decrease in TIMP-1. Show more

Keywords: MMP-9, TIMP-1, obesity, metabolic syndrome, preclinical carotid atherosclerosis, OSAS, CKD

DOI: 10.3233/CH-201094

Citation: Clinical Hemorheology and Microcirculation, vol. 78, no. 4, pp. 401-416, 2021

Authors: Caimi, G. | Urso, C. | Brucculeri, S. | Amato, C. | Carlisi, M. | Lo Presti, R.

Article Type: Research Article

Abstract: We present a cohort of 100 subjects [43 men and 57 women; median age 66.00(25) ] who were tested using carotid ultrasound to identify subclinical carotid atherosclerosis (SCA). We have evaluated the behaviour of whole blood viscosity (WBV) at high (450 s–1 ) and low (0.51 s–1 ) shear rates, plasma viscosity (450–1 ), hematocrit and mean erythrocyte aggregation. When compared to normal control subjects, using the Mann-Whitney test, we observed in SCA patients a significant increase in WBV only. The results were substantial after having divided the SCA subjects according to the cardiovascular risk factors (CRFs) and the degree of …insulin resistance; the research was performed using two surrogate indexes such as TG/HDL-C and TyG. With the division carried out according to CRFs, employing the Kruskal-Wallis test, results show a significant increase in WBV (at high and low shear rates), in plasma viscosity, in erythrocyte aggregation and plasma fibrinogen level. Whereas by dividing them into the median of TG/HDL-C and TyG, we noticed a significant increase in WBV (at high and low shear rates) and in erythrocyte aggregation in the two groups with high TG/HDL-C ratio and with high TyG; having found an increased level of plasma fibrinogen in the latter. The data underlines the role of the main hemorheologic aspects in subclinical carotid atherosclerosis being closely correlated to the CRFs and different degrees of insulin resistance. Show more

Keywords: Subclinical carotid atherosclerosis, hemorheological determinants, traditional cardiovascular risk factors, insuline-resistence, uric acid

DOI: 10.3233/CH-211105

Citation: Clinical Hemorheology and Microcirculation, vol. 78, no. 4, pp. 417-428, 2021

Authors: Zuo, Dongsheng | Yang, Kefeng | Wu, Size

Article Type: Research Article

Abstract: BACKGROUND: The contrast-enhanced ultrasound (CEUS) liver imaging reporting and data system (LI-RADS) is a relative new algorithm for hepatocellular carcinoma (HCC) assessment. OBJECTIVE: To validate the diagnostic efficiency of the intravascular perfusion based CEUS LI-RADS for HCC. METHODS: Archives of 873 patients with focal liver lesions (FLLs) undergoing CEUS were reviewed, and target images were read by two sonologists independently according to the CEUS LI-RADS. The diagnostic performance was calculated and compared. RESULTS: Assessment with reference to CEUS LI-RADS, 87 of 218 FLLs (39.9%) were categorized as LR-5, 131 of 218 FLLs (60.1%) were …categorized as non-LR-5, 19 of 99 HCCs were categorized as non-LR-5, and 7 of 119 non-HCCs were categorized as LR-5. The sensitivity, specificity, AUROC, positive and negative predictive values of CEUS LI-RADS for diagnosing HCC were 80.81%(95%CI: 71.7%–88.0%), 94.1%(95%CI: 88.3%–97.6%), 0.87 (95%CI: 0.82–0.92), 91.9%(95%CI: 84.1%–96.7%), and 85.5%(95%CI: 78.3%–91.0%), respectively. CONCLUSIONS: The diagnostic efficiency of the intravascular perfusion based CEUS LI-RADS for the evaluation of HCCs is very good. Show more

Keywords: Liver, focal liver lesion (FLL), hepatocellular carcinoma (HCC), contrast-enhanced ultrasound (CEUS), liver imaging reporting and data system (LI-RADS)

DOI: 10.3233/CH-211164

Citation: Clinical Hemorheology and Microcirculation, vol. 78, no. 4, pp. 429-437, 2021

Authors: Piao, Jinxiang | Yoo, Chaeyoung | Kim, SunYoung | Whang, Youn-Wha | Shin, Sehyun | Choi, Cheol Ung

Article Type: Research Article

Abstract: BACKGROUND: Analyzing responsiveness to P2Y12 therapy is vital to preventing thrombotic and hemorrhagic complications in patients with cardiovascular diseases. OBJECTIVE: This study evaluates a new Anysis-P2Y12 assay system against VerifyNow-P2Y12 in cardiac patients and analyzes the P2Y12 low-response rates of the two devices with various cutoff values. METHODS: In total, 125 citrated blood samples were collected from cardiac patients referred for a P2Y12 antiplatelet response test. In the Anysis assay, the test result was the migration distance (MD) until the blood flow stops, which is comparable to both P2Y12 reaction units and percent inhibition obtained using …VerifyNow. RESULTS: The MDs without and with P2Y12 were 182±30 and 264±12 mm, respectively (p  < 0.0001). Compared to VerifyNow-P2Y12, the sensitivity and specificity of Anysis-200 were 96.8% and 88.7%, respectively. Cohen’s kappa coefficient between the two devices was 0.761, indicating a high agreement. However, there was an apparent difference in the low-response rate to P2Y12, which was 36.5% for VerifyNow and 5.9% for Anysis. CONCLUSIONS: The performance of the newly developed platelet function assay, Anysis-P2Y12 was equivalent to that of VerifyNow-P2Y12 in terms of sensitivity and specificity. The Anysis-P2Y12 assay may help screen patients with abnormal P2Y12 non-responsiveness. Show more

Keywords: Platelet function, antiplatelet, P2Y12, Anysis, VerifyNow

DOI: 10.3233/CH-211104

Citation: Clinical Hemorheology and Microcirculation, vol. 78, no. 4, pp. 439-448, 2021

Authors: Zhang, Lei | Li, Qiulai | Chen, Yanxia | Zhu, Qiao

Article Type: Research Article

Abstract: BACKGROUND: Oxidized low-density lipoprotein (ox-LDL) could induce endothelial injury and played a vital role in the progression and development of atherosclerosis. This study aimed to investigate the role of Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) in ox-LDL-induced human umbilical vascular endothelial cells (HUVECs) injury and the potential mechanisms. METHODS: Cell proliferation and apoptosis were evaluated by Cell Counting Kit-8 (CCK-8) assay and flow cytometry assay, respectively. The levels of lactate dehydrogenase (LDH), reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide (NO) were detected by corresponding detection kits, respectively. Quantitative real-time PCR (qRT-PCR) was …conducted to measure the expression of OIP5-AS1 or microRNA-30c-5p (miR-30c-5p) in HUVECs. Binding between OIP5-AS1 and miR-30c-5p was predicted through bioinformatics analysis and confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP). Western blot was used to analyze p-IκB, IκB, p-p65 and p65 levels. RESULTS: In HUVECs, exposure to ox-LDL led to a decrease in cell viability and an increase in LDH release and apoptosis with concomitant enhancement of oxidative stress, as evidenced by increased ROS and MDA generation, as well as decreased SOD activity and NO levels, while OIP5-AS1 knockdown or miR-30c-5p upregulation could rescue these effects above. Mechanically, OIP5-AS1 functioned as a sponge of miR-30c-5p. OIP5-AS1-induced injury and apoptosis, oxidative stress and activation of NF-κB pathway were reversed by miR-30c-5p in ox-LDL-treated HUVECs. CONCLUSION: OIP5-AS1 contributed to ox-LDL-treated HUVECs injury by activation of NF-κB pathway via miR-30c-5p. Show more

Keywords: Atherosclerosis, ox-LDL, OIP5-AS1, miR-30c-5p, NF-κB pathway, endothelial injury, oxidative stress injury

DOI: 10.3233/CH-211130

Citation: Clinical Hemorheology and Microcirculation, vol. 78, no. 4, pp. 449-460, 2021