Clinical Hemorheology and Microcirculation

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ISSN / EISSN : 1386-0291 / 1875-8622
Published by: IOS Press (10.3233)
Total articles ≅ 2,627
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Ashna George, Chenna Deepika, Ganesh Mohan, Riya, Vinu Rajendran, Shamee Shastry, Jayaraj Mymbilli Blarakrishnan, Shwethapriya Rao
Clinical Hemorheology and Microcirculation, pp 1-6; https://doi.org/10.3233/ch-221514

Abstract:
BACKGROUND: The assessment of ADAMTS13 factor activity and inhibitor levels was conducted in severe COVID-19 patients as an observational study. RESULTS: A total of 14 patients were included and the average ADAMTS13 activity level at the time of admission was 28.54±30.74% (range 1.83–86.67%) which was reduced compared to controls (88.09±14.77). Nine patients had reduced ADAMTS13 factor activity (<40%) and 77.7% among them had severe deficiency (15 IU/mL) only in two patients and an overall mean value was 8.15±5.8. Elevated D-Dimer and length of hospital stay had significant correlation with ADAMTS13 activity (–0.247 and 0.306 respectively). No features of thrombotic microangiopathy were observed and hence no plasma exchange was performed. CONCLUSION: Reduced ADAMTS13 factor activity without inhibitor development may give a clue to the disease progress in COVID19.
Kun Wang, Yi Dong, Hong Han, Jiaying Cao, Jingwen Bao, Wen-Ping Wang
Clinical Hemorheology and Microcirculation, pp 1-12; https://doi.org/10.3233/ch-221511

Abstract:
OBJECTIVE: This study aimed to evaluate the diagnostic performance of two-dimensional shear wave elastography (2D-SWE) with a propagation map in evaluating the degree of hepatic fibrosis in patients with liver tumors before resection. METHODS AND MATERIALS: From January 2020 to April 2021, 128 patients with liver tumors were prospectively enrolled, including 20 benign liver tumors and 108 malignant liver tumors. 2D-SWE with a propagation map technology was used to measure the stiffness of liver parenchyma 2 cm away from the tumor. The median value of five measurements was used in this study. The stage of hepatic fibrosis was graded in accordance with Scheuer standard. Spearman correlation was used to analyze the correlation between liver fibrosis stage and the liver stiffness. Univariate and multivariate linear regression analyses were used to determine significant affecting factors for liver stiffness value. The diagnostic performance of 2D-SWE with a propagation map in predicting fibrosis stage was evaluated by receiver operating characteristic curve analysis. RESULTS: The median liver stiffness value in patients with benign liver tumors was lower than that in patients with malignant liver tumors (6.0 kPa vs. 9.4 kPa, p < 0.05). The median liver stiffness values in patients with primary liver cancer were higher than that in patients with benign liver tumors and other types of malignant liver tumors (9.6 kPa vs. 6.0 kPa, p < 0.05). The liver stiffness measured by 2D-SWE was highly correlated with the fibrosis stage confirmed by postoperative pathology (r = 0.834, p < 0.05). For the liver stiffness value, PLT,TB,ALB and fibrosis stage are significantly associated with liver stiffness. The median liver stiffness values in stages S0–S4 of fibrosis were 6.0, 7.2, 8.0, 9.4, and 12.6 kPa, respectively. The areas under the ROC curve of S≥1, S≥2, S≥3, and S = 4 as predicted by SWE were 0.932, 0.945, 0.945, and 0.916, respectively. According to the Youden index, the optimal critical values for predicting fibrosis S≥1, S≥2, S≥3, and S = 4 were 6.8 (sensitivity of 89.69% and specificity of 93.55%), 7.5 (sensitivity of 87.50 % and specificity of 95.00 %), 8.3 (sensitivity of 87.14 % and specificity of 87.93 %) and 9.8 (sensitivity of 79.55 % and specificity of 86.90 %) kPa. CONCLUSION: 2D-SWE with a propagation map could noninvasively and accurately predict the staging of liver fibrosis in patients with liver tumors before resection.
Pu Zhang, Weiping Wang, Meilan Li
Clinical Hemorheology and Microcirculation, pp 1-18; https://doi.org/10.3233/ch-211259

Abstract:
BACKGROUND: Dysfunction of endothelial cells in the arterial vasculature is an essential contributor to the pathogenesis of atherosclerosis. Circular RNAs (circRNAs) exert important regulatory functions in endothelial cell dysfunction. Here, we explored the precise role and mechanism of circ_0050486 in regulating endothelial cell injury induced by oxidized low-density lipoprotein (ox-LDL). METHODS: Circ_0050486, microRNA (miR)-182-5p and myeloid differentiation primary response gene 88 (MyD88) were quantified by quantitative real-time PCR or western blot. Cell viability, proliferation and apoptosis were examined by MTS, 5-Ethynyl-2’-Deoxyuridine (EdU), and flow cytometry assays, respectively. Direct relationship between miR-182-5p and circ_0050486 or MYD88 was verified by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. RESULTS: Circ_0050486 was upregulated in atherosclerosis serum and ox-LDL-treated human aortic endothelial cells (HAECs). Silencing of circ_0050486 suppressed HAEC injury induced by ox-LDL. Mechanistically, circ_0050486 targeted miR-182-5p, and the effects of circ_0050486 silencing were partially due to the upregulation of miR-182-5p. MYD88 was a direct target of miR-182-5p, and miR-182-5p-mediated inhibition of MYD88 attenuated ox-LDL-evoked HAEC injury. Circ_0050486 bound to miR-182-5p to regulate MYD88 expression. Additionally, the NF-κB signaling pathway was involved in the regulation of circ_0050486/miR-182-5p/MYD88 axis in ox-LDL-treated HAECs. CONCLUSION: Our study identifies the functional role of circ_0050486 in ox-LDL-induced endogenous cell injury and establishes a mechanism of circ_0050486 function by affecting MYD88 through competitively binding to shared miR-182-5p.
Ernst-Michael Jung, Friedrich Jung, Niklas Verloh, Michael Haimerl, Lukas Lürken, Simon Jage, Christian Stroszczynski, Gregor Scharf
Clinical Hemorheology and Microcirculation, pp 1-8; https://doi.org/10.3233/ch-221427

Abstract:
BACKGROUND: Ultrasound follow-up of transjugular intrahepatic portosystemic shunt (TIPS) is challenging due to the bent course of the stent-graft. OBJECTIVE: Aim of this retrospective study was to assess to which extent the combination of HR flow with Glazing Flow improves hemodynamic assessment in the ultrasound follow-up of TIPS. METHODS: Comparative studies with CCDS and High Resolution (HR)-Flow with Glazing Flow were evaluated regarding image quality and artifacts on a 5-point scale (0 = cannot be assessed up to 5 = maximum image quality without artifacts). In all cases, an experienced examiner performed the examinations with a 1–6 MHz probe (Resona 7, Mindray). RESULTS: 61 ultrasound examinations in 48 patients were performed; the mean patient age was 54±14.2 years. The use of HR-Flow with Glazing Flow resulted in an improved flow display in 55/61 cases (90.2% ). Both methods correlated well (r = 0.71), but HR flow with Glazing flow values were in general higher than CCDS values. The reading resulted in an average value of 2.52±0.54 for CCDS and 3.52±0.57 for HR flow with Glazing flow (p = 0.013). CONCLUSION: The combination of HR-Flow and Glazing Flow results in improved flow representation and reduction of artifacts in the ultrasound follow-up of TIPS.
Xian-Quan Shi, Yunyun Dong, XiaoQu Tan, Peipei Yang, Chunmei Wang, Wei Feng, Yuxuan Lin, Linxue Qian
Clinical Hemorheology and Microcirculation, pp 1-12; https://doi.org/10.3233/ch-221456

Abstract:
OBJECTIVE: This study was performed to investigate the accuracy of conventional ultrasound (US), contrast-enhanced US (CEUS), and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in assessing the size of breast cancer. METHODS: In total, 49 breast cancer lesions of 48 patients were included in this study. The inclusion criteria were the performance of total mastectomy or breast-conserving surgery for treatment of breast cancer in our hospital from January 2017 to December 2020 with complete pathological results, as well as the performance of conventional US, CEUS, and DCE-MRI examinations with complete results. The exclusion criteria were non-mass breast cancer shown on conventional US or DCE-MRI, including that found on CEUS with no boundary with surrounding tissues and no confirmed tumor scope; a tumor too large to be completely displayed in the US section, thus affecting the measurement results; the presence of two nodules in the same breast that were too close to each other to be distinguished by any of the three imaging methods; and treatment with preoperative chemotherapy. Preoperative conventional US, CEUS, and DCE-MRI examinations were performed. The postoperative pathological results were taken as the gold standard. The lesion size was represented by its maximum diameter. The accuracy, overestimation, and underestimation rates of conventional US, CEUS, and DCE-MRI were compared. RESULTS: The maximum lesion diameter on US, CEUS, DCE-MRI and pathology were 1.62±0.63 cm (range, 0.6–3.5 cm), 2.05±0.75 cm (range, 1.0–4.0 cm), 1.99±0.74 cm (range, 0.7–4.2 cm) and 1.92±0.83 cm (range, 0.5–4.0 cm), respectively. The lesion size on US was significantly smaller than that of postoperative pathological tissue (P < 0.05). However, there was no significant difference between the CEUS or DCE-MRI results and the pathological results. The underestimation rate of conventional US (55.1%, 27/49) was significantly higher than that of CEUS (20.4%, 10/49) and DCE-MRI (24.5%, 12/49) (P < 0.001 and P = 0.002, respectively). There was no significant difference in the accuracy of CEUS (36.7%, 18/49) and DCE-MRI (34.7%, 17/49) compared with conventional US (26.5%, 13/49); however, the accuracy of both groups tended to be higher than that of conventional US. The overestimation rate of CEUS (42.9%, 21/49) and DCE-MRI (40.8%, 20/49) was significantly higher than that of conventional US (18.4%, 9/49) (P = 0.001 and P = 0.015, respectively). CONCLUSIONS: CEUS and DCE-MRI show similar performance when evaluating the size of breast cancer. However, CEUS is more convenient, has a shorter operation time, and has fewer restrictions on its use. Notably, conventional US is more prone to underestimate the size of lesions, whereas CEUS and DCE-MRI are more prone to overestimate the size.
S. Lau, M. Gossen, A. Lendlein, F. Jung
Clinical Hemorheology and Microcirculation, Volume 81, pp 191-203; https://doi.org/10.3233/ch-211294

Abstract:
In vivo endothelialization of polymer-based cardiovascular implant materials is a promising strategy to reduce the risk of platelet adherence and the subsequent thrombus formation and implant failure. However, endothelial cells from elderly patients are likely to exhibit a senescent phenotype that may counteract endothelialization. The senescence status of cells should therefore be investigated prior to implantation of devices designed to be integrated in the blood vessel wall. Here, human umbilical vein endothelial cells (HUVEC) were cultivated up to passage (P) 4, 10 and 26/27 to determine the population doubling time and the senescence status by four different methods. Determination of the senescence-associated β-galactosidase activity (SA-β-Gal) was carried out by colorimetric staining and microscopy (i), as well as by photometric quantification (ii), and the expression of senescence-associated nuclear proteins p16 and p21 as well as the proliferation marker Ki67 was assessed by immunostaining (iii), and by flow cytometry (iv). The population doubling time of P27-cells was remarkably greater (103±65 h) compared to P4-cells (24±3 h) and P10-cell (37±15 h). Among the four different methods tested, the photometric SA-β-Gal activity assay and the flow cytometric determination of p16 and Ki67 were most effective in discriminating P27-cells from P4- and P10-cells. These methods combined with functional endothelial cell analyses might aid predictions on the performance of implant endothelialization in vivo.
Wei Xu, Lei Qian, Xiaoyan Yuan, Yong Lu
Clinical Hemorheology and Microcirculation, Volume 81, pp 241-253; https://doi.org/10.3233/ch-211232

Abstract:
BACKGROUND: MicroRNAs (miRNAs) have emerged as crucial players in the initiation and development of atherosclerosis (AS), and the low miR-223-3p level is observed in AS patients. However, the function and mechanism behind miR-223-3p in AS progression have not been fully elucidated. METHOD: In the present study, THP-1 cells treated with oxidized low-density lipoprotein (ox-LDL) were employed as the cell model of AS. The expression levels of miR-223-3p, NLR family pyrin domain containing 3 (NLRP3), caspase-1, pro-caspase-1, cleaved interleukin 18 (IL-18), cleaved IL-1β, and forkhead box O3 (FOXO3) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot (WB) analyses. The relationship between miR-223-3p and FOXO3 or NLRP3 was determined using a dual-luciferase reporter assay. The production of IL-1β, IL-18, IL-6, and TNF-α was examined by Enzyme-linked immunosorbent assay (ELISA). RESULTS: MiR-223-3p was decreased in AS patients and ox-LDL-induced THP-1 cells, and its upregulation downregulated the abundance of NLRP3, caspase-1, cleaved IL-18, cleaved IL-1β, IL-1β, IL-6, and TNF-α in THP-1 cells treated with ox-LDL or not, and the depletion of miR-223-3p revealed an opposite phenomenon. NLPR3 and FOXO3 were identified as two authentic targets of miR-223-3p. Knockdown of NLRP3 or FOXO3 reversed the stimulatory effect of the miR-223-3p inhibitor on the inflammatory responses of THP-1 cells. CONCLUSIONS: Our data indicate that miR-223-3p inhibited ox-LDL-mediated NLRP3 inflammasome activation via directly targeting NLRP3 and FOXO3 in THP-1 cells, which offered a prospective therapeutic target for AS therapy.
David Astapenko, Adela Tomasova, Alena Ticha, Radomir Hyspler, Huey Shin Chua, Mubashar Manzoor, Roman Skulec, Christian Lehmann, Robert G. Hahn, Manu Lng Malbrain, et al.
Clinical Hemorheology and Microcirculation, Volume 81, pp 205-219; https://doi.org/10.3233/ch-221401

Abstract:
BACKGROUND: Coronavirus disease (COVID-19) associated endotheliopathy and microvascular dysfunction are of concern. OBJECTIVE: The objective of the present single-center observational pilot study was to compare endothelial glycocalyx (EG) damage and endotheliopathy in patients with severe COVID-19 (COVID-19 group) with patients with bacterial pneumonia with septic shock (non-COVID group). METHODS: Biomarkers of EG damage (syndecan-1), endothelial cells (EC) damage (thrombomodulin), and activation (P-selectin) were measured in blood on three consecutive days from admission to the intensive care unit (ICU). The sublingual microcirculation was studied by Side-stream Dark Field (SDF) imaging with automatic assessment. RESULTS: We enrolled 13 patients in the non-COVID group (mean age 70 years, 6 women), and 15 in the COVID-19 group (64 years old, 3 women). The plasma concentrations of syndecan-1 were significantly higher in the COVID-19 group during all three days. Differences regarding other biomarkers were not statistically significant. The assessment of the sublingual microcirculation showed improvement on Day 2 in the COVID-19 group. Plasma levels of C-reactive protein (CRP) were significantly higher on the first two days in the COVID-19 group. Plasma syndecan-1 and CRP were higher in patients suffering from severe COVID-19 pneumonia compared to bacterial pneumonia patients. CONCLUSIONS: These findings support the role of EG injury in the microvascular dysfunction in COVID-19 patients who require ICU.
Marinka Hoek, Michelle Schultz, Sajee Alummoottil, Natalie Aneck-Hahn, Kgomotso Mathabe, Janette Bester
Clinical Hemorheology and Microcirculation, Volume 81, pp 221-232; https://doi.org/10.3233/ch-211353

Abstract:
BACKGROUND: Increased risk of thromboembolic events is associated with prostate cancer, specifically linked to activation of tissue factor. Vitamin D has potential anticoagulant effects by the downregulation of tissue factor expression. OBJECTIVES: To evaluate the effects on clot formation, the morphological and viscoelastic profiles of prostate cancer patients, before and after ex vivo supplementation of Vitamin D was studied. METHODS: Participants were recruited into a metastatic, non-metastatic and reference group. Whole blood samples were treated ex vivo with a dose of 0.5μg/kg Calcitriol. Clot kinetics were assessed using Thromboelastography®. Morphology of the blood components were studied using scanning electron microscopy (SEM). RESULTS: Results from the Thromboelastography® and SEM indicated no major differences between the non-metastatic group before and after treatment compared to the reference group. The Thromboelastography® showed that the metastatic group had an increased viscoelastic profile relating to a hypercoagulable state. Visible changes with regards to platelet activation and fibrin morphology were demonstrated with SEM analysis of the metastatic group. The viscoelastic and morphological properties for the non-metastatic group after treatment improved to be comparable to the reference group. CONCLUSION: Vitamin D supplementation may lead to a more favorable viscoelastic profile, with less dangerous clots forming.
Ying Duan, Yangyang Zhu, Fang Nie, Ling Guan, Yingying Jia, Kundi Chen, Weili Wang
Clinical Hemorheology and Microcirculation, Volume 81, pp 255-269; https://doi.org/10.3233/ch-221398

Abstract:
OBJECTIVE: To improving diagnosis of axillary lymph node metastasis (ALNM), we assessed the value of combining clinicopathological, conventional ultrasound, SWE features in the cT1-2N0 breast cancer patients. METHODS: Retrospective analysis of 285 patients with cT1-2N0 breast cancer who underwent preoperative ultrasound examination of the lesion and axillary, with shear wave elastography (SWE) of the lesions. According to the postoperative pathological results, they were divided into ≤2 metastatic ALNs group (low nodal burden, LNB) and > 2 metastatic ALNs group (high nodal burden, HNB). Binary logistic regression analysis was used to screen independent risk factors and establish prediction models. The best cut-off value of continuous variables is determined by the receiver operating characteristic curve, and the performance of the prediction model is evaluated. RESULTS: Presence of lymphovascular invasion (OR = 7.966, P = 0.010), tumor size (OR = 2.485, P = 0.019), Emean of intratumor (OR = 0.939, P = 0.002) and cortical thickness of lymph node (OR = 9.277, P < 0.001) were independent risk predictors for HNB of cT1-2N0 Group. The predictive model of combined method had better performance in predicting HNB of cT1-2N0 compared with models based on SWE and conventional ultrasound alone (area under the curve: 0.824 vs 0.658, P < 0.001; 0.824 vs 0.789, P = 0.035). CONCLUSIONS: The predictive models of combined method obtained from significant clinicopathological and ultrasonographic features can potentially improve the diagnosis and individual treatment of ALNM in patients with cT1-2N0 breast cancer.
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