Clinical Hemorheology and Microcirculation - Volume 81, issue 3

Authors: Lau, S. | Gossen, M. | Lendlein, A. | Jung, F.

Article Type: Research Article

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 . Show more

Keywords: Ageing, population doubling time, senescence-associated β-galactosidase, cell cycle inhibitors, p16, p21, Ki67

DOI: 10.3233/CH-211294

Citation: Clinical Hemorheology and Microcirculation, vol. 81, no. 3, pp. 191-203, 2022

Authors: Astapenko, David | Tomasova, Adela | Ticha, Alena | Hyspler, Radomir | Chua, Huey Shin | Manzoor, Mubashar | Skulec, Roman | Lehmann, Christian | Hahn, Robert G. | Malbrain, Manu LNG | Cerny, Vladimir

Article Type: Research Article

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. Show more

Keywords: pneumonia, sepsis, glycocalyx

DOI: 10.3233/CH-221401

Citation: Clinical Hemorheology and Microcirculation, vol. 81, no. 3, pp. 205-219, 2022

Authors: Hoek, Marinka | Schultz, Michelle | Alummoottil, Sajee | Aneck-Hahn, Natalie | Mathabe, Kgomotso | Bester, Janette

Article Type: Research Article

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. Show more

Keywords: Prostate cancer, Vitamin D, thromboelastography® , thrombosis, inflammation

DOI: 10.3233/CH-211353

Citation: Clinical Hemorheology and Microcirculation, vol. 81, no. 3, pp. 221-232, 2022

Authors: Martocchia, A. | Ialungo, S. | Dulcetti, A. | Malena, D.M. | Proietta, M. | Del Porto, F. | Landolfi, F. | Sesti, G. | Sergi, D. | Martelletti, P.

Article Type: Research Article

Abstract: OBJECTIVE: This study aims to evaluate the bedside use of the pocket-sized ultrasound (US) device for the detection of the intracavitary effusions. METHODS: We randomly enrolled 40 patients admitted to S. Andrea Hospital of Rome. Every patient received a clinical and biochemical evaluation and a bedside US examination to detect and estimate the intracavitary (pleural, pericardial and intra-abdominal) effusions; the US measurements have been compared to the computed tomography (CT) scans (as gold standard). RESULTS: The patients presented a high prevalence of effusions: right pleural 16/40 = 40% (esteemed volume 236.3±500.7 ml, mean±standard deviation m ±SD), left pleural 8/40 = 20% …(127.0±377.4 ml), pericardial 12/40 = 30% (47.5±72.8 ml) and intra-abdominal effusions 5/40 = 12.5% of cases (110.9±600.6 ml). Linear regression analysis showed a significant correlation between US and CT measurements: pleural r  = 0.973 p  <  1×10–38 , pericardial r  = 0.927 p  <  1×10–39 , intra-abdominal space r  = 0.921 p  <  1×10–59 . The accuracy of the bedside US at the pleural, pericardial and abdominal level was respectively 98%, 93% and 96% (Cohen’s kappa coefficient 0.966, 0.841 and 0.833). CONCLUSIONS: The present study showed a high prevalence of the intracavitary effusions and a high accuracy of the bedside US. The bedside US by a pocket-sized device is promising tool for its advantages of reproducibility and non-invasiveness of the device. Show more

Keywords: Bedside ultrasound, intracavitary effusions, comorbidity, computed tomography

DOI: 10.3233/CH-221402

Citation: Clinical Hemorheology and Microcirculation, vol. 81, no. 3, pp. 233-240, 2022

Authors: Xu, Wei | Qian, Lei | Yuan, Xiaoyan | Lu, Yong

Article Type: Research Article

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. Show more

Keywords: Atherosclerosis, microRNA-223-3p, inflammasome, FOXO3, NLRP3

DOI: 10.3233/CH-211232

Citation: Clinical Hemorheology and Microcirculation, vol. 81, no. 3, pp. 241-253, 2022

Authors: Duan, Ying | Zhu, Yangyang | Nie, Fang | Guan, Ling | Jia, Yingying | Chen, Kundi | Wang, Weili

Article Type: Research Article

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. Show more

Keywords: Ultrasound, axillary lymph node, early breast cancer, shear-wave elastography

DOI: 10.3233/CH-221398

Citation: Clinical Hemorheology and Microcirculation, vol. 81, no. 3, pp. 255-269, 2022